tahir99-VRG & vip.persianss.

ir
 · I

tahir99-VRG & vip.persianss.ir

 · III

Duus’
Topical Diagnosis
in Neurology
An atom y, Physiology, Sign s,
Sym ptom s
5th edition

Math ias Baeh r, MD

Professor of Neu rology an d Ch airm an
Dep artm en t of Neu rology
Un iversit y of Gött in gen
Göt tin gen , Germ any
R G
-V
Mich ael Frotsch er, MD
9 . i r
Hertie Sen ior Research Professor

i r 9 & ns s
for Neu roscien ce an d Ch airm an
Dep artm en t of Stru ct u ral Neu robiology
h a
ta r s i
Cen ter for Molecu lar Neu robiology
Ham bu rg (ZMNH)
p e
Un iversit y of Ham bu rg
i p .
Ham bu rg, Germ any
v W ith con tribu t ion s by
W ilh elm Ku eker

Fou n din g au th or Peter Du u s

40 0 illu stration s, m ost in color,

by Professor Gerh ard Sp itzer an d Barbara Gay

Th iem e
Stu t tgart · New York

tahir99-VRG & vip.persianss.ir

 IV ·

Library of Congress Cataloging-in-Publication Data Im po rtant note : Medicin e is an ever-ch an gin g scien ce un -
dergoin g con tin u al developm en t. Research an d clin ical ex-
Baeh r, Math ias.
perien ce are con tin u ally exp an din g our kn ow ledge, in p ar-
[Du us’ n eu rologisch -topisch e Diagn ostik. En glish ]
ticu lar ou r kn ow ledge of proper treatm en t an d dru g th er-
Duu s’ topical diagn osis in n eu rology : an atom y,
apy. In sofar as th is book m en tion s any dosage or application ,
Physiology, sign s, sym ptom s/Math ias Baeh r,
readers m ay rest assu red th at th e auth ors, editors, an d p ub-
Mich ael Frotsch er ; w ith con tribution s by
lish ers h ave m ade every effort to en su re th at su ch refer-
Wilh elm Ku eker ; tran slated by Eth an Tau b ;
en ces are in accordan ce w ith the state of know ledge at the
Illu strated by Gerh ard Spitzer. 5th , rev. ed.
time of production of the book.
p. ; cm .
Neverth eless, th is does n ot involve, im ply, or express any
Rev. tran slation of th e 8th Germ an ed. c20 03.
gu aran tee or respon sibility on th e p art of th e p ublish ers in
In cludes in dex.
respect to any dosage in stru ction s an d form s of application s
ISBN 978-3-13-612805-3 (GTV : alk. pap er)
stated in th e book. Every user is requested to examine care-
1. Nervou s system Diseases Diagn osis. 2. Neu roan atom y.
fully th e m an ufactu rers’ leaflets accom panyin g each dru g
3. An atom y, Path ological. 4. Nervou s system Path ophysi-
an d to ch eck, if n ecessary in con sultation w ith a physician or
ology. I. Frotsch er,
specialist, w h eth er th e dosage sch edules m en tion ed th erein
M. (Mich ael), 1947- . II. Du us, Peter, 1908-. Top ical
or th e con train dication s stated by th e m an ufactu rers differ
diagn osis in n eu rology. III. Title. IV. Title: Topical
from th e statem en ts m ade in th e presen t book. Su ch exam i-
diagn osis in n eu rology. [DNLM: 1. Nervou s System
n ation is particu larly im portan t w ith drugs th at are eith er
Diseases–diagn osis. 2. Nervou s System –an atom y &
rarely used or h ave been n ew ly released on th e m arket.
h istology. 3. Nervous System –physiopath ology.
Every dosage sch edu le or every form of ap plication used is
WL 141 B139d 2011]
en tirely at th e user’s ow n risk an d respon sibility. Th e
RC347.D8813 2011
au th ors an d pu blish ers requ est every user to rep ort to th e
616.8’04754 dc22 2011016421
pu blish ers any discrepan cies or in accuracies n oticed. If
errors in th is w ork are fou n d after p ublication , errata w ill be

1st Brazilian 1st Greek edition 1992 page.

G
posted at w w w.th iem e.com on th e p roduct description
R
-V
(Portuguese) edition 1985 2nd Greek edition 2009
2nd Brazilian
(Portuguese) edition 1990
1st Indonesian
9 . i r
1st Chinese edition 1996
edition 1996
i r 9 & ns
Th is book is an auth orized an d revised tran slation of th e 9th
s
Germ an edition pu blish ed an d copyrigh ted 20 09 by Georg
h
1st Italian edition 1987 Th iem e Verlag, Stu ttgart, Germ any. Title of th e Germ an
a
1st English edition 1983
2nd English edition 1989 ta
1st Japanese edition 1982
r s i
edition : Neu rologisch -topisch e Diagn ostik. An atom ie—
Fu n ktion —Klin ik.
3rd English edition 1998
2nd Japanese edition 1984
3rd Japanese edition 1988
p e
1st French edition 1998
p .
4th Japanese edition 1999
i
Con tribu tor: Wilh em Ku eker, MD, Radiological Clin ic, De-
p artm en t of Neu roradiology, Un iversity Hospital Tü bin gen ,
1st Germ an edition 1976
2nd Germ an edition 1980
v
1st Korean edition 1990
Germ any

4th edition tran slated by Eth an Tau b, MD, Klin ik im Park,

1st Polish edition 1990
3rd Germ an edition 1983 Zu rich , Sw itzerlan d. Updates tran slated by Geraldin e
4th Germ an edition 1987 1st Portuguese edition 2008 O’Su llivan , Dublin , Rep. of Irelan d
5th Germ an edition 1990
1st Russian edition 1996 Illustrators: Gerh ard Spitzer, Fran kfurt/M, Germ any;
6th Germ an edition 1995
2nd Russian edition 2009 Barbara Gay, Stu ttgart, Germ any
7th Germ an edition 2001
8th Germ an edition 20 03 1st Spanish edition 1985
9th Germ an edition 2009
1st Turkish edition 2001
Som e of th e p roduct n am es, paten ts, an d registered design s
© 2012 Georg Th iem e Verlag,
referred to in th is book are in fact registered tradem arks or
Rü digerstrasse 14, 70469 Stu ttgart,
p roprietary n am es even th ough specific referen ce to th is
Germ any
fact is n ot alw ays m ade in th e text. Th erefore, th e app ear-
h ttp://w w w.th iem e.de
an ce of a n am e w ith ou t design ation as proprietary is n ot to
Th iem e New York, 333 Seven th Aven u e, be con stru ed as a represen tation by th e p ublish er th at it is
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by copyrigh t. Any u se, exploitation , or com m ercialization
Cover design : Th iem e Pu blish in g Grou p ou tside th e n arrow lim its set by copyrigh t legislation ,
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tahir99-VRG & vip.persianss.ir


Preface
In 20 05 w e pu blish ed a com plete revision of Du us’
textbook of topical diagn osis in n eu rology, th e first
n ew edition sin ce th e death of its origin al auth or,
Professor Peter Du u s, in 1994. Feedback from read-
ers w as extrem ely positive an d th e book w as tran s-
lated in to n u m erou s lan gu ages, provin g th at th e
con cept of th is book w as a su ccessful on e: com bin -
in g an in tegrated p resen tation of basic n eu -
roan atom y w ith t h e su bject of n eurological syn -
drom es, in cludin g m odern im agin g tech n iqu es. In
th is regard w e th an k ou r n eu roradiology col-
leagu es, an d especially Dr. Kueker, for providin g us
w ith im ages of very h igh qu ality.
In th is fifth edition of “Du u s,” w e h ave preserved
th e rem arkably effective didactic con cept of th e
book, w h ich particularly m eet s th e n eeds of m edi-
cal stu den ts. Modern m edical cu rricula require in -
tegrative kn ow ledge, an d m edical stu den ts sh ould
be tau gh t h ow to apply th eoret ical kn ow ledge in a
clin ical settin g an d, on th e oth er h an d, to recogn ize
clin ical sym ptom s by delvin g in to th eir basic
-V
9 9
kn ow ledge of n euroan atom y an d n eu rophysiology.
h i r
Our book fulfils th ese requ irem en ts an d illust rates
th e im portan ce of basic n eu roan atom ical kn ow l- & ns
ta
edge for subsequ en t practical w ork, as it in clu des
s i a
actu al case st udies. We h ave color-coded th e sec-
e r
tion h eadin gs to en able readers to distin gu ish at a
. p
v p
glan ce betw een n euroan atom ical (blu e) an d clin i-
i
cal (green ) m aterial, w ith ou t disruptin g th e th e-
m atic con tin uity of th e text.
V
Alth ou gh th e book w ill be u sefu l to advan ced
stu den ts, also physician s or n eurobiologists in ter-
ested in en rich in g th eir kn ow ledge of n eu -
roan atom y w ith basic in form ation in n eu rology, or
for revision of th e basics of n eu roan atom y w ill
ben efit even m ore from it.
Th is book does n ot preten d to be a textbook of
clin ical n eu rology. Th at w ou ld go beyon d th e scope
of th e book an d also con t radict th e basic con cept
described above. First an d forem ost w e w an t to de-
m on strate h ow, on th e basis of th eoretical an a-
tom ical kn ow ledge an d a good n eurological exam i-
n ation , it is p ossible to localize a lesion in th e
n ervou s system an d com e to a decision on fu rth er
diagn ostic step s. Th e cau se of a lesion is in itially
irrelevan t for th e p rim ary topical diagn osis, an d
elucidation of th e etiology takes place in a secon d
stage. Our book con tain s a cursory overview of th e
R G
m ajor n eurological disorders, an d it is n ot in ten ded
to replace th e system atic an d com preh en sive
coverage offered by stan dard n eu rological text-
i r
books.
s .
We h ope th at th is n ew “Duu s,” like th e earlier
edition s, w ill m erit th e appreciation of its
au dien ce, an d w e look forw ard to receivin g read-
ers’ com m en ts in any form .
Professor M. Baehr
Professor M. Frotscher
tahir99-VRG & vip.persianss.ir
 VI · Preface

Contents

1 Elements of the Nervous System ............................................. 2

Info rm atio n Flo w in the Nervo us System . 2 Functio nal Gro ups o f Ne uro ns . . . . . . . . . . . . 7

Ne uro ns and Synapses . . . . . . . . . . . . . . . . . . . . 2 Glial Cells . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7

Neu ron s . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2
De velo pm ent o f the Ne rvo us Syste m . . . . . . 8
Syn apses . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4

Ne uro transm itters and Recepto rs . . . . . . . . . 7

2 Somatosensory System . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 12

Periphe ral Co m po ne nts o f the So m ato - Posterior Colu m n s . . . . . . . . . . . . . . . . . . . . . . . . . 28

senso ry Syste m and Peripheral Regulato ry An terior Spin oth alam ic Tract . . . . . . . . . . . . . . 30
Circuits . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 12 Lateral Spin oth alam ic Tract . . . . . . . . . . . . . . . . 30
Recep tor Organ s . . . . . . . . . . . . . . . . . . . . . . . . . . 12 Oth er Afferen t Tracts of th e Spin al Cord . . . . 31
Periph eral Nerve, Dorsal Root Gan glion ,
Central Pro ce ssing o f So m ato senso ry
Posterior Root . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Periph eral Regulatory Circuits . . . . . . . . . . . . . .
14
18 R G
Info rm atio n . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 32

Central Co m po ne nts o f the So m ato - -V So m ato se nso ry Deficits due to Le sio ns at

i r
senso ry System . . . . . . . . . . . . . . . . . . . . . . . . . . .
9 9 24
s .
Specific Sites alo ng the So m ato senso ry

Posterior an d An terior Spin ocerebellar

h i r & ns
Pathw ays . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 32

ta
Tracts . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 25
s i a
e r
3 Motor System . p
.................................................................... 36

Ce ntral Co m po nents o f the Mo to r System v i p Co m plex Clinical Syndro m e s due to

and Clinical Syndro m es o f Le sio ns Affect- Le sio ns o f Specific Co m po nents o f the
ing Them . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 36 Ne rvo us Syste m . . . . . . . . . . . . . . . . . . . . . . . . . . 45
Motor Cortical Areas . . . . . . . . . . . . . . . . . . . . . . 36 Spin al Cord Syn drom es . . . . . . . . . . . . . . . . . . . . 45
Corticospin al Tract (Pyram idal Tract) . . . . . . . 38 Vascular Spin al Cord Syn drom es . . . . . . . . . . . 56
Corticon u clear (Corticobulbar) Tract . . . . . . . . 39 Nerve Root Syn drom es (Radicu lar
Oth er Cen tral Com p on en ts of th e Motor Syn drom es) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 57
System . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 39 Plexus Syn drom es . . . . . . . . . . . . . . . . . . . . . . . . . 62
Lesion s of Cen tral Motor Path w ays . . . . . . . . . 41 Periph eral Nerve Syn drom es . . . . . . . . . . . . . . . 67
Syn drom es of th e Neu rom u scu lar Ju n ction
Peripheral Co m po nents o f the Mo to r
an d Mu scle . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 72
System and Clinical Syndro m e s o f Lesio ns
Affecting Them . . . . . . . . . . . . . . . . . . . . . . . . . . . 43
Clin ical Syn drom es of Motor Un it Lesion s . . . 44

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 Contents · VII

4 Brainstem ......................................................................... 74

Surface Anato m y o f the Brainstem . . . . . . . . 74
Medu lla . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 74
Pon s . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 75
Mid brain . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 75
Cranial Ne rves . . . . . . . . . . . . . . . . . . . . . . . . . . . . 77
Origin , Com p on en ts, an d Fu n ction s . . . . . . . . . 77
Olfactory System (CN I) . . . . . . . . . . . . . . . . . . . . 81
Visual System (CN II) . . . . . . . . . . . . . . . . . . . . . . 84
Eye Movem en ts (CN III, IV, an d VI) . . . . . . . . . 89
Trigem in al Nerve (CN V) . . . . . . . . . . . . . . . . . . . 103
Facial Nerve (CN VII) an d Nervu s
In term ediu s . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 109
Vestibulococh lear Nerve (CN VIII)—Coch lear
Com p on en t an d th e Organ of Hearin g . . . . . . 113
Vestibulococh lear Nerve (CN VIII)—
Vestibular Com pon en t an d Vestibular
System . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 120
Vagal System (CN IX, X, an d th e Cran ial
Portion of XI) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 126
Hyp oglossal Nerve (CN XII) . . . . . . . . . . . . . . . . 132
Topo graphical Anato m y o f the Brainstem . 134
In tern al Stru ctu re of th e Brain stem . . . . . . . . . 134
Brainstem Diso rders . . . . . . . . . . . . . . . . . . . . . . 145
Isch em ic Brain stem Syn drom es . . . . . . . . . . . . 145

5 Cerebellum ....................................................................... 158

Surface Anato m y . . . . . . . . . . . . . . . . . . . . . . . . . 158 Cerebellar Functio n and Ce rebe llar

Syndro m es . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 164
Internal Structure . . . . . . . . . . . . . . . . . . . . . . . . 159
Vestibulocerebellum . . . . . . . . . . . . . . . . . . . . . . . 164
Cerebellar Cortex . . . . . . . . . . . . . . . . . . . . . . . . . . 159
Sp in ocerebellu m . . . . . . . . . . . . . . . . . . . . . . . . . . 165
Cerebellar Nu clei . . . . . . . . . . . . . . . . . . . . . . . . . . 160
Cerebrocerebellu m . . . . . . . . . . . . . . . . . . . . . . . . 166
Afferen t an d Efferen t Projection s of th e
Cerebellar Cortex an d Nu clei . . . . . . . . . . . . . . . 162 Cerebellar Diso rders . . . . . . . . . . . . . . . . . . . . . . 167
Cerebellar Isch em ia an d Hem orrh age . . . . . . . 167
Co nne ctio ns o f the Ce re be llum w ith
Cerebellar Tum ors . . . . . . . . . . . . . . . . . . . . . . . . . 167
Other Parts o f the Nervo us Syste m . . . . . . . . 162

6 Diencephalon and Autonomic Nervous System ........................... 170

Lo catio n and Co m po nents o f the Hypo thalam us . . . . . . . . . . . . . . . . . . . . . . . . . . . . 178

Die ncephalo n . . . . . . . . . . . . . . . . . . . . . . . . . . . . 170 Location an d Com pon en ts . . . . . . . . . . . . . . . . . 178
Hyp oth alam ic Nu clei . . . . . . . . . . . . . . . . . . . . . . 179
Thalam us . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 172
Afferen t an d Efferen t Projection s of th e
Nu clei . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 172
Hyp oth alam u s . . . . . . . . . . . . . . . . . . . . . . . . . . . . 180
Position of th e Th alam ic Nuclei in
Fu n ction s of th e Hyp oth alam u s . . . . . . . . . . . . 184
Ascen din g an d Descen din g Path w ays . . . . . . . 172
Fu n ction s of th e Th alam u s . . . . . . . . . . . . . . . . . 176 Peripheral Auto no m ic Ne rvo us Syste m . . . 188
Syn drom es of Th alam ic Lesion s . . . . . . . . . . . . 176 Fu n d am en tals . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 188
Th alam ic Vascular Syn drom es . . . . . . . . . . . . . . 177 Sym path etic Nervou s System . . . . . . . . . . . . . . 190
Parasym path etic Nervous System . . . . . . . . . . 192
Epithalam us . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 177
Auton om ic In nervation an d Fun ction al
Subthalam us . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 178 Distu rban ces of In dividu al Organ s . . . . . . . . . . 193
Visceral an d Referred Pain . . . . . . . . . . . . . . . . . 199

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 VIII · Contents

7 Limbic System .................................................................... 202

Anato m ical Overview . . . . . . . . . . . . . . . . . . . . . 202 Functio ns o f the Lim bic Syste m . . . . . . . . . . . 206
In tern al an d Extern al Con n ection s . . . . . . . . . . 203 Types of Mem ory . . . . . . . . . . . . . . . . . . . . . . . . . 206
Mem ory Dysfu n ction —th e Am n estic
Majo r Co m po nents o f the Lim bic System . 203
Syn drom e an d Its Cau ses . . . . . . . . . . . . . . . . . . 208
Hip p ocam p u s . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 203
Microan atom y of th e Hip pocam p al
Form ation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 203
Am ygdala . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 205

8 Basal Ganglia ..................................................................... 214

Prelim inary Rem arks o n Term ino lo gy . . . . 214 Functio n and Dysfunctio n o f the Basal
Ganglia . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 219
The Ro le o f the Basal Ganglia in the Mo to r
Clin ical Syn drom es of Basal Gan glia
System : Phylo genetic Aspe cts . . . . . . . . . . . . . 214
Lesion s . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 219
Co m po nents o f the Basal Ganglia and
The ir Connectio ns . . . . . . . . . . . . . . . . . . . . . . . . 215
Nu clei . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 215
Con n ection s of th e Basal Gan glia . . . . . . . . . . . 217

9 Cerebrum ......................................................................... 226

De velo pm ent . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 226 Association Fibers . . . . . . . . . . . . . . . . . . . . . . . . . 236

Com m issu ral Fibers . . . . . . . . . . . . . . . . . . . . . . . 238
Gro ss Anatom y and Subdivisio n o f the
Cerebrum . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 228 Functio nal Lo calizatio n in the Cerebral
Gyri an d Su lci . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 228 Co rte x . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 238
Prim ary Cortical Fields . . . . . . . . . . . . . . . . . . . . 239
Histo lo gical Organizatio n of the Cerebral
Association Areas . . . . . . . . . . . . . . . . . . . . . . . . . 247
Co rte x . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 231
Fron tal Lobe . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 248
Lam in ar Arch itectu re . . . . . . . . . . . . . . . . . . . . . . 231
High er Cortical Fu n ction s an d Th eir
Cerebral White Matter . . . . . . . . . . . . . . . . . . . . 235 Im pairm en t by Cortical Lesion s . . . . . . . . . . . . 248
Projection Fibers . . . . . . . . . . . . . . . . . . . . . . . . . . 235

10 Coverings of the Brain and Spinal Cord;

Cerebrospinal Fluid and Ventricular System ............................... 260

Co ve rings o f the Brain and Spinal Co rd . . . 260 Cerebro spinal Fluid and Ventricular
Du ra Mater . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 260 System . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 263
Arach n oid . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 262 Stru ctu re of th e Ven tricu lar System . . . . . . . . 263
Pia Mater . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 262 Cerebrospin al Flu id Circu lation an d
Resorp tion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 263
Distu rban ces of Cerebrosp in al Flu id
Circu lation —Hydroceph alu s . . . . . . . . . . . . . . . . 266

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 Contents · IX

11 Blood Supply and Vascular Disorders

of the Central Nervous System . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 270

Arteries o f the Brain . . . . . . . . . . . . . . . . . . . . . . 270 Cerebral Ische m ia . . . . . . . . . . . . . . . . . . . . . . . . 283

Extradu ral Course of th e Arteries of th e Arterial Hypoperfusion . . . . . . . . . . . . . . . . . . . . 283
Brain . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 270 Particular Cerebrovascular Syn drom es . . . . . . 295
Arteries of th e An terior an d Middle Cran ial Im paired Ven ou s Drain age from th e Brain . . 302
Fossae . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 273
Intracranial Hem o rrhage . . . . . . . . . . . . . . . . . 305
Arteries of th e Posterior Fossa . . . . . . . . . . . . . 275
In tracerebral Hem orrh age (Non trau m atic) . . 305
Collateral Circulation in th e Brain . . . . . . . . . . 278
Su barach n oid Hem orrh age . . . . . . . . . . . . . . . . . 307
Veins o f the Brain . . . . . . . . . . . . . . . . . . . . . . . . 279 Su bdu ral an d Ep id u ral Hem atom a . . . . . . . . . . 311
Su perficial an d Deep Vein s of th e Brain . . . . . 279
Vascular Syndro m es o f the Spinal Co rd . . . 312
Du ral Sin u ses . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 280
Arterial Hypoperfusion . . . . . . . . . . . . . . . . . . . . 312
Blo o d Supply o f the Spinal Co rd . . . . . . . . . . 281 Im paired Ven ou s Drain age . . . . . . . . . . . . . . . . . 312
Arterial An astom otic Netw ork . . . . . . . . . . . . . 281 Sp in al Cord Hem orrh age an d Hem atom a . . . 314
Ven ous Drain age . . . . . . . . . . . . . . . . . . . . . . . . . . 283

Further Reading ....................................................................... 315

Index ..................................................................................... 319

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 X · Contents

Abbreviations

5-HT3 seroton in LPH lipotropin

ACA an terior cerebral artery LTM lon g-term m em ory
ACTH adren ocorticotrop ic h orm on e (corti- MCA m iddle cerebral artery
cotropin ) MD m edial dorsal n u cleu s of th e th alam u s
ADH an tidiu retic h orm on e MEG m agn etoen ceph alography
AIDS acqu ired im m u n odeficien cy syn drom e MIF m elan ocyte-stim u latin g h orm on e-
AMPA α-am in o-3-hydroxy-5-m ethyl-4-isox- in h ibitin g factor
azolepropion ate acid m .l. m edial lem n iscu s
ARAS ascen din g ret icu lar act ivatin g system MLF m edial lon gitu din al fasciculu s
Asp aspartate MP m etacarp oph alan geal
BAEP brain stem au ditory evoked poten tials MRF m elan ocyte-stim u latin g h orm on e-
BPPV ben ign paroxysm al p osition in g releasin g factor
vertigo MRI m agn etic reson an ce im gin g
CA corn u am m on is MSH m elan ocyte-stim u latin g h orm on e
CCA com m on carotid artery NMDA N-m ethyl- D-aspartate
CNS cen tral n ervou s system PCA posterior cerebral artery
CRF corticotropin -releasin g factor PET posit ron em ission tom ography
CSF cerebrospin al flu id PICA posterior in ferior cerebellar artery
CT com p uted tom ography PIF prolactin -in h ibitin g factor
DREZ dorsal root en try zon e (also called t h e (= dop am in e)
Redlich –Oberstein er zon e) PPRF param edian pon tin e reticular form a-
ECA extern al carotid artery tion
ECG electrocardiography/electrocardio- PRF prolactin -releasin g factor
gram PRL prolactin
EEG electroen ceph alography/elect roen - Py pyram idal tract
ceph alogram rCBF region al cerebral blood flow
EMG electrom yography/electrom yogram r.n . red n ucleus
EPSP excitatory postsyn aptic poten tial rtPA recom bin an t tissue plasm in ogen acti-
FLAIR flu id-at ten uated inversion recovery vator
fMRI fu n ction al m agn etic reson an ce SCD subacu te com bin ed degen eration
im agin g SNg su bstan tia nigra
FSH follicle-stim u latin g h orm on e sp .-th . spin oth alm ic tract
GABA γ-am in obu tyric acid SRIF som atotropin in h ibit in g factor
GH (STH) grow t h h orm on e (som atot ropic STM sh ort-term m em ory
h orm on e) STN subt h alm ic n u cleu s
GHRH grow th -h orm on e-releasin g h orm on e T3 triiodothyron in e
Glu glutam ate T4 tetraiodothyron in e (thyroxin e)
Gn RH gon adotrop in -releasin g h orm on e Th th alam u s
Gpe globu s pallidu s TRH thyrotropin -releasin g h orm on e
GPi globu s pallidu s, in tern al segm en t TSH thyroid-stim u latin g h orm on e
HIV h u m an im m u n odeficien cy viru s VA ven tral an terior n u cleus
HMSN h ereditary m otor an d sen sory poly- VEP visual evoked poten tials
n eu ropathy VI ven tral in term ediate n ucleu s
Hz Hertz VL ven tral lateral n u cleus
ICA in tern al carotid artery VOR vestibulo-ocular reflex
INO in tern uclear oph th alm oplegia VPL ven tral posterolateral n ucleu s of th e
IP in terph alan geal th alam u s
IPSP in h ibitory postsyn aptic poten tial VPM ven tral p osterom edial n u cleus of th e
LH luten in izin g h orm on e th alam u s

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 1

1 Elements of the
Nervous System
Information Flow in the
Nervous System . . . . . . . . . . . . . . . . . . 2
Neurons and Synapses . . . . . . . . . . . . . 2
Neurotransmitters and Receptors . . . . 7
Functional Groups of Neurons . . . . . . . 7
Glial Cells . . . . . . . . . . . . . . . . . . . . . . . . 7
Development of the Nervous
System . . . . . . . . . . . . . . . . . . . . . . . . . . 8

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1 2
1 Elements of the Nervous System
Th e n ervous system is com posed of cells, called
neurons, th at are sp ecialized for in form ation p ro-
cessin g an d tran sm ission . Neuron s m ake con tact
w ith each oth er at ju n ction s called synapses, at
w h ich in form ation is tran sferred from on e n eu ron
to th e n ext by m ean s of ch em ical m essen ger
Information Flow in the Nervous
System
In form ation flow in th e n ervous system can be
broken dow n sch em atically in to th ree steps
(Fig. 1.1): an extern al or in tern al stim u lus im pin g-
in g on th e sen se organ s in duces th e gen eration of
n erve im pu lses th at travel tow ard th e cen tral
n ervou s system (CNS) (afferent impulses); com -
plex processin g occu rs w ith in th e CNS (informa-
tion processing); an d, as th e product of th is pro-
cessin g, th e CNS gen erates im pu lses th at travel
tow ard th e periph ery (efferent impulses) an d ef-
fect th e (m otor) resp on se of t h e organ ism to th e
stim u lus. Th u s, w h en a pedestrian sees a green
traffic ligh t, afferen t im pu lses are gen erated in th e
opt ic n erves an d visual system th at convey in for-
m ation about th e sp ecific color p resen t. Th en , at
h igh er levels in th e CNS, th e stim ulu s is in terpreted
an d assign ed a m ean in g (green ligh t = go). Efferen t
im pu lses to th e legs th en effect th e m otor respon se
(crossin g th e street).
In th e sim plest case, in form ation can be tran s-
ferred directly from th e afferen t to th e efferen t
CNS
processing
Afferent impulses Efferent impulses,
from receptors e.g., to the skeletal
at the body surface m uscles
or in the internal organs
Fig. 1.1 Basic organization of information processing in
the nervous system
su bstan ces called neurotransmitters. In gen eral,
n eu ron s can be divided in to tw o classes: exci-
tatory an d inhibitory. Th e organ ization of t h e
n ervou s system is easier to un derstan d after a
brief con sideration of its (on togen etic) develop-
m en t.
arm , w ith ou t any in terven in g com p lex processin g
in th e CNS; th is is w h at h appen s, for exam ple, in an
in trin sic m u scle reflex su ch as th e kn ee-jerk
(patellar) reflex.
Neurons and Synapses
Neurons
Th e neurons an d th eir processes (see below ) an d
th e synapses (see p. 4) are respon sible for th e flow
of in form ation in th e n ervous system . At th e syn -
apses, in form ation is t ran sferred from on e n eu ron
to th e n ext by m ean s of ch em ical su bstan ces called
n eu rotran sm itters.
Dendrites and axons. Neuron s tran sfer in form ation
in on e direction on ly becau se th ey are bipolar: th ey
receive in form at ion from ot h er n eu ron s at on e en d,
an d tran sm it in form ation to ot h er n euron s at th e
oth er en d.
Th e receptive structures of a n erve cell, called
dendrites, are bran ch ed processes attach ed to th e
cell body. Neuron s vary con siderably w ith regard
to th e n um ber an d bran ch in g pattern of th eir den -
drites. Th e forw ard conducting structure is th e
axon, w h ich in h u m an s can be up to a m eter in
len gth . In con trast to th e variable n um ber of den -
drites, each n eu ron p ossesses on ly a single axon . At
its distal en d, th e axon splits in to a n um ber of ter-
m in al bran ch es, each of w h ich en ds in a so-called
term in al bouton th at m akes con tact w ith th e n ext
n eu ron (Fig. 1.2).
Th e lon g periph eral p rocesses of th e pseudo-
un ipolar n euron s of t h e spin al gan glia are an im -
portan t special case. Th ese are th e fibers th at relay
in form ation regardin g touch , pain , an d tem pera-
tu re from th e body surface to th e CNS. Alth ou gh
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 Neurons and Synapses · 3
1
th ey are receptive structu res, th ey n on eth eless
possess t h e structu ral ch aracteristics of axon s an d
are design ated as such .
Dendrites Barr
Th e troph ic (n utritive) cen ter of th e n eu ron is it s body
cell body (soma or perikaryon), w h ich con tain s th e
cell n ucleu s an d various differen t types of su b-
Nucleolus
cellular organ elles. Perikaryon

Nucleus
Axonal transport. Th e n eu rotran sm itters, or th e
en zym es catalyzin g th eir biosyn th esis, are syn -
th esized in th e perikaryon an d th en carried dow n
axon al m icrot ubu les to th e en d of th e axon in a Axon hillock

process kn ow n as axoplasm ic tran sport . Th e n eu- Axon (neurite)

rotran sm it ter m olecu les are stored in syn aptic
vesicles in side th e term in al bou ton s (each bou ton Myelin sheath
con tain s m any syn aptic vesicles). Axoplasm ic
tran sport, gen erally speakin g, can be in eith er
direct ion —from th e cell body tow ard th e en d of
th e axon (anterograde transport), or in th e
reverse direction (retrograde transport). Rapid Collateral axon
axoplasm ic tran sport proceeds at a speed of 20 0–
40 0 m m /day. Th is is distin ct from axoplasm ic
flow, w h ose sp eed is 1–5 m m /day. Axoplasm ic
tran sport is exploited in th e research laboratory Collateral axon
by an terograde an d retrograde tracer tech n iques
for th e an atom ical dem on st ration of n eu ral pro-
jection s (Fig. 1.3).

Axon myelination. Axon s are surroun ded by a

sh eath of m yelin (Fig. 1.4). Th e m yelin sh eath ,
w h ich is form ed by oligodendrocytes (a special
class of glial cells) in th e cen tral n ervou s system
an d by Schw ann cells in th e periph eral n ervou s
system , is a sh eet like con tin u ation of th e oligoden -
drocyte or Sch w an n cell m em bran e th at w rap s it- Axon ending (term inal)
self arou n d th e axon m u ltip le t im es, providin g with term inal bouton

electrical in sulation . Many oligoden drocytes or

Sch w an n cells form th e m yelin surroun din g a
sin gle axon . Th e segm en ts of m yelin sh eath form ed
by tw o adjacen t cells are sep arated by an area of
un covered axon al m em bran e called a node of Ran-
vier. Becau se of th e in su latin g p roperty of m yelin ,
an action poten tial cau ses depolarization on ly at
th e n odes of Ranvier; th u s, n eu ral excitation ju m ps
from on e n ode of Ranvier to th e n ext, a process
kn ow n as saltatory conduction. It follow s th at
n eu ral con du ction is fastest in n euron s th at h ave
th ick in su latin g m yelin w ith n odes of Ranvier
sp aced w idely apart. On th e oth er h an d, in axon s
th at lack a m yelin coverin g, excitation m u st travel
relatively slow ly dow n t h e en tire axon al m em -
Fig. 1.2 Structure of a neuron (schem atic drawing).
From : Kahle W and Frotscher M: Color Atlas of Hum an Anat-
omy, Vol. 3, 6th ed., Thiem e, Stuttgart, 2010.
bran e. Betw een th ese tw o extrem es t h ere are
axon s w ith m yelin of in term ediate t h ickn ess. Th u s,
axon s are divided in to thickly myelinated, thinly
myelinated, an d unmyelinated axons (n erve
fibers); th ese classes are also design ated by th e let-
ters A, B, an d C. Th e th ickly m yelin ated A fibers are
of 3–20 µm diam eter an d con du ct at speeds u p to
120 m /s. Th e th in ly m yelin ated B fibers are up to
3 µm t h ick an d con duct at speeds up to 15 m /s. Th e

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1 4 · 1 Elem ents of the Nervous System
Fig. 1.3 Tracing of neuronal projections w ith retro-
grade and anterograde tracer substances. Tracer sub-
stances, such as fluorescent dyes, are injected either at the
site of origin or at the destination of the neuronal pathway
in question. The tracer substances are then transported
along the neurons, either from the cell bodies to the axon
term inals (anterograde transport) or in the reverse direc-
tion (retrograde transport). It is thus possible to trace the
entire projection from one end to the other.
a Retrograde transport.
b Retrograde transport from m ultiple projection areas of a
single neuron.
c Anterograde transport from a single cell body into m ul-
tiple projection areas.
From : Kahle W and Frotscher M: Color Atlas of Hum an Anat-
omy, vol. 3, 6th ed., Thiem e, Stuttgart, 2010.
6
5
7 2
Fig. 1.4 Nerve fiber in the central nervous system, w ith
oligodendrocyte and myelin sheath (schem atic drawing).
1, Oligodendrocyte. 2, Axon. 3, Myelin sheath. 4, Node of
Ranvier. 5, Inner m esaxon. 6, Outer m esaxon. 7, Pockets of
cytoplasm . From : Kahle W and Frotscher M: Color Atlas of
Hum an Anatomy, Vol. 3, 6th ed., Thiem e, Stuttgart, 2010.
un m yelin ated C fibers con du ct n o faster th an
2 m /s.
Synapses
General structure. As late as th e 1950s, it w as st ill
un clear w h eth er n eu ron s w ere con n ected to each
oth er in a con tin uou s n etw ork (syn cytium ), w h ich
w ould th eoretically allow rapid electrical com -
m u n ication betw een n euron s, or w h eth er each
n eu ron w as en tirely en closed in its ow n m em -
bran e. Su bsequ en t visualization of syn ap ses u n der
th e electron m icroscope settled th e qu estion : th ere
is n o direct spatial con tin u ity betw een n euron s.
Th e axon en ds on on e side of th e syn apse, an d
n eu ral im pu lses are conveyed across it by special
tran sm itter substan ces (Fig. 1.5). Th e axon term in al
(bou ton ) is th e presynaptic part of th e syn apse, an d
th e m em bran e of th e cell receivin g th e tran sm itted
in form ation is th e postsynaptic part . Th e p resyn -
aptic an d postsyn aptic m em bran es are separated
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by th e syn aptic cleft. Th e bouton con tain s vesicles
filled w ith th e n eu rotran sm itter subst an ce.
Exam in ation of syn apses u n der th e electron m i-
croscope reveals specialized, osm ioph ilic th icken -
in gs of th e presyn aptic an d p ostsyn aptic m em -
bran es, w h ich are m ore pron ou n ced on t h e postsy-
n aptic side in so-called asymmetrical synapses,
an d are app roxim ately equally th ick on bot h sides
in so-called symmetrical synapses. Th ese tw o
types of syn apse are also kn ow n , after th eir origi-
n al describer, as Gray type I an d Gray type II syn-
apses, respect ively. Asym m etrical syn apses w ere
fou n d to be excitatory an d sym m etrical syn ap ses
to be in h ibitory (see below for th e con cepts of exci-
tation an d in h ibition ). Th is hypoth esis w as later
con firm ed by im m u n ocytoch em ical stu dies usin g
an tibodies directed again st n eurotran sm itter su b-
stan ces an d th e en zym es involved in th eir bio-
syn th esis.
Synaptic transmission (Fig. 1.6) is essen tially a
sequen ce of th ree differen t processes:
¼ Th e excitatory im pu lse (action potential) arriv-
in g at th e axon term in al depolarizes th e presy-
n aptic m em bran e, cau sin g voltage-depen den t
calciu m ch an n els to open . As a result, calciu m
ion s flow in to th e term in al bouton an d th en in -
teract w ith variou s protein s to cau se fusion of
syn aptic vesicles w ith th e p resyn aptic m em -
bran e. Th e n eu rotran sm it ter m olecu les w it h in
th e vesicles are th ereby released in to th e syn ap-
tic cleft.
¼ Th e n eu rot ran sm itter m olecu les diffu se across
th e syn aptic cleft an d bin d to specific receptors
on t h e postsyn aptic m em bran e.
¼ Th e bin din g of n eurotran sm itter m olecules to
receptors causes ion ch an n els to open , in du cin g
ion ic curren ts th at cau se eith er a depolarization
or a hyperp olarization of th e postsyn aptic
m em bran e—i.e., eith er an excitatory postsynap-
tic potential (EPSP) or an inhibitory postsynaptic
potential (IPSP). Th u s, syn aptic tran sm ission re-
sult s in eit h er an excit ation or an in h ibition of
th e postsyn aptic n eu ron .
In addition to th ese fast-actin g tran sm itter-gated
or ligand-gated ion channels, th ere are also G-pro-
tein-coupled receptors th at gen erate a m u ch slow er
respon se by m ean s of an in tracellu lar sign al cas-
cade.
Neurons and Synapses · 5
1
7
6
4
5
1
2
3
Fig. 1.5 Synaptic structure (schem atic drawing). 1, Pre-
synaptic m em brane with gridlike thickening, leaving hexa-
gonal spaces in between. 2, Synaptic cleft. 3, Postsynaptic
m em brane. 4, Synaptic vesicle. 5, Fusion of a synaptic ves-
icle with the presynaptic m em brane (so-called Ω [om ega]
figure), with release of the neurotransm itter (green) into
the synaptic cleft. 6, Vesicle with neurotransm itter
m olecules taken back up into the term inal bouton. 7, Axon
filam ents. From : Kahle W and Frotscher M: Color Atlas of
Hum an Anatomy, Vol. 3, 6th ed., Thiem e, Stuttgart, 2010.
1
4 5
K+
Na +
4
K+
Na +
Mg 2+ 2
Ca 2+
Glutamate 3
Fig. 1.6 Synaptic transmission at a glutamatergic (exci-
tatory) synapse (schem atic drawing). The arriving action
potential induces an influx of Ca 2+ (1), which, in turn, causes
the synaptic vesicles (2) to fuse with the presynaptic m em -
brane, resulting in the release of neurotransm itter (in this
case, glutam ate) into the synaptic cleft (3). The neu-
rotransm itter m olecules then diffuse across the cleft to the
specific receptors in the postsynaptic m em brane (4) and
bind to them , causing ion channels (5) to open, in this case
Na + channels. The resulting Na + influx, accom panied by a
Ca 2+ influx, causes an excitatory depolarization of the post-
synaptic neuron (excitatory postsynaptic potential, EPSP).
This depolarization also rem oves a blockade of the so-called
NMDA receptor by Mg 2+ ions. From : Kahle W and Frotscher
M: Taschenatlas der Anatom ie, vol. 3, 8th ed., Thiem e,
Stuttgart, 2002.
1 6 · 1 Elem ents of the Nervous System
Chemical and electrical synapses. Th e t ype of syn -
aptic tran sm ission described above, involvin g th e
release an d receptor bin din g of a n eu rot ran sm itter,
is th e typ e m ost com m on ly foun d. Th ere are also
so-called elect rical syn apses in w h ich th e excita-
tion is tran sm itted directly to th e n ext n eu ron
across a gap junction.
Types of synapses. Syn ap ses m ediate th e tran sfer of
in form ation from on e n eu ron to th e n ext; th e syn -
apses th at brin g in form ation to a particu lar cell are
kn ow n as its input synapses. Most inp ut syn apses
are to be fou n d on a cell’s den drites (axodendritic
synapses). Th e den drites of m any n eu ron s (e.g., cor-
tical pyram idal cells) p ossess th orn like p rocesses,
th e dendritic spines, th at en able th e com partm en -
talization of syn aptic inpu t. Many spin es con tain a
spine apparatus for th e in tern al storage of calciu m
ion s. Th e syn apses on den dritic spin es are m ain ly
asym m et rical, excit atory syn apses.
Inpu t syn apses are fou n d n ot on ly on th e den -
drites bu t also on th e cell body itself (perikaryon ;
axosomatic synapses) an d even on th e axon an d its
in itial segm en t, th e axon h illock (axo -axonal syn-
apses).
Convergence and divergence of synaptic connec-
tions. In gen eral, each in dividual n eu ron receives
in form ation th rou gh syn ap ses from m any differen t
n eu ron s an d n eu ron types (convergence of in for-
m ation tran sfer). Th e n eu ron can , in tu rn , m ake
syn aptic con tact w it h a large n um ber of oth er n eu -
Fig. 1.7 Three types of
neuronal inhibition.
a, Recurrent inhibition.
b, Forward inhibition.
c, Disinhibition. From :
Kahle W and Frotscher M:
Taschenatlas der Anatom ie,
vol. 3, 8th ed., Thiem e,
Stuttgart, 2002.
ron s th rough n u m erou s collateral axon al bran ch es
(divergence of in form at ion tran sfer).
Excitation and inhibition. Th e n ervous system is
con stru cted in su ch a w ay th at each n eu ron can be
in on e of tw o basic states at any m om en t: eith er
th e n eu ron is electrically disch argin g an d tran s-
m ittin g in form ation via syn apses to oth er n eu ron s,
or else it is silen t. Excitatory inpu t to th e n euron
cau ses it to disch arge, w h ile in h ibitory inpu t
cau ses it to be silen t.
It follow s th at n euron s can be classified as exci-
tatory an d in h ibitory in term s of th eir effect on
th e n eu ron s to w h ich th ey provide inpu t. Exci-
tatory neurons are u su ally prin cip al n euron s (e.g.,
th e pyram idal cells of th e cerebral cortex), w h ich
often project over lon g dist an ces an d t h u s h ave
lon g axon s. Inhibitory neurons, on th e ot h er h an d,
are often in tern eu ron s an d h ave sh ort axon s.
Principles of neuronal inhibition (Fig. 1.7). Collater-
als of excitatory cells can act ivate in h ibitory in ter-
n eu ron s, w h ich th en in h ibit th e prin cipal n eu ron
itself (recurrent inhibition, a form of n egative feed-
back). In forw ard inhibition, collaterals of p rin cipal
n eu ron s activate in h ibitory in tern eu ron s th at th en
in h ibit oth er prin cipal n eu ron s. Wh en an in h ibi-
tory n eu ron in h ibits an oth er in h ibitory n euron , th e
result in g decrease in in h ibition of th e postsyn aptic
p rin cip al cell causes a n et in crease in its activity
(disinhibition).

Neurotransmitters and
Receptors
Excitatory and inhibitory neurotransmitters. In
classic n eu roan atom ical stu dies, n euron s w ere
divided in to tw o m ajor types on th e basis of th eir
sh ape an d th e len gt h of th eir project ion s: prin cipal
n eu ron s w it h distan t projection s w ere called Golgi
type I n eu ron s, w h ile in tern eu ron s w ith sh ort
axon s w ere called Golgi type II n euron s. Curren tly,
n eu ron s are u su ally classified accordin g to th eir
neurotransm itter phenotype, w h ich gen erally de-
term in es w h eth er th ey are excitatory or in h ibitory.
Th e com m on est excitatory n eu rotran sm itter in t h e
CNS is glutamate, w h ile th e com m on est in h ibitory
n eu rotran sm itter is γ-aminobutyric acid (GABA).
Th e in h ibitory n eu rotran sm itter in th e sp in al cord
is glycine. Acetylcholine an d norepinephrine are
th e m ost im portan t n eu rotran sm itters in th e au -
ton om ic n ervous system bu t are also fou n d in th e
CNS. Oth er im portan t n eu rotran sm itters in clu de
dopamine, serotonin, an d variou s neuropeptides,
m any of w h ich h ave been (an d con tin u e to be)
iden tified; th ese are fou n d m ain ly in in tern eu ron s.
Ligand-gated receptors. Ligan d-gated ion ch an n els
are con stru cted of m u ltiple su bun its th at span th e
cell m em bran e. Th e bin din g of n eu rotran sm itter to
th e receptor op en s th e ion ch an n el (i.e., m akes it
perm eable) for on e or m ore particular sp ecies of
ion .
Excitatory am ino acid receptors. Glu tam ate recep-
tors are subdivided in to th ree types called AMPA,
NMDA, an d kainate receptors. Glutam ate bin din g to
an AMPA receptor resu lts in an in flu x of Na + ion s,
w h ich dep olarizes th e cell. Th e activation of an
NMDA receptor also cau ses an Na + in flux, accom -
pan ied by a Ca 2+ in flux. Th e NMDA receptor,
h ow ever, can be activated on ly after th e blockade
of it s ion ch an n el by a m agn esiu m ion is rem oved;
th is, in turn , is accom plish ed th rou gh an AMPA-
receptor-in du ced m em bran e depolarization
(Fig. 1.6). Th e excitatory n eurotran sm itter glu ta-
m ate th us h as a graded effect: it activates AMPA re-
ceptors first an d NMDA receptors later, after th e
m em bran e h as been depolarized.
Inhibitory GABA and glycine receptors. Th e activa-
tion of eit h er of th ese tw o types of receptor causes
Glial Cells · 7
1
an in flu x of n egat ively ch arged ch loride ion s, an d
th us a hyperpolarization of th e postsyn aptic cell.
Oth er types of ligan d-gated ion ch an n el in clu de
th e nicotinic acetylcholine receptor an d th e sero-
ton in (5-HT3 ) receptor.
G-protein-coupled receptors. Th e respon se to a
st im u lus actin g th rough a G-protein -cou pled re-
ceptor lasts con siderably lon ger, as it results from
th e activation of an in tracellu lar sign al cascade. Th e
respon se m ay con sist of ch an ges in ion ch an n els or
in gen e exp ression . Exam ples of G-protein -cou pled
receptors in clude m uscarin ic acetylch olin e recep-
tors an d m etabotropic glu tam ate receptors.
Functional Groups of Neurons
As discussed earlier, n euron s are cu rren t ly
classified accordin g to th e n eu rotran sm itters th at
th ey release. Th u s, on e speaks of th e glutam atergic,
GABAergic, cholinergic, an d dopam inergic system s,
am on g oth ers. Th ese system s h ave distin ct proper-
ties. Glu tam atergic n eu ron s m ake poin t-to-p oin t
con n ection s w ith th eir target cells, w h ile th e
dopam in ergic system , for exam ple, h as rath er m ore
diffu se con n ection s: a sin gle dopam in ergic n eu ron
gen erally projects to a large n u m ber of target n eu -
ron s. Th e con n ection s of th e GABAergic system are
particu larly h igh ly specialized. Som e GABAergic
n eu ron s (basket cells) m ake n um erous syn aptic
con n ection s on to th e cell body of th e postsyn aptic
n eu ron , form in g a basketlike stru ctu re arou n d it;
oth ers form m ain ly axoden dritic or axo-axon al
syn apses. Th e latter are fou n d at th e axon h illock.
Neurotransm itter analogues or receptor blockers can
be applied pharm acologically for th e specific en -
h an cem en t or w eaken in g of th e effects of a partic-
ular n eu rotran sm itter on n euron s.
Glial Cells
Th e n u m erically m ost com m on cells in th e n ervou s
system are, in fact, n ot th e n eu ron s, bu t th e glial
cells (also called glia or n eu roglia). Th ese cells play
an in dispen sable su pportive role for th e fun ction of
n eu ron s. Th e th ree typ es of glial cells in th e CNS
1 8 · 1 Elem ents of the Nervous System
are t h e astroglial cells (astrocytes), oligoden droglia
(oligoden drocytes), an d m icroglial cells.
Astrocytes are divided in to tw o types: p roto-
plasm ic an d fibrillary. In th e in tact n ervou s system ,
astrocytes are respon sible for th e m ain ten an ce of
th e in tern al environ m en t (h om eostasis), particu-
larly w ith respect to ion con cen tration s. Fin e astro-
cyte processes su rrou n d each syn apse, sealin g it off
from its su rroun din gs so th at th e n eu rotran sm it ter
can n ot escap e from th e syn aptic cleft. Wh en th e
cen tral n ervous system is in ju red, astrocytes are
respon sible for th e form ation of scar tissu e (glio-
sis).
Th e oligodendrocytes form th e m yelin sh eat h s
of th e CNS (see p. 7). Th e microglial cells are ph ago-
cytes th at are activated in in flam m atory an d
degen erative p rocesses affectin g th e n ervou s sys-
tem .
Development of the Nervous
System
A detailed discu ssion of th e develop m en t of th e
n ervou s system w ou ld be beyon d th e scope of th is
book an d n ot direct ly relevan t to its pu rpose. Th e
physician sh ou ld u n derstan d som e of th e basic
prin ciples of n eu ral developm en t, h ow ever, as
develop m en tal dist urban ces accou n t for a large
n u m ber of diseases affectin g th e n ervou s system .
Th e n ervou s system develops from th e (in itially)
lon git udin ally orien ted neural tube, w h ich con sists
of a solid w all an d a cen tral flu id-filled cavity. Th e
cran ial portion of th e n eural tube grow s m ore ex-
ten sively th an th e rest to form three distinct brain
vesicles, th e rhom bencephalon (h in dbrain ), th e
m esencephalon (m idbrain ), an d th e prosencephalon
(forebrain ). Th e prosen ceph alon , in tu rn , becom es
fu rth er differen tiated in to a cau dal part, th e dien-
cephalon, an d th e m ost cran ial portion of th e en tire
n eu ral tube, th e paired telencephalon (en dbrain ).
Th e cen tral cavit y of th e tw o telen ceph alic ven -
tricles com m u n icates w ith th at of th e dien -
ceph alon th rou gh th e in terven tricular foram en
(destin ed to becom e th e foram en of Mon ro). Th e
cen tral cavity u n dergoes its greatest en largem en t
in th e areas w h ere th e n eu ral tu be h as its m ost
pron oun ced grow th ; th u s, th e lateral ven t ricles
form in th e t w o h alves of th e telen ceph alon , th e
th ird ven tricle w ith in th e dien ceph alon , an d th e
fou rth ven tricle in th e brain stem . In th ose seg-
m en ts of th e n eu ral tu be th at grow to a relatively
lesser exten t, su ch as th e m esen ceph alon , n o ven -
tricle is form ed (in th e fu lly develop ed organ ism ,
th e cerebral aqu edu ct ru n s th rou gh th e m esen -
ceph alon ).
Over th e course of vertebrate phylogeny, pro-
gressive en largem en t of th e telen ceph alon h as
cau sed it to overlie th e brain stem an d to rotate
back on itself in sem icircular fash ion . Th is rotation
is reflected in th e stru ctu re of variou s com pon en ts
of th e telen ceph alic gray m atter, in cludin g th e cau -
date n u cleus an d h ippocam pu s; in th e cou rse of
certain w h ite m atter tracts, such as th e forn ix; an d
in th e sh ape of th e lateral ven tricles, each of w h ich
is com p osed of a fron tal h orn , a cen tral portion
(atriu m ), an d a tem poral h orn , as sh ow n in
Fig. 10.3, p . 262.
Cellular proliferation. Im m ature n euron s (n eu ro-
blasts) proliferate in th e ven tricu lar zon e of th e
n eu ral tu be, i.e., th e zon e n eigh borin g its cen tral
cavity. It is a m ajor aim of cu rren t research in n eu -
roem bryology to u nveil th e m olecular m ech an ism s
con trollin g n eu ron al proliferation .
Neuronal migration. New ly form ed n erve cells
leave th e ven tricu lar zon e in w h ich th ey arise, m i-
gratin g alon g radially orien ted glial fibers tow ard
th eir defin itive location in th e cortical plate. Migra-
tory processes are described in greater detail on
pp. 227 ff.
Grow th of cellular processes. On ce th ey h ave ar-
rived at th eir destin ation s, th e postm igratory n eu-
roblasts begin to form den drites an d axon s. On e of
th e m ajor qu estion s in n eu robiology today is h ow
th e n ew ly sprou ted axon s fin d th eir w ay to th eir
correct targets over w h at are, in som e cases, very
lon g distan ces. Im portan t roles are p layed in th is
process by m em bran e-bou n d an d soluble factors
th at are presen t in a con cen tration gradien t, as
w ell as by extracellular m atrix protein s. Th ere are
ligan d–receptor system s th at exert both attractive
an d repulsive in flu en ces to steer th e axon in to th e
appropriate target area. Th ese system s can n ot be
described in greater detail h ere.
Synaptogenesis. Th e axon term in als, h avin g fou n d
th eir w ay to th eir targets, proceed to form syn aptic
con tacts. Recen t stu dies h ave sh ow n th at th e for-

m ation of syn apses, an d of den dritic spin es, is ac-
tivity-depen den t. Mu ch eviden ce su ggests th at
n ew syn apses can be laid dow n th rou gh ou t th e
lifespan of th e in dividu al, providin g th e basis of
adaptive processes su ch as learn in g an d m em ory.
Developm ent of the Nervous System · 9
1
Physiological neuronal death (program m ed cell
death , apoptosis). Many n eu ron s die as th e CNS
develop s, presu m ably as p art of th e m ech an ism
en ablin g th e precise an d specific form ation of in -
tern euron al con n ection s. Th e regu lation of n eu-
ron al su rvival an d n eu ron al death is a m ajor topic
of cu rren t research .
1 10 · 1 Elem ents of the Nervous System
 2

2 Somatosensory
System
Peripheral Components of the
Somatosensory System and
Peripheral Regulatory Circuits . . . . . . . 12
Central Components of the
Somatosensory System . . . . . . . . . . . . 24
Central Processing of Somatosensory
Information . . . . . . . . . . . . . . . . . . . . . . 32
Somatosensory Deficits due
to Lesions at Specific Sites along
the Somatosensory Pathw ays . . . . . . . 32
2 12
2 Somatosensory System
After a prelim in ary ch apter on t h e stru ctu ral ele-
m en ts of th e n ervou s system , th e discu ssion of its
m ajor fu n ction al com pon en ts an d m ech an ism s
n ow begin s w ith th e perceptual processes m edi-
ated by receptor organs: as depicted earlier in
Figure 1.1, th ese organ s are th e site of origin of in -
form at ion flow in th e n ervou s system , in accor-
dan ce w ith t h e basic organ izin g prin cip le, percep-
tion processin g respon se. Som atosen sory im -
pulses from th e p eriph ery are con ducted alon g an
afferent nerve fiber to its n eu ron al cell body, w h ich
lies in a dorsal root ganglion (spinal ganglion). Th e
im pu lses are th en con du cted onw ard in to th e
Peripheral Components of the
Somatosensory System and
Peripheral Regulatory Circuits
Receptor Organs
Receptors are specialized sen sory organ s th at reg-
ister physical an d ch em ical ch an ges in th e extern al
an d in tern al environ m en t of t h e organ ism an d
convert (tran sduce) th em in to th e electrical im -
pu lses th at are processed by th e n ervou s system .
Th ey are fou n d at th e periph eral en d of afferen t
n erve fibers. Som e receptors in form th e body
abou t ch an ges in th e n earby extern al environ m en t
(exteroceptors) or in th e distan t extern al environ -
m en t (teleceptors, su ch as th e eye an d ear). Propri-
oceptors, su ch as th e labyrin th of th e in n er ear,
convey in form ation abou t th e p osition an d m ove-
m en t of th e h ead in space, ten sion in m u scles an d
ten don s, th e position of th e join ts, th e force
n eeded to carry out a particu lar m ovem en t, an d so
on . Fin ally, processes w it h in th e body are reported
on by enteroceptors, also called visceroceptors (in -
clu din g osmoceptors, chemoceptors, an d barocep-
tors, am on g oth ers). Each type of receptor re-
spon ds to a stim u lus of th e appropriate, sp ecific
kin d, p rovided th at th e in ten sity of th e stim ulu s is
above th resh old.
Sen sory receptor organ s are abu n dan t ly p resen t
in th e skin bu t are also fou n d in deeper region s of
th e body an d in th e viscera.
central nervous system, w ith ou t any in terven in g
syn apses, alon g t h e cen tral process (axon ) of th e
sam e n eu ron . Th is axon m akes syn aptic con tact
w ith a second neuron in th e spin al cord or brain -
stem , w h ose axon , in tu rn , proceeds fu rth er cen -
trally, an d crosses the midline to th e opposite side
at som e level alon g its path . Th e third neuron lies
in th e thalamus, th e so-called “gatew ay to con -
sciousn ess”; it projects to variou s cortical areas,
m ost im portan tly th e prim ary som atosen sory
cortex, w h ich is located in th e postcentral gyrus of
th e parietal lobe.
Receptors in the Skin
Most receptors in th e skin are exteroceptors. Th ese
are divided in to t w o classes: (1) free n erve en din gs
an d (2) en capsu lated en d organ s.
Th e en cap su lated, differen tiated en d organ s are
probably m ain ly respon sible for th e m ediation of
epicrit ic sen sory m odalities su ch as fin e touch , dis-
crim in ation , vibration , p ressu re, an d so forth ,
w h ile th e free n erve en din gs m ediate protopath ic
m odalities such as pain an d tem p eratu re. Th e evi-
den ce for th is fu n ction al distin ction is in com plete,
h ow ever (see below ).
Various receptor organ s of th e skin an d its ap-
pen dages are depicted in Figu re 2.1, in clu din g
mechanoreceptors (for tou ch an d p ressu re), ther-
moreceptors (for w arm an d cold), an d nociceptors
(for pain ). Th ese receptors are located m ain ly in
th e zon e betw een th e ep iderm is an d th e con n ec-
tive tissue. Th e skin can th us be regarded as a
sen sory organ th at covers th e en tire body.
Special receptor organs. Th e peritrichial nerve
endings aroun d t h e h air follicles are fou n d in all
areas of h air-bearin g skin an d are activated by th e
m ovem en t of h airs. In con trast, th e tactile cor-
puscles of Meissner are foun d on ly on glabrou s
skin , particu larly on th e palm s an d soles bu t also
on th e lips, th e tip of th e ton gue, an d th e gen it als,
an d respon d best to tou ch an d ligh t pressu re. Th e
laminated Vater–Pacini corpuscles (pacin ian cor-
pu scles) are foun d in deep er layers of th e skin ,
especially in th e area betw een th e cut is an d th e
subcu tis, an d m ediate pressu re sen sation s. Th e end
 Peripheral Com ponents of the Som atosensory System and Peripheral Regulatory Circuits · 13
2
bulbs of Krause w ere on ce th ou gh t to be cold re-
ceptors, w h ile th e corpuscles of Ruffini w ere
th ough t to be w arm receptors, but th ere is som e
dou bt abou t th is at presen t. Free n erve en din gs
h ave been foun d to be able to tran sm it in form ation
abou t w arm th an d cold as w ell as about posit ion .
In th e corn ea, for exam ple, on ly free n erve en din gs
are presen t to tran sm it in form ation abou t all of
th ese sen sory m odalities. Aside from th e receptor
types specifically m en tion ed h ere, t h ere are also
m any oth ers in th e skin an d elsew h ere w h ose
fu n ction m ostly rem ain s u n clear.

Free nerve endings (Fig. 2.1) are fou n d in th e clefts

betw een epiderm al cells, an d som et im es also on
m ore specialized cells of n eu ral origin , su ch as th e
tactile disks of Merkel. Free n erve en din gs are p re-
sen t, h ow ever, n ot just in th e skin but in pract ically
all organ s of th e body, from w h ich th ey convey
n ociceptive an d th erm al in form ation relatin g to
cellular in jury. Merkel’s disks are m ain ly located in
th e pads of th e fin gers an d respon d to tou ch an d
ligh t p ressu re.

Receptors in Deeper Regions of the Body

A secon d grou p of receptor organ s lies deep to th e
skin , in th e m u scles, ten don s, fasciae, an d join ts
(Fig. 2.2). In th e m u scles, for exam ple, on e fin ds
m uscle sp in dles, w h ich respon d to stretch in g of
th e m u sculature. Oth er types of receptors are
fou n d at th e t ran sit ion betw een m uscles an d ten -
don s, in th e fasciae, or in join t capsules.
Muscle spindles are very th in , spin dle-sh aped bo-
dies th at are en closed in a con n ective-tissue cap-
sule an d lie bet w een th e striated fibers of th e
skelet al m uscu latu re. Each m u scle sp in dle it self
usu ally con tain s 3–10 fin e striated m uscle fibers,
w h ich are called intrafusal muscle fibers in con -
trast to th e extrafusal fibers of th e m u scular tissu e
proper. Th e tw o en ds of each spin dle, com posed of
con n ective tissu e, are fixed w ith in th e con n ective
tissu e betw een m uscle fascicles, so th at th ey m ove
in con ju n ction w ith th e m u scle. An afferen t n erve
fiber called an an n ulospiral en din g or prim ary
en din g w in ds arou n d th e m iddle of th e m u scle
spin dle. Th is afferen t fiber h as a very th ick m yelin
sh eath an d belon gs to th e m ost rapidly con du ctin g
grou p of n erve fibers in th e body, th e so-called Ia
fibers. For fu rth er details, see p . 18 ff. (m on osyn ap-
tic in trin sic m u scle reflex; polysyn aptic reflexes).
Fig. 2.1 Somatosensory receptors in the skin. a Free
nerve ending (pain, tem perature). b Tactile disk of Merkel.
c Peritrichial nerve endings around a hair follicle (touch).
d Tactile corpuscle of Meissner. e Vater−Pacini corpuscle
(pressure, vibration). f End bulb of Krause (cold?). g Ruffini
corpuscle (warm th?).
Golgi tendon organs con tain fin e n erve en din gs,
derived from bran ch es of th ickly m yelin ated n erve
fibers, th at su rrou n d a grou p of collagen ou s ten don
fibers. Th ey are en closed in a con n ective-tissue
capsu le, are located at th e ju n ction betw een ten -
don an d m u scle, an d are con n ected in series to th e
adjacen t m uscle fibers. Like m u scle sp in dles, th ey
respon d to st ret ch (i.e., ten sion ), bu t at a h igh er
th resh old (see Fig. 2.12, p. 22).
Other receptor types. In addition to th e m uscle
sp in dles an d Golgi ten don organ s, receptor types in
th e deep tissu es in clu de th e lam in ated Vater–
2 14 · 2 Som atosensory System

Pacin i corpu scles an d th e Golgi–Mazzon i cor-

puscles as w ell as oth er term in al n erve en din gs
th at m ediate pressure, pain , etc.

Peripheral Nerve, Dorsal Root

Ganglion, Posterior Root
Th e fu rth er “w ay station s” th rou gh w h ich an affer-
en t im pulse m u st travel as it m akes it s w ay to th e
CNS are th e p eriph eral n erve, th e dorsal root gan -
glion , an d th e posterior n erve root, th rou gh w h ich
it en ters th e spin al cord.

Peripheral nerve. Action poten tials arisin g in a re-

ceptor organ of on e of th e types described above
are con du cted cen trally alon g an afferen t fiber,
w h ich is th e periph eral process of th e first som a-
tosen sory n eu ron , w h ose cell body is located in a
dorsal root gan glion (see p. 16). Th e afferen t fibers
from a circu m scribed area of th e body run togeth er
in a periph eral n erve; su ch n erves con tain n ot on ly
fibers for su perficial an d deep sen sation (som atic
afferent fibers) bu t also efferen t fibers to striated
m u scle (som atic efferent fibers) an d fibers in n er-
vat in g th e in tern al organ s, t h e sw eat glan ds, an d
vascu lar sm ooth m u scle (visceral afferent an d
visceral efferent fibers). Fibers (axon s) of all of th ese
types are bu n dled togeth er in side a series of con -
n ective-tissu e coverin gs (en don eu rium , peri-
n eu riu m , an d epin eu riu m ) to form a “n erve cable”
(Fig. 2.3). Th e perin eu riu m also con tain s th e blood
Fig. 2.2 Receptors in muscle, tendons, and fascia. a An-
nulospiral ending of a m uscle spindle (stretch). b Golgi ten- vessels th at su pply th e n erve (vasa nervorum ).
don organ (tension). c Golgi−Mazzoni corpuscle (pressure).
Nerve plexus and posterior root. On ce th e perip h -
eral n erve en ters th e spin al can al th rough t h e in -
tervertebral foram en , th e afferen t an d efferen t
Unmyelinated Myelinated, fibers go th eir sep arate w ays: th e periph eral n erve
Blood vessel fibers, mostly segmented
automatic divides in to its tw o “sources,” th e an terior an d
fibres, m otor
Fat or sensory posterior sp in al roots (Fig. 2.4). Th e an terior root
con tain s th e efferen t n erve fibers exitin g th e spin al
cord, w h ile th e posterior root con tain s th e afferen t
fibers en terin g it. A direct t ran sit ion from th e p e-
riph eral n erve to t h e spin al n erve roots is foun d,
h ow ever, on ly in th e th oracic region . At cervical
an d lu m bosacral levels, n erve plexu ses are in ter-
Endoneurium
posed betw een t h e periph eral n erves an d th e spi-
Perineurium n al n erve roots (th e cervical, brach ial, lu m bar, an d
Epineurium sacral plexu ses). In t h ese plexu ses, w h ich are lo-
cated outside th e spin al can al, th e afferen t fibers of
Fig. 2.3 Cross section of a mixed peripheral nerve
th e periph eral n erves are redistributed so th at
fibers from each in dividual n erve ultim ately join
 Peripheral Com ponents of the Som atosensory System and Peripheral Regulatory Circuits · 15
2
Fig. 2.4 Nerve root seg-
ments and their relation-
Posterior root
ship to the vertebral
bodies. a Anatomy of the

8
anterior and posterior spi-

C
–
nal roots.

1
Dorsal ram us

C
b Enum eration of the nerve
root segm ents and the
T1
levels of exit of the spinal
T1
nerves from the spinal
T2
canal. The spinal cord
T3 grows to a shorter final
T4 length than the vertebral
T5 colum n, so that the nerve
roots (proceeding caudally)
T6
m ust travel increasingly
Anterior root Ventral ramus T7
long distances to reach

2
1
T
their exit foram ina. See

–
T8

1
T
also p. 45, Chapter 3
T9
(Motor System ).
T10

T11

T12

5
L
–
1
L
5
S
–
1
S
Coccygeal nn. and
filum term inale

spin al n erves at m u ltip le segm en tal levels
(Fig. 2.5). (In an alogou s fash ion , th e m otor fibers of
a sin gle segm en tal n erve root travel to m u ltiple pe-
riph eral n erves; cf. Fig. 2.5 an d p. 62 ff. in Ch ap-
ter 3.) Th e redistribu ted afferen t fibers th en en ter
th e spin al cord at m u ltiple levels an d ascen d a vari-
able distan ce in t h e spin al cord before m akin g syn -
aptic con t act w ith th e secon d sen sory n euron ,
w h ich m ay be at or n ear th e level of th e en terin g af-
feren t fibers or, in som e cases, as h igh as t h e brain -
stem . Th u s, in gen eral, a perip h eral n erve is com -
posed of fibers from m ultiple radicular segm en ts;
th is is true of both afferen t an d efferen t fibers.
Digression: Anatom y of the spinal roots and nerves.
In total, th ere are 31 pairs of spin al n erves; each
spin al n erve is form ed by t h e jun ction of an an te-
rior an d a p osterior n erve root w ith in th e spin al
2 16 · 2 Som atosensory System
Nerve root (posterior root)
Spinal
cord Plexus Peripheral n.
a
b tral portion of th e root, an d th e sm all an d th in ly
Nerve root Plexus Peripheral n.
Radicular (anterior root)
segments
Fig. 2.5 Redistribution of afferent and efferent nerve
fibers in a nerve plexus. The sensory fibers contained in a
single peripheral nerve are distributed to m ultiple dorsal
spinal nerve roots, and, analogously, the m otor fibers of a
single nerve root are distributed to m ultiple peripheral
nerves. a In the periphery, the sensory fibers of a single
radicular segm ent are grouped together once again to
supply a characteristic segm ental region of the skin (der-
m atom e). b Radicular and peripheral nerve innervation of
m uscle: each m uscle is supplied by a single peripheral
nerve, which, however, generally contains fibers from m ul-
tiple nerve roots (so-called polyradicular or plurisegm ental
innervation).
can al. Th e n u m berin g of t h e sp in al n erves is based
on th at of th e vertebral bodies (Fig. 2.4). Even
th ough th ere are on ly seven cervical vertebrae,
th ere are eight pairs of cervical n erves, because th e
h igh est spin al n erve exits (or en ters) th e spin al
can al ju st above th e first cervical vertebra. Th u s,
th is n erve, th e first cervical n erve (C1), exits th e
spin al can al betw een th e occipital bon e an d th e
first cervical vertebra (atlas); th e rem ain in g cervi-
cal n erves, dow n to C7, exit above th e corresp on d-
in gly n u m bered vertebra; an d C8 exits betw een
th e seven th (low est) cervical vertebra an d t h e first
th oracic vertebra. At th oracic, lu m bar, an d sacral
levels, each spin al n erve exits (or en ters) th e sp in al
can al below th e correspon din gly n um bered verte-
bra. Th ere are, th erefore, ju st as m any pairs of
n erves in each of th ese region s as th ere are verte-
brae (12 th oracic, 5 lu m bar, an d 5 sacral) (Fig. 2.4).
Derm atom e Lastly, th ere is a sin gle p air of coccygeal n erves (or,
occasion ally, m ore th an on e p air).
Spatial organization of som atosensory fibers in the
posterior root. Nerve im pu lses relat in g to differen t
som atosen sory m odalities origin ate in differen t
types of periph eral receptor an d are con du cted
cen trally in sep arate group s of afferen t fibers,
w h ich are spatially arran ged in th e posterior root in
a ch aracteristic pattern . As sh ow n in Figu re 2.15
(p. 25), th e m ost th ickly m yelin ated n erve fibers,
w h ich origin ate in m u scle spin dles, ru n in th e m e-
dial portion of th e root; th ese fibers are respon sible
for proprioception . Fibers origin atin g in receptor
organ s, w h ich m ediate th e sen ses of tou ch , vibra-
tion , pressu re, an d discrim in ation , ru n in th e cen -
m yelin ated fibers m ediatin g pain an d tem p eratu re
Myotome
sen sation run in it s lateral portion .
Dorsal root ganglion. Th e dorsal root gan glion is
m acroscopically visible as a sw ellin g of th e dorsal
root, im m ediately proxim al to it s ju n ction w it h t h e
ven tral root (Fig. 2.4). Th e n eu ron s of th e dorsal root
gan glion are pseu dou n ipolar, i.e., th ey possess a
sin gle process th at divides in to tw o p rocesses a
sh ort distan ce from th e cell, in a T-sh ap ed con figu-
rat ion . On e of th ese tw o processes travels to th e re-
ceptor organ s of th e periph ery, givin g off n u m erou s
collateral bran ch es alon g th e w ay, so th at a sin gle
gan glion cell receives inpu t from m u ltip le receptor
organ s. Th e oth er process (th e cen t ral process)
travels by w ay of th e posterior root in to th e spin al
cord, w h ere it eith er m akes syn aptic con tact w ith
th e secon d sen sory n eu ron im m ediately, or else as-
cen ds tow ard th e brain stem (see Fig. 2.17, p. 27).
Th ere are n o syn apses w ith in th e dorsal root gan -
glion itself.
Somatosensory Innerva tion by Nerve Roots
and Periphera l Nerves
Th e fibers of in dividual n erve roots are redis-
tributed in to m u ltiple periph eral n erves by w ay of
th e plexu ses (cf. p. 14 ff.), an d each n erve con tain s
fibers from m u ltiple adjacen t radicu lar segm en ts
(see also Figs. 3.31, 3.32, an d 3.33, pp. 63, 64). Th e
fibers of each radicu lar segm en t regrou p in th e pe-
riph ery, h ow ever (Fig. 2.5), to in n ervate a particu -
 Peripheral Com ponents of the Som atosensory System and Peripheral Regulatory Circuits · 17
2
Fig. 2.6 Segmental inner-
vation of the skin (after
Ophthalm ic n.
C2 Hansen−Schliack). a Ante-
C2 Maxillary n. Trigem inal n. rior view. b Posterior view.
C3
Mandibular n. C3
C4
C4
T2
C5 T3
T2 T4
T3 T5
C5 T4
T5 T6
T6 T7
T7 T8
C6 T1
T8 T9
T10
T1 T9 T11
T10 T12
L1
T11
T12 C6 L2
S5
L1
C7 L3 S4
S2 C8
C7 L2
S3
C8
L4
L3
S2
S1

L4 L5

L5

S1
S1
L4
S1 L5

lar segm en tal area of th e skin (dermatome). Each
derm atom e correspon ds to a sin gle radicular seg-
m en t, w h ich , in tu rn , correspon ds to a sin gle “sp i-
n al cord segm en t.” Th e latter term is u sed even
th ough th e m atu re sp in al cord n o lon ger displays
its origin al m etam eric segm en tation .
Th e derm atom es on th e an terior an d posterior
body su rfaces are sh ow n in Figure 2.6. Th e m et-
am eric organ ization of th e derm atom es is easiest
to see in th e th oracic region .
As sh ow n in Figure 2.5, th e derm atom es of
n eigh borin g roots overlap con siderably, so th at a
lesion con fin ed to a sin gle root often causes a
barely discern ible sen sory deficit, or n on e at all.
Sensory deficits due to radicular lesions. A de-
m on strable sen sory deficit in a segm en tal distribu -
tion is u su ally fou n d on ly w h en m u ltiple adjacen t
n erve roots are involved by a lesion . As each der-
m atom e corresp on ds to a p articu lar sp in al cord or
radicular level, th e derm atom e(s) in w h ich a
sen sory deficit is located is a h igh ly valu able in -
dicator of th e level of a lesion involvin g th e spin al
cord or on e or m ore n erve roots. Th e sch em atic
represen tation of Figu re 2.7 is in ten ded for didactic
purposes, to h elp th e stu den t rem em ber w h ere th e
bou n daries betw een th e cervical, th oracic, lu m bar,
an d sacral derm atom al areas are located.
Th e derm atom es for th e sen se of touch overlap
to a greater exten t th an th ose for pain an d
tem peratu re. It follow s th at, in a lesion of on e or
tw o adjacen t roots, a derm atom al deficit of touch
is gen erally h ard to dem on strate, w h ile on e of pain
an d tem peratu re sen sat ion is m ore readily ap-
paren t. Th us, n erve root lesion s can be m ore sen si-
tively detected by testin g for hypalgesia or an alge-
sia, rath er th an hypesth esia or an esth esia.
2 18 · 2 Som atosensory System
C2
T1
L1 S1
Fig. 2.7 Segmental innervation of the skin: simplified
diagram of dermatomal topography
Sensory deficits due to peripheral nerve lesions. It
is easy to see w hy a lesion affectin g a n erve plexu s
or a periph eral n erve produ ces a sen sory deficit of
an en tirely differen t type th an a radicu lar lesion . As
plexu s lesion s u su ally cause a prom in en t m otor
deficit in addition , w e w ill defer fu rth er discu ssion
of p lexus lesion s to th e n ext ch apter on th e m otor
system (pp. 62–66).
Wh en a periph eral n erve is in jured, th e fibers
w ith in it, derived from m u ltiple n erve roots, can n o
lon ger rejoin in th e periph ery w ith fibers derived
from th e sam e n erve roots bu t belon gin g to oth er
periph eral n erves—in ot h er w ords, th e fibers in t h e
in ju red n erve can n o lon ger reach th eir assign ed
derm atom es. Th e sen sory deficit th u s h as a differ-
en t dist ribu tion from th at of th e derm atom al defi-
cit seen after a radicu lar in jury (Fig. 2.8). Fu rt h er-
m ore, th e cu tan eou s areas in n ervated by in -
dividu al p eriph eral n erves overlap m u ch less th at
th ose in n ervated by adjacen t n erve roots. Sen sory
deficit s du e to periph eral n erve lesion s are, th ere-
fore, m ore readily app aren t th an t h ose due to
radicular lesion s.
Peripheral Regulatory Circuits
In th e n ext section after th is on e, w e w ill trace th e
ascen din g fiber path w ays respon sible for pain an d
tem peratu re sen sation , an d for sen sory m odalities
such as touch an d pressure, as th ey travel up t h e
sp in al cord an d in to th e brain . Before doin g so,
h ow ever, w e w ill explain th e fu n ction of a n u m ber
of im portan t periph eral regu latory circuits. Even
th ough th e cu rren t ch apter is devoted to th e
sen sory system , it w ill be u sefu l, in t h is lim ited
con text, to describe n ot on ly th e afferen t (sen sory)
arm of th ese regu latory circu its, bu t th eir efferen t
(m otor) arm as w ell.
Monosyna ptic a nd Polysyna ptic Reflexes
Monosynaptic intrinsic reflex. As illust rated in
Figure 2.11 (p. 22), th e large-diam eter afferent
fiber arisin g in a m uscle spin dle gives off m any ter-
m in al bran ch es sh ortly after en terin g th e spin al
cord; som e of th ese bran ch es m ake direct syn aptic
con tact on to n euron s in th e gray m atter of th e
an terior h orn . Th ese n euron s, in turn , are t h e origin
of efferen t m otor fibers, an d are th erefore called
motor anterior horn cells. Th e efferent neurites
exit th e spin al cord by w ay of th e an terior root an d
th en travel, alon g p erip h eral n erves, to th e skeletal
m u scles.
A n eural loop is th us created from a skeletal
m u scle to th e spin al cord an d back again , com -
p osed of tw o n eu ron s—an afferen t sen sory n eu ron
an d an efferen t m otor n eu ron . Th is loop con sti-
tutes a sim ple, m on osyn aptic reflex arc. Becau se
th e arc begin s an d en ds in th e sam e m uscle, th e as-
sociated reflex is called an intrinsic (or propriocep-
tive) muscle reflex.
Such m on osyn apt ic reflex arcs provide th e n eu -
roan atom ical basis for t h e regu lation of m uscle
len gth (see below ).
Reflex relaxation of antagonist m uscles. In a strict
sen se, th e m on osyn aptic reflex is n ot t ruly m on o-
syn aptic, becau se it also h as a polysyn apt ic com -
pon en t. Th e reflex is m an ifested n ot only in con -
traction of th e m u scle in question , bu t also in re-
laxation of its an tagon ist m u scle(s). Th e in h ibition
of m uscle cells th at leads t h ese m uscles to relax is a
polysyn aptic process occu rrin g by w ay of in ter-
 Peripheral Com ponents of the Som atosensory System and Peripheral Regulatory Circuits · 19
2
Fig. 2.8 Innervation of
Ophthalm ic n. Ophthalm ic n. the skin by peripheral
Mandibular n. Trigem inal n. Greater occipital n. nerves. a Anterior view.
Maxillary n. Lesser occipital n.
Great auricular n.
b Posterior view. c The
Great auricular n. Dorsal ram i areas innervated by the
Transverse cervical n. of cervical nn. three divisions of the
Supraclavicular nn. Supraclavicular nn. trigem inal nerve and by
Ventral ram i
of thoracic nn. the cervical cutaneous
Lateral rami nerves.
Dorsal ram i of thoracic nn.
Axillary n.
Lateral cutaneous ram i of intercostal nn.
Intercostobrachial n.
Posterior brachial cutaneous n.
Medial brachial cutaneous n.
Posterior antebrachial cutaneous n.
Lateral antebrachial cutaneous n.
Medial antebrachial
cutaneous n.
Radial n.
Ulnar n. Ilio-
Median n. hypo-
gastric n.
Iliohypogastric n. Cluneal nn.
Genitofem oral n. Dorsal ram i
Ilioinguinal n. of lum bar nn.
Obturator n. Dorsal ram i
of sacral nn.
Lateral fem oral cutaneous n.
Posterior fem oral cutaneous n.
Fem oral n.
Com m on peroneal (fibular) n.
Superficial peroneal (fibular) n.

Saphenous n.

Sural n.
Saphenous n.
Deep peroneal Lateral plantar n.
(fibular) n. Medial plantar n.

V1

Greater occipital n. C2 – C3
V2

Lesser occipital n. C2
V3
Great auricular n. C2 – C3

Transverse cervical n. C2 – C3

n eu ron s in th e spin al gray m atter. Were th is n ot Wh en a fin ger tou ch es a h ot stove, th e h an d is

th e case, ten sion in th e an tagon ist m u scles w ould
cou n teract agon ist con traction (see Fig. 2.14, p. 24).
Polysynaptic flexor reflex. An oth er im portan t re-
flex arc is th at of th e polysyn apt ic flexor reflex, a
protective and flight reflex th at is m ediated by
m any in tern eu ron s an d is th u s polysynaptic.
pulled back w ith ligh tn in g sp eed, before any pain is
felt . Th e act ion poten t ials t h at arise in t h e cu -
tan eous receptor (n ociceptor) for th is reflex travel
by w ay of afferen t fibers to th e su bst an tia gelat i-
n osa of th e spin al cord, w h ere th ey are th en relayed,
across syn apses, in to cells of various types belon g-
in g to th e cord’s in trin sic n eu ron al apparatu s
2 20 · 2 Som atosensory System
Funicular neuron
Lissauer zone
Commissural
neuron
Association
neuron
Interneuron
Fasciculus
proprius Motor neuron
Fig. 2.9 Intrinsic neurons and polysynaptic connections
in the spinal cord. Note: interneurons are also called “in-
tercalated” or “internuncial” neurons (from Latin nuntius,
m essenger).
(in tern eu ron s, association n eu ron s, an d com m is-
sural n eu ron s). Som e of th ese cells—part icu larly
th e association n eu ron s—project th eir processes
m ultiple sp in al levels up w ard an d dow nw ard, in
th e so-called fascicu lu s proprius (Fig. 2.9). After
crossin g m ult iple syn apses, excitatory im p ulses fi-
n ally reach th e m otor n eu ron s an d travel alon g
th eir efferen t axon s in to th e spin al n erve roots, pe-
riph eral n erves, an d m uscle, producin g th e m uscu -
lar con traction th at p ulls th e h an d back from th e
stove.
A reflex of th is type requ ires th e coordin ated
con traction of m ultiple m uscles, w h ich m u st con -
tract in th e righ t sequ en ce an d w ith th e righ t in -
ten sit y, w h ile ot h ers (th e an tagon ist m u scles)
m ust relax at th e app ropriate tim es. Th e in trin sic
n eu ron al apparatus of th e spin al cord is th e com -
pu terlike, in tercon n ected n et w ork of cells th at
m akes th is process possible.
In an oth er paradigm atic situ ation , steppin g on a
sh arp rock gen erates n ociceptive im pu lses th at in -
itiate a com plex but unvaryin g sequ en ce of even ts
(Fig. 2.10): th e pain fu l foot is raised by flexion of
th e h ip, kn ee, an d an kle, w h ile th e opposite leg is
exten ded so th at t h e in dividu al can stan d on it
alon e (crossed extensor reflex). Th e su dden redis-
tribution of w eigh t does n ot cau se th e in dividu al to
fall over, becau se it is im m ediately com pen sated
for by reflex con t raction of m u scles of th e trun k,
sh ou lders, arm s, an d n eck, m ain tain in g th e body’s
uprigh t posture. Th is process requires syn aptic
com m u n ication am on g m any differen t n eu ron s in
th e spin al cord, w ith sim u ltan eou s participat ion of
th e brain stem an d cerebellu m . All of th is h appen s
in a fraction of a secon d; on ly afterw ard does th e
in dividual feel p ain , look to see w h at cau sed it, an d
ch eck w h et h er th e foot h as been in ju red.
Th ese m on osyn aptic an d polysyn aptic reflexes
are un con sciou s processes occurrin g m ain ly in th e
sp in al cord, yet th e last exam ple sh ow s th at h igh er
com pon en ts of th e CNS m ust often be activated at
th e sam e tim e, e.g., to preserve balan ce (as in th e
exam ple).
Regula tion of Muscle Length a nd Tension
As discussed above, m on osyn aptic an d p olysyn ap-
tic reflex arcs serve differen t p urposes: p olysyn ap-
tic reflex arcs m ediate protective an d fligh t re-
spon ses, w h ile m on osyn aptic reflex arcs are in cor-
porated in fun ct ion al circuits th at regu late th e
len gth an d ten sion of skeletal m u scle. Each m u scle,
in fact, con tain s tw o servo-con trol (feedback) sys-
tem s:
¼ A control system for length, in w h ich th e n u -
clear bag fibers of th e m uscle spin dles serve as
len gth receptors
¼ A control system for tension, in w h ich th e Golgi
ten don organ s an d th e n u clear ch ain fibers of
th e m u scle sp in dles serve as ten sion receptors
Stretch and tension receptors. Muscle spindles are
receptors for both stretch (len gth ) an d ten sion .
Th ese tw o distin ct m odalities are subserved by tw o
differen t kin ds of in trafu sal fibers, th e so-called
n uclear bag an d n u clear ch ain fibers (Figs. 2.11 an d
2.12). Fibers of both of th ese typ es are typically
sh orter an d th in n er th an extrafu sal m u scle fibers.
Th e tw o types of in trafu sal fiber are depicted sep a-
rately for didactic reason s in Figu res 2.11 an d 2.12,
but, in reality, th e sh orter an d th in n er n u clear
ch ain fibers are directly att ach ed to th e som ew h at
lon ger n uclear bag fibers. Mu scle spin dles gen er-
ally con sist of t w o n u clear bag fibers an d fou r or
five n uclear ch ain fibers. In th e m iddle of a n u clear
 Peripheral Com ponents of the Som atosensory System and Peripheral Regulatory Circuits · 21
2
bag fiber, th e in trafusal m uscle fibers w iden to a
Cerebrum
form a bag con tain in g about 50 n uclei, w h ich is
covered by a n etw ork of sen sory n erve fibers
Brainstem
kn ow n as a prim ary or an n u lospiral en din g (from
Latin annulus, rin g). Th is sp iral en din g reacts very Cerebellum
sen sitively to m u scle st retch , m ain ly registerin g
changes in m uscle len gth ; t h e n u clear bag fibers
are th u s st retch receptors. Th e n u clear ch ain fibers,
on th e oth er h an d, m ain ly register a persisten tly
stretch ed state of th e m uscle, an d are th us ten sion
receptors.

Maintenance of constant muscle length. Th e extra-

fu sal m u scle fibers h ave a certain len gth at rest,
w h ich th e organ ism alw ays tries to m ain tain con -
stan t. Wh en ever th e m u scle is stretch ed beyon d
th is len gth , th e m u scle spin dle is stretch ed alon g
w ith it. Th is gen erates action p oten tials in th e an -
n u lospiral en din g, w h ich travel very rapidly in Ia
afferen t fibers an d are t h en relayed across a syn -
apse to m otor n euron s in th e an terior h orn of t h e
spin al cord (Fig. 2.11). Th e excited m otor n eu ron s
fire im p ulses t h at t ravel in equ ally rapidly con -
du ct in g, large-diam eter α 1 efferen t fibers back to
th e w orkin g extrafusal m uscle fibers, causin g th em
to con tract to th eir form er len gth . Any stretch of
th e m uscle in du ces th is respon se.
Th e physician tests th e in tactn ess of th is regu -
latory circuit w ith a quick tap on a m u scle ten don ,
e.g., th e patellar ten don for elicitat ion of t h e quad-
riceps (kn ee-jerk) reflex. Th e resu ltin g m u scu lar
st retch activates th e m on osyn aptic reflex arc. In -
trin sic m u scle reflexes are of m ajor value for local-
ization in clin ical n eu rology becau se th e reflex arc
for a particu lar m u scle occu pies on ly on e or tw o
radicu lar or spin al cord segm en ts; t h u s, a fin din g
of an abn orm al reflex en ables t h e physician to
in fer th e level of th e un derlyin g radicular or spin al
lesion . Th e m ore im portan t in trin sic m u scle re-
flexes in clin ical practice, th e m an n er in w h ich
th ey are elicited, an d t h e segm en ts th at p artici-
pate in th eir reflex arcs are sh ow n in Figu re 2.13.
It sh ou ld be realized th at the clin ical elicit ation of
in trin sic m uscle reflexes is an artificial even t: a
brief m u scular stretch such as th at produced w ith
a reflex h am m er is a rarity in everyday life.

Reflex relaxation of antagonist m uscles. Th e reflex Painful stim ulus

con tract ion of a st ret ch ed m u scle to m ain tain con -
stan t len gth is accom pan ied by reflex relaxation of
its an tagon ist m u scle(s). Th e regu latory circu it for Fig. 2.10 Flexor reflex w ith polysynaptic connections
2 22 · 2 Som atosensory System

Fig. 2.11 Regulatory cir-

Central Pyramidal cuit for muscle length
input tract

Nuclear bag muscle spindle

with annulospiral ending:
receptor for changes in
m uscle length (stretch)

Ia fiber

γ 1 m otor
neuron

α fiber
γ 1 fibers

Renshaw cell α1 m otor neuron

Fig. 2.12 Regulatory cir-

Pyram idal Reticulospinal Tendon organ (Golgi organ): cuit for muscle tension
tract tract receptor for m uscle tension

Nuclear chain m uscle spindle

with a primary ending and
a flower-spray ending
Tonic stretch reflex

II fiber
Ib fiber

α2 fiber
γ 2 fiber
Ia fiber

γ 2 m otor neuron
α2 m otor neuron

th is likew ise begin s in th e m u scle spin dles. Th e n u -
clear ch ain fibers of m any m u scle spin dles con tain
secon dary en din gs called flow er-spray endings in
addition to th e prim ary (an n u lospiral) en din gs dis-
cu ssed above. Th ese secon dary en din gs react to
stretch as th e prim ary en din gs do, bu t th e afferen t
im pu lses gen erated in th em travel cen trally in II
fibers, w h ich are th in n er th an th e Ia fibers as-
sociated w it h th e prim ary en din gs. Th e im p ulses
are relayed via spin al in tern eu ron s to produ ce a
n et in h ibition —an d th u s relaxation —of th e an tago-
n ist m u scle(s) (reciprocal an tagon ist in h ibition ,
Fig. 2.14).
Setting of target values for muscle length. Th ere is
a special m otor system w h ose fun ction is to set ad-
ju stable target valu es in th e regu latory circu it for
m u scle len gth .
As sh ow n in Figu re 2.11, th e an terior h orn of
th e spin al cord con tain s n ot on ly th e large
α m otor n eu ron s but also th e sm aller γ m otor
n eu ron s. Th ese cells project th eir axon s (γ fibers)
 Peripheral Com ponents of the Som atosensory System and Peripheral Regulatory Circuits · 23
2
Fig. 2.13 The most im-
portant intrinsic muscle
reflexes
C5
C6
Biceps C6
C7

Muscolo-
Radial n.
cutaneous n.
Triceps

Radius
Ulna

Biceps reflex Triceps reflex

L2

L3

L4
L5
S1
Femorale n.
S2
Quadriceps Tibial n.
fem oris

Gastro-
cnem ius

Quadriceps re fle x Trice ps surae re fle x

(patellar reflex, (Achilles reflex,
knee-jerk reflex) ankle-jerk reflex)

to th e sm all, striated in trafu sal fibers of th e
m uscle spin dles. Excitation by γ fibers in du ces
con traction of th e in trafu sal m u scle fibers at
eith er en d of a m u scle spin dle. Th is stretch es th e
m idportion of th e spin dle, leadin g th e an n u lospi-
ral en din g to fire action poten tials, w h ich , in tu rn ,
elevate ten sion in th e w orkin g m u scle.
Th e γ m otor n eu ron s are u n der t h e in flu en ce of
several descen din g m otor path w ays, in cludin g th e
pyram idal, reticulospin al, an d vest ibu lospin al
tracts. Th ey th u s serve as in term ediaries for th e
con trol of m u scle ton e by h igh er m otor cen ters,
w h ich is clearly an im p ortan t aspect of volun tary
m ovem en t. Th e γ efferen ts en able precise con trol
of volu n t ary m ovem en ts an d also regulate th e
2 24 · 2 Som atosensory System
Annulospiral
receptor
+
Association
Motor neuron neuron
Agonist
Contrac- Antagonist
tion Relaxation
+
–
– tion of all of th e posterior roots. Restin g ton e, th ere-
– Interneuron Fasciculus
proprius
– Adaptation of m uscle tone to gravity and m ovem ent.
Fig. 2.14 Monosynaptic reflex w ith polysynaptic inhibi-
tion of antagonist muscles
sen sitivit y of t h e stretch receptors. Wh en th e in -
trafusal m u scle fibers con tract an d stretch th e
m idportion of a m uscle spin dle, th e th resh old of
th e stretch receptors is low ered, i.e., th ey require
m uch less m uscu lar stretch to be activated. In th e
n orm al situation , th e target m uscle len gth th at is
to be m ain tain ed is au tom atically set by th e
fu sim otor (γ) in n ervat ion of th e m u scle.
If both t h e prim ary receptors (n u clear bag fibers
w ith an n u lospiral en din gs) an d th e secon dary re-
ceptors (n uclear ch ain fibers w ith flow er-spray
en din gs) are slow ly stretch ed, th e respon se of th e
spin dle receptors is stat ic, i.e., u n ch an gin g in tim e.
On th e oth er h an d, if th e prim ary receptors are very
rap idly st retch ed, a dyn am ic (rapidly ch an gin g) re-
spon se en sues. Both th e static an d th e dyn am ic re-
spon ses are con trolled by efferen t γ n euron s.
Static and dynam ic γ m otor neurons. Th ere are pre-
sum ed to be tw o t ypes of γ m otor n eu ron s, dy-
n am ic an d static. Th e form er in n ervate m ain ly th e
in trafu sal n uclear bag fibers, th e latter m ain ly th e
in trafusal n uclear ch ain fibers. Excitation of n u-
clear bag fibers by dyn am ic γ n eu ron s in duces a
st ron g, dyn am ic respon se m ediated by th e an -
n ulospiral en din g, w h ile excitation of n u clear
ch ain fibers by static γ n euron s in du ces a static,
ton ic respon se.
Muscle tone. Every m u scle possesses a certain
degree of ton e, even in its m axim ally relaxed (rest-
in g) state. In th e clin ical n eu rological exam in ation ,
th e physician assesses m u scle ton e by n otin g th e
resistan ce to passive m ovem en t of th e lim bs (e.g.,
flexion an d exten sion ).
Total loss of m u scle ton e can be produced ex-
perim en tally eith er by tran section of all of th e an te-
rior roots or, p erh aps m ore su rprisin gly, by tran sec-
fore, is n ot a propert y of th e m u scle itself, bu t rath er
is m ain tain ed by th e reflex arcs described in th is
sect ion .
Th e h u m an body is con tin ually su bject to th e
earth ’s gravitation al field. Wh en an in dividu al
stan ds or w alks, an ti-gravity m u scles m u st be acti-
vated (am on g t h em t h e qu adriceps fem oris, t h e
lon g exten sors of th e trun k, an d th e cervical
m u scles) to keep th e body erect.
Wh en a h eavy object is lifted, th e ton e n orm ally
presen t in th e qu adriceps m u scle n o lon ger su ffices
to keep th e body erect. Bu cklin g at th e kn ees can be
preven ted on ly by an im m ediate in crease in quad-
riceps ton e, w h ich occurs as a resu lt of ton ic in t rin -
sic reflexes in du ced by t h e stretch in g of t h e m u scle
an d of th e m u scle spin dles w ith in it. Th is feedback
m ech an ism or servom ech an ism en ables au tom atic
adapt ation of t h e ten sion in a m u scle to t h e load
th at is placed upon it. Th u s, w h en ever an in dividu al
stan ds, w alks, or lifts, action poten tials are con -
stan tly bein g relayed back an d forth to en su re th e
m ain ten an ce of th e correct am ou n t of m u scle ten -
sion .
Central Components of the
Somatosensory System
Havin g traced th e path of afferen t im pu lses from
th e periph ery to th e spin al cord in th e precedin g
section s, w e w ill n ow proceed to discu ss th eir
fu rth er cou rse w it h in th e cen tral n ervou s system .
Root entry zone and posterior horn. In dividu al so-
m atosen sory fibers en ter th e spin al cord at th e
dorsal root en try zon e (DREZ; also called th e Red-
lich –Oberstein er zon e) an d th en give off n u m erou s
collaterals th at m ake syn aptic con tact w ith oth er

Crossed anterio Lateral spinothalam ic tract
spinocerebellar (pain, tem perature)
tract
Posterior colum ns
Cuneate Gracile
fasciculus fasciculus
(of Burdach) (of Goll)
Posterior spinocerebellar
tract
Anterior spinocerebellar
tract
Lateral spino-
thalam ic tract
Spinotectal tract
Spino-olivary tract
Anterior spinothalam ic tract
Fig. 2.15 Position of fibers of different somatosensory modalities in the posterior root and root entry zone, and their
further course in the spinal cord
n eu ron s w ith in th e cord. Fibers su bservin g differ-
en t sen sory m odalities occupy differen t position s
in th e spin al cord (Fig. 2.15). It is im portan t to n ote
th at th e m yelin sh eath s of all afferen t fibers be-
com e con siderably th in n er as th e fibers traverse
th e root en try zon e an d en ter th e posterior h orn .
Th e type of m yelin ch an ges from periph eral to cen -
tral, an d th e m yelin atin g cells are n o lon ger
Sch w an n cells, but rath er oligoden drocytes.
Th e afferen t fiber path w ays of th e spin al cord
subservin g in dividual som atosen sory m odalit ies
(Fig. 2.16) w ill n ow be described in dividu ally.
Posterior and Anterior
Spinocerebellar Tracts
Som e of th e afferen t im pu lses arisin g in organ s of
th e m u scu loskeletal system (th e m u scles, ten don s,
an d join ts) travel by w ay of th e spin ocerebellar
tracts to th e organ of balan ce an d coordin at ion , th e
cerebellum . Th ere are tw o such tracts on each side,
on e an terior an d on e posterior (Fig. 2.16a).
Posterior spinocerebellar tract. Rapidly con du ctin g
Ia fibers from th e m uscle spin dles an d ten don or-
gan s divide in to n u m erou s collaterals after en ter-
Central Com ponents of the Som atosensory System · 25
2
Posterior
Anterior spinocerebellar tract
colum ns
Posterior spinocerebellar tract
Proprioception (unconscious)
Muscle spindle and tendon organ
(to the cerebellum and forebrain)
Proprioception, vibration, touch,
pressure, discrimination
(to the thalam us and cerebral cortex)
Touch, pressure
Pain, temperature
Medial bundle
Lateral bundle
Motor fiber
in g th e spin al cord. Som e of th ese collateral fibers
m ake syn aptic con tact directly on to th e large
α m otor n eu ron s of th e an terior h orn (m on osyn ap-
tic reflex arc, Figs. 2.15 an d 2.11). Oth er collateral
fibers arisin g at th oracic, lu m bar, an d sacral levels
term in ate in a colum n -sh ap ed n u cleu s occu pyin g
th e base of th e posterior h orn at levels C8–L2,
w h ich is variously n am ed th e in term ediolateral
cell colum n , th oracic n ucleus, Clarke’s colu m n , an d
Stillin g’s n u cleus. Th e postsyn aptic secon d n eu-
ron s w ith cell bodies lyin g in th is n ucleus are th e
origin of th e posterior spin ocerebellar t ract, w h ose
fibers are am on g t h e m ost rapidly con du ctin g of
any in th e body. Th e posterior spin ocerebellar tract
ascen ds th e spin al cord ipsilaterally in th e posterior
portion of th e lateral fu n icu lu s an d th en travels by
w ay of th e in ferior cerebellar p edu n cle to th e cere-
bellar verm is (p. 165; Figs. 2.16a an d 2.17). Afferen t
fibers arisin g at cervical levels (i.e., above th e level
of th e in term ediolateral cell colu m n ) travel in th e
cu n eate fascicu lu s to m ake a syn apse on to th eir
correspon din g secon d n eu ron s in th e accessory
cu n eate n ucleus of th e m edulla (Fig. 2.17), w h ose
out put fibers ascen d to t h e cerebellu m .
2 26 · 2 Som atosensory System

Fig. 2.16 Major fiber

Via superior 3rd neuron tracts of the spinal cord
m edullary velum
and the sensory modali-
Anterior spinocere- ties that they subserve.
bellar tract, Thalam us
2nd neuron
a The anterior and poste-
Verm is Medial rior spinocerebellar tracts.
Posterior spinocere-
lem niscus b The posterior funiculus
bellar tract 2nd neuron
Cuneate (posterior colum ns). c The
2nd neuron nucleus anterior spinothalam ic
Thoracic nucleus Gracile and gracile
fasciculus tract. d The lateral
(Clarke’s colum n, nucleus
Stilling’s nucleus) Cuneate spinothalam ic tract.
fasciculus
1st neuron
1st neuron

a Unconscious proprioception b Position sense, vibration, pressure,

discrimination, touch
3rd neuron 3rd neuron
Thalam us Thalam us

Anterior spino-
2nd neuron
thalam ic tract

2nd neuron

Lateral spinothalam ic
tract
Substantia gelatinosa
1st neuron

1st neuron

c Coarse touch and pressure pe rception d Pain, tempe rature (also tickle, itch,
sexual sensations)

Anterior spinocerebellar tract. Oth er afferen t Ia
fibers en terin g th e sp in al cord form syn apses w ith
fu n icu lar n euron s in th e posterior h orn s an d in th e
cen tral portion of th e spin al gray m atter (Figs. 2.15,
2.16a, an d 2.17). Th ese secon d n eu ron s, w h ich are
fou n d as low as th e low er lum bar segm en ts, are th e
cells of origin of th e an terior spin ocerebellar tract,
w h ich ascen ds th e sp in al cord both ipsilaterally and
contralaterally to term in ate in t h e cerebellu m . In
con trast to th e posterior spin ocerebellar tract, th e
an terior spin ocerebellar tract t raverses t h e floor of
th e fourth ven tricle to th e m idbrain an d th en turn s
in a posterior direction to reach th e cerebellar ver-
m is by w ay of th e su perior cerebellar p edu n cle an d
th e su perior m edu llary velu m . Th e cerebellu m re-
ceives afferen t p roprioceptive inp ut from all re-
gion s of th e body; its polysyn aptic efferen t outp ut,
in tu rn , in fluen ces m u scle ton e an d th e coordi-
 Central Com ponents of the Som atosensory System · 27
2
Fig. 2.17 Spinal cord
w ith major ascending
pathw ays and their
further course to target
structures in the cere-
brum and cerebellum
(schem atic drawing)

3rd neuron Paleo-

cerebellum

Lateral spino-

,
e
thalam ic

s
Posterior spino-

v
u
i
o
tract

t
cerebellar tract

p
m
e
y
c
o
Anterior spino-

n
i
o
r
p
m
cerebellar tract

o
o
r
P
h
Medial
lem niscus Dorsal external arcuate fibers
Cuneate nucleus and gracile nucleus
Accessory cuneate nucleus
2nd neuron
Posterior spino- Proprioceptio n
cerebellar (m uscle spindles,
tract Golgi organs, joint
bodies, etc.)

Anterior Position sense,

spino- vibration, pre ssure,
cerebellar discrimination,
tract touch
(cutaneous receptors,
Anterior m uscle and tendon
spino- 1st neuron receptors, Vater–Pacini
thalam ic corpuscles)
tract
Pressure, touch
(peritrichial nerve
endings and various
cutaneous receptors)

Pain, temperature
(free nerve endings,
Krause and Ruffini
corpuscles?)

n ated action of t h e agon ist an d an tagon ist m u scles tion of m ovem en t involves oth er, n onpyram idal
(syn ergistic m u scles) th at participate in stan din g, path w ays an d both α an d γ m otor n euron s. All of
w alkin g, an d all oth er m ovem en ts. Th u s, in addi- th ese p rocesses occu r u n con sciou sly.
tion to th e low er regu latory circu its in th e spin al
cord itself, w h ich w ere described in earlier sec-
tion s, th is h igh er fun ction al circu it for th e regula-
2 28 · 2 Som atosensory System

To the posterior Posterior Columns

colum n nuclei
We can feel th e position of ou r lim bs an d sen se th e
degree of m u scle ten sion in th em . We can feel t h e
w eigh t of t h e body restin g on ou r soles (i.e., w e
“feel th e grou n d un der our feet”). We can also per-
ceive m otion in th e join ts. Th u s, at least som e pro-
priocept ive im pu lses m ust reach con sciou sn ess.
Cuneate fasciculus, Su ch im pu lses are derived from receptors in
from upper lim b m u scles, ten don s, fasciae, join t capsu les, an d con -
n ective tissu e (Vater–Pacin i an d Golgi–Mazzon i
corpu scles), as w ell as cutan eou s receptors. Th e af-
feren t fibers conveyin g t h em are th e distal
processes of pseudou n ipolar n euron s in th e spin al
gan glia. Th e cen t ral processes of th ese cells, in
tu rn , ascen d th e sp in al cord an d term in ate in th e
posterior colum n n u clei of th e low er m edu lla (Figs.
2.16b an d 2.17).

Central continuation of posterior column path-

Gracile fasciculus,
from lower lim b
Fig. 2.18 Posterior funiculus, containing the posterior
colum ns: gracile fasciculus (m edial, afferent fibers from
lower lim b) and cuneate fasciculus (lateral, afferent fibers
from upper lim b)
w ays. In th e posterior fu n icu lu s of th e spin al cord,
th e afferen t fibers derived from th e low er lim bs oc-
cupy th e m ost m edial position . Th e afferen t fibers
from th e u pper lim bs join th e cord at cervical levels
an d lie m ore laterally, so th at th e posterior fu n icu lu s
h ere con sists of tw o colum n s (on eith er side): th e
m edial gracile fasciculus (colu m n of Goll), an d th e
lateral cuneate fasciculus (colu m n of Bu rdach ). Th e
fibers in t h ese colu m n s term in ate in t h e corre-
sp on din gly n am ed n uclei in th e low er m edu lla, i.e.,
th e gracile n u cleus an d cu n eate n u cleu s, respec-
tively. Th ese posterior colu m n n uclei con tain th e
secon d n eu ron s, w h ich p roject th eir axon s to th e
thalam us (bu lboth alam ic tract). All of th e bu l-
bot h alam ic fibers cross th e m idlin e to th e oth er side
as th ey ascen d, form in g th e m edial lem niscus (Figs.
2.16b an d 2.17). Th ese fibers traverse th e m edu lla,
pon s, an d m idbrain an d term in ate in th e ventral
posterolateral nucleus of th e t h alam u s (VPL, p. 173;
Fig. 6.4, p. 174). Here t h ey m ake syn aptic con tact
w ith th e th ird n eu ron s, w h ich , in tu rn , give off th e
thalam ocortical tract; th is tract ascen ds by w ay of
th e internal capsule (posterior to th e pyram idal
tract) an d th rough th e corona radiata to th e prim ary
som atosen sory cortex in th e postcentral gyrus. Th e
som atotopic organ ization of th e posterior colu m n
path w ay is preserved all th e w ay u p from th e spin al
cord to th e cerebral cortex (Fig. 2.19 a). Th e som ato-
topic projection on th e postcen tral gyrus resem bles
a person stan din g on h is h ead—an inverted
“h om un culu s” (Fig. 9.19, p. 240).
 Central Com ponents of the Som atosensory System · 29
2
Fig. 2.19 Course of the
Postcentral sensory pathw ays by w ay
gyrus of the thalamus and in-
Arm Shoulder Head ternal capsule to the
Forearm Neck cerebral cortex
Hand Trunk
Finger Hip
IV V Thigh
III
II
Thumb
Leg
Eye
Face Toes,
genitalia
Upper lip

Lower lip

Jaw
Tail of caudate nucleus
Tongue
Pharynx Th
a la
Abdom en, m
us
viscera Pa
lli
Pu du
ta m
m
en Internal
capsule
Head of
caudate
Insula nucleus

Claustrum
Corticospinal tract
Medial lem niscus
Lateral spinothalamic tract

Posterior column lesions. Th e posterior colum n s
m ain ly tran sm it im pu lses arisin g in th e prop rio-
ceptors an d cu tan eous receptors. If th ey are dys-
fu n ction al, t h e in dividual can n o lon ger feel th e
position of h is or h er lim bs; n or can h e or sh e rec-
ogn ize an object laid in t h e h an d by th e sen se of
tou ch alon e or iden tify a n u m ber or letter draw n by
th e exam in er’s fin ger in th e palm of th e h an d. Spa-
tial discrim in ation betw een tw o stim u li delivered
sim u ltan eou sly at differen t sites on th e body is n o
lon ger p ossible. As th e sen se of pressure is also dis-
tu rbed, t h e floor is n o lon ger secu rely felt u n der
th e feet; as a result, both stan ce an d gait are im -
paired (gait ataxia), particu larly in th e dark or w ith
th e eyes closed. Th ese sign s of posterior colu m n
disease are m ost pron ou n ced w h en th e posterior
colu m n s th em selves are affected, bu t th ey can also
be seen in lesion s of th e posterior colu m n n uclei,
th e m edial lem n iscu s, th e th alam u s, an d th e post-
cen tral gyru s.
The clinical signs of a posterior colum n lesion are,
th erefore, th e follow in g:
¼ Loss of the sense of position and m ovem ent
(kin esth etic sen se): th e patien t can n ot state th e
position of h is or h er lim bs w ith ou t lookin g.
¼ Astereognosis: th e p atien t can n ot recogn ize an d
n am e objects by th eir sh ape an d w eigh t usin g
th e sen se of tou ch alon e.
¼ Agraphesthesia: th e patien t can n ot recogn ize by
tou ch a n u m ber or letter draw n in th e palm of
th e h an d by th e exam in er’s fin ger.
¼ Loss of tw o-point discrim ination.
¼ Loss of vibration sense: th e patien t can n ot per-
ceive th e vibration of a tun in g fork placed on a
bon e.
2 30 · 2 Som atosensory System
¼ Positive Rom berg sign: Th e patien t can n ot st an d
for any len gth of tim e w ith feet togeth er an d
eyes closed w ith ou t w obblin g an d p erh aps fal-
lin g over. Th e loss of proprioceptive sen se can
be com pen sated for, to a con siderable exten t, by
open in g th e eyes (w h ich is n ot th e case, for ex-
am p le, in a p atien t w ith a cerebellar lesion ).
The fibers in th e posterior colum n s origin ate in th e
pseudou n ip olar n eu ron s of th e spin al gan glia, bu t
th e fibers in th e an terior an d posterior
spin oth alam ic tracts do n ot; th ey are derived from
th e second n euron s of t h eir respective p ath w ays,
w h ich are located w ith in th e spin al cord
(Fig. 2.16c, d, p . 26).
Anterior Spinothalamic Tract
Th e im pu lses arise in cu tan eou s receptors (p er-
itrich ial n erve en din gs, tactile corpu scles) an d are
con du cted alon g a m oderately th ickly m yelin ated
periph eral fiber to th e pseu doun ipolar dorsal root
gan glion cells, an d th en ce by w ay of t h e posterior
root in to th e spin al cord. In side th e cord, t h e cen -
tral processes of th e dorsal root gan glion cells
travel in th e posterior colu m n s som e 2–15 seg-
m en ts upw ard, w h ile collaterals travel 1 or 2 seg-
m en ts dow nw ard, m akin g syn aptic con tact on to
cells at variou s segm en tal levels in th e gray m atter
of the posterior horn (Fig. 2.16c, p. 26). Th ese cells
(th e secon d n eu ron s) th en give rise to th e an terior
spin oth alam ic tract, w h ose fibers cross in th e an te-
rior sp in al com m issu re, ascen d in th e con tralateral
an terolateral fu n icu lu s, an d term in ate in th e ven-
tral posterolateral nucleus of th e thalam us, toget h er
w ith th e fibers of th e lateral spin oth alam ic tract
an d th e m edial lem n iscus (Fig. 2.17, p. 27). Th e
th ird n eu ron s in th is th alam ic n ucleu s th en project
th eir axon s to th e postcentral gyrus in th e
thalam ocortical tract.
Lesions of the anterior spinothalamic tract. As ex-
plain ed above, th e cen tral fibers of th e first n eu -
ron s of th is t ract ascen d a variable distan ce in t h e
ipsilateral posterior colu m n s, givin g off collaterals
alon g th e w ay to t h e secon d n eu ron s, w h ose fibers
th en cross th e m idlin e an d ascen d fu rth er in th e
contralateral an terior spin oth alam ic tract. It fol-
low s th at a lesion of th is tract at a lum bar or
th oracic level gen erally cau ses m in im al or n o im -
pairm en t of touch , becau se m any ascen din g im -
pu lses can circu m ven t th e lesion by w ay of th e
ipsilateral portion of th e path w ay. A lesion of th e
an terior spin oth alam ic tract at a cervical level,
h ow ever, w ill p rodu ce m ild hyp esth esia of th e con -
tralateral low er lim b.
Lateral Spinothalamic Tract
Th e free n erve en din gs of th e skin are th e perip h -
eral receptors for n oxiou s an d th erm al stim uli.
Th ese en din gs con stitu te th e en d organ s of th in
grou p A fibers an d of n early un m yelin ated grou p C
fibers th at are, in tu rn , th e periph eral processes of
pseu doun ipolar n euron s in th e spin al gan glia. Th e
cen tral processes pass in th e lateral p ortion of th e
posterior roots in to th e sp in al cord an d th en divide
lon gitudin ally in to sh ort collaterals th at term in ate
w ith in on e or tw o segm en ts in th e su bstan tia
gelat in osa, m akin g syn apt ic con tact w ith funicular
neurons (secon d n eu ron s) w h ose processes form
th e lateral spin oth alam ic tract (Fig. 2.16d, p. 26).
Th ese p rocesses cross th e m idlin e in th e an terior
spin al com m issure before ascen din g in th e con -
tralateral lateral fu n icu lu s to th e th alam u s. Like th e
posterior colu m n s, th e lateral spin oth alam ic tract
is som atotopically organ ized; h ere, h ow ever, th e
fibers from th e low er lim b lie laterally, w h ile th ose
from th e tru n k an d u pper lim b lie m ore m edially
(Fig. 2.20).
Th e fibers m ediatin g p ain an d tem perature sen -
sation lie so close to each oth er th at th ey can n ot be
an atom ically separated. Lesion s of th e lateral
spin oth alam ic tract th us im pair both sen sory m od-
alities, th ough n ot alw ays to th e sam e degree.
Central continuation of the lateral spinothalamic
tract. Th e fibers of th e lateral spin oth alam ic tract
travel up th rou gh th e brain stem togeth er w ith
th ose of th e m edial lem n iscus in th e spinal lem nis-
cus, w h ich term in ates in th e ventral posterolateral
nucleus of th e th alam us (VPL, pp. 172, 173; see
Fig. 6.4, p. 174, an d Fig. 2.19). Th e th ird n eu ron s in
th e VPL project via th e thalam ocortical tract to th e
postcentral gyrus in t h e parietal lobe (Fig. 2.19).
Pain an d tem perature are p erceived in a rou gh
m an n er in th e th alam u s, bu t fin er distin ction s are
n ot m ade u n til th e im p ulses reach th e cerebral cor-
tex.
Lesions of the lateral spinothalamic tract. Th e
lateral spin oth alam ic tract is th e m ain path w ay for
 Central Com ponents of the Som atosensory System · 31
2
Fig. 2.20 Somatotopic
Posterior funiculus organization of spinal
Sem ilunar tract cord tracts in cross sec-
Fasciculus Fasciculus (com ma of Schultz)
Substantia gelatinosa tion. The lam inae of Rexed
cuneatus gracilis
Dorsolateral tract (of Burdach) (of Goll) S are also designated with
(Lissauer’s tract) L
T Rom an num erals (cytoar-
Posterior spinocerebellar C
chitectural organization of
tract
Lateral corticospinal
the spinal gray m atter).
tract I–III S
IV
Thoracic nucleus

L
Lo
V

w
T

er
Rubrospinal and

lim
VI

Tr
U

b
p
reticulospinal tracts

n
C

k
er
lim
S

b
X VII
C T L
Reticular formation
VIII
Anterior spino-
IX
cerebellar tract
Lateral spinothalam ic
tract

e
Olivospinal tract

r
u
n
t
Spinotectal tract

a
i
a
r
P
e
Spino-olivary tract

p
Pressure

m
Anterior spinothalam ic tract

e
T
Touch
Vestibulospinal tract
Reticulospinal tract
Tectospinal tract
Anterior corticospinal
tract

pain an d tem peratu re sen sation . It can be n eu ro-
surgically tran sected to relieve pain (cordotomy);
th is op eration is m u ch less com m on ly perform ed
today th an in th e past, becau se it h as been su p-
plan ted by less invasive m eth ods an d also because
th e relief it provides is often on ly tem p orary. Th e
latter ph en om en on , lon g recogn ized in clin ical ex-
perien ce, su ggests th at pain -related im pu lses
m igh t also ascen d th e sp in al cord alon g oth er
routes, e.g., in sp in ospin al n eu ron s belon gin g to
th e fascicu lu s prop riu s.
If th e lateral spin oth alam ic tract is t ran sected in
th e ven tral portion of th e spin al cord, pain an d
tem peratu re sen sation are deficien t on th e op-
posite side on e or tw o segm en ts below th e level of
th e lesion , w h ile th e sen se of tou ch is preserved
(dissociated sensory deficit).
Other Afferent Tracts of the Spinal
Cord
In addition to th e sp in ocerebellar an d spin o-
th alam ic tracts discussed above, th e spin al cord
con tain s yet oth er fiber p ath w ays ascen din g to
variou s target structu res in t h e brain stem an d deep
subcort ical n u clei. Th ese pat h w ays, w h ich origin ate
in th e dorsal h orn of th e spin al cord (secon d afferen t
n eu ron ) an d ascen d in its an terolateral fu n icu lu s,
in clude th e spinoreticular, spinotectal, spino -
olivary, and spinovestibular tracts. Th e sp in ovesti-
bu lar tract is foun d in th e cervical spin al cord, from
C4 upw ard, in th e area of th e (descen din g) vesti-
bu lospin al tract an d is probably a collateral path w ay
of th e posterior sp in ocerebellar tract.
Figu re 2.20 is a sch em atic draw in g of th e variou s
sen sory (ascen din g) t racts, as seen in a cross sec-
tion of th e spin al cord. Th e m otor (descen din g)
tracts are also in dicated, so th at th e sp atial rela-
tion sh ips betw een th e various tracts can be appre-
ciated. Fin ally, in addition to th e ascen din g an d de-
scen din g t racts, th e spin al cord also con t ain s a so-
called in trin sic ap paratu s, con sistin g of n euron s
th at project up w ard an d dow nw ard over several
spin al segm en ts in th e fasciculu s p ropriu s (Fig. 2.9,
p. 20).
2 32 · 2 Som atosensory System
Central Processing of
Somatosensory Information
Figu re 2.17 traces all of t h e sen sory p ath w ays dis-
cu ssed above, in sch em atically sim p lified form an d
in sp atial relation to on e an oth er, as th ey ascen d
from th e posterior roots to th eir ult im ate targets in
th e brain . Th e sen sory th ird n eu ron s in th e
th alam u s sen d th eir axon s th rough th e posterior
lim b of th e in tern al capsu le (posterior to th e py-
ram idal tract) to th e prim ary som atosen sory cor-
tex, w h ich is located in th e p ostcen tral gyru s
(Brodm an n cytoarch itectu ral areas 3a, 3b, 2, an d 1).
Th e th ird n eu ron s th at term in ate h ere m ediate
superficial sen sation , tou ch , pressu re, pain ,
tem peratu re, an d (partly) proprioception (Fig. 2.19,
p. 29).
Sensorimotor integration. In fact, n ot all of th e
sen sory afferen t fibers from t h e th alam u s term i-
n ate in th e som atosen sory cortex; som e term in ate
in th e prim ary m otor cortex of th e precen tral
gyrus. Th u s, th e sen sory an d m otor cortical fields
overlap to som e exten t, so th at th e precen tral an d
postcen tral gyri are som etim es togeth er desig-
n ated th e sensorimotor area. Th e in tegration of
fu n ction occurrin g h ere en ables in com in g sen sory
in form ation to be im m ediately converted to ou tgo-
in g m otor im p ulses in sen sorim otor regu latory cir-
cu its, about w h ich w e w ill h ave m ore to say later.
Th e descen din g pyram idal fibers em ergin g from
th ese circu its gen erally term in ate directly—
w ith ou t any in terven in g in tern eu ron s—on m otor
n eu ron s in th e an terior h orn . Fin ally, even th ou gh
th eir fu n ction s overlap, it sh ou ld be rem em bered
th at th e precen tral gyru s rem ain s alm ost en tirely a
m otor area, an d th e postcen tral gyru s rem ain s al-
m ost en tirely a (som ato)sen sory area.
Differentiation of somatosensory stimuli by their
origin and quality. It h as already been m en tion ed
th at som atosen sory represen tation in th e cerebral
cortex is spatially segregated in som atotopic fash -
ion : th e inverted sen sory h om u n cu lu s h as been
en cou n tered in Figu re 2.19 an d w ill be seen again
in Figu re 9.19, p . 240. But som atosen sory represen -
tation in th e cerebral cortex is also spatially segre-
gated by m odality: pain , tem perature, an d th e
oth er m odalities are rep resen ted by distin ct areas
of t h e cortex.
Alt h ou gh th e differen t sen sory m odalit ies are
already spat ially segregated in th e th alam u s, con -
scious differen t iation am on g t h em requ ires th e
participation of th e cerebral cortex. High er fun c-
tion s, su ch as discrim in ation or th e exact determ i-
n ation of th e site of a stim u lus, are cortex-depen d-
en t.
A u n ilateral lesion of the som atosensory cortex pro-
du ces a su btotal im pairm en t of th e perception of
n oxiou s, th erm al, an d tactile stim uli on th e op-
posite side of th e body; con tralateral discrim in a-
tion an d position sen se, h ow ever, are totally lost, as
th ey depen d on an in tact cortex.
Stereognosis. Th e recogn ition by tou ch of an object
laid in th e h an d (stereogn osis) is m ediated n ot ju st
by th e prim ary sen sory cortex, bu t also by associa-
tion areas in th e parietal lobe, in w h ich th e in -
dividual sen sory featu res of th e object, su ch as its
size, sh ap e, con sisten cy, tem p eratu re, sh arpness/
du lln ess, softn ess/h ardn ess, etc., can be in tegrated
an d com pared w ith m em ories of earlier tact ile ex-
perien ces.
Astereognosis. In ju ry to an area in t h e in ferior p or-
tion of th e parietal lobe im pairs th e ability to rec-
ogn ize objects by touch w ith th e con tralateral
h an d. Th is is called astereogn osis.
Somatosensory Deficits due to
Lesions at Specific Sites along
the Somatosensory Pathw ays
Figure 2.21 sh ow s som e typical sites of lesion s
alon g th e som atosen sory path w ays; th e corre-
sp on din g sen sory deficits are discu ssed below.
¼ A cortical or subcortical lesion in th e sen -
sorim otor area correspon din g to t h e arm or leg
(a an d b, respectively, in Fig. 2.21) cau ses p ares-
th esia (tin glin g, etc.) an d n u m bn ess in th e con -
tralateral lim b, w h ich are m ore p ron ou n ced dis-
tally th an proxim ally. An irritative lesion at th is
site can produ ce a sen sory focal seizu re w h en
spon tan eou s (epileptic) disch arge of th e in -
flam ed/dam aged n erve cells occu rs; becau se
th e m otor cortex lies directly adjacen t, th ere are
often m otor disch arges as w ell (jackson ian
 Som atosensory Deficits due to Lesions at Specific Sites along the Som atosensory Pathways · 33
2
Fig. 2.21 Potential sites
of lesions along the so-
b
matosensory pathw ays.
For the corresponding clini-
cal syndrom es, see text,
p. 32 ff.

a
Thalam us

Spinal lem niscus

(anterior and lateral
spinothalam ic tract)

Lateral spinothalam ic
tract

Trigem inal lem niscus

Principal sensory
nucleus of the trigem inal n.
g
Spinal nucleus and
Medial lem niscus tract of the trigem inal n.
f
Gracile nucleus
and cuneate nucleus

Lateral spinothalam ic
tract

Anterior spinothalam ic
tract Posterior colum n pathways
h
k

seizu re, see textbooks of n eu rology for th e
classification of epileptic seizu res).
¼ A lesion of all sensory pathw ays below the
thalamus (c) elim in ates all qu alities of sen sa-
tion on t h e opposite side of th e body.
¼ If all som atosen sory pat h w ays are affected ex-
cept th e path w ay for pain an d tem perature (d),
th ere is hypesth esia on t h e opp osite side of th e
body an d face, bu t pain an d tem perature sen sa-
tion are u n im paired.
¼ Conversely, a lesion of the trigeminal lemniscus
an d of th e lateral sp in oth alam ic tract (e) in th e
brain stem im pairs pain an d tem perature sen sa-
tion on th e opposite side of th e body an d face,
bu t does n ot im pair ot h er som atosen sory m od-
alit ies.
¼ If th e medial lemniscus and anterior
spinothalamic tract (f) are affected, all som a-
tosen sory m odalities of th e con tralateral h alf of
th e body are im paired, except pain an d
tem perature.
¼ Lesions of the spinal nucleus and tract of the
trigeminal nerve an d of th e lateral spino-
thalamic tract (g) im pair pain an d tem perature
2 34 · 2 Som atosensory System

sen sation on th e ipsilateral h alf of th e face an d
th e con t ralateral h alf of th e body.
¼ Posterior column lesions (h) cau se loss of posi-
tion an d vibration sen se, discrim in ation , et c.,
com bin ed w ith ipsilateral ataxia (see Case Pre-
sen t ation 1).
¼ If th e posterior horn of the spinal cord is af-
fected by a lesion (i), ipsilateral p ain an d
tem peratu re sen sation are lost, bu t oth er m od-
alit ies rem ain in tact (dissociated sen sory defi-
cit).
¼ A lesion affect in g multiple adjacent posterior
roots (j) causes radicular pain an d paresth esiae,
as w ell as im pairm en t or loss of all sen sory
m odalities in th e affected area of th e body, in
addition to hypoton ia or aton ia, areflexia, an d
ataxia if t h e roots su pply th e up per or low er
lim b.

Case Presentation 1: Subacute Combined Degenera tion

An 80-year-old wom an was hospitalized because of m arked
shortness of breath with dyspnea. The patient reported
that she had been suffering from an increasingly unsteady
gait and burning sensations throughout her body for about
a year and a half. The shortness of breath had developed in
the previous m onth and had worsened dram atically in the
past few weeks. The only previous disease reported by the
patient was “stom ach inflam m ation.”
On detailed exam ination by the adm itting neurologist, the
patient was in obviously poor condition, dehydrated and
with m arked dyspnea. Neurological exam ination revealed
spastic tetraparesis, which was m ore m arked in the legs,
with increased intrinsic m uscle reflexes despite the pre-
sence of obvious m uscle atrophy, especially on the trunk.
There was also evidence of severe spinal ataxia, severely dis-
turbed position sense, and hypesthesia and hypalgesia that
increased distally below about T8. Vibration sense in the
legs was alm ost absent (pallanesthesia). The neurologist
ordered pulm onary function tests because of the dyspnea, Fig. 2.22 Advanced subacute degeneration (funicular
along with MRI of the cervical and thoracic spine because of myelosis) w ith symptoms of paraplegia. On MRI of the
the neurological abnorm alities. cervical spine (C6 level), signal enhancem ent is seen in the
The pulm onary function tests revealed m arkedly posterior and anterolateral colum ns. This appearance is
dim inished expiratory volum e and reduced vital capacity. typical of advanced funicular myelosis.
Blood gases confirm ed global respiratory insufficiency with
reduced O2 and elevated CO2 levels. Blood chem istry re-
vealed a m arkedly reduced vitam in B12 level, and vitam ins classical posterior and pyram idal tracts but also the anterior
B6 , C, D, and folic acid were also low. MRI of the cervical and horns (quadriplegic syndrom e).
thoracic spine showed m arked signal enhancem ent in the The patient’s respiratory insufficiency was the result of
posterior and lateral colum ns and also in the anterior horns paresis of the respiratory m uscles (destruction of the inner-
(Fig. 2.22). vating m otor neurons).
Discussion with her fam ily physician revealed that the Because of the poor blood gases, the patient required con-
patient had known chronic atrophic gastritis with intrinsic trolled ventilation for several weeks. After correction of the
factor deficiency but that she had obtained vitam in B12 re- dehydration, electrolyte disturbances, and hypovitam ino-
placem ent therapy very irregularly in recent years. All of the sis, the patient recovered slowly and was transferred to a
findings together confirm ed the diagnosis of advanced sub- geriatric rehabilitation clinic 2 m onths following her initial
acute com bined degeneration, which involved not only the hospitalization.
 3

3 Motor System
Central Components of the Motor
System and Clinical Syndromes of
Lesions Affecting Them . . . . . . . . . . . . 36
Peripheral Components of the Motor
System and Clinical Syndromes of
Lesions Affecting Them . . . . . . . . . . . . 43
Complex Clinical Syndromes due to
Lesions of Specific Components of
the Nervous System . . . . . . . . . . . . . . . 45
3 36
3 Motor System
Th e m otor im pu lses for volu n tary m ovem en t are
m ain ly gen erated in th e precentral gyrus of th e
fron tal lobe (p rim ary m otor cortex, Brodm an n
area 4) an d in t h e adjacen t cortical areas (first
motor neuron). Th ey t ravel in th e lon g fiber path -
w ays (m ain ly th e corticonuclear and corticospinal
tracts/pyram idal path w ay), passin g th rou gh th e
brainstem an d dow n th e spinal cord to th e anterior
horn, w h ere th ey m ake syn aptic con tact w ith th e
second motor neuron—u su ally by w ay of on e or
m ore in terven in g in tern euron s.
Th e n erve fibers em ergin g from area 4 an d th e
adjacen t cortical areas togeth er m ake u p th e py-
ramidal tract, w h ich is t h e qu ickest an d m ost
direct con n ection betw een th e prim ary m otor area
an d th e m otor n eu ron s of th e an terior h orn . In ad-
dition , oth er cortical areas (esp ecially th e prem o-
tor cortex, area 6) an d subcortical n uclei (espe-
cially th e basal gan glia, cf. p. 214, Ch apter 8) partic-
ipate in th e n eural con trol of m ovem en t. Th ese
areas form com plex feedback loops w ith on e
an oth er an d w ith th e prim ary m otor cortex an d
cerebellu m ; th ey exert an in flu en ce of th e an terior
Central Components of the
Motor System and Clinical
Syndromes of Lesions Affecting
Them
Th e cen tral port ion of th e m otor system for volun -
tary m ovem en t con sists of th e prim ary m otor cor-
tex (area 4) an d th e adjacent cortical areas (p articu -
larly th e prem otor cortex, area 6), an d th e corti-
cobulbar an d corticospinal tracts to w h ich th ese
cortical areas give rise (Figs. 3.1 an d 3.2).
Motor Cortical Areas
Th e prim ary m otor cortex (precen tral gyru s,
Fig. 3.1) is a ban d of cortical tissu e th at lies on th e
opposite side of t h e cen tral su lcu s from th e p ri-
m ary som atosen sory cortex (in th e postcen tral
gyru s) an d, like it, exten ds u pw ard an d past th e su -
perom edial edge of t h e h em isph ere on to its m edial
h orn cells by w ay of several distin ct fiber path -
w ays in th e spin al cord. Th eir fun ct ion is m ain ly to
m odu late m ovem en t an d to regulate m uscle ton e.
Im pu lses gen erated in th e secon d m otor n eu-
ron s of t h e m otor cran ial n erve n u clei an d th e
an terior h orn of th e sp in al cord pass th rou gh th e
anterior roots, th e nerve plexuses (in th e cervical
an d lum bosacral region s), an d th e peripheral
nerves on th eir w ay to th e skeletal m uscles. Th e
im pulses are conveyed to th e m u scle cells th rou gh
th e motor end plates of th e n eu rom u scular jun c-
tion .
Lesion s of th e first m otor n euron in th e brain or
sp in al cord u sually p rodu ce spastic paresis, w h ile
lesion s of th e secon d m otor n eu ron in th e an terior
h orn , an terior root, periph eral n erve, or m otor en d
plate usually produce flaccid paresis. Motor defi-
cits rarely appear in isolation as th e resu lt of a le-
sion of th e n ervou s system ; th ey are usually ac-
com pan ied by sen sory, auton om ic, cogn itive, an d/
or n eu ropsych ological deficit s of variou s kin ds,
depen din g on t h e site an d n atu re of th e causative
lesion .
2
1 3
4 6aα 6aβ
8
8
Fig. 3.1 Primary motor area/precentral gyrus (area 4),
premotor cortex (area 6), and prefrontal eye field (area
8). For the functions of these areas, see text p. 36 ff.
surface. Th e area rep resen tin g t h e th roat an d
laryn x lies at th e in ferior en d of th e prim ary m otor
cortex; above it, in sequ en ce, are th e areas rep re-
sen t in g th e face, u pp er lim bs, trun k, an d low er
lim bs (Fig. 3.2). Th is is th e inverted “m otor hom un-
 Central Com ponents of the Motor System and Clinical Syndrom es of Lesions Affecting Them · 37
3
Fig. 3.2 Course of the
Thorax, abdom en pyramidal tract, upper
Shoulder portion: the corona radiata
Upper Thigh
lim b and internal capsule
Hand Leg

Finger V Toes

IV Bladder, rectum
III
Precentral gyrus
II
Thum b
Neck, face
Tongue
Dorsal Vision, hearing
Jaw Tem poropontine tract

Larynx,
Somatic sensation
pharynx
Pa Thalam us
lli
Pu du
t m
am Genu of internal capsule
en
Head of caudate nucleus
Insula
Frontopontine tract
Claustrum Frontothalam ic tract

Lentiform nucleus
Ventral
Corticospinal tract

culus,” corresp on din g to th e “som atosen sory

h om u n cu lus” of th e postcen tral gyru s th at w as dis- Molecular layer
cu ssed in Ch apter 2 (see Fig. 9.19, p. 240).
External
Motor neurons are fou n d n ot on ly in area 4 bu t granular layer
also in th e adjacen t cortical areas. Th e fibers m edi-
atin g fin e volun tary m ovem en ts, h ow ever, origi- External
pyramidal layer
n ate m ain ly in th e precen tral gyru s. Th is is th e site
of th e ch aracteristic, large pyram idal neurons (Betz Internal
cells), w h ich lie in th e fifth cellu lar layer of th e cor- granular layer
tex an d sen d th eir rapidly con du ctin g, th ickly m y-
Internal
elin ated axon s (Fig. 3.3) in to th e pyram idal tract. pyramidal layer
Th e pyram idal tract w as on ce t h ou gh t to be en -
tirely com p osed of Betz cell axon s, but it is n ow
kn ow n th at th ese accoun t for on ly 3–4 % of its
fibers. Th e largest fiber con tin gen t in fact origi- Multiform layer
n ates from th e sm aller pyram idal an d fu siform
cells of Brodm an n areas 4 an d 6. Axon s derived
from area 4 m ake u p abou t 40 % of all pyram idal
tract fibers; th e rem ain der com e from ot h er fron tal
areas, from areas 3, 2, an d 1 of th e pariet al som a- Fig. 3.3 Microarchitecture of the motor cortex (Golgi
tosen sory cortex (sen sorim otor area), an d from stain)
oth er areas in th e parietal lobe (Fig. 3.1). Th e m otor
n eu ron s of area 4 subserve fin e, volu n tary m ove-
3 38 · 3 Motor System

Fig. 3.4 Course of the

Precentral gyrus pyramidal tract

From area 8

Thalamus
Caudate
nucleus
(tail)

Lentiform
nucleus
Internal capsule
Caudate nucleus (head) Midbrain
Cortico-
m esencephalic tract III
Corticonuclear tract IV Corticopontine tract

Corticospinal Cerebral peduncle

(pyram idal) tract ( = crus cerebri)

V
Pons
VI
VII

IX
X
Pyramid XII Medulla
XI
Decussation of the pyramids
C1
Lateral corticospinal
Anterior corticospinal
tract (crossed)
tract (uncrossed)

Motor end plate

m en t of th e con tralateral h alf of th e body; th e py-

ram idal t ract is, accordin gly, crossed (see Fig. 3.4).
Direct electrical stim u lation of area 4, as durin g a
n eu rosu rgical procedu re, gen erally in duces con -
traction of an in dividu al m u scle, w h ile stim u lation
of area 6 in du ces m ore com plex an d exten sive
m ovem en ts, e.g., of an en tire u pper or low er lim b.
Corticospinal Tract (Pyramidal Tract)
Th is tract origin ates in th e m otor cortex an d travels
th rough th e cerebral w hite m atter (coron a radiata),
th e posterior lim b of th e internal capsule (w h ere
th e fibers lie very close togeth er), th e cen tral por-
tion of th e cerebral peduncle (crus cerebri), th e
pons, an d th e base (i.e., th e an terior portion ) of th e
 Central Com ponents of the Motor System and Clinical Syndrom es of Lesions Affecting Them · 39
m edulla, w h ere th e tract is extern ally eviden t as a
sligh t prot ru sion called th e pyram id. Th e m edul-
lary pyram ids (th ere is on e on eith er side) give th e
tract its n am e. At th e low er en d of th e m edu lla,
80–85 % of th e pyram idal fibers cross to th e oth er
side in t h e so-called decussation of the pyram ids.
Th e fibers th at do n ot cross h ere descen d th e spin al
cord in th e ipsilateral an terior fun iculu s as th e
anterior corticospinal tract; th ey cross farth er
dow n (u su ally at t h e level of th e segm en t th at th ey
sup ply) th rough th e an terior com m issu re of th e
spin al cord (cf. Fig. 3.6). At cervical an d th oracic
levels, th ere are probably also a few fibers th at re-
m ain u n crossed an d in n ervate ipsilateral m otor
n eu ron s in th e an terior h orn , so th at th e n u ch al
an d trun cal m u scu latu re receives a bilateral corti-
cal in n ervation .
Th e m ajority of pyram idal tract fibers cross in th e
decu ssat ion of th e pyram ids, th en descen d th e spi-
n al cord in th e con tralateral lateral fun icu lus as th e
lateral corticospinal tract. Th is t ract sh rin ks in cross-
section al area as it travels dow n th e cord, becau se
som e of its fibers term in ate in each segm en t alon g
th e w ay. Abou t 90 %of all pyram idal tract fibers en d
in syn apses on to in tern eu ron s, w h ich th en tran sm it
th e m otor im pu lses onw ard to th e large α m otor
neu ron s of th e an terior h orn , as w ell as to th e
sm aller γ m otor n euron s (Fig. 3.4).
Corticonuclear (Corticobulbar) Tract
Som e of t h e fibers of t h e pyram idal tract bran ch off
from th e m ain m ass of t h e tract as it passes
th rough th e m idbrain an d th en take a m ore dorsal
cou rse tow ard th e m otor cran ial n erve n u clei (Figs.
3.4 an d 4.54, pp. 38, 138). Th e fibers su pplyin g
th ese brain stem n u clei are partly crossed an d
partly un crossed (for fu rth er details, cf. Ch apter 4,
p. 77 ff. “Cran ial Nerves”). Th e n u clei receivin g py-
ram idal tract inpu t are th e on es t h at m ediate vol-
un tary m ovem en ts of th e cran ial m u scu latu re
th rough cran ial n erves V (th e trigem in al n erve), VII
(th e facial n erve), IX, X, an d XI (th e glossoph aryn -
geal, vagu s, an d accessory n erves), an d XII (th e hy-
poglossal n erve).
Corticomesencephalic tract. Th ere is also a con tin -
gen t of fibers travelin g toget h er w ith t h e cort i-
con uclear tract th at arises, n ot in areas 4 an d 6, but
rat h er in area 8, th e fron tal eye field (Figs. 3.1 an d
3.4). Th e im pu lses in th ese fibers m ediate con ju-
3
gate eye m ovem en ts (p. 94), w h ich are a com plex
m otor process. Because of its sp ecial origin an d
fu n ction , th e p ath w ay origin atin g in t h e fron t al eye
fields h as a separate n am e (th e corticom esen -
ceph alic tract), th ough m ost auth ors con sider it a
part of th e corticon u clear tract.
Th e corticom esen ceph alic tract ru n s in tan dem
w ith th e pyram idal tract (ju st rostral to it, in th e
posterior lim b of th e in tern al capsule) an d th en
h eads dorsally tow ard th e n uclei of th e cran ial
n erves th at m ediate eye m ovem en ts, i.e., cran ial
n erves III, IV, an d VI (th e oculom otor, troch lear, an d
abdu cen s n erves). Area 8 in n ervates th e eye
m uscles exclu sively in syn ergistic fash ion , rath er
th an in dividu ally. Stim u lation of area 8 in du ces
con ju gate gaze deviation to th e opposite side. Th e
fibers of th e corticom esen ceph alic tract do n ot ter-
m in ate directly on to th e m otor n euron s of cran ial
n erve n uclei III, IV, an d VI; th e an atom ical situ ation
h ere is com p licated an d in com pletely un derstood,
an d is discussed furth er in Ch apter 4 (p. 75 ff.).
Other Central Components of the
Motor System
A n u m ber of cen tral path w ays beside th e py-
ram idal t ract p lay m ajor roles in th e con trol of
m otor fun ction (Fig. 3.5). On e im portan t grou p of
fibers (t h e corticopontocerebellar tract) conveys
in form ation from th e cerebral cortex to th e cere-
bellu m , w h ose ou tpu t in t urn m odu lates plan n ed
m ovem en ts (cf. Ch apter 5 “Cerebellu m ”). Oth er
fibers t ravel from th e cortex to th e basal ganglia
(m ain ly th e corp us striatum = caudate n u cleu s an d
put am en ), th e substantia nigra, th e brain stem re-
ticular formation, an d oth er n u clei (e.g., in th e m id-
brain tect um ). In each of th ese st ru ctu res, th e im -
pulses are processed an d conveyed onw ard, via in -
tern eu ron s, to efferen t tracts th at project to th e
m otor n eu ron s of th e an terior h orn —th e tectospi-
n al, ru brospin al, reticu losp in al, vestibu lospin al,
an d oth er tract s (Fig. 3.6). Th ese tracts en able th e
cerebellum , basal gan glia, an d brain stem m otor
n uclei to in fluen ce m otor fu n ction in th e spin al
cord. (For fu rth er details, see Ch apter 4 “Brain -
stem ,” an d Ch apter 8 “Basal Gan glia.”)
Lateral and medial motor tracts in the spinal cord.
Th e m otor tracts in th e sp in al cord are an atom i-
cally an d fu n ction ally segregated in to tw o group s:
a lateral group, com prisin g th e corticospin al an d
3 40 · 3 Motor System

Fig. 3.5 Brain structures

4 6aα 6aβ 8 involved in motor func-
2 tion and the descending
1 tracts that originate in
3
them

Frontopontine tract
Parieto - Corticospinal tract
tem poropontine tract with extrapyram idal
Occipito - fibers
m esencephalic tract
Thalam us
Putam en and
globus pallidus

Head of caudate nucleus

Tegm ental nuclei

Red nucleus
Substantia nigra

Pontine nuclei
From the cerebellum Py To the cerebellum
(fastigial nucleus)

Reticular formation

Lateral vestibular
nucleus

Central tegm ental

tract
Inferior olive
Pyram id
Rubrospinal tract Reticulospinal
Olivospinal tract tract
Vestibulospinal tract Tectospinal tract
Lateral corticospinal Anterior corticospinal
tract tract

rubrospin al tracts, an d a m edial group, com prisin g
th e reticulospin al, vestibu losp in al, an d tectospin al
tracts (Kuypers, 1985). Th e lateral tracts m ain ly
project to th e distal m u scu latu re (especially in th e
up per lim bs) an d also m ake sh ort propriospin al
con n ection s. Th ey are prim arily respon sible for
volun tary m ovem en ts of th e forearm s an d h an ds,
i.e., for precise, h igh ly differen tiated, fin e m otor
con trol. Th e m edial tracts, in con trast, in n ervate
m otor n euron s lyin g m ore m edially in th e an terior
h orn an d m ake relatively lon g prop riosp in al con -
n ection s. Th ey are prim arily respon sible for m ove-
m en ts of th e tru n k an d low er lim bs (stance and
gait).

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 Central Com ponents of the Motor System and Clinical Syndrom es of Lesions Affecting Them · 41
3
Fig. 3.6 Synapses of the
Lateral corticospinal Anterior corticospinal
tract tract descending motor tracts
Olivospinal tract Reticulospinal tract onto anterior horn neu-
Rubrospinal tract Tectospinal tract rons
Vestibulospinal tract Descending somatosensory
fiber from posterior root

Semilunar fasciculus
(comm a of Schultz)
Annulospiral fiber (Ia)
Golgi fiber (Ib)

α 1 fiber
γ fiber

Lesions of Central Motor Pathw ays th e m edial descen din g tracts are dam aged (e.g., in
a spin al cord lesion ). Th e p ath ophysiology of sp as-
Pathogenesis of central spastic paresis. In th e acu te
ticity is still poorly un derstood, bu t th e accessory
ph ase of a lesion of th e corticospin al tract, th e deep
m otor pathw ays clearly play an im portan t role, be-
ten don reflexes are hypoactive an d th ere is flaccid
cau se an isolated, pu rely cortical lesion does n ot
w eakn ess of th e m u scles. Th e reflexes retu rn a few
cau se spasticity.
days or w eeks later an d becom e hyperactive, be-
cause th e m u scle spin dles resp on d m ore sen si-
Syndrome of central spastic paresis. Th is syn drom e
tively to stretch th an n orm al, p articu larly in th e
con sists of:
up per lim b flexors an d th e low er lim b exten sors.
¼ Dim in ish ed m u scular stren gth an d im paired
Th is hypersen sit ivity is du e to a loss of descen din g
fin e m otor con t rol
cen tral in h ibitory con trol of th e fusim otor cells
¼ Spastic in creased ton e
(γ m otor n euron s) th at in n ervate th e m u scle
¼ Abn orm ally brisk stretch reflexes, possibly w ith
spin dles. Th e in trafusal m u scle fibers are, th ere-
clon us
fore, perm an en tly activated (prestret ch ed) an d re-
¼ Hypoactivity or absen ce of exteroceptive re-
spon d m ore readily t h an n orm al to fu rth er stretch -
flexes (abdom in al, plan tar, an d crem asteric re-
in g of th e m u scle. A disturban ce of th e regulatory
flexes)
circuit for m uscle length probably occurs (cf.
¼ Path ological reflexes (Babin ski, Opp en h eim ,
p. 22 ff.), in w h ich th e up per lim b flexors an d low er
Gordon , an d Men del–Bekh terev reflexes, as w ell
lim b exten sors are set to an abn orm ally sh ort tar-
as disin h ibition of th e fligh t respon se), an d
get len gth . Th e resu lt is spastic increased tone an d
¼ (in it ially) Preserved m u scle bu lk
hyperreflexia, as w ell as so-called pyram idal tract
signs an d clonus. Am on g th e pyram idal tract sign s
Loca lization of Lesions in the Centra l Motor
are certain w ell-kn ow n fin din gs in th e fin gers an d
System
toes, such as th e Babinski sign (ton ic exten sion of
th e big toe in respon se to strokin g of th e sole of th e A lesion involvin g th e cerebral cortex (a in Fig. 3.7),
foot). such as a tum or, an in farct, or a trau m atic in ju ry,
Sp astic paresis is alw ays du e to a lesion of th e cau ses w eakn ess of part of th e body on th e op-
cen tral n ervou s system (brain an d/or sp in al cord) posite side. Hem iparesis is seen in t h e face an d
an d is m ore pron oun ced w h en both th e lateral an d h an d (brachiofacial w eakness) m ore frequen tly

tahir99-VRG & vip.persianss.ir

3 42 · 3 Motor System

Fig. 3.7 Sites of potential

Upper lim b lesions of the pyramidal
Tem poropontine
a Lower lim b tract. For the correspond-
Vision,
Face hearing Lower lim b ing clinical syndrom es, see

l
a
text p. 41 ff.

d
Trunk

t
i
Somatic

c
m
a
Upper lim b

a
r
sensation

t
r
y
Face

P
Frontopontine
b Internal Fronto-
capsule thalam ic

Tem poropontine
Occipitopontine
III
Py Frontopontine

Parieto-
pontine Cerebral
peduncle
VII
d
Rubrospinal
and tecto- VI
e XII spinal
tracts VII
f

Py

Pons
Rubrospinal
and tecto-
spinal tracts
g XII

XII
Pyramid

th an elsew h ere, because th ese parts of th e body
h ave a large cortical rep resen tation . Th e typical
clin ical fin din g associated w ith a lesion in site (a) is
a predom in an tly dist al paresis of t h e u pper lim b,
m ost seriou s fun ction al con sequ en ce of w h ich is
an im pairm en t of fin e m otor con trol. Th e w eakn ess
is in com plete (paresis rath er th an plegia), an d it is
flaccid, rat h er t h an spastic, becau se th e accessory
(n onpyram idal) m otor path w ays are largely
sp ared. An irritat ive lesion at site (a) can cause
focal (jackson ian ) seizu res (w h ich are described
fu rth er in n eu rology textbooks).
If th e internal capsule (b in Fig. 3.7) is involved (e.g.,
by h em orrh age or isch em ia), t h ere w ill be a con-
tralateral spastic hem iplegia—lesion s at t h is level
affect both pyram idal an d n onpyram idal fibers, be-
cau se fibers of th e tw o types are in close proxim ity

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 Peripheral Com ponents of the Motor System and Clinical Syndrom es of Lesions Affecting Them · 43
h ere. Th e corticon uclear tract is involved as w ell,
so th at a con tralateral facial palsy resu lts, perh aps
accom pan ied by a cen t ral hypoglossal nerve palsy.
No oth er cran ial n erve deficits are seen , h ow ever,
becau se t h e rem ain in g m otor cran ial n erve n u clei
are bilaterally in n ervated. Th e con t ralateral paresis
is flaccid at first (in th e “sh ock ph ase”) bu t be-
com es spastic w ith in h ou rs or days becau se of con -
com itan t dam age to n onpyram idal fibers.
Lesion s at t h e level of the cerebral peduncle (c in
Fig. 3.7), su ch as a vascu lar process, a h em orrh age,
or a t um or, produ ce con tralateral spastic hem i-
paresis, possibly accom pan ied by an ipsilateral
ocu lom otor n erve palsy (cf. Weber syn drom e,
p. 153).
Pontine lesions involvin g th e pyram idal tract (d in
Fig. 3.7; e.g., a tum or, brain stem isch em ia, a
h em orrh age) cau se contralateral or possibly bi-
lateral hem iparesis. Typically, n ot all of th e fibers of
th e pyram idal tract are involved, because its fibers
are spread over a w ider cross-sect ion al area at th e
pon tin e level th an elsew h ere (e.g., at th e level of
th e in tern al capsu le). Fibers in n ervatin g th e facial
an d hypoglossal n u clei h ave already m oved to a
m ore dorsal position before reach in g th is level;
th u s, an accom p anyin g cen tral facial or hypoglos-
sal palsy is rare, th ou gh th ere m ay be an accom -
panyin g ip silateral trigem in al n erve deficit or
abducen s palsy (see Figs. 4.66 an d 4.67, pp . 153,
154).
A lesion of th e medullary pyramid (e in Fig. 3.7;
usually a tu m or) can dam age th e pyram idal tract
fibers in isolation , as th e n onpyram idal fibers are
fu rth er dorsal at th is level. Flaccid contralateral
hem iparesis is a possible result . Th e w eakn ess is
less th an total (i.e., p aresis rath er th an p legia), be-
cau se th e rem ain in g descen din g path w ays are pre-
served.
Lesions of the pyramidal tract in the spinal cord. A
lesion affectin g th e pyram idal tract at a cervical
level (f Fig. 3.7; e.g., a tu m or, m yelitis, trau m a)
cau ses ipsilateral spastic hem iplegia: ipsilateral be-
cau se th e tract h as already crossed at a h igh er
level, an d spastic becau se it con tain s n onpyram idal
as w ell as pyram idal fibers at th is level. A bilateral
lesion in th e u pper cervical spin al cord can cau se
qu adriparesis or qu adrip legia.
3
A lesion affectin g th e pyram idal tract in th e
thoracic spin al cord (g in Fig. 3.7; e.g., trau m a, m y-
elitis) cau ses spast ic ip silateral m on oplegia of t h e
low er lim b. Bilateral involvem en t causes paraple-
gia.
Peripheral Components of the
Motor System and Clinical
Syndromes of Lesions Affecting
Them
Th e periph eral portion of th e m otor system com -
prises t h e m otor cran ial n erve n uclei of th e brain -
stem , th e m otor an terior h orn cells of th e spin al
cord, th e an terior roots, th e cervical an d lu m -
bosacral n erve plexu ses, th e periph eral n erves, an d
th e m otor en d plates in skeletal m u scle.
Anterior horn cells (α and γ m otor neurons). Th e
fibers n ot on ly of th e pyram idal t ract bu t also of t h e
nonpyram idal descen din g path w ays (th e reti-
cu lospin al, tectospin al, vestibu lospin al, an d ru-
brosp in al tracts, am on g oth ers), as w ell as afferen t
fibers from th e posterior roots, term in ate on th e
cell bodies or den drites of th e larger an d sm aller
α m otor n eu ron s. Fibers of all of th ese types also
m ake syn aptic con tact w ith th e sm all γ m otor n eu-
ron s, p artly directly, an d partly th rou gh in terven -
in g in tern euron s an d th e association an d com m is-
sural n euron s of th e in trin sic n euron al apparatu s
of th e spin al cord (Fig. 3.6). Som e of th ese syn apses
are excitatory, oth ers in h ibitory. Th e th in , u n m yeli-
nated n eu rites of th e γ m otor n euron s in n ervate
th e in trafusal m u scle fibers. In con trast to th e
pseudou n ip olar n eu ron s of th e spin al gan glia, t h e
an terior h orn cells are m u ltipolar. Th eir den drites
receive syn aptic con t act from a w ide variety of af-
feren t an d efferen t system s (Fig. 3.6).
Th e fu n ction al groups an d n uclear colu m n s of
neu ron s in th e an terior h orn are n ot separated
from on e an oth er by an atom ically discern ible
borders (cf. Fig. 2.5b, p. 16). In th e cervical spin al
cord, th e m otor n euron s for th e u pper lim bs lie in
th e lateral portion of th e gray m atter of th e an te-
rior h orn ; th ose for th e trun cal m u scles lie in its
m edial portion . Th e sam e som atotopic prin ciple
app lies in th e lu m bar sp in al cord, w h ere th e low er
lim bs are represen ted laterally, th e tru n k m edially.
tahir99-VRG & vip.persianss.ir
3 44 · 3 Motor System
Inhibition of anterior horn cells by Renshaw cells.
Am on g th e variou s types of in tern eu ron s of th e
an terior h orn , t h e Ren sh aw cells deserve sp ecial
m en tion (Fig. 2.11, p . 22). Th ese sm all cells receive
syn aptic con tact from collateral axon s of th e large
α m otor n eu ron s. Th eir axon s th en project back
on to th e an terior h orn cells an d in h ibit th eir activ-
ity. Ren sh aw in h ibit ion is an exam ple of a spin al
n egative feedback loop th at stabilizes th e activity
of m otor n eu ron s.
Anterior roots. Th e n eu rites of th e m otor n eu ron s
exit th e an terior aspect of th e spin al cord as root-
lets (fila radicularia) an d join togeth er, form in g th e
an terior roots. Each an terior root join s th e corre-
spon din g posterior root ju st distal to th e dorsal
root gan glion to form a spin al n erve, w h ich th en
exits th e spin al can al th rou gh th e in tervertebral
foram en .
Peripheral nerve and motor end plate. Th ere is on e
pair of spin al n erves for each segm en t of th e body.
Th e spin al n erves con tain afferen t som atosen sory
fibers, efferen t som atic m otor fibers, efferen t au -
ton om ic fibers from th e lateral h orn s of th e spin al
gray m atter, an d afferen t au ton om ic fibers (cf.
p. 14). At cervical an d lu m bosacral levels, th e spin al
n erves join to form th e n erve plexuses, w h ich , in
tu rn , give rise to th e perip h eral n erves th at in n er-
vate th e m uscu latu re of th e n eck an d lim bs (Figs.
3.31, 3.32, an d 3.34).
Th e th ick, m yelin ated, rapidly con du ctin g
n eu rites of th e large α m otor n euron s are called α 1
fibers (Fig. 2.11, p. 22). Th ese fibers t ravel to th e
w orkin g m uscu latu re, w h ere th ey divide in to a
h igh ly variable n um ber of bran ch es th at term in ate
on m u scle fibers. Syn aptic im pu lse tran sm ission
occurs at th e n eu rom u scular jun ct ion s (m otor en d
plates).
Motor unit. An an terior h orn cell, it s n eu rites, an d
th e m u scle fibers it in n ervates are collect ively
term ed a m otor un it (Sh errin gton ). Each m otor
un it con stitutes th e fin al com m on path w ay for
m ovem en t-related im pu lses arrivin g at th e an te-
rior h orn cell from h igh er levels: its activity is in -
flu en ced by im pu lses in a w ide variety of m otor
tracts th at origin ate in differen t areas of th e brain ,
as w ell as by im pu lses derived from in trasegm en -
tal an d in tersegm en tal reflex n eu ron s of t h e sp in al
cord. All of th ese m ovem en t-related im pu lses are
in tegrated in th e m otor u n it, an d th e result of th is
in tegration is tran sm itted to th e m u scle fibers.
Mu scles p articip atin g in fin ely differen tiated
m ovem en ts are sup plied by a large n um ber of
an terior h orn cells, each of w h ich in n ervates on ly a
few (5–20) m u scle fibers; su ch m u scles are t h u s
com posed of sm all m otor units. In con t rast , large
m u scles th at con tract in relatively u n differen tiated
fash ion , su ch as t h e gluteal m u scles, are sup plied
by relatively few an terior h orn cells, each of w h ich
in n ervates 10 0–50 0 m u scle fibers (large m otor
units).
Clinical Syndromes of Motor Unit
Lesions
Flaccid paralysis is caused by in terru ption of m otor
un its at any site, be it in th e an terior h orn , on e or
m ore an terior roots, a n erve plexu s, or a periph eral
n erve. Motor u n it dam age cuts off th e m uscle
fibers in th e m otor u n it from both volun tary an d
reflex in n ervation . Th e affected m uscles are ex-
trem ely w eak (plegic), an d th ere is a m arked
dim in u tion of m uscle ton e (hypotonia), as w ell as a
loss of reflexes (areflexia) because th e m on osyn ap-
tic stretch reflex loop h as been in terru pted. Mu scle
atrop hy sets in w it h in a few w eeks, as th e m u scle is
gradu ally replaced by con n ective tissu e; after
m on th s or years of p rogressive atrophy, th is re-
placem en t m ay be com plete. Th us, th e an terior
h orn cells exert a troph ic in fluen ce on m u scle
fibers, w h ich is n ecessary for th e m ain ten an ce of
th eir n orm al stru ctu re an d fu n ction .
The syndrome of flaccid paralysis con sists of th e
follow in g:
¼ Dim in u tion of raw stren gth
¼ Hypoton ia or aton ia of th e m u scu latu re
¼ Hyporeflexia or areflexia
¼ Muscle atrophy
Th e lesion can u su ally be localized m ore specifi-
cally to th e an terior h orn , th e an terior root(s), th e
n erve plexus, or th e periph eral n erve w ith th e aid
of electrom yography an d electron eurography
(n erve con duction studies). If p aralysis in a lim b or
lim bs is accom pan ied by som atosen sory an d auto-
n om ic deficits, th en th e lesion is presu m ably distal
to th e n erve roots an d is th u s located eith er in th e
n erve plexus or in th e periph eral n erve. Flaccid
paralysis is on ly rarely du e to a cortical lesion (cf.
tahir99-VRG & vip.persianss.ir
 Com plex Clinical Syndrom es due to Lesions of Specific Com ponents of the Nervous System · 45
p. 41); in such cases, th e reflexes are preserved or
even exaggerated, an d t h e m uscle ton e is n orm al
or in creased.
Complex Clinical Syndromes due
to Lesions of Specific
Components of the Nervous
System
Dam age to in dividu al com pon en ts of th e n ervous
system gen erally does n ot cau se an isolated m otor
deficit of th e kin d described up to th is poin t.
Rath er, m otor deficits are usually accom p an ied by
som atosen sory, special sen sory, au ton om ic, cogn i-
tive, an d/or n eu ropsych ological deficits of variable
type an d exten t dep en din g on th e site an d exten t
of th e lesion . Th e com plex clin ical syn drom es due
to lesion s in sp ecific region s of th e brain (telen -
cep h alon , dien ceph alon , basal gan glia, lim bic sys-
tem , cerebellum , an d brain stem ) w ill be described
in th e corresp on din g ch apters. In th is section , w e
w ill p resen t th e typical syn drom es arisin g from le-
sion s of th e spin al cord, n erve root s, plexu ses, pe-
riph eral n erves, m otor en d plates, an d m u scu la-
tu re.
Spinal Cord Syndromes
Becau se th e spin al cord con tain s m otor, sen sory,
an d auton om ic fibers an d n u clei in a tigh t sp atial
relation sh ip w ith on e an oth er, lesion s of t h e spin al
cord can cause a w ide variety of n eurological defi-
cits, w h ich can be com bin ed w ith each oth er in
m any differen t w ays. Carefu l clin ical exam in ation
usually en ables h igh ly precise localization of th e
lesion , bu t on ly if th e exam in er possesses adequate
kn ow ledge of th e an atom y of th e relevan t m otor,
sen sory, an d au ton om ic pat h w ays. Th u s, th is sec-
tion w ill begin w ith a brief discu ssion of clin ical
an atom y. Th e in dividu al spin al pat h w ays h ave al-
ready been discu ssed on pp. 25 ff. (afferen t pat h -
w ays) an d 38, 39. (efferen t pat h w ays).
General anatomical preliminaries. Th e spin al cord,
like th e brain , is com posed of gray m atter an d
w h ite m atter. Th e w h ite m atter con tain s ascen din g
an d descen din g fiber tracts, w h ile th e gray m atter
con tain s n euron s of differen t kin ds: th e an terior
3
h orn s con tain m ostly m otor n eu ron s (see p. 43 ff.),
th e lateral h orn s m ostly au ton om ic n eu ron s, an d
th e posterior h orn s m ostly som atosen sory n euron s
participatin g in a n u m ber of differen t afferen t
path w ays (see below an d Ch apter 2). In addition ,
th e spin al cord con tain s an in trin sic n eu ron al ap -
paratu s con sistin g of in tern eu ron s, association
n eu ron s, an d com m issural n eu ron s, w h ose
processes ascen d an d descen d in th e fascicu lu s
proprius (Fig. 2.9, p. 20).
In th e adu lt, th e spin al cord is sh orter th an th e
vertebral colu m n : it exten ds from t h e cran iocervi-
cal ju n ction to about th e level of th e in tervertebral
disk betw een th e first an d secon d lu m bar verte-
brae (L1–L2) (Fig. 2.4, p. 15; th is m ust be born e in
m in d w h en localizin g th e level of a sp in al process).
Th e segm en ts of th e n eu ral tube (prim itive spin al
cord) correspon d to th ose of th e vertebral colum n
on ly up to th e th ird m on t h of gestat ion , after w h ich
th e grow th of th e sp in e progressively ou tstrips th at
of th e spin al cord. Th e n erve roots, h ow ever, still
exit from t h e spin al can al at th e n u m erically corre-
spon din g levels, so th at th e low er th oracic an d
lu m bar roots m u st travel an in creasin gly lon g dis-
tan ce th rough th e subarach n oid space to reach th e
in tervertebral foram in a th rou gh w h ich th ey exit.
Th e spin al cord en ds as th e conus medullaris (or
con us term in alis) at th e L1 or L2 level (rarely at L3).
Below th is level, th e lum bar sac (th eca) con tain s
on ly n erve root filam en ts, t h e so-called cauda
equina (“h orse’s tail”; Fig. 3.22).
Th e fan like filam en ts of th e n erve roots still dis-
play th e origin al m etam eric structu re of th e spin al
cord, but th e cord itself sh ow s n o segm en tal divi-
sion . At tw o sites, h ow ever, th e spin al cord is som e-
w h at sw ollen , n am ely at th e cervical an d lumbar
enlargements. Th e form er con tain s th e segm en ts
correspon din g to th e up per lim bs (C4–T1), w h ich
form th e brach ial p lexus; th e latter con tain s th e
on es for th e low er lim bs (L2–S3), w h ich form t h e
lu m bosacral plexu s (Fig. 2.4, p. 15).
Spinal cord lesions occasion ally affect on ly th e
w h ite m atter (e.g., posterior colu m n lesion s) or
on ly th e gray m atter (e.g., acute poliom yelitis), bu t
m ore often affect both . In th e follow in g para-
graph s, th e m an ifestation s of typical spin al cord
syn drom es w ill be presen ted from a topical poin t
of view. For com p leten ess, a n um ber of syn drom es
ch aracterized prim arily or exclu sively by som a-
tosen sory deficits w ill also be presen ted h ere.
tahir99-VRG & vip.persianss.ir
3 46 · 3 Motor System

fin ed to a sm all area w it h in th e cord. Involvem en t

of th e an terior h orn s causin g flaccid paresis is rare,
an d h em ip aresis or paraparesis is even rarer. Elec-
trom yograp hy can dem on strate a segm en tal m otor
deficit in u p to 2/ 3 of all cases, but , becau se h erp es
zoster is u su ally fou n d in th e th oracic area, th e
T6
deficit ten ds to be fu n ction ally in sign ifican t, an d
Herpes
zoster m ay escape th e patien t’s n otice. In som e cases, th e
cu tan eou s lesion is absen t (h erpes sin e h erpete).
Herp es zoster is relatively com m on , w ith an in ci-
Fig. 3.8 Syndrome of the dorsal root ganglion den ce of 3–5 cases per 10 0 0 person s per year; im -
m u n ocom prom ised in dividuals (e.g., w ith AIDS,
m align an cy, or im m u n osupp ression ) are at ele-
vated risk. Treatm en t w ith topical derm atological
m edication as w ell as aciclovir, or an oth er sp ecific
virustatic agen t, is recom m en ded. Even w ith ap-
propriate treatm en t, posth erp etic n eu ralgia in th e
affected area is a n ot u n com m on com p lication . It
can be treated sym ptom atically w ith variou s m edi-
C4 – T6 All
somatosensory cation s, in clu din g carbam azepin e an d gabapen tin .
modalities

Posterior root syndrome (Fig. 3.9). If tw o or m ore

Fig. 3.9 Posterior root syndrome
adjacen t posterior roots are com pletely divided,
e.g., ow in g to traum atic in ju ry, sen sation in th e
correspon din g derm atom es is partially or totally
lost. In com plete posterior root lesion s affect differ-
en t sen sory m odalities to variable exten t s, w it h
pain sen sation u su ally bein g m ost stron gly af-
fected. Becau se th e lesion in terru pts th e p eriph eral
Hypesthesia
reflex arc, t h e sensory deficit is accom pan ied by
T8
Ataxia, hyp oton ia an d hyporeflexia or areflexia in t h e
asynergia, m u scles su pplied by th e affected roots. Th ese typ i-
loss of
position sense cal deficits are produ ced on ly if m u ltip le adjacen t
roots are affected.
Fig. 3.10 Posterior column syndrome

Posterior column syndrome (Fig. 3.10). Th e poste-

Syndromes due to Lesions of Individua l
Spina l Tracts a nd Nuclea r Areas a nd the
Associa ted Periphera l Nerves
Syndrome of the dorsal root ganglion (Fig. 3.8). In -
fection of on e or m ore spin al gan glia by a n eu-
rotrop ic virus occu rs m ost com m on ly in th e
th oracic region an d cau ses pain fu l eryt h em a of th e
correspon din g derm atom e(s), follow ed by th e for-
m ation of a variable n u m ber of cu tan eou s vesicles.
Th is clin ical pictu re, called herpes zoster, is as-
sociated w ith very u npleasan t, stabbin g pain an d
paresth esiae in th e affected area. Th e in fection
m ay p ass from th e spin al gan glia in to th e spin al
cord itself, but, if it does, it usu ally rem ain s con -
rior colu m n s can be secon darily involved by path o-
logical p rocesses affectin g th e dorsal root gan glion
cells an d th e posterior roots. Lesion s of th e poste-
rior colum n s typically im pair position an d vibra-
tion sen se, discrim in ation , an d stereogn osis; th ey
also produce a positive Rom berg sign , as w ell as
spin al ataxia t h at w orsen s sign ifican t ly w h en th e
eyes are closed (u n like cerebellar ataxia, w h ich
does n ot). Posterior colum n lesion s also often pro-
du ce hyp ersen sitivity to pain . Possible causes in -
clude vitam in B12 deficien cy (e.g., in “fu n icu lar m y-
elosis”; see p . 47), AIDS-associated vacu olar m y-
elopathy, an d spin al cord com pression (e.g., in cer-
vical spin al sten osis). Tabes dorsalis du e to syph ilis
is rare in North Am erica an d Western Eu rope bu t is
 Com plex Clinical Syndrom es due to Lesions of Specific Com ponents of the Nervous System · 47
an in creasin gly com m on t ype of p osterior colu m n
distu rban ce in oth er parts of th e w orld.
Posterior horn syndrome (Fig. 3.11) can be a clin i-
cal m an ifestation of syrin gom yelia, h em atom yelia,
an d som e in tram edullary sp in al cord tu m ors,
am on g oth er con dit ion s. Like posterior root le-
sion s, posterior h orn lesion s produce a segm en tal
som atosen sory deficit; yet, rath er th an im pairin g
all sen sory m odalities like posterior root lesion s,
posterior h orn lesion s sp are th e m odalities su b-
served by th e posterior colu m n s, i.e., epicrit ic an d
proprioceptive sen se. “On ly” p ain an d tem p eratu re
sen sation are lost in t h e correspon din g ipsilateral
segm en ts, because t h ese m odalities are con du cted
cen trally th rou gh a secon d n euron in t h e posterior
h orn (w h ose axon ascen ds in th e lateral
spin ot h alam ic tract). Loss of pain an d tem perature
sen sation w ith sp arin g of posterior colum n sen se
is called a dissociated som atosensory deficit. Th ere
m ay be spon tan eou s pain (deafferen tation pain ) in
th e an algesic area.
Pain an d tem peratu re sen sation are in tact below
th e level of t h e lesion , as th e lateral spin oth alam ic
tract, lyin g in th e an terolateral fu n icu lus, is u n -
dam aged an d con t in u es to con duct th ese m odali-
ties cen trally.
Gray matter syndrome (Fig. 3.12). Dam age to th e
cen tral gray m atter of th e spin al cord by syrin go-
m yelia, h em atom yelia, in tram edullary spin al cord
tu m ors, or oth er p rocesses in terru pts all of t h e
fiber path w ays passin g th rou gh t h e gray m at ter.
Th e m ost prom in en tly affected fibers are t h ose
th at origin ate in posterior h orn cells an d con duct
coarse pressu re, touch , pain , an d tem peratu re sen -
sation ; th ese fibers decussate in t h e cen tral gray
m atter an d th en ascen d in th e an terior an d lateral
spin oth alam ic tracts. A lesion affectin g th em pro-
du ces a bilateral dissociated sen sory deficit in th e
cu tan eou s area su pplied by th e dam aged fibers.
Syringomyelia is ch aracterized by th e form ation
of on e or m ore fluid-filled cavities in t h e spin al
cord; th e an alogous disease in th e brain stem is
called syrin gobu lbia. Th e cavities, called syringes,
can be form ed by a n u m ber of differen t m ech a-
n ism s an d are distribu ted in differen t ch aracteris-
tic pattern s depen din g on th eir m ech an ism of for-
m ation . Som e syrin ges are an expan sion of th e cen -
tral can al of th e spin al cord, w h ich m ay or m ay n ot
com m un icate w ith th e fou rth ven tricle; oth ers are
3
C5 – C8
Analgesia,
therm -
anesthesia
Fig. 3.11 Posterior horn syndrome
Py
Weakness, spastic
C4 – T4
Weakness, flaccid
Analgesia
therm anesthesia
Fig. 3.12 Gray matter syndrome
a h ollow in g-ou t of t h e p aren chym a an d are sepa-
rate from th e cen tral can al. Th e term “hydrom y-
elia” is som etim es used loosely for com m u n icatin g
syrin ges of t h e cen tral can al, but it properly refers
to an idiop ath ic, con gen ital varian t of syrin gom y-
elia in w h ich th e syrin x com m u n icates w ith t h e
subarach n oid space, an d sh ou ld on ly be used in
th is sen se. Syrin gom yelia m ost com m on ly affects
th e cervical spin al cord, typically produ cin g loss of
pain an d tem peratu re sen sation in th e sh ou lders
an d upp er lim bs. A p rogressively expan din g syrin x
can dam age th e lon g tracts of th e spin al cord, p ro-
du cin g spastic (para)paresis an d disturban ces of
bladder, bow el, an d sexu al fu n ction . Syrin gobu lbia
often cau ses un ilateral atrophy of th e ton gue,
hyp algesia or an algesia of t h e face, an d variou s
types of nystagm us dep en din g on th e site an d con -
figu ration of th e syrin x.
Th e syndrome of combined lesions of the posterior
columns and corticospinal tracts (funicular myelo-
sis) (Fig. 3.13; cf. Case Presen tation 1 on p. 34) is
m ost com m on ly p rodu ced by vitam in B12 defi-
cien cy du e to a lack of gastric in trin sic factor (e.g.,
in atroph ic gastritis), an d is kn ow n in such cases as
“su bacu te com bin ed degen eration ,” or SCD. Foci of
dem yelin ation are foun d in th e cervical an d
3 48 · 3 Motor System

th oracic region s in th e posterior colum n s (70–

80 %), an d som ew h at less com m on ly in th e py-
ram idal tracts (40–50 %), w h ile th e gray m atter is
Weakness, usu ally sp ared. Posterior colu m n dam age causes
spastic
loss of position an d vibration sen se in th e low er
Hypesthesia lim bs, resultin g in spin al ataxia an d a positive
T6 Rom berg sign (un stable stan ce w ith eyes closed).
Ataxia, asynergia, Th e accom panyin g pyram idal tract dam age cau ses
loss of
position sense spastic p araparesis w ith hyperreflexia an d bilateral
Babin ski sign s.
Fig. 3.13 Combined posterior column and corticospinal
tract syndrome (funicular myelosis) Anterior horn syndrome (Fig. 3.14). Both acu te
poliom yelitis an d spin al m u scle atrophy of variou s
types specifically affect th e an terior h orn cells,
particu larly in th e cervical an d lu m bar en large-
m en ts of th e spin al cord.
In poliomyelitis (a viral in fect ion ), a variable
n um ber of an terior h orn cells are acu tely an d irre-
versibly lost, m ain ly in t h e lum bar region , causin g
C7 – C8 flaccid paresis of th e m u scles in th e correspon din g
Weakness,
flaccid segm en ts. Proxim al m u scles ten d to be m ore
stron gly affected th an distal on es. Th e m u scles be-
com e atroph ic an d, in severe cases, m ay be
Fig. 3.14 Anterior horn syndrome com pletely replaced by con n ective tissu e an d fat. It
is rare for all of th e m u scles of a lim b to be affected,
becau se th e an terior h orn cells are arran ged in lon g
vertical colum n s w ith in th e spin al cord (Fig. 2.10).

Combined anterior horn and pyramidal tract syn-

drome (Fig. 3.15) is seen in amyotrophic lateral
sclerosis as th e resu lt of degen eration of both cort i-
Weakness, cal an d spin al m otor n eu ron s. Th e clin ical picture is
flaccid
a com bin ation of flaccid an d sp astic paresis.
Weakness, Muscle atrop hy, appearin g early in th e course of
spastic
th e disease, is gen erally so severe th at th e deep
ten don reflexes w ould ordin arily be absen t, if on ly
Fig. 3.15 Combined anterior horn and pyramidal tract
syndrome (amyotrophic lateral sclerosis) th e low er m otor n eu ron s w ere affected. Yet, be-
cau se of th e sim u ltan eou s dam age of th e upp er
m otor n euron s (w ith con sequ en t pyram idal tract
degen eration an d sp asticity), th e reflexes often re-
m ain elicitable an d m ay even be exaggerated. Ac-
com panyin g degen eration of th e m otor cran ial
n erve n u clei can cau se dysarth ria an d dysph agia
(progressive bu lbar palsy).

Syndrome of the corticospinal tracts (Fig. 3.16).

Weakness, Loss of cortical m otor n eu ron s is follow ed by
spastic
degen eration of th e corticospin al tracts in a n um -
ber of differen t diseases, in clu din g primary lateral
Fig. 3.16 Syndrome of the corticospinal tracts (progres- sclerosis (a varian t of am yotroph ic lateral sclerosis)
sive spastic spinal paralysis) an d th e rarer form of h ereditary spastic spinal
 Com plex Clinical Syndrom es due to Lesions of Specific Com ponents of the Nervous System · 49
paralysis. Th e m ost com m on su bform of th is dis-
ease is due to a m utation of th e gen e for an ATPase
of th e AAA fam ily on ch rom osom e 2; t h e disease
appears in ch ildh ood an d progresses slow ly t h ere-
after. Patien t s com plain in itially of a feelin g of
h eavin ess, th en of w eakn ess in th e low er lim bs.
Spast ic paraparesis w it h a sp astic gait distu rban ce
gradu ally develops an d w orsen s. Th e reflexes are
brisker t h an n orm al. Spastic paresis of t h e upp er
lim bs does n ot develop u n til m uch later.
Syndrome of combined involvement of the poste-
rior columns, spinocerebellar tracts, and (possibly)
pyramidal tracts (Fig. 3.17). Wh en t h e path ological
process affects all of th ese system s, t h e differen tial
diagn osis sh ould in clude spin ocerebellar ataxia of
Friedreich type, th e axon al form of a h ereditary
n eu ropathy (HSMN II), an d oth er ataxias.
Ch aracteristic clin ical m an ifestation s are pro-
du ced by th e lesion s in each of th e involved sys-
tem s. Friedreich ataxia begin s before age 20 w ith
loss of dorsal root gan glion cells, leadin g to poste-
rior colu m n degen eration . Th e clin ical resu lt is an
im pairm en t of position sen se, tw o-poin t discrim i-
n ation , an d stereogn osis, w ith spin al ataxia an d a
positive Rom berg sign . Pain an d tem peratu re sen se
are largely or com pletely spared. Th e ataxia is
severe, becau se both t h e posterior colu m n s an d
th e sp in ocerebellar tracts are involved; it is eviden t
w h en th e patien t tries to w alk, stan d, or sit, as w ell
as in t h e fin ger–n ose–fin ger an d h eel–kn ee–sh in
tests. Th e patien t’s gait is u n coordin ated, w ith
fest in at ion , an d also becom es spastic over tim e as
th e pyram idal tracts progressively degen erate.
Abou t h alf of all patien ts m an ifest skeletal de-
form ities su ch as scoliosis or pes cavu s (th e so-
called “Friedreich foot”).
Accordin g to Hardin g, Friedreich ataxia can be
diagn osed w h en th e follow in g clin ical criteria are
m et:
¼ Progressive at axia of n o ot h er kn ow n cau se,
begin n in g before age 25 years
¼ Au tosom al recessive in h erit an ce
¼ Absen t deep ten don reflexes in th e low er lim bs
¼ Posterior colu m n distu rban ce
¼ Dysarth ria w ith in five years of on set
The diagn osis can be defin itively establish ed by
m olecu lar gen etic testin g to reveal th e un derlyin g
gen etic defect, a trin u cleotide expan sion on ch ro-
m osom e 9.
3
Weakness, spastic
Hypesthesia
Lateral colum n ataxia
Ataxia, asynergia
Fig. 3.17 Syndrome of combined involvement of the
posterior columns, spinocerebellar tracts, and
(possibly) pyramidal tracts
Analgesia,
thermanesthesia
Weakness, spastic
Weakness, flaccid
Loss of all
sensory modalities
Hypesthesia,
loss of position sense
and discrimination
Fig. 3.18 Spinal cord hemisection syndrome (Brown−
Séquard syndrom e)
Th e spinal cord hemisection syndrome (Brow n–
Séqu ard syn drom e, Fig. 3.18) is rare an d u su ally in -
com plete; its m ost com m on cau ses are spin al
trau m a an d cervical disk h ern iation . In terru ption
of th e descen din g m otor path w ays on on e side of
th e spin al cord causes an in itially flaccid, ip silateral
paresis below th e level of th e lesion (spin al sh ock),
w h ich later becom es spastic an d is accom pan ied
by hyp erreflexia, Babin ski sign s, an d vasom otor
distu rban ces. At th e sam e tim e, th e in terru ption of
th e posterior colu m n s on on e side of th e spin al
cord cau ses ip silateral loss of p osition sen se, vibra-
tion sen se, an d tactile discrim in ation below th e
level of th e lesion . Th e ataxia th at w ou ld n orm ally
be cau sed by th e posterior colu m n lesion can n ot be
dem on strated becau se of th e coexistin g ipsilateral
paresis. Pain an d tem perature sen sation are spared
on th e side of t h e lesion , becau se th e fibers sub-
servin g th ese m odalities h ave already crossed to
th e oth er side to ascen d in th e lateral spin o-
th alam ic tract, bu t pain an d tem perature sen sation
are lost contralaterally below th e level of th e lesion ,
becau se th e ipsilateral (crossed) spin ot h alam ic
tracts are in terru pted.
3 50 · 3 Motor System
C8
C8
T10
T10
L1
L1 L1
Fig. 3.19 Spinal cord transection at different segmen-
tal levels
Sim ple tact ile sen sation is n ot im p aired, as th is
m odality is subserved by tw o differen t fiber path -
w ays: th e posterior colum n s (un crossed) an d t h e
an terior spin oth alam ic t ract (crossed). Hem isec-
tion of th e cord leaves on e of th ese tw o path w ays
in tact for tactile sen sation on eith er side of th e
body—th e con tralateral p osterior colum n s for th e
side con tralateral to th e lesion , an d th e con -
tralateral an terior spin oth alam ic tract for th e side
ipsilateral to it.
Aside from th e in terrupt ion of t h e lon g tract s,
th e an terior h orn cells m ay be dam aged to a vari-
able exten t at th e level of th e lesion , possibly cau s-
in g flaccid paresis. Irritation of th e posterior roots
m ay also cau se paresth esiae or radicular pain in
th e correspon din g derm atom es at th e u pp er
border of th e sen sory distu rban ce.
Spina l Cord Tra nsection Syndromes
General Sym ptom atology and Clinical Course
of Transection Syndrom es
Acute spinal cord transection syndrome (Fig. 3.19).
Th e com plete spin al cord tran section syn drom e is
m ost com m on ly caused by trau m a, less com m on ly
by in flam m ation or in fection (tran sverse m yelitis).
Acu te sp in al cord traum a in itially produ ces so-
called spinal shock, a clin ical pictu re w h ose
path ophysiology is in com pletely u n derstood.
Below th e level of th e lesion th ere is com plete, flac-
cid paralysis, an d all m odalities of sen sation are
lost. Bladder, bow el, an d sexu al fu n ction are lost as
w ell. On ly th e bu lbocavern osus reflex is preserved—
an im portan t poin t for th e diagn ostic differen t ia-
tion of th is con dition from polyradiculitis, in w h ich
it is typically absen t. Th ere are also troph ic ch an ges
below th e level of th e lesion , in part icular,
dim in ish ed sw eatin g an d dist urbed t h erm oregu la-
tion . Th ere is a m arked ten den cy to develop decu -
bit us u lcers. Th e up per border of th e sen sory defi-
cit (th e “sen sory level”) is often dem arcated by a
zon e of hyp eralgesia.
In th e days an d w eeks after th e causative even t,
th e spin al n eu ron s gradu ally regain th eir fun ction ,
at least in p art, but rem ain cut off from m ost of th e
cen trally derived n eural im pu lses th at n orm ally
regulate th em . Th ey th us becom e “au ton om ous,”
an d so-called spinal automatisms appear. In m any
cases, a stim u lu s below th e level of th e lesion in -
du ces su dden flexion of th e h ip, kn ee, an d an kle
(flexor reflex); if th e spin al cord tran section syn -
drom e is com plete, th e lim bs retain th e flexed
posit ion for a lon g tim e after th e st im u lu s becau se
of a spastic elevation of m uscle ton e. (In in -
com plete sp in al cord tran section syn drom e, on th e
oth er h an d, th e legs are in itially flexed upon stim u -
lation , but th en retu rn to th eir origin al position .)
Defecation an d urin at ion gradually fun ction again ,
bu t are n o lon ger u n der volu n tary con trol; in stead,
th e bladder an d bow el are em ptied reflexively on ce
th ey are filled to a certain poin t. Detru sor–sph in c-
ter dyssyn ergia causes u rin ary reten tion an d
frequ en t , reflexive m ictu rition (p. 196). Th e deep
ten don reflexes an d m u scle ton e gradu ally retu rn
an d can becom e path ologically elevated. Sexu al
poten cy, h ow ever, does n ot retu rn .
 Com plex Clinical Syndrom es due to Lesions of Specific Com ponents of the Nervous System · 51
Case Presentation 1: Incomplete Spina l Cord Tra nsection Syndrome due to
Pa ra infectious Myelitis
The patient, a 33-year-old architect, was sent to hospital by
her fam ily physician after com plaining of ascending pins-
and-needles paresthesiae in the lower lim bs and trunk. She
had had a febrile “cold” two weeks earlier. There was no
weakness or disturbance of bladder or bowel function.
Clinical exam ination revealed im pairm ent of epicritic sensa-
tion below the C5 level, but no paresis or other neurological
abnorm alities. CSF exam ination yielded an inflam m atory
picture, with no evidence of chronic CNS inflam m ation (CSF
electrophoresis revealed no oligoclonal bands). MRI of the
cervical spinal cord revealed a signal abnorm ality in the cord
a b
c d
Fig. 3.20 Parainfectious myelitis. a The sagittal T2-
weighted im age reveals a lesion with hyperintense signal in
the spinal cord at the level of the C2 vertebral body. b The
T1-weighted sequence after the adm inistration of contrast
medium reveals m arked enhancem ent of the lesion. c In
3
at the level of the C2 vertebral body. The rest of the MRI ex-
am ination was norm al. The clinical diagnosis was parainfec-
tious myelitis following a viral upper respiratory tract infec-
tion, causing incom plete spinal cord lesion syndrom e.
The signs and sym ptom s regressed com pletely under treat-
m ent with cortisone. To date, no other lesions have
developed elsewhere in the CNS.
The MRI abnorm ality in this case would also have been con-
sistent with a diagnosis of m ultiple sclerosis, which could be
excluded only on the basis of the CSFfindings and the further
course of illness.
the axial T2-weighted im age, the lesion is seen to occupy
the central portion of the cord. d Contrast enhancem ent in
the lesion is seen again in the axial T1-weighted im age after
the adm inistration of contrast m edium .
3 52 · 3 Motor System
Case Presentation 2: Pa ra pa resis due to Spina l Cord Compression by a n Epidura l Tumor
(Lymphoma )
The patient, a 34-year-old office worker, was in the 34th
week of pregnancy when she noted increasing weakness of
both lower lim bs and im paired sensation on the lower half
of the body. She said the sensory disturbance had begun on
the inner surface of the thighs and then spread along the
legs and, finally, upward onto the trunk. She had had in-
creasing difficulty with urination for several weeks, but had
attributed this to pregnancy.
Clinical exam ination revealed spastic paraparesis with bi-
lateral Babinski signs and a sensory deficit below T10 affect-
a b
Fig. 3.21 Epidural lymphoma compressing the spinal
cord. a The sagittal T2-weighted im age reveals severe spi-
nal cord com pression due to a m ass displacing the dura
mater and the cord ventrally. b A m oderate degree of ho-
mogeneous contrast enhancem ent in the tum or is seen in
the sagittal T1-weighted im age after the adm inistration of
Progressive spinal cord transection syndrome.
Wh en sp in al cord tran section syn drom e arises
gradu ally rath er th an sudden ly, e.g., because of a
slow ly grow in g t um or, spin al sh ock does n ot arise.
Th e t ran section syn drom e in su ch cases is u sually
partial, rath er th an com plete. Progressively severe
ing touch and position sense and, to a lesser extent, the
protopathic m odalities as well. MRI revealed a large m ass in
the thoracic spinal canal, com pressing the spinal cord and
displacing it anteriorly.
An em ergency cesarean section was perform ed, and the
tum or was neurosurgically rem oved im m ediately after-
ward. Histopathological exam ination revealed lym phom a.
The neurological deficits resolved com pletely, and no other
m anifestations of lym phom a were found.
contrast m edium ; the tum or has not spread intradurally.
c Axial T1-weighted im age after the adm inistration of con-
trast m edium . The lym phom a fills m ost of the spinal canal
and displaces the spinal cord ventrally and to the right. The
cord is significantly darker than the contrast-enhancing
tum or.
sp astic paraparesis develops below th e level of th e
lesion , accom pan ied by a sen sory deficit, bow el,
bladder, an d sexu al dysfun ct ion , an d auton om ic
m an ifestation s (abn orm al vasom otor regu lation
an d sw eat in g, ten den cy to decu bit us u lcers).
 Com plex Clinical Syndrom es due to Lesions of Specific Com ponents of the Nervous System · 53
Spinal Cord Transection Syndrom es at Different
Levels
Cervical spinal cord transection syndrome. Spin al
cord tran section above th e level of th e th ird cervi-
cal vertebra is fatal, as it abolish es breath in g (total
loss of fu n ction of th e ph ren ic an d in tercostal
n erves). Such p atien ts can survive on ly if th ey can
be artificially ven tilated w ith in a few m in utes of
th e cau sat ive in ju ry, w h ich is very rarely th e case.
Tran section at low er cervical levels produ ces qu ad-
riparesis w ith involvem en t of t h e in tercostal
m uscles; breath in g m ay be dan gerously im paired.
Th e u pper lim bs are affected to a variable exten t
dep en din g on th e level of th e lesion . Th e level can
be determ in ed fairly p recisely from th e sen sory
deficit fou n d on clin ical exam in ation .
Thoracic spinal cord transection syndrome. Tran -
section of th e upp er th oracic cord sp ares th e up per
lim bs bu t im pairs breath in g an d m ay also cau se
paralytic ileu s t h rou gh involvem en t of th e
splan ch n ic n erves. Tran section of th e low er
th oracic cord spares th e abdom in al m uscles an d
does n ot im p air breath in g.
Lumbar spinal cord transection syndrome. Trau -
m atic tran section of th e spin al cord at lu m bar
levels often causes especially severe disturban ces
becau se of con com itan t dam age of th e m ajor su p-
plyin g artery of th e low er spin al cord, th e great
radicu lar artery (of Adam kiew icz). Th e result is in -
farction of th e en tire lu m bar and sacral spin al cord
(cf. Case Presen tation 3 on p. 55).
Epiconus syndrome, cau sed by a sp in al cord lesion
at t h e L4 to S2 level, is relat ively rare (Fig. 3.22a
an d b). Un like con u s syn drom e (see below ), it is as-
sociated w ith sp astic or flaccid paresis of t h e low er
lim bs, depen din g on th e precise level of th e lesion .
Th ere is w eakn ess or tot al paralysis of h ip extern al
rotation (L4–S1) an d exten sion (L4–L5), an d
possibly also of kn ee flexion (L4–S2) an d flexion
an d exten sion of th e an kles an d toes (L4–S2). Th e
Ach illes reflex is absen t, w h ile th e kn ee-jerk reflex
is preserved. Th e sen sory deficit exten ds from L4 to
S5. Th e bladder an d bow el em pty on ly reflexively;
sexual poten cy is lost, an d m ale pat ien ts often h ave
priapism . Th ere is tran sien t vasom otor paralysis, as
w ell as a tran sien t loss of sw eatin g.
3
Conus syndrome, du e to a spin al cord lesion at or
below S3 (Fig. 3.22), is also rare. It can be caused by
spin al tu m ors, isch em ia, or a m assive lu m bar disk
h ern iation .
An isolated lesion of th e con us m edu llaris pro-
du ces th e follow in g n eu rological deficits:
¼ Detrusor areflexia w ith urin ary reten tion an d
overflow in con tin en ce (con tin u al drip pin g,
p. 196)
¼ Fecal in con tin en ce
¼ Im poten ce
¼ Saddle an esth esia (S3–S5)
¼ Loss of th e an al reflex
The low er lim bs are n ot paretic, an d th e Ach illes
reflex is preserved (L5–S2).
If con u s syn drom e is produced by a tum or, th e
lum bar an d sacral roots descen din g alon gside th e
con us w ill be affected soon er or later (Fig. 3.22). In
such cases, th e m an ifestation s of con u s syn drom e
are accom pan ied by deficits due to involvem en t of
th e cauda equin a: w eakn ess of th e low er lim bs,
an d m ore exten sive sen sory deficits th an are seen
in pu re con us syn drom e.
Cauda equina syndrome involves th e lu m bar an d
sacral n erve roots, w h ich descen d alon gside an d
below th e con u s m edu llaris, an d th rou gh th e lu m -
bosacral su barach n oid space, to th eir exit
foram in a; a tu m or (e.g., epen dym om a or lipom a) is
th e u su al cau se. Patien ts in itially com p lain of
radicu lar pain in a sciatic distribu tion , an d of
severe bladder p ain th at w orsen s w ith cou gh in g or
sneezin g. Later, variably severe radicu lar sen sory
deficits, affectin g all sen sory m odalities, arise at L4
or low er levels. Lesion s affectin g th e u pper port ion
of th e cau da equ in a produ ce a sen sory deficit in t h e
legs an d in th e saddle area. Th ere m ay be flaccid
paresis of th e low er lim bs w ith areflexia; u rin ary
an d fecal in con tin en ce also develop , alon g w ith
im paired sexu al fu n ction . With lesion s of th e low er
portion of th e cauda equ in a, th e sen sory deficit is
exclu sively in th e saddle area (S3–S5), an d t h ere is
n o low er lim b w eakn ess, bu t urin ation , defecation ,
an d sexu al fu n ction are im paired. Tu m ors affect in g
th e cauda equ in a, un like con u s tum ors, produ ce
slow ly an d irregu larly progressive clin ical m an ifes-
tation s, as th e in dividual n erve roots are affected
w ith variable rapidity, an d som e of th em m ay be
spared u n t il late in th e cou rse of th e illn ess.
3 54 · 3 Motor System

L1
Dural sac
L2
Subarachnoid L1 b
space (open)
L3 L1

L4

Epiconus L5 Spinal dura

mater
S1 L2
S2
S3 Sub -
Conus S4 arachnoid
medullaris S5 space
C Nerve
L3 root
Nerve root surrounded
surrounded Peripheral n. by p ia m ater
by spinal surrounded by
L4 epineurium
pia m ater

Filum
term inale S1

c
Cauda e quina L5

S1 S5

Co
S2

S3
S4
S5
Two coccygeal ganglia a

Fig. 3.22a The epiconus, the conus medullaris, and the
cauda equina, w ith the topographical relationships of
the nerve roots to the vertebral bodies and interverte-
bral disks.
a Posterior view, after opening of the dural sac (theca) and
the spinal arachnoid. For the typical syndrom es produced
by lesions affecting the epiconus, conus m edullaris, and
cauda equina, see text, p. 53.
b Lateral view, after rem oval of the lateral arches of the
vertebrae and opening of the dural sac, revealing the topo-
graphy of the spine, disks, and nerve roots.
c A funnel-shaped outpouching of the dura m ater with
openings for the anterior (ventral) and posterior (dorsal)
roots.
 Com plex Clinical Syndrom es due to Lesions of Specific Com ponents of the Nervous System · 55
3
Case Presentation 3: Lumbosacra l Spina l Cord Infa rction due to Acute Ischemia in the Territory
of the Anterior Spina l Artery (Anterior Spina l Artery Syndrome)
This retired 81-year-old wom an stated that she had fallen were m ore severely im paired than touch and position
on the m orning of adm ission because of sudden weakness sense.
in both lower lim bs. She had intense back pain im m ediately MRI revealed an area of signal abnorm ality in the lower por-
thereafter, which she attributed to the fall. The lower lim bs tion of the spinal cord, epiconus, and conus m edullaris. At
rem ained weak, and she becam e incontinent of urine and the level of the conus, the signal abnorm ality encom passed
stool. She had previously suffered from “thinning of the nearly the entire cross-sectional area of the cord. These find-
bones” with occasional painful fractures, but there had ings and the clinical m anifestations are consistent with spi-
never before been any weakness. Exam ination on adm is- nal cord infarction due to acute ischem ia in the territory of
sion revealed flaccid paraplegia, vesical and anal sphincter the anterior spinal artery.
dysfunction, and a sensory deficit on the lower lim bs and On further follow-up, the neurological deficits rem ained
lower portion of the trunk. Pain and tem perature sensation stable, without any worsening or im provem ent over tim e.

a b c d

e f
Fig. 3.23 Acute spinal ischemia in the territory of the
anterior spinal artery. Im ages obtained 12 hours (a, b, e)
and 3 days (c, d, f, g) after the onset of sym ptom s. The
osteoporotic vertebral body fractures seen on these im ages
were old and bore no relation to the acute neurological syn-
drom e. a The sagittal T2-weighted im age reveals central
hyperintensity of the spinal cord in and above the conus
m edullaris. b The T1-weighted im age reveals m ild contrast
enhancem ent. c Three days later, m arked hyperintensity
can be seen in the spinal cord on the T2-weighted im age.
g
d The contrast enhancem ent has not increased. (e, f, g)
Axial T2-weighted im ages. e At first, only the spinal gray
m atter is hyperintense. f Three days later, m ost of the spinal
cord is hyperintense; only the dorsal portion of the cord,
supplied by the posterolateral vessels, is still of norm al sig-
nal intensity. Thus, the neural pathway for epicritic sensa-
tion is less affected than the pathways for protopathic sen-
sation and m otor function. g These changes can be fol-
lowed downward into the conus m edullaris.
3 56 · 3 Motor System
Vascular Spinal Cord Syndromes
Th e blood su pply of th e spin al cord an d th e clin ical
syn drom es resu ltin g from lesion s of in dividual spi-
n al cord vessels are described in Ch apter 11, on
p. 281 ff. an d p. 312 ff.
Spina l Cord Tumors
Com plete or part ial sp in al cord tran section syn -
drom e (in cludin g con us syn drom e an d cau da
equin a syn drom e) is often cau sed by a tu m or. Spi-
n al cord tum ors are classified in to th ree types,
based on th eir localization (Fig. 3.24):
¼ Extradural tu m ors (m etastasis, lym ph om a,
plasm acytom a)
¼ In tradural extram edullary tum ors (m en in -
giom a, n eu rin om a)
¼ In tradural in tram edu llary tu m ors (gliom a,
epen dym om a)
Extradural neoplasms (Fig. 3.24a an d b) ten d to
grow rapidly, often p rodu cin g progressively severe
m an ifestat ion s of spin al cord com p ression : spastic
paresis of th e p arts of th e body su pplied by th e spi-
n al cord below th e level of th e lesion , an d, later,
bladder an d bow el dysfun ct ion . Pain is a com m on
feature. Dorsally situ ated tu m ors m ain ly cau se
sen sory distu rban ces; lateral com pression of th e
spin al cord can produce Brow n–Séquard syn drom e
(p. 49).
Intradural extramedullary tumors m ost com m on ly
arise from th e vicin ity of th e posterior roots
(Fig. 3.24 c). Th ey in itially produ ce radicular p ain
an d p aresth esiae. Later, as th ey grow, th ey cau se
in creasin g com pression of th e posterior roots an d
th e spin al cord, first th e posterior colu m n s an d
th en th e pyram idal tract in th e lateral fun iculu s.
Th e resu lt is a progressively severe spastic paresis
of th e low er lim b, an d paresth esiae (p articu larly
cold paresth esiae) in both low er lim bs, accom -
pan ied by a distu rban ce of both epicritic an d p ro-
prioceptive sen sation , at first ipsilaterally an d th en
bilaterally. Th e sen sory distu rban ce u sually as-
cen ds from caudal to cran ial un til it reach es th e
level of th e lesion . Th e spin e is ten der to percu ssion
at th e level of th e dam aged n erve root s, an d th e
pain is m arkedly exacerbated by cough in g or
sn eezin g. Th e pain cau sed by posterior colu m n in -
volvem en t is of “rh eu m atic” quality an d in itially
arises at th e distal en ds of th e lim bs. Hyperest h esia
is n ot un com m on in th e derm atom es su pplied by
th e affected n erve roots; th is m ay be u seful for
clin ical localization of th e level of th e lesion . As th e
spin al cord com pression progresses, it even tu ally
leads to bladder an d bow el dysfun ction .
Ventrally situated tumors (Fig. 3.24 c) can in -
volve t h e an terior n erve root s on on e or both sides,
cau sin g flaccid paresis, e.g., of th e h an ds (w h en th e
tu m or is in th e cervical region ). As th e tum or
grow s, it com presses th e pyram idal tract, cau sin g
spastic p aresis of th e ipsilateral low er lim b at first,
an d later of both low er lim bs. Tract ion on th e sp i-
n al cord due to stretch in g of th e den ticulate liga-
m en ts m ay fu rth er dam age th e pyram idal tract. If
th e com pressive lesion is an terolateral to th e cord,
con tralateral pain an d tem perature sen sation m ay
Fig. 3.24 Spinal cord
tumors. (a, b) Extradural
tum or; a dorsal to the spi-
nal cord, b ventral to the
spinal cord. c Intradural ex-
tram edullary tum or (dum b-
bell tum or with intraspinal,
intraforam inal, and extra-
foram inal portions).
d Intradural intram edullary
tum or.
 Com plex Clinical Syndrom es due to Lesions of Specific Com ponents of the Nervous System · 57
be affected. With ven tral as w ith dorsal tu m ors,
progressive spin al cord com pression even tu ally
leads to bladder an d bow el dysfun ction .
Intradural intramedullary spinal cord tumors
(Fig. 3.24 d) can be distin guish ed from extram edu l-
lary tum ors by th e follow in g clin ical features:
¼ Th ey rarely cau se radicular pain , in stead caus-
in g atypical (burn in g, du ll) pain of diffuse local-
ization .
¼ Dissociated sen sory deficits can be an early
fin din g.
¼ Bladder an d bow el dysfu n ction appear early in
th e cou rse of tu m or grow th .
¼ Th e sen sory level (upp er border of th e sen sory
deficit) m ay ascen d, because of lon gitu din al
grow th of th e tu m or, w h ile th e sen sory level as-
sociated w it h extram edullary tu m ors gen erally
rem ain s con stan t, becau se of tran sverse
grow th .
¼ Mu scle atrop hy due to involvem en t of th e an te-
rior h orn s is m ore com m on th an w ith ex-
tram edu llary tum ors.
¼ Spast icity is on ly rarely as severe as t h at pro-
du ced by ext ram edu llary tu m ors.
High cervical tumors can produce bu lbar m an ifes-
tation s as w ell as fasciculation s an d fibrillation s in
th e affected lim b. Extram edullary tu m ors are
m uch m ore com m on overall th an in tram edu llary
tum ors.
Tumors at the level of the foramen magnum
(m en in giom a, n eu rin om a) often in itially m an ifest
th em selves w ith pain , p aresth esia, an d hypesth e-
sia in th e C2 region (occip ital an d great auricu lar
n erves). Th ey can also cau se w eakn ess of th e ster-
n ocleidom astoid an d t rapeziu s m uscles (accessory
n erve).
Dumbbell tumors (or h ourglass tum ors) are so
called becau se of th eir un ique an atom ical con figu -
ration (Fig. 3.24c). Th ese are m ostly n eu rin om as
th at arise in th e in tervertebral foram en an d th en
grow in tw o direction s: in to th e spin al can al an d
out w ard in to t h e paravertebral sp ace. Th ey com -
press th e sp in al cord laterally, even t ually p rodu c-
ing a partial or com plete Brow n–Séqu ard syn -
drom e.
3
Nerve Root Syndromes (Radicular
Syndromes)
Preliminary remarks on anatomy. As discu ssed in
th e last ch apter, th e spin al n erves are form ed by
th e u n ion of th e posterior an d an terior roots.
After exitin g from th e spin al can al, th e fibers of
th e sp in al n erves at differen t segm en tal levels re-
group to form th e th ree plexu ses (Fig. 2.5, p. 16)—
cervical, brach ial, an d lum bosacral (see p. 62 ff.).
Th e periph eral n erves em ergin g from th ese plex-
uses each con tain fibers from m ultiple n erve roots.
Th is redistribu tion of n erve fibers in th e p lexuses is
th e reason w hy th e territories in n ervated by th e
n erve roots differ from th ose in n ervated by th e pe-
riph eral n erves. Each n erve root su pplies a ch arac-
teristic area of th e skin (derm atom e) an d in n er-
vates a ch aracteristic grou p of m uscles (m yotom e).
Most m u scles receive n erve fibers from m ore th an
on e n erve root (polyradicu lar in n ervation ). Th e
few m uscles receivin g m ost or all of th eir in n erva-
tion from a sin gle n erve root are called segm en t-
in dicatin g m u scles. Th ese m atters are discu ssed
m ore fu lly in Ch apter 2 on p. 16 ff.
Syndrome of nerve root involvement (radicu lar
syn drom e). Th e n erve roots are particu larly
vu ln erable to dam age at or n ear th eir passage
th rough th e in tervertebral foram in a. Com m on
cau ses in clu de stenosing processes (n arrow in g of
th e foram in a, e.g., due to bony overgrow t h ), disk
protrusion, an d disk herniation com pressin g th e
exitin g n erve root (Fig. 3.25). Oth er processes,
such as in fectiou s diseases of th e vertebral bo-
dies, tu m ors, an d trau m a, can also dam age th e
spin al n erve roots as th ey em erge from th e sp in al
can al.
Radicu lar lesion s p rodu ce th e follow in g charac-
teristic manifestations:
¼ Pain an d sen sory deficit in th e correspon din g
derm atom e
¼ Greater im p airm en t of pain sen sation th an of
th e oth er sen sory m odalities
¼ Redu ced stren gth in segm en t-in dicatin g
m uscles an d, rarely an d in severe cases, m u scle
atrop hy
¼ Reflex deficits correspon din g to th e dam aged
root(s) (Fig. 2.13, p. 23)
¼ Absen ce of auton om ic deficits (of sw eatin g,
piloerection , an d vasom otor fu n ction ) in th e
lim bs, becau se th e sym path etic an d parasym pa-
3 58 · 3 Motor System
th etic fibers join th e p eriph eral n erves distal to
th e n erve roots an d are th u s spared by radicu lar
lesion s
Motor deficits in th e segment-indicating muscles
of th e in dividu al m otor roots are useful for th e
clin ical an d electrom yograph ic localization of
radicu lar lesion s at cervical an d lu m bar levels. Th e
m ore im portan t segm en t-in dicatin g m u scles are
listed in Fig. 3.27 an d Fig. 3.29.
Ra dicula r Syndromes in Osteochondrosis a nd
Disk Degeneration
Degen erative disorders of t h e vertebrae an d in ter-
vertebral disks are t h e m ost com m on cau se of
radicu lar lesion s.
Th e in tervertebral disks are com posed of a
pu lpy in n er portion (n u cleu s pu lposu s) su r-
rou n ded by a fibrous rin g (an n u lu s fibrosu s). Th e
disks are n o lon ger su pplied by blood vessels on ce
th e developm en t of th e spin e is com plete. Th ere-
fore, as th e in dividu al ages, th e disks gradu ally lose
th eir elasticity an d turgor an d are less able to serve
as sh ock absorbers for th e spin e. Th is cau ses diffi-
cu lties prim arily in th e m ore m obile portion s of
th e spin e, i.e., th e cervical an d lu m bar region s.
Osteochondrosis involves degen erat ion of th e
disk an d of th e cartilagin ous base an d en d plates of
th e vertebral bodies. Th is resu lts in sclerosis of th e
cartilagin ou s tissu e an d in deform ation of th e
vertebral bodies. Th e in tervertebral disks lose
h eigh t, an d th e vertebral bodies on eith er side are
brou gh t closer togeth er. Th ere is also bony over-
Fig. 3.25 a Posterolateral
disk herniation at the L4−
5 level. The injured root is
not the L4 root, which exits
through the L4−5 inter-
vertebral foram en, but
rather the L5 root, which is
m edial to it and passes be-
hind the L4−5 interverte-
bral disk. b Central disk
herniation at L4−5 with
com pression of the cauda
equina.
grow th of th e facet join ts (spondylarthrosis) an d of
th e vertebral bodies th em selves (m ain ly in th e cer-
vical region , uncovertebral arthrosis). Th ese
processes cau se sten osis of th e in tervertebral
foram in a, w ith com pression of t h e tissues w ith in
th em , in clu din g th e n erve roots (Figs. 3.26 an d
3.28).
Cervical Root Lesions of Degenerative Origin
Cervical radicu lar syn drom es are n early alw ays
du e to foram in al sten osis of th is type, cau sed by
osteoch on drosis. Th e en d plates of t h e cervical
vertebrae are n orm ally som ew h at elevated on
eith er side of th e vertebral body, w h ere th ey form
th e u n cin ate processes, creatin g a saddlelike struc-
tu re. Wh en a cervical in tervertebral disk degen er-
ates, th e vertebral body above sin ks like a w edge
in to th e saddlelike depression of th e on e below,
cau sin g in creasin g p ressu re on th e u n cin ate
processes. Bon e rem odelin g occu rs, th rough w h ich
th e u n cin ate p rocesses are gradu ally disp laced
laterally an d dorsally, an d th e in tervertebral
foram in a gradually becom e n arrow er (Fig. 3.26).
Cervical osteoch on drosis is m ost com m on ly
fou n d at C5–C6 an d C6–C7, an d often also at C3–C4
an d C7–T1. Sten osis can affect on e or m ore foram in a
to a variable exten t, eith er un ilaterally or bilaterally.
Th u s, eith er m on osegm en tal or p lurisegm en tal
radicular m an ifestation s m ay be p rodu ced. Th e
m ost com m on sym ptom s are segm en tal pain an d
paresth esiae, w h ich are attribu table to n erve root
irritation . More severe root involvem en t m an ifests
itself as sen sory, m otor, an d reflex deficits in th e
 Com plex Clinical Syndrom es due to Lesions of Specific Com ponents of the Nervous System · 59
Uncinate
process
Artery
and vein
in fat
Nerve
roots
a b
Uncinate
process
c d
correspon din g segm en t(s). In addition to disk
degen eration , th ere m ay be con com itan t arth rotic
ch an ges of th e facet join ts t h at restrict th e m obility
of th e cervical spin e in th e involved segm en ts.
Individual cervical radicular syndromes (Fig. 3.27)
are ch aracterized by t h e follow in g deficits:
¼ C3, C4: pain in th e n eck an d sh oulder; rarely,
partial diaph ragm atic palsy
¼ C5: p ain w ith or w ith out hypalgesia in t h e C5
derm atom e; deltoid an d biceps w eakn ess
¼ C6: pain w ith or w ith out hypalgesia in th e C6
derm atom e; biceps an d brach ioradialis w eak-
n ess; dim in ish ed biceps reflex
¼ C7: p ain w ith or w it h ou t p aresth esia or hy-
palgesia in th e C7 derm atom e; triceps an d pro-
n ator teres w eakn ess; possible th en ar atrophy;
dim in ish ed triceps reflex
¼ C8: p ain w ith or w it h ou t p aresth esia or hy-
palgesia in th e C8 derm atom e; w eakn ess an d
3
Fig. 3.26 Intervertebral
foramina of the cervical
spine from C3 to C7.
a Norm al width of the
foram ina. b Foram inal ste-
nosis caused by disk
degeneration (drawn from
a dissected anatom ical
specim en). c Plane of sec-
tion of d and e. d Norm al
uncinate processes. e Unci-
nate processes deform ed
by intervertebral disk
generation.
e
possibly atrophy of th e hypoth en ar m u scles;
dim in ish ed tricep s an d Tröm n er reflexes
Lum bar Root Lesions of Degenerative Origin
In th e lu m bar region , th e in tervertebral disks are
th ick, an d th e base an d en d plates are flat;
degen erative disease can cause p rotru sion or
h ern iation (prolapse) of on e or m ore disks, an d th e
displaced disk tissu e can th en directly com press
th e n erve roots an d spin al gan glia. In addition ,
w h en ever a disk space is n arrow ed by osteoch on -
drosis, th e in tervertebral foram in a becom e n ar-
row er, w h ich can also cau se n erve root com p res-
sion an d radicu lar p ain (Fig. 3.28).
Disk degen eration m ost com m on ly affects t h e
low est tw o lu m bar disks, L5–S1 an d L4–L5, an d less
com m on ly th e L3–L4 disk.
Figu re 3.22b sh ow s th e in tim ate spatial rela-
tion sh ip of th e lu m bar vertebral bodies, in terverte-
3 60 · 3 Motor System

Fig. 3.27 Segment-indi-

cating muscles and cu-
tane ous sensory distribu-
tion of the C6, C7, and C8
nerve roots (after Mum en-
thaler and Schliack).
Biceps
Triceps
brachii m .
brachii m .

Biceps Triceps C7 C8
reflex reflex

Brachio-
radialis m .

Pronator
teres m .

Thenar
m uscles

Hypo-
thenar
muscles

C6 C7 C8

Fig. 3.28 a Intervertebral

foramen of normal w idth
between L5 and S1, with
dorsal root ganglion.
b Stenotic intervertebral
foramen with deform ation
of the dorsal root ganglion
by the superiorly displaced
inferior articular process
(drawn from a dissected
anatom ical specim en).

bral disks, an d n erve roots. Th e n erve root exits th e
lu m bar spin al can al in its du ral sleeve rou gh ly at
th e level of t h e u pper th ird of th e vertebral body,
proceedin g obliquely in a ven trocau dal direction to
th e in tervertebral foram en , th e up per portion of
w h ich con tain s th e dorsal root gan glion . Th u s, a
dorsolateral disk prot ru sion does n ot directly af-
fect th e n erve root exit in g at t h e correspon din gly
n u m bered level; rath er, it im pin ges on th e n erve
root of th e n ext segm en t below, w h ich passes be-
h in d th e disk at th is level, on its w ay to its ow n ,
low er-lyin g foram en (Fig. 3.25). On ly a far lateral
disk prolapse can directly com p ress th e corre-
sp on din gly n um bered n erve root.
Th e L5–S1 in tervertebral disk is often som ew h at
n arrow er th an th e oth ers, because th e lum bar lor-
dosis is m ost pron ou n ced at th is level. As a resu lt,
an L5–S1 disk h ern iation can im pin ge on both th e
L5 an d S1 n erve roots, causin g a com bin ed L5 an d
S1 syn drom e.
 Com plex Clinical Syndrom es due to Lesions of Specific Com ponents of the Nervous System · 61
Vastus
lateralis m .
Vastus
m edialis m .
Knee-jerk
reflex
Extensor
hallucis
longus m .
Tibialis
anterior m .
Extensor
digitorum
brevis m .
L4 L5
In th e lu m bar region as in th e cervical region ,
disk h ern iation m ost com m on ly m an ifests itself
w ith sym ptom s of radicu lar irritation (pain an d
paresth esia) in th e affected segm en ts. More severe
radicu lar dam age produces segm en tal sen sory an d
m otor deficits.
A patien t sufferin g from lu m bar radicular irrita-
tion syn drom e m ay report th e abrupt cessat ion of
sciatic p ain an d th e sim u ltan eou s appearan ce of
w eakn ess or a sen sory deficit. Th is situ ation arises
w hen th e n erve root fibers su dden ly cease con -
du ctin g im p ulses, im plyin g th e im pen din g death
of th e n erve root. Em ergen cy n eu rosu rgical
decom p ression of th e affected root is in dicated.
A large disk prolap se can also, in rare cases,
pen etrate th e posterior lon gitu din al ligam en t in a
dorsom edial position an d pass in to th e lum bar spi-
n al can al, cau sin g cauda equin a syn drom e (“m as-
sive prolapse”; Fig. 3.25b an d Fig. 3.30).
3
Fig. 3.29 Segment-indi-
cating muscles and cu-
taneous sensory distribu-
tion of the L4, L5, and S1
nerve roots (after Mum en-
thaler and Schliack).
Triceps
surae m .
Peroneus
longus m .
Peroneus
brevis m .
Ankle-jerk
reflex
S1
Acute sciatica (“ch arley-h orse”) is n ot n eces-
sarily th e result of radicu lar irritation or in ju ry.
An ot h er very com m on cau se is th e en t rap m en t of
parts of th e join t capsu le in th e in tervertebral join t.
Degen erative disease of th e spin e is th e m ost im -
portan t predisposin g factor for th is con dition as
w ell. Wh en th e in tervertebral disk is n arrow ed, th e
in tervertebral join t facets are displaced in su ch a
w ay as to n arrow th e n eu ral foram in a (Fig. 3.28).
Th e spin e loses h eigh t an d th e join t capsu les
slacken , so th at certain m ovem en ts can in du ce en -
trapm en t of part of th e capsu le in side th e join t.
Ch iropractic m an ipu lation can brin g rap id relief in
such cases.
Individual lumbar radicular syndromes (Fig. 3.29)
are ch aracterized by t h e follow in g deficits:
¼ L3: pain w ith or w ith ou t paresth esia in th e L3
derm atom e; quadriceps w eakn ess; dim in ish ed
3 62 · 3 Motor System
Case Presentation 4: Massive L4/5 Disk Herniation with Upwa rdly Displaced Fragment
This 37-year-old engineer suddenly felt severe pain in the
low back while lifting weights in a fitness studio. Shortly af-
terward, he noted a sensory abnorm ality in the right thigh
and weakness in the right knee, but nonetheless continued
with his exercise routine. A few hours later, he had m ore
severe pain and num bness in the right lower lim b, and the
sensory abnorm ality was present in the left lower lim b also,
as well as in the perianal region. He could no longer em pty
his bladder.
He sought em ergency m edical attention. Exam ination on
adm ission to the hospital revealed severe weakness of the
lower lim b m usculature from L4 downward on the right,
a b c
Fig. 3.30 L4/5 disk herniation w ith upw ardly displaced
fragment. a The sagittal T2-weighted im age reveals com -
pression of the rootlets of the cauda equina, which are seen
as dark filam ents surrounded by bright cerebrospinal fluid.
The conus m edullaris lies at L1. b The large disk herniation is
or absen t qu adriceps reflex (patellar or kn ee-
jerk reflex)
¼ L4: pain w ith or w ith out paresth esia or hyp alge-
sia in th e L4 derm atom e; quadriceps w eakn ess;
dim in ish ed qu adriceps reflex
¼ L5: pain w ith or w ith ou t paresth esia or hypal-
gesia in th e L5 derm atom e; w eakn ess of th e
exten sor h allucis lon gu s an d often also of th e
exten sor digitorum brevis; loss of th e tibialis
posterior reflex
¼ S1: pain w ith or w it h ou t parest h esia or hy-
palgesia in th e S1 derm atom e; w eakn ess of th e
peron ei, gastrocn em iu s, an d soleus m uscles;
loss of th e gastrocn em iu s reflex (Ach illes or
an kle-jerk reflex).
and from L5 downward on the left. There was m arkedly
dim inished sensation in all m odalities in a saddle distribu-
tion, as well as flaccid bladder paralysis with incipient over-
flow incontinence.
MRI revealed a large disk herniation originating at the L4−L5
level, with a cranially displaced free intraspinal fragm ent
com pressing nearly the entire cauda equina (acute cauda
equina syndrom e).
The patient was im m ediately transferred to the neurosurgi-
cal service for an em ergency procedure. The herniated disk
tissue was surgically rem oved the sam e evening, and the
neurological deficits resolved com pletely thereafter.
seen equally well on the T1-weighted im age. It evidently
originates in the L4−L5 disk space. c In the axial T1-
weighted im age, the lum en of the spinal canal is seen to be
nearly entirely filled with prolapsed disk tissue. The hernia-
tion is ventral and on the right side (arrow).
Plexus Syndromes
Th e cervical plexus is form ed by n erve roots C2–C4,
th e brachial plexus by n erve roots C5–T1, an d th e
lumbosacral plexus by n erve roots L1–S3.
Lesions of the Cervica l Plexus
Th e cervical plexu s (Fig. 3.31) occu pies a relatively
sh eltered position an d is th us rarely in ju red. Un i-
lateral or bilateral ph ren ic n erve dysfu n ction (C3,
C4, an d C5) is m ore com m on ly cau sed by a m edi-
astin al p rocess th an by a cervical p lexus lesion .
 Com plex Clinical Syndrom es due to Lesions of Specific Com ponents of the Nervous System · 63
3
Fig. 3.31 The cervical
plexus (schem atic drawing)
Suboccipital n.

Greater occipital n. C1

Hypoglossal n.
Lesser occipital n.
(CN XII)

Great C2
auricular n.
Superior
cervical
ganglion

C3

Transverse
cervical n.

C4

Ansa
cervicalis

Supraclavicular nn.
C5

To the Phrenic n.
brachial plexus

Lesions of the Brachia l Plexus Causes of Brachial Plexus Lesions

Brach ial plexus lesion s are classified in to tw o
types, u pp er an d low er, on clin ical an d pragm atic
grou n ds. Th e an atom y of th e brach ial plexu s is
sh ow n in Fig. 3.32.
In upper brachial plexus palsy (Du ch en n e–Erb
palsy), due to a lesion of th e C5 an d C6 n erve roots,
th e deltoid, biceps, brach ialis, an d brach ioradialis
m uscles are p aretic. Th ere is a sen sory deficit over-
lyin g th e deltoid m uscle an d on th e radial side of
th e arm an d h an d.
In low er brachial plexus palsy (Klu m pke palsy), due
to a lesion of th e C8 an d T1 n erve roots, th e w rist
an d fin ger flexors an d t h e in trin sic m uscles of t h e
h an d are paretic. Occasion ally, Horn er syn drom e is
presen t in addition . Th ere are prom in en t troph ic
abn orm alities of th e h an d an d fin gers.
Traum a, usually du e to road acciden ts or sportin g
in ju ries, is by far th e m ost com m on cau se of dam -
age to th e brach ial p lexus. Men are m u ch m ore
frequ en tly affected th an w om en . Most patien ts are
betw een 20 an d 30 years old.
Brach ial plexu s dam age also h as m any etiologies
oth er th an traum a: com pression syndrom es in th e
area of th e sh ou lder (scalen e syn drom e; com p res-
sion by safety belts, ru cksack straps, etc.; costo-
clavicu lar syn drom e; hyperabdu ction syn drom e);
tum ors (e.g., apical lu n g tu m or w ith Pan coast syn -
drom e); inflam m atory-allergic lesions (n eu ralgic
sh ou lder am yotrophy); an d birth injuries.
Scalene syndrome (Fig. 3.33). Th e cords of th e
brach ial plexus pass th rou gh th e so-called scalen e
h iatu s, w h ich is delim ited by th e an terior an d
m iddle scalen e m u scles an d th e first rib. Th e h iatus
3 64 · 3 Motor System

Fig. 3.32 The brachial

plexus (schem atic drawing)
C4

Dorsal scapular n. C5

C6

Suprascapular n. C7

C8
Lateral cord
(C5 – C7 )
T1
Posterior cord
(C5 – T1 )

Medial cord
(C8 – T1 ) Phrenic n.

Musculo- Subclavius n.
cutaneous n. Lateral
pectoral n.
Medial
pectoral n.

Median n.
Long thoracic n.
Radial n.
Subscapular n.
Axillary n.
Ulnar n. Thoracodorsal n.

n orm ally h as en ough room for th e cords of th e

brach ial p lexu s an d th e su bclavian artery, w h ich
C5 accom pan ies th em , bu t path ological abn orm alities
such as th ose associated w ith a cervical rib can
Anterior critically n arrow th e h iatu s. In su ch cases, th e
scalene m . C6 cords of th e brach ial p lexus an d th e su bclavian
Cervical rib artery m u st pass over th e att ach m en t of th e cervi-
cal rib to th e first (th oracic) rib an d are vu ln erable
Fibrous band C7
to com pression at th is site. Th e m ost prom in en t
Brachial plexus sym ptom of scalen e syn drom e (a typ e of t h oracic
T1
ou tlet syn drom e) is p osition -depen den t pain radi-
atin g in to t h e up per lim b. Parest h esia an d hy-
pesth esia are often presen t, especially on th e uln ar
side of th e h an d. In severe, lon gstan din g cases,
th ere m ay be w eakn ess of Klum p ke type (see
p. 63). Dam age to th e sym path etic n erve fibers
Subclavian a. travelin g w ith th e subclavian artery frequ en tly
1st rib cau ses vasom otor distu rban ces as w ell.

Fig. 3.33 Scalene syndrome (thoracic outlet syndrom e)

due to a cervical rib.
 Com plex Clinical Syndrom es due to Lesions of Specific Com ponents of the Nervous System · 65
3
Fig. 3.34 The lum-
L1 bosacral plexus (schem atic
drawing)

Iliohypogastric n. L2

Ilioinguinal n.

L3
s
u
x
Genitofemoral n.
e
l
p
r
a
b
m
u
Lateral femoral cutaneous n.
L
L4

Obturator n.

L5
Femoral n.

S1

S2
Superior gluteal n.
Inferior gluteal n.
S3
s
u
x
e
S4
l
Sciatic n.
p
l
a
r
Com m on peroneal (com m on fibular) n. S5
c
a
S
Tibial n.

Posterior fem oral cutaneous n.

Coccygeal n.
Pudendal n.

plexu s (w h ich w ou ld be an alogous to n eu ralgic

Lesions of the Lumbosacra l Plexus
Here, too, lesion s m ay be classified in to tw o typ es:
lum bar plexu s lesion s an d sacral plexu s lesion s.
Th e an atom y of th e lu m bosacral plexu s is sh ow n in
Fig. 3.34.
Lumbar plexus lesions (L1, L2, an d L3) are less
com m on th an brach ial plexu s lesion s, becau se of
th e sh eltered location of th e lu m bar p lexus. Th e
cau ses of dam age to both plexu ses are largely th e
sam e. Th ere are, h ow ever, practically n o cases of
in flam m atory-allergic dysfu n ction of th e lum bar
sh ou lder am yotrophy). On t h e oth er h an d, m eta-
bolic distu rban ces such as diabetes m ellitu s are
m ore likely to affect th e lum bar plexu s th an th e
brach ial plexu s.
Sacral plexus lesions. Th e sacral plexus is form ed
by n erve roots L4, L5, an d S1 th rough S3. Th e m ost
im portan t n erves em ergin g from th e sacral plexu s
are th e com m on peron eal an d tibial n erves, w h ich
are join ed togeth er as th e sciatic n erve in its cou rse
dow n th e posterior th igh . Th e tw o n erves separate
from on e an oth er ju st above th e kn ee an d t h en
3 66 · 3 Motor System

Fig. 3.35 The course of

selected important peri-
Musculo-
pheral nerves
cutane-
ous n. Ulnar n.
Median n.

Superior
and inferior
gluteal nn.

Femo -
ral n.

Sciatic n.
Obtura-
tor n.

Posterior
cord

Axillary n. Saphen-
ous n.
Radial n.

Tibial n.

Peroneal n.

Ulnar n.

follow th eir in dividual p ath s fu rth er dow n th e leg
(Fig. 3.35).
Th e com m on peron eal n erve m ain ly in n ervates
th e exten sors of th e foot an d toe, w h ile th e tibial
n erve in n ervates th e plan tar flexors an d m ost of
th e in t rin sic m u scles of th e foot. A lesion of th e
com m on peron eal n erve, or of th e com m on pero-
n eal portion of th e sciatic n erve, w eaken s th e ex-
ten sors, cau sin g a foot drop (steppage gait); a le-
sion of th e tibial n erve w eaken s th e plan tar flexors,
m akin g toe-w alkin g im p ossible. Peron eal n erve
palsy is m ore frequ en t th an tibial n erve p alsy, be-
cau se th e cou rse of th e tibial n erve is relatively
sh eltered. Peron eal n erve palsy im pairs sen sat ion
on th e lateral surface of th e leg an d t h e dorsu m of
th e foot, w h ile tibial n erve palsy im p airs sen sation
on th e sole.
 Com plex Clinical Syndrom es due to Lesions of Specific Com ponents of the Nervous System · 67
3
Peripheral Nerve Syndromes
Tran section of a m ixed periph eral n erve causes
flaccid paresis of th e m u scle(s) su pplied by t h e
n erve, a sensory deficit in th e distribu tion of th e in -
terru pted afferen t fibers of th e n erve, an d auton-
om ic deficits.
Wh en th e con tin u ity of an axon is disru pted,
degen eration of t h e axon as w ell as of its m yelin
sh eath begin s w ith in h ou rs or days at th e site of
th e in ju ry, travels distally dow n th e axon , an d is
usually com p lete w ith in 15–20 days (so-called sec-
on dary or w allerian degeneration).
Dam aged axon s in th e cen tral n ervous system
lack th e ability to regen erate, bu t dam aged axon s
in periph eral n erves can do so, as lon g as th eir m y-
elin sh eath s rem ain in tact to serve as a tem plate
for th e regrow in g axon s. Even w h en a n erve is
com pletely tran sected, resu tu rin g of th e su n dered
en ds can be follow ed by n ear-com plete regen era-
tion of axon s an d restoration of fu n ction al activity.
Electrom yography (EMG) an d n erve con du ction
stu dies are often very h elp fu l in assessin g th e
severit y of a p eriph eral n erve in ju ry an d t h e
ch an ces for a good recovery.
Figu re 3.35 illustrates th e an atom ical cou rse of a
Fig. 3.36 Typical appearance of peripheral nerve pal-
n um ber of im portan t periph eral n erves th at are sies affe cting the hand. a Wrist drop (radial nerve palsy).
com m on ly in ju red. Figure 3.36 sh ow s typical clin i- b Claw hand (ulnar nerve palsy). c Pope’s blessing (m edian
cal p ict ures of radial, m edian , an d u ln ar n erve p al- nerve palsy). d Monkey hand (com bined m edian and ulnar
sies. nerve palsy). The areas of sensory deficit are shaded blue.
Th e m ore com m on causes of isolated periph eral
n erve palsies are: com pression of a n erve at an
an atom ically vuln erable poin t or bott len eck
w ell as of a feelin g of sw ellin g in th e w rist or th e
(scalen e syn drom e, cu bital tu n n el syn drom e, car-
en tire h an d. Th e pain can often be elicited clin i-
pal t un n el syn drom e, peron eal n erve in ju ry at th e
cally by tap pin g th e carpal tu n n el (positive Tin el
fibu lar h ead, t arsal tu n n el syn drom e); traum atic
sign ). A fin din g of slow ed n erve con du ction
injury (in clu din g iatrogen ic lesion s, e.g., pun cture
th rough th e carpal tu n n el on n eurography of th e
an d in jection in ju ries); an d ischem ia (e.g., in com -
m edian n erve is con firm atory. Trop h ic abn orm ali-
partm en t syn drom e an d, less com m on ly, in in fec-
ties an d atrophy of th e lateral th en ar m uscles (ab-
tiou s/in flam m atory processes).
du ctor p ollicis brevis an d oppon en s pollicis) are
com m on in advan ced cases. Th e m edian n erve
Ca rpa l Tunnel Syndrome
con tain s an u n u su ally large proportion of au to-
Carp al tu n n el syn drom e (Fig. 3.37a) is cau sed by n om ic fibers; th u s, m edian n erve lesion s are a
m edian n erve dam age in th e carp al tun n el, w h ich frequ en t cause of com p lex region al pain syn drom e
can be n arrow ed at th e site w h ere th e n erve passes (previou sly called reflex sym path etic dystrophy, or
un der th e tran sverse carpal ligam en t (flexor reti- Su deck syn drom e).
n aculu m ). Patien ts typically com plain of pain an d
paresth esiae in th e affected h an d, w h ich are espe-
cially severe at n igh t an d m ay be felt in th e en tire
up per lim b (brach ialgia paresth etica n octurn a), as
3 68 · 3 Motor System

Fig. 3.37 a Carpal tunnel

w ith median nerve (carpal
Flexor Median n.
tunnel syndrom e). b Cubi-
retinaculum
tal tunne l syndrome: pres-
sure palsy of the ulnar
Carpal tunnel
nerve due to external com -
pression or dislocation.

Ulnar n.

a b

Ulna r Nerve Lesions—Cubita l Tunnel
Syndrome
Uln ar n erve palsy is th e secon d m ost com m on p e-
riph eral n erve con dition , after m edian n erve palsy.
Th e uln ar n erve is particu larly vuln erable to in ju ry
at th e site of its passage t h rou gh th e cu bital tu n n el,
on th e m edial side of th e exten sor aspect of th e
elbow (Fig. 3.37b). It can be dam aged h ere by acu te
trau m a or, even m ore com m on ly, by ch ron ic pres-
sure, e.g., by h abitually prop pin g u p th e arm on a
h ard surface, w h ich m ay be an u n avoidable pos-
tu re in certain occupation s. Paresth esia an d hypes-
th esia in th e u ln ar portion of th e h an d are accom -
pan ied, in advan ced cases, by at rophy of th e hy-
poth en ar m u scles an d of th e addu ctor p ollicis
(u ln ar n erve p alsy w ith claw h an d).
Polyneuropa thies
m otor, au ton om ic), or by th e distribu tion of n eu ro-
logical deficits (m on on europathy m u ltiplex, distal-
sym m etric, proxim al). Polyn eu ropath ies an d poly-
n eu ritides h ave m any cau ses, an d th eir diagn osis
an d treatm en t are accordin gly com plex. A m ore
detailed discussion of th ese disorders w ou ld be
beyon d t h e scope of th is book.
Differentia l Dia gnosis of Radicula r a nd
Periphera l Nerve Lesions
Th e fu n ction s of in dividu al m u scles an d th eir
radicular (segm en tal) an d periph eral n erve in n er-
vat ion are listed in Table 3.1. Th e in form ation in
th is table can be u sed to determ in e w h eth er
m u scle w eakn ess in a particu lar distribu tion is due
to a radicular or a periph eral n erve lesion , an d to
localize th e lesion to th e particu lar root or n erve
th at is affected.

A p ath ological process affectin g m u ltip le periph -

eral n erves is called polyn eu ropathy, an d an in fec-
tiou s or in flam m atory process affectin g m ultiple
periph eral n erves is called polyn eu ritis. Poly-
n eu ropath ies can be classified by h istological–
structu ral criteria (axon al, dem yelin atin g, vascu -
lar-isch em ic), by t h e system s th ey affect (sen sory,
 Com plex Clinical Syndrom es due to Lesions of Specific Com ponents of the Nervous System · 69
3
Table 3.1 Segmental and Peripheral Innervation of Muscles

Function Muscle Nerve

I. Cervica l plexus, C1–C4

Cervical nerves
Flexion, extension, rotation, and lateral flexion of the Deep m uscles of the neck C1–C4
neck (also sternocleidom astoid and
trapezius)
Elevation of the upper rib cage, inspiration Scalene m uscles C3–C5

Phrenic nerves
Inspiration Diaphragm C3, C4, C5

II. Brachial plexus, C5–T1

Medial and lateral pectoral

nerves
Adduction and internal rotation of the arm and depres- Pectoralis m ajor C5–T1
sion of the shoulder from posterior to anterior Pectoralis m inor

Long thoracic nerve

Fixation of the scapula on lifting of the arm (protrac- Serratus anterior C5–C7
tion of the shoulder)

Dorsal scapular nerve

Elevation and adduction of the scapula toward the Levator scapulae C4–C5
spine Rhom boids

Suprascapular nerve
Elevation and external rotation of the arm Supraspinatus C4–C6
External rotation of the arm at the shoulder Infraspinatus C4–C6

Thoracodorsal nerve
Internal rotation of the arm at the shoulder, and adduc- Latissim us dorsi C5–C8
tion from anterior to posterior as well as depression of Teres m ajor (from the posterior cord of
the elevated arm Subscapularis the brachial plexus)

Axillary nerve
Lateral elevation (abduction) of the arm up to the hori- Deltoid C5–C6
zontal position
External rotation of the arm Teres m inor C4–C5

Musculocutaneous ne rve
Flexion of the arm and forearm , supination Biceps brachii C5–C6
Elevation and adduction of the arm Coracobrachialis C5–C7
Elbow flexion Brachialis C5–C6

Median nerve
Flexion and radial deviation of the hand Flexor carpi radialis C6–C7
Pronation Pronator teres C6–C7
Wrist flexion Palm aris longus C7–T1
Flexion of the interphalangeal (IP) joint of the thum b Flexor pollicis longus C6–C8
Flexion of the proxim al IP joints of the 2nd through Flexor digitorum superficialis C7–T1
5th fingers
Flexion of the distal IP joints of the 2nd and 3rd fingers Flexor digitorum profundus C7–T1
(radial part)
Abduction of 1st m etacarpal Abductor pollicis brevis C7–T1
3 70 · 3 Motor System

Table 3.1 Segmental and Peripheral Innervation of Muscles (continued)

Function Muscle Nerve

Median nerve
Flexion of the m etacarpophalangeal (MP) joint of the Flexor pollicis brevis C7–T1
thum b
Opposition of 1st m etacarpal Opponens pollicis brevis C6–C7
Flexion of MP joints and extension of IP joints of 2nd Lum bricals I, II C8–T1
and 3rd fingers

Ulnar nerve
Flexion of MP joints and extension of IP joints of 4th Lum bricals III, IV C8–T1
and 5th fingers
Flexion and ulnar deviation of the hand Flexor carpi ulnaris C7–T1
Flexion of the distal IP joints of the 4th and 5th fingers Flexor digitorum profundus C7–T1
(ulnar part)
Abduction of 1st m etacarpal Adductor pollicis C8–T1
Abduction of 5th finger Abductor digiti quinti C8–T1
Opposition of 5th finger Opponens digiti quinti C7–T1
Flexion of MP joint of 5th finger Flexor digiti quinti brevis C7–T1
Flexion of MP and extension of IP joints of 3rd, 4th, and Interossei (palm ar and dorsal) C8–T1
5th fingers; also ab- and adduction of these fingers

Radial nerve
Elbow extension Triceps brachii, anconeus C6–C8
Elbow flexion Brachioradialis C5–C6
Extension and radial deviation of hand Extensor carpi radialis C6–C8
Extension at MP joints of 2nd through Extensor digitorum C6–C8
5th fingers; spreading of the fingers;
dorsiflexion of the hand
Extension of 5th finger Extensor digiti quinti C6–C8
Extension and ulnar deviation of hand Extensor carpi ulnaris C6–C8
Supination Supinator C5–C7
Abduction of 1st m etacarpal, radial Abductor pollicis longus C6–C7
extension of the hand
Extension of thum b at MP joint Extensor pollicis brevis C7–C8
Extension of thum b at IP joint Extensor pollicis longus C7, C8
Extension of 2nd finger at MP joint Extensor indicis proprius C6–C8

Intercostal nerves
Elevation of the ribs, expiration, Valsalva m aneuver, Thoracic and abdom inal
anteroflexion and lateral flexion of the trunk m uscles

III. Lumba r plexus, T12–L4

Femoral nerve
Hip flexion and internal rotation Iliopsoas L1–L3
Hip flexion and external rotation; knee flexion and Sartorius L2–L3
internal rotation
Knee extension Quadriceps fem oris L2–L4
 Com plex Clinical Syndrom es due to Lesions of Specific Com ponents of the Nervous System · 71
3
Table 3.1 Segmental and Peripheral Innervation of Muscles (continued)

Function Muscle Nerve

Obturator nerve
Thigh adduction Pectineus L2–L3
Adductor longus L2–L3
Adductor brevis L2–L4
Adductor m agnus L3–L4
Gracilis L2–L4
Thigh adduction and external rotation Obturator externus L3–L4

IV. Sacral plexus, L5–S1

Superior gluteal nerve

Thigh abduction and internal rotation Gluteus m edius L4–S1
Gluteus m inim us
Hip flexion; thigh abduction and internal rotation Tensor fasciae latae L4–L5
Thigh abduction and external rotation Piriform is L5–S1

Inferior gluteal nerve

Hip extension Gluteus m axim us L4–S2
Obturator internus L5–S1
External rotation of the thigh Gem elli L4–S1
Quadratus fem oris L4–S1

Sciatic nerve
Knee flexion Biceps fem oris L4–S2
Sem itendinosus L4–S1
Sem im em branosus L4–S1

Deep peroneal nerve

Dorsiflexion and supination of the foot Tibialis anterior L4–L5
Extension of toes and foot Extensor digitorum L4–S1
longus
Extension of 2nd through 5th toes Extensor digitorum brevis L4–S1
Extension of great toe Extensor hallucis longus L4–S1
Extensor hallucis brevis L4–S1

Superficial peroneal nerve

Dorsiflexion and pronation of the foot Peroneal m uscles L5–S1

Tibial nerves
Plantar flexion of the foot in supination Gastrocnem ius L5–S2
Soleus
(together called triceps surae)
Supination and plantar flexion of the foot Tibialis posterior L4–L5
Flexion of distal IP joints of 2nd through 5th toes; plan- Flexor digitorum longus L5–S2
tar flexion of the foot in supination
Flexion of IP joint of great toe Flexor hallucis longus L5–S2
Flexion of proxim al IP joints of 2nd through 5th toes Flexor digitorum brevis S1–S3
Flexion of MP joints of toes, abduction and adduction Plantar m uscles of the foot S1–S3
of toes

Pudendal nerve
Closure of bladder and bowel Vesical and anal S2–S4
sphincters
3 72 · 3 Motor System
Syndromes of the Neuromuscular
Junction and Muscle
Myasthenia
Abn orm al fatigabilit y of striated m u scle is th e car-
din al m an ifestation of disorders of th e n euro-
m uscu lar ju n ction . Exercise-dependent w eakness
often affects th e extraocu lar m u scles first, causin g
ptosis or diplopia, as th e m otor un its of th ese
m uscles con tain on ly a sm all n u m ber of m u scle
fibers. Patien ts w ith gen eralized m yasth en ia also
suffer from dysph agia an d exercise-depen den t ,
m ain ly proxim al w eakn ess of skeletal m u scle. Th e
m ost com m on cau se of th e m yasth en ic syn drom e
is m yasth en ia gravis (older term : m yasth en ia
gravis pseudoparalytica), an autoim m u n e disease
in w h ich th e body form s an tibodies again st th e
acetylch olin e receptors or ot h er com pon en ts of th e
m otor en d plate. Too few receptors are left for ade-
qu ate sign al t ran sm ission , so th at th e m u scles can
n o lon ger be su fficien tly excited by th e n erves th at
in n ervate th em . Th e electrom yograp h ic correlate is
a dim in u tion in size (“decrem en t”) of th e m uscle
action poten tial on repetitive electrical st im u lation
of an affected m u scle. Myasth en ia gravis is diag-
n osed on th e basis of th e typical clin ical m an ifesta-
tion s, th e electrom yograp h ic decrem en t, th e de-
m on stration of circu latin g an tibodies to th e acetyl-
ch olin e receptor or oth er autoan tibodies, an d th e
im provem en t of w eakn ess up on adm in istration of
a sh ort-actin g acetylch olin esterase in h ibitor, such
as edrop h on iu m ch loride. Th e disorder can be
treated effectively w ith lon ger-actin g acetylch o-
lin esterase in h ibitors, im m u n e sup pression , an d
addition ally (in som e you n ger patien ts) thy-
m ectom y.
Myopa thy
In con trast to m yasth en ia, th e m yopath ies (p ri-
m ary disorders of m u scle) gen erally cau se slow ly
progressive, n on -exercise-depen den t w eakn ess.
Myop ath ic m u scle atrophy is less severe th an n eu-
rogen ic m u scle at rophy an d is partially con cealed
by fatt y replacem en t of m u scle tissu e (lip osis, also
called lip om atosis), so th at th ere m ay be a discre-
pan cy betw een th e n orm al or p seu dohypertroph ic
appearan ce of m uscle an d t h e actu al degree of
w eakn ess. Th ere are n o sen sory or au ton om ic defi-
cits, n or are th ere fasciculation s, w h ich w ould
im ply a n eu rogen ic lesion . Myalgia an d m u scle
sp asm s are m ore com m on in m etabolic th an in
con gen ital m yopath ies.
Th e m any types of m yopathy in clu de th e
m u scu lar dystrop h ies (X-lin ked recessive, auto-
som al dom in an t, an d recessive), m etabolic m y-
op ath ies, m yoton ic dystroph ies (w ith addition al
m an ifestation s su ch as cataract, fron tal baldn ess,
an d oth er system ic abn orm alities, as in Stein ert–
Batten–Cursch m an n dystrop hy), an d m yositides. A
system atic discu ssion of th ese diseases w ould be
beyon d th e scope of th is book. Th e m ost im portan t
in form ation for th e differen tial diagn osis of m y-
opathy is derived from a detailed fam ily h istory,
clin ical exam in ation , laboratory tests (particularly
creatin e kin ase), an d electrom yograp hy, as w ell as
from m olecu lar gen etic an alysis, w h ich h as be-
com e h igh ly soph isticated in recen t years an d can
n ow provide an u n equ ivocal diagn osis in m any
cases. Th is, in tu rn , en ables a m ore reliable progn o-
sis an d w ell-foun ded gen etic cou n selin g.
 4

4 Brainstem
Surface Anatomy of the Brainstem . . . 74
Cranial Nerves . . . . . . . . . . . . . . . . . . . . 77
Topographical Anatomy of
the Brainstem . . . . . . . . . . . . . . . . . . . . 134
Brainstem Disorders . . . . . . . . . . . . . . . 145
4 74
4 Brainstem
Th e brain stem is th e m ost caudally situated an d
phylogen et ically oldest portion of th e brain . It is
grossly su bdivided in to th e medulla oblongata
(u su ally called sim ply th e medulla), pons, an d mid-
brain (or mesencephalon). Th e m edulla is th e ros-
tral con tin u ation of th e sp in al cord, w h ile th e m id-
brain lies ju st below t h e dien cep h alon ; th e pon s is
th e m iddle portion of th e brain stem . Ten of th e 12
pairs of cranial nerves (CN III–XII) exit from th e
brain stem an d are prim arily respon sible for th e in -
n ervation of th e h ead an d n eck. CN I (th e olfactory
n erve) is th e in itial segm en t of th e olfactory path -
w ay; CN II (th e optic n erve) is, in fact, n ot a periph -
eral n erve at all, bu t rath er a t ract of t h e cen tral
n ervou s system .
Th e brain stem con tain s a large n u m ber of fiber
path w ays, in cludin g all of t h e ascending and de-
scending pathw ays lin kin g t h e brain w ith t h e pe-
riph ery. Som e of th ese path w ays cross t h e m idlin e
as th ey pass t h rou gh th e brain stem , an d som e of
th em form syn apses in it before con tin uin g alon g
th eir path . Th e brain stem also con tain s m any nu-
clei, in cludin g th e nuclei of cranial nerves III
through XII; th e red nucleus an d substantia nigra
of th e m idbrain , th e pontine nuclei, an d th e olivary
nuclei of th e m edulla, all of w h ich play an im por-
tan t role in m otor regu latory circu its; an d th e n u-
clei of th e quadrigeminal plate of th e m idbrain ,
w h ich are im portan t relay station s in th e visual
an d auditory pat h w ays. Furth erm ore, practically
th e en tire brain stem is p erm eated by a diffu se n et-
w ork of m ore or less “den sely packed” n euron s
Surface Anatomy of the
Brainstem
Th e three brainstem segments, i.e., th e m idbrain ,
pon s, an d m edu lla, h ave clearly defin ed borders on
th e ven tral surface of th e brain stem (Fig. 4.1a).
Medulla
Th e m edu lla exten ds from th e site of exit of th e
roots of th e first cervical n erve (C1), at th e level of
th e foram en m agn um , to its jun ction w ith th e p on s
2.5–3 cm m ore rost rally.
(th e reticular formation), w h ich con tain s th e es-
sen t ial autonomic regulatory centers for m any
vital bodily fu n ction s, in clu din g cardiac activity,
circulation , an d respiration . Th e reticu lar form a-
tion also sen ds activatin g im pu lses to th e cerebral
cortex th at are n ecessary for th e m ain ten an ce of
con sciousn ess. Descen din g path w ays from th e re-
ticular form ation in flu en ce th e activity of th e sp i-
n al m otor n eu ron s.
Becau se th e brain stem con tain s so m any differ-
en t n uclei an d n erve path w ays in such a com pact
sp ace, even a sm all lesion w ith in it can produ ce
n eu rological deficits of several differen t types oc-
cu rrin g sim u ltan eou sly (as in th e variou s brain-
stem vascular syndromes). A relatively com m on
brain stem fin din g is so-called crossed paralysis or
alternating hemiplegia, in w h ich cran ial n erve
deficits ipsilateral to th e lesion are seen in com bi-
n ation w ith paralysis of th e con tralateral h alf of
th e body.
In gen eral, cran ial n erve deficits can be
classified as supranuclear, i.e., cau sed by a lesion
in a descen din g path w ay from h igh er cen ters, u su -
ally th e cerebral cortex, w h ich term in ates in th e
correspon din g cran ial n erve n u cleu s in th e brain -
stem ; nuclear, if th e lesion is in t h e cran ial n erve
n ucleu s itself; fascicular, if th e lesion involves
n erve root fibers before th eir exit from th e brain -
stem ; or peripheral, if th e lesion involves th e
cran ial n erve proper after its exit from th e brain -
stem . Th e type of deficit produced depen ds on th e
site of th e lesion .
Dorsal view. Th e gracile tubercles are seen on eith er
side of th e m idlin e, flan ked by th e cuneate
tubercles (Fig. 4.1b). Th ese sm all p rotrusion s are
produ ced by th e un derlyin g gracile n u cleus an d
cu n eate n ucleu s of both sides. Th ese are th e relay
n u clei in w h ich th e posterior colu m n fibers of th e
spin al cord form syn apses on to th e secon d n euron s
of th e afferen t path w ay, w h ich , in tu rn , project by
w ay of th e m edial lem n iscu s to th e th alam us. Th e
rostral border of t h e m edulla is defin ed by a lin e
draw n th rou gh th e caudal portion of th e m iddle
cerebellar pedu n cles. Th e floor of th e fourth ven -
tricle, or rhom boid fossa, is bou n ded laterally by th e
in ferior an d su perior cerebellar pedu n cles an d

divided in to rostral an d cau dal portion s by th e
striae m edullares, w h ich con tain fibers ru n n in g
from th e arcu ate n u clei to th e cerebellum . Th e
cau dal part of th e floor con tain s a n um ber of pro-
tru sion s (tubercles) produ ced by th e u n derlyin g
cran ial n erve n uclei, in clu din g th e vagal triangle
(or “trigon e”; dorsal n u cleus of th e vagus n erve),
th e hypoglossal triangle (n u cleu s of th e hypoglossal
n erve), an d th e vestibular area (vestibu lar an d
coch lear n u clei), w h ile th e rostral part con tain s th e
facial t ubercle, w h ich is produced by th e fibers of
th e facial n erve as th ey cou rse arou n d th e abdu-
cen s n u cleu s. Th e roof of th e fourth ven tricle is
m ade up of th e sup erior m edullary velu m , th e
cerebellar p edu n cles, an d th e cerebellu m itself.
Ventral and lateral view s. A ven tral view of th e
m edu lla (Fig. 4.1a) reveals th e pyram ids, w h ich
len d th eir n am es to th e pyram idal tracts, w h ose
fibers cou rse th rou gh t h em . Th e pyram idal decus-
sation can also be seen h ere. Lateral to th e pyram id
on eith er side is an oth er p rot ru sion called th e
olive, w h ich con tain s th e inferior olivary nucleus.
Th e hypoglossal nerve (XII) em erges from th e
brain stem in t h e ven trolateral su lcus betw een th e
pyram id an d th e olive. Th e n uclei of th e hyp oglos-
sal n erve, like th ose of th e n erves to th e extraocular
m uscles, are located n ear th e m idlin e in th e brain -
stem , in th e basal lam in a. Dorsal to th e olive, th e
roots of th e accessory (XI), vagus (X), an d glos-
sopharyngeal (IX) nerves em erge from t h e brain -
stem in a vertically orien ted row (Fig. 4.1a an d c).
Fu rt h er dorsally, bet w een th e exit of th ese n erves
an d th e dorsolateral su lcu s, lies th e tuberculum
cinereum , form ed by th e n ucleu s of th e spin al tract
of t h e trigem in al n erve. Th is is also th e site of th e
posterior spin ocerebellar tract, w h ich ascen ds to
th e cerebellu m by w ay of t h e in ferior cerebellar
pedun cle (restiform body).
Pons
Ventral view. Th e pon s (“bridge”) is so called be-
cau se, w h en view ed from th e fron t, it appears to
con n ect th e tw o cerebellar h em isph eres to each
oth er w ith a broad ban d of h orizon tally disposed
fibers, w h ich is boun ded caudally by th e m edu lla
an d rostrally by t h e cerebral pedun cles (cru ra cere-
bri) of th e m idbrain . Th e descen din g corticopontine
fibers form a syn apse w ith th eir secon d n eu ron s on
th e ipsilateral side of th e pon s, w h ich give rise to
Surface Anatom y of the Brainstem · 75
4
th ese h orizon tally disp osed pon tocerebellar fibers,
w h ich th en , in turn , cross th e m idlin e an d travel by
w ay of th e m iddle cerebellar pedun cle to th e cere-
bellu m . A sh allow groove in th e m idlin e of t h e ven -
tral aspect of th e pon s con tain s th e vertically
cou rsin g basilar artery. Th e groove is n ot cau sed by
th e artery, but rath er by th e bu lges on eith er side
produ ced by th e pyram idal tracts as th ey descen d
th rough th e basis pon tis.
Lateral view. Th e lateral view (Fig. 4.1c) reveals th e
h orizon tally disposed pon tin e fibers com in g to-
geth er to form th e m iddle cerebellar peduncle
(brach iu m pon tis). Th e trigem inal nerve (CNV)
em erges from th e pon s just m edial to th e origin of
th e m iddle cerebellar pedun cle.
Dorsal view. Th e dorsal aspect of th e pon s form s
th e su perior portion of th e floor of th e fou rth ven -
tricle. It takes th e form of a trian gle w h ose base is a
h orizon tal lin e defin in g th e border betw een th e
dorsal aspects of th e pon s an d th e m edu lla. At
eith er en d of t h is lin e, th e fou rth ven tricle open s
in to th e su barach n oid space th rou gh a lateral aper-
ture (foram en of Luschka). Th e unp aired m edian
aperture of th e fou rth ven tricle (foram en of
Magendie) is seen at th e cau dal en d of th e ven tricle
(Fig. 4.1c). Th e roof of th e fourth ven tricle is
form ed by th e su perior cerebellar p edu n cles (bra-
ch ia con ju n ct iva) an d th e su perior m edu llary
velu m .
Midbrain
Th e m idbrain (m esen ceph alon ) lies betw een th e
pon s an d th e dien cep h alon .
Ventral view. Th e ven tral view reveals tw o prom i-
n en t bu n dles of fibers convergin g on to th e pon s.
Th ese are th e cerebral peduncles, or, as th ey are al-
tern atively called, th e crura cerebri (sin gu lar: crus
cerebri). Th e groove betw een th e pedu n cles,
kn ow n as th e in terp edu n cu lar fossa, is th e site of
em ergen ce of t h e tw o oculom otor nerves (CN III)
from th e brain stem . Th e cerebral pedun cles disap-
pear caudally as th ey en ter th e pon s; rostrally, th ey
are en circled by th e optic tracts before en terin g th e
cerebral h em isph eres (Fig. 4.1a).
Dorsal view. Th e dorsal asp ect of th e m idbrain (th e
m idbrain tectum , i.e., “roof”) con tain s fou r protru-
4 76 · 4 Brainstem

Mam illary Pulvinar

body Tectal lam ina Tela choroidea of
(quadrigem inal plate) the third ventricle
Crus cerebri Optic
tract Medial Epiphysis
geniculate
body Superior m edullary
velum
Lateral
geniculate
body

Pons

Superior
cerebellar
peduncle

Middle Floor of
cerebellar the fourth
peduncle ventricle

Inferior Facial
cerebellar colliculus
Inferior olive peduncle Vestibular
Pyram id Striae m edullares of area
Pyram idal the fourth ventricle Tubercle of the
decussation
Hypoglossal nucleus cuneatus
Antero- triangle Area postrema
lateral
sulcus Vagal triangle Tubercle of the
Tuberculum nucleus gracilis
a cinereum Obex
(a) Brachium of the b
superior colliculus Superior colliculus (vision)

(b) Brachium of the Inferior colliculus (hearing)

inferior colliculus
Superior m edullary velum
Medial geniculate
body (hearing) Floor of the fourth ventricle
Lateral egress of the fourth
ventricle (foram en of Luschka)
Median egress of the fourth
ventricle (foram en of Magendie)
Tuberculum cinereum
Lateral geniculate (overlies the nucleus of the
body (vision) spinal tract of the trigem inal n.)

Crus cerebri Posterior m edian sulcus

Pons Posterolateral sulcus

Anterolateral
Inferior sulcus
olive

Fig. 4.1 Brainstem. a Ventral view. b Dorsal view. c Lateral view.

sion s collect ively term ed th e quadrigem inal plate.
Visu al in form ation is processed in th e u pper tw o
protru sion s (th e superior colliculi), w h ile au ditory
in form ation is processed in th e low er tw o protru-
sion s (th e inferior colliculi), w h ich are som ew h at
sm aller. Th e trochlear nerve (CN IV) em erges from
th e brain stem ju st below th e in ferior collicu lu s on
eith er side an d th en courses ven t rally arou n d th e
cerebral pedun cle. It is th e on ly cran ial n erve th at
em erges from th e dorsal aspect of t h e brain stem .
Lateral view. Th e tw o sm all protru sion s lyin g
lateral to th e quadrigem in al plate are th e m edial
geniculate body (an auditory relay area) an d th e
lateral geniculate body (a visu al relay area). Th e
gen icu late bodies are com pon en ts of th e th alam us
an d th u s belon g n ot to th e brain stem but to th e
dien ceph alon .
For didactic reason s, th e in tern al stru ctu re of
th e brain stem w ill be presen ted after th e cran ial
n erves h ave been discu ssed.

Sensory Motor
Accessory (autonom ic)
nucleus = Edinger–
Mesencephalic nucleus and Westphal nucleus
tract of the trigem inal n. Nucleus of the oculomotor n.
Nucleus of the trochlear n.
Principal sensory nucleus
of the trigem inal n. Motor nucleus of the
trigem inal n.
Cranial Nerves · 77
4
Fig. 4.2 Cranial nerve
nuclei, dorsal view (sche-
m atic drawing). The som a-
tosensory and special
sensory nuclei are shown
on the left side of the
figure, the m otor and para-
sym pathetic nuclei on the
right.

Nuclei of the Superior and inferior

vestibular n. salivatory nuclei
Nucleus of Nucleus am biguus
the cochlear n.

Nucleus of the tractus solitarius Nucleus cuneatus

Spinal nucleus and tract Dorsal nucleus of the vagus n.
of the trigem inal n. Nucleus of the hypoglossal n.
Nucleus gracilis
Nucleus of the accessory n.

h ow ever, th at th e secon d cran ial “n erve”—th e optic

Cranial Nerves
Origin, Components, and Functions
Figu re 4.2 is a sch em atic dorsal view of th e brain -
stem , in w h ich th e m otor an d parasym path etic
cran ial n erve n uclei are sh ow n on th e righ t an d th e
som atosen sory an d special sen sory n u clei are
sh ow n on th e left. Lateral view s sh ow in g th e an a-
tom ical relation s of th e m otor an d p arasym pa-
th etic n u clei, an d of th e som atosen sory an d sp ecial
sen sory n uclei, are foun d in Figu res 4.3 an d 4.4, re-
spectively.
Th e origin , com pon en ts, an d fu n ction of th e in -
dividu al cran ial n erves are listed in Table 4.1. Figure
4.5 provides a syn optic view of th e sites of em er-
gen ce of all 12 cran ial n erves from th e brain stem ,
th eir fu n ction al com pon en ts, an d th eir p erip h eral
sites of origin an d term in ation . All 12 cran ial n erves
are seen in t h e figu re, from I (olfactory n erve) to XII
(hypoglossal n erve); it sh ou ld be born e in m in d,
n erve—is actu ally n ot a periph eral n erve at all, bu t
rath er a tract of th e cen tral n ervou s system .
Recall th at spin al n erve fibers can be classified
as som atic afferen t, som atic efferen t , visceral af-
feren t, an d visceral efferen t . Th e classification of
cran ial n erve fibers is a little m ore com plicated,
for tw o reason s. Som e of th e cran ial n erve fibers
are special sen sory fibers arisin g from th e sen se
organ s of th e h ead (vision , h earin g, taste, sm ell).
Furth erm ore, som e of th e efferen t cran ial n erve
fibers arise in n u clear areas th at are em bryologi-
cally derived from th e bran ch ial arch es; th ese
fibers in n ervate m u scles of bran ch ial origin .
Th ere resu lts a seven fold classification of cran ial
n erve fibers, as follow s:
¼ Som atic afferent fibers (p ain , tem perat ure,
tou ch , pressure, an d p roprioceptive sen se from
receptors in th e skin , join ts, ten don s, etc.)
¼ Visceral afferent fibers, w h ich carry im pu lses
(pain ) from th e in tern al organ s
4 78 · 4 Brainstem

Fig. 4.3 Motor and para-

sympathetic cranial nerve
III Accessory (autonomic) nucleus nuclei, lateral view (sche-
= Edinger–Westphal nucleus m atic drawing)

III Nucleus of the oculomotor n.

IV Nucleus of the trochlear n.

V Motor nucleus of the

trigem inal n.

VI Nucleus of the abducens n.

VII Nucleus of the facial n.

Superior salivatory nucleus

Inferior salivatory nucleus
Nervus
interm edius X Dorsal nucleus of the vagus n.
(secretory)
XII Nucleus of the hypoglossal n.

Nucleus ambiguus

XI Nucleus of the accessory n.

¼ Special som atic afferent fibers carryin g im pu lses
from special receptors (eye, ear)
¼ Special visceral afferent fibers carryin g im pu lses
related to taste an d sm ell
¼ General som atic efferent fibers carryin g m otor
im pu lses to th e skeletal m uscu latu re (ocu lom o-
tor, troch lear, abdu cen s, an d hypoglossal
n erves)
¼ Visceral efferent fibers in n ervat in g th e sm ooth
m uscles, th e cardiac m u scu lature, an d th e
glan ds (both sym path etic an d parasym path etic)
¼ Special branchial efferent fibers in n ervatin g
m u scles th at are derived from th e m esoderm al
bran ch ial arch es, i.e., th e m otor portion s of th e
facial n erve (2n d bran ch ial arch ), glossoph aryn -
geal n erve (3rd bran ch ial arch ), an d vagu s n erve
(4th bran ch ial arch an d below )
Th e cran ial n erves exit from th e sku ll th rough th e
open in gs (foram in a, fissures, can als) depicted on
th e left side in Figu re 4.6. Th e cu t-off n erve stu m ps
in th eir corresp on din g open in gs are sh ow n on th e
righ t.
 Cranial Nerves · 79
4
Fig. 4.4 Somatosensory
and special sensory
cranial nerve nuclei,
lateral view (schem atic
drawing)

V Mesencephalic nucleus
and tract of the
trigeminal n.
V Principal sensory nucleus
of the trigem inal n.

VIII Nucleus of the vestibular n.

Trigeminal
(gasserian)
ganglion
VIII Nucleus of the cochlear n.

Nervus interm edius

(somatosensory,
taste)

Nucleus of the tractus

solitarius

V Spinal nucleus and tract

of the trigem inal n.

Table 4.1 The Cranial Nerves

Name Components Origin Function

I. Olfactory nerve Special visceral afferent Olfactory cells of the Olfaction

(or olfactory olfactory epithelium
fasciculus)

II Optic nerve Special som atic afferent Retina, retinal ganglion Vision
(or optic fasciculus) cells

III. Oculomotor nerve
(a) Som atic efferent
(b) Visceral efferent
(parasym pathetic)
(c) Som atic afferent
Nucleus of the oculum otor
nerve (m idbrain)
Edinger−Westphal nuclei
Proprioceptors in the
extraocular m uscles
Innervates superior, inferior,
and m edial rectus m uscles,
inferior oblique m uscle, and
levator palpebrae m uscle
Sphincter pupillae m uscle,
ciliary m uscle
Proprioception

IV. Trochlear nerve (a) Som atic efferent Nucleus of the trochlear Superior oblique m uscle
nerve (m idbrain)
(b) Som atic afferent Proprioceptors Proprioception
4 80 · 4 Brainstem
Table 4.1 The Cranial Nerves (Continued)
Na me
V. Trigeminal nerve
1st branchial arch
VI. Abducens nerve
VII. Facial nerve
Nervus interm edius
2nd branchial arch
VIII. Vestibulocochlear
nerve
IX. Glossopharyngeal
nerve
3rd branchial arch
X. Vagus nerve
4th branchial arch
XI. Accessory nerve
XII. Hypoglossal ne rve
Components
(a) som atic afferent
(b) Branchial efferent
(c) Som atic afferent
Som atic efferent
(a) Branchial efferent
(b) Visceral efferent
(c) Special visceral afferent
(d) Som atic afferent
Special som atic afferent
(a) Branchial efferent
(b) Visceral efferent (para-
sym pathetic)
(c) Special visceral afferent
(d) Visceral afferent
(e) Som atic afferent
(a) Branchial efferent
(b) Visceral efferent
(c) Visceral afferent
(d) Special visceral afferent
(e) Som atic afferent
(a) Branchial efferent
(b) Som atic efferent
Som atic efferent
Origin
Bipolar cells in the sem i-
lunar ganglion
Motor nucleus of the
trigem inal nerve
Proprioception
Nucleus of the abducens
nerve
Nucleus of the facial nerve
Superior salivatory nucleus
Geniculate ganglion
Geniculate ganglion
(a) Vestibular ganglion
(b) Spiral ganglion
Nucleus am biguus
Inferior salivatory nucleus
Inferior ganglion
Superior ganglion
Superior ganglion
Nucleus am biguus
Dorsal nucleus of the vagus
nerve
Inferior (nodose) ganglion
Superior (jugular) ganglion
Nucleus am biguus
Anterior horn cells
Nucleus of the hypoglossal
nerve
Function
Sensation on the face and in
the nasal and oral cavities
Muscles of m astication
Proprioception
Lateral rectus m uscle
Muscles of facial expression,
platysm a, stylohyoideus
m uscle, digastric m uscle
Nasal and lacrim al glands,
salivation, sublingual and
subm andibular glands
Taste (anterior 2/ 3 of tongue)
External ear, portions of the
auditory canal, external
surface of the tympanic
m em brane (som atosensory)
Equilibrium , cristae of the
sem ilunar canals, m aculae of
the utricle and saccule
Hearing, organ of Corti
Stylopharyngeus muscle,
pharyngeal m uscles
Salivation
Parotid gland
Taste (posterior 1/ 3 of the
tongue)
Som atosensory: posterior 1/ 3
of the tongue and pharynx
(gag reflex)
Middle ear, eustachian tube
(som atosensory)
Muscles of the larynx and
pharynx
Thoracic and abdom inal
viscera (parasym pathetic)
Abdom inal cavity (som a-
tosensory)
Taste: epiglottis
Auditory canal, dura m ater
(som atosensory)
Muscles of the larynx and
pharynx
Sternocleidom astoid and
trapezius m uscles
Muscles of the tongue

Olfactory System (CN I)
Th e olfactory path w ay (Figs. 4.7 an d 4.8) is com -
posed of th e olfactory epith elium of th e n ose, th e
olfactory n erve (CN I), th e olfactory bu lb an d tract,
an d a cortical area (t h e paleocortex) exten din g
from th e u n cus of th e tem p oral lobe across t h e
an terior p erforated su bstan ce to th e m edial su r-
face of t h e fron tal lobe un der t h e gen u of th e cor-
pu s callosu m .
Cranial Nerves · 81
4
Fig. 4.5 Cranial nerves:
sites of exit from the
brainstem, components,
and distribution
Th e olfactory epithelium occup ies an area of about
2 cm 2 in th e roof of each n asal cavity, overlyin g
portions of th e su perior n asal con ch a an d of th e
n asal septu m . It con tain s receptor cells, su pportive
cells, an d glan ds (Bow m an ’s glan ds) th at secrete a
serou s fluid, th e so-called olfactory m u cus, in
w h ich arom atic su bstan ces are probably dissolved.
Th e sensory cells (olfactory cells) are bipolar cells
w h ose p eriph eral processes term in ate in th e ol-
factory h airs of th e olfactory epit h elium .
4 82 · 4 Brainstem

Fig. 4.6 Sites of exit of

the cranial nerves from
the skull. The exit
foram ina are shown on the
Cribriform left, the transected cranial
plate (I)
nerves on the right.
Optic canal (II) I Olfactory bulb
Superior orbital
fissure (III, IV, VI, II Optic n.
V [ophthalm ic n.])
III Oculomotor n.

Carotid canal IV Trochlear n.

Ophthalm ic n.
Foram en rotundum
(V [maxillary n.]) Maxillary n.
Mandibular n. V
Foram en ovale
Trigem inal Trigem inal n.
(V [mandibular n.])
ganglion
Foram en lacerum
Motor root
Internal VI Abducens n.
acoustic m eatus VII Facial n. and
(VII, VIII) nervus
interm edius
VIII Vestibulo-
cochlear n.
IX Glossopha-
Jugular foram en ryngeal n.
(IX, X, XI)
X Vagus n.
Hypoglossal XI Accessory n.
canal (XII) XII Hypoglossal n.

Olfactory nerve and olfactory bulb. Th e cen tral
processes (n eurites) of th e olfactory cells coalesce
in to bun dles con tain in g h un dreds of u n m yelin ated
fibers surrou n ded by a Sch w an n -cell sh eath . Th ese
fila olfactoria, abou t 20 on eith er side, are, in fact,
th e olfactory n erves (CN I is th u s com posed of p e-
riph eral n erve fibers, bu t is n ot a sin gle periph eral
n erve in th e u su al sen se). Th ey pass th rou gh sm all
h oles in th e cribriform (“sievelike”) p late an d en ter
th e olfactory bulb, w h ere th ey form th e first syn -
apse of th e olfactory pat h w ay. Alth ou gh it is n ot
physically located in th e cerebral cortex, th e ol-
factory bu lb is act ually a piece of th e telen -
ceph alon . With in it, com p lex syn apses are m ade
on to th e den drites of m itral cells, t ufted cells, an d
gran u le cells.
Olfactory pathw ay. Th e first n euron of th e ol-
factory path w ay is th e bipolar olfactory cell; th e
secon d n eu ron s are th e m itral an d tufted cells of th e
olfactory bu lb. Th e n eu rites of th ese cells form th e
olfactory tract (2n d n euron ), w h ich lies adjacen t to
an d ju st below th e fron tobasal (orbitofron tal) cor-
tex. Th e olfactory tract divides in to th e lateral an d
m edial olfactory striae in fron t of th e an terior per-
forated substan ce; an oth er portion of it term in ates
in th e olfactory trigone, w h ich also lies in fron t of
th e an terior perforated substan ce. Th e fibers of th e
lateral stria travel by w ay of th e lim en in su lae to
th e am ygdala, sem ilunar gyrus, an d am bient gyrus
(prepyriform area). Th is is th e site of th e 3rd n eu -
ron , w h ich p rojects to t h e an terior portion of th e
parahippocam pal gyrus (Brodm ann area 28, con -
tain in g th e cortical projection fields an d associa-
tion area of th e olfactory system ). Th e fibers of th e
m edial stria term in ate on n u clei of th e septal area
below th e gen u of th e corpus callosu m (su bcallosal
area) an d in fron t of th e anterior com m issure.
Fibers em ergin g from th ese n u clei p roject, in tu rn ,
to th e op posite h em isph ere an d to th e lim bic sys-
 Cranial Nerves · 83
4
Fig. 4.7 The olfactory
Longitudinal striae nerve and tract and the
Striae m edullares olfactory pathw ay
of the thalam us
Medial olfactory
stria
Subcallosal area Habenulo-
interpedun-
cular tract

Habenular
nucleus

Olfactory bulb Inter-

peduncular
nucleus
Medial
forebrain
bundle
Tegm ental
nuclei
Dorsal
Olfactory e pithe lium longitudinal
Lateral Area 28
bipolar olfactory cells fasciculus
olfactory (entorhinal
stria area)
Uncus with Prepiriform Reticular
amygdaloid body area formation

Fig. 4.8 The olfactory

nerve and tract as seen
Olfactory bulb Olfactory tract from below

Me dial olfactory
stria Tem poral pole

Lateral olfactory
stria
Lim en insulae
Prepiriform
Anterior area
perforated substance Amygdaloid
body
Am bient gyrus
Diagonal
Sem ilunar
band of
gyrus
Broca
Uncus

tem . Th e olfactory p ath w ay is th e on ly sen sory
path w ay th at reach es th e cerebral cortex w it h ou t
goin g th rough a relay in th e th alam u s. It s cen t ral
con n ection s are com plex an d still in com pletely
kn ow n .
Connections of the olfactory system w ith other
brain areas. An appetizin g arom a excites th e ap-
petite an d in du ces reflex salivation , w h ile a fou l
sm ell in du ces n au sea an d th e u rge to vom it, or
even actual vom itin g. Th ese processes also involve
th e em otion s: som e odors are pleasan t , oth ers
4 84 · 4 Brainstem
unp leasan t. Such em otion s probably com e abou t
th rough con n ection s of th e olfactory system w ith
th e hyp ot h alam u s, th alam u s, an d lim bic system .
Am on g its ot h er con n ection s, th e septal area sen ds
association fibers to th e cin gu late gyrus.
Th e m ain con n ection s of th e olfactory system
w ith au ton om ic areas are th e m edial forebrain
bundle an d th e striae m edullares thalam i (Fig. 6.9,
p. 180). Th e m edial forebrain bu n dle run s laterally
th rou gh th e hypoth alam us an d gives off bran ch es to
hypot h alam ic n u clei. Som e of its fibers con tin u e
in to th e brain stem to term in ate in auton om ic cen -
ters in th e reticu lar form ation , th e salivatory n u clei,
an d t h e dorsal n ucleu s of t h e vagus n erve. Th e striae
m edu llares th alam i term in ate in th e h aben u lar n u-
cleus; th is path w ay th en con tin u es to th e in ter-
pedun cu lar n ucleu s an d t h e brain stem ret icular for-
m ation (Fig. 6.9, p. 180).
Disturbances of smell can be classified as eith er
qu an titative or qu alitat ive. Quan titative distur-
ban ces of sm ell in clude hyposm ia (dim in ish ed
sm ell) an d anosm ia (absen ce of sm ell). Th ey are al-
w ays du e eith er to periph eral dam age of t h e ol-
factory n erve (e.g., becau se of rh in itis, t raum a w ith
disrupt ion of t h e n erve fibers in t h e cribriform
plate, or side effects of m edicat ion ), or to cen tral
dam age of t h e secon d n eu ron in th e olfactory bu lb
an d/or tract (olfactory groove m en in giom a is a
classic cau se). Qu alitative disturban ces of sm ell,
also kn ow n as parosm ias, m ay con sist of an un -
pleasan t cacosm ia (e.g., fecal odor) or of hyper-
osm ia (abn orm ally in ten se sm ell). Th ey are u su ally
du e to cen tral dysfu n ction , as in tem poral lobe
epilepsy.
Visual System (CN II)
Visua l Pa thwa y
Th e retina (Fig. 4.9a) is th e receptor su rface for
visual in form ation . Like th e opt ic n erve, it is a por-
tion of th e brain , despite its physical location at
th e periph ery of th e cen tral n ervous system . Its
m ost im portan t com pon en ts are th e sensory re-
ceptor cells, or photoreceptors, an d several types of
neurons of t h e visu al path w ay. Th e deep est cellu -
lar layer of th e retin a con tain s th e p h otoreceptors
(rods an d con es); th e tw o m ore su perficial layers
con tain th e bipolar n eu ron s an d th e gan glion
cells.
Rods and cones. Wh en ligh t falls on th e retin a, it in -
du ces a ph otoch em ical reaction in th e rods an d
con es, w h ich leads to th e gen eration of im p ulses
th at are u ltim ately prop agated to th e visual cortex.
Th e rods w ere lon g th ou gh t to be respon sible for
th e perception of brigh tn ess an d for vision in dim
ligh t, w h ile th e con es w ere th ou gh t to su bserve
color perception an d vision in brigh t ligh t. More
recen t research , h ow ever, h as cast dou bt on th ese
hyp oth eses. Th e u n derlyin g m ech an ism s of th ese
processes are probably m uch m ore com plex bu t
can n ot be discussed h ere in any fu rth er detail.
Th e fovea is the site of sh arpest vision in th e ret-
in a an d con tain s on ly con es, w h ich project on to
th e bipolar cells of th e n ext n eu ron al layer in a on e-
to-on e relation sh ip. Th e rem ain der of th e retin a
con tain s a m ixture of rods an d con es.
Th e retin al im age of a visu ally p erceived object
is up side-dow n an d w ith left an d righ t inverted,
ju st like th e im age on th e film in a cam era.
Optic nerve, chiasm, and tract. Th e retin al bipolar
cells receive inpu t on to th eir den drites from th e
rods an d con es an d tran sm it im pu lses fu rth er cen -
trally to th e gan glion cell layer. Th e lon g axon s of
th e gan glion cells pass th rou gh th e optic papilla
(disk) an d leave th e eye as th e optic n erve, w h ich
con tain s abou t 1 m illion fibers. Half of th ese fibers
decu ssate in th e optic chiasm : th e fibers from th e
tem poral h alf of each retin a rem ain u n crossed,
w h ile th ose from th e n asal h alf of each retin a cross
to th e opp osite side (Fig. 4.9a).
Th u s, at position s distal (posterior) to th e optic
ch iasm , fibers from t h e tem poral h alf of th e ipsi-
lateral retin a an d th e n asal h alf of th e con tralateral
ret in a are u n ited in th e optic tract.
A sm all con tin gen t of optic n erve fibers
bran ch es off t h e optic tract s an d travels to th e su -
perior collicu li an d to n u clei in th e pretectal area
(see Fig. 4.26). Th ese fibers con stitu te th e afferen t
arm of variou s visu al reflexes, an d, in particu lar, of
th e im portan t pupillary light reflex, w h ich w ill be
discu ssed fu rth er below (p. 101).
Lateral geniculate body, optic radiation, and visual
cortex. Th e optic t ract term in ates in th e lateral
geniculate body, w h ich con tain s six cellu lar layers.
Most of th e optic tract fibers en d h ere, form in g syn -
apses w ith lateral gen iculate n eu ron s. Th ese, in
tu rn , em it fibers th at ru n in th e h in dm ost portion of
th e in tern al capsule (Fig. 3.2, p. 37) an d t h en form a
 Cranial Nerves · 85
4
Fig. 4.9 The optic nerve
Optic n. and the visual pathw ay.
3rd neuron: a Com position of the retina
Ganglion
cells
(schem atic drawing). b The
visual pathway, with sites

t
h
g
2nd neuron of possible lesions. c The

i
L
Bipolar cells corresponding visual field
deficits.

1st neuron

s
e
s
Rods

l
u
p
and

m
I
cones
Pigm ent
epithelium
Fovea Periphery
a Visual cortex

Optic n.

Optic tract

4th neuron
Lateral
Optic radiation
geniculate
body

c
Are a Superior striate area
s
7
19 an
1
d 18 Calcarine sulcus
a
e
r
b
A
Inferior striate area

broad ban d th at cou rses arou n d th e tem poral an d
occipit al h orn s of th e lateral ven tricle, t h e so-called
optic radiation (of Gratiolet; see Fig. 4.10). Th e
fibers of th e optic radiat ion term in ate in th e visual
cortex, w h ich is located on th e m edial surface of th e
occipit al lobe, w ith in , above, an d below th e cal-
carin e fissu re (Brodm ann area 17). Fibers derived
from th e m acula occu py th e largest area of th e
visual cortex (Fig. 4.11). Area 17 is also kn ow n as
th e striate cortex because it con tain s th e stripe of
Gen n ari, a w h ite ban d com posed of h orizon t ally
run n in g fibers, w h ich can be seen w ith th e n aked
eye in section ed an atom ical sp ecim en s.
Somatotopic organization of the visual pathw ay.
Alth ou gh th e fibers of th e visual path w ay partially
decu ssate in th e optic ch iasm , a strict poin t-to-
poin t som atotopic organ ization of th e in dividu al
n erve fibers is preserved all th e w ay from th e ret-
in a to th e visu al cortex.
Visu al in form ation is tran sm itted cen trally as
follow s. An object located in t h e left visu al field
4 86 · 4 Brainstem

Optic radiation for im pairm en t or loss of vision in th e affected eye.

lower half of the Brief episodes of visual im p airm en t in a sin gle
visual field
eye, last in g from a few secon ds to several
m in u tes (“tran sien t m on ocular blin dn ess”), are
design ated amaurosis fugax an d are gen erally
cau sed by m icroem bolism in to th e retin a. In such
cases, th e in tern al carotid artery is often th e
Meyer’s
loop source of em boli an d sh ou ld be investigated for a
possible sten osis.

Calcarine area
Lesions of the optic chiasm, su ch as th ose produ ced
Optic radiation for upper
half of the visual field by a pit uitary tum or, cran iop h aryn giom a, or
Chiasm
Lateral Lateral m en in giom a of th e tu berculum sellae, gen erally af-
ventricle geniculate
(inferior horn) body fect th e decu ssat in g fibers in th e cen tral portion of
th e ch iasm . Th e resu lt is partial blin dn ess for ob-
Fig. 4.10 The optic radiation (of Gratriolet)
jects in th e tem poral h alf of th e visu al field of
eith er eye, i.e., bitemporal hemianopsia (th e
“blin ker ph en om en on ,” w h ere th e referen ce is to a
gives rise to im ages on th e n asal h alf of th e left ret-
h orse’s blin kers). Fibers in th e low er portion of th e
in a an d th e tem poral h alf of th e righ t retin a. Optic
ch iasm , derived from t h e low er p ortion of th e ch i-
n erve fibers derived from th e n asal h alf of th e left
asm , are com m on ly affected first by such pro-
retin a cross to th e left side in th e optic ch iasm to join
cesses; th u s, bitem poral up per quadran tan opsia is
th e fibers from th e tem poral h alf of th e righ t retin a
a com m on early fin din g. On ly color vision m ay be
in th e righ t optic tract. Th ese fibers th en p ass to a
im paired at first.
relay station in th e righ t lateral gen iculate body, an d
Less com m on ly, h ow ever, a lesion of th e ch iasm
th en by w ay of th e righ t optic radiation in to th e
can cause binasal hemianopsia, e.g., w h en a tu m or
righ t visu al cortex. Th e righ t visu al cortex is th u s re-
h as grow n aroun d th e ch iasm an d com p resses it
spon sible for th e perception of objects in th e left
from both sides (th u s m ain ly affectin g th e laterally
visual field; in an alogou s fash ion , all visu al im -
located, u n crossed fibers derived from th e tem -
pu lses relat in g to th e righ t visual field are tran s-
poral h alves of th e tw o retin as, w h ich are re-
m itted th rou gh th e left optic tract an d radiation in to
sp on sible for p erception in th e n asal h em ifield of
th e left visu al cortex (Fig. 4.9b).
each eye). An eurysm s of t h e in tern al carot id artery
Visu al fibers derived from th e m acu la are fou n d
an d basilar m en in git is are fu rth er possible cau ses,
in th e tem poral portion of th e optic disk an d in th e
bu t th e bin asal h em ian op sia in such cases is rarely
cen tral portion of th e optic n erve (Fig. 4.12). Dam -
pure.
age to th ese fibers can be seen by oph th alm oscopy
Bitem poral an d bin asal h em ian opsia are both
as atrop hy of t h e tem poral p ortion of th e disk
term ed heteronymous, becau se th ey affect op-
(tem poral pallor).
posite h alves of th e visual fields of th e tw o eyes:
th e form er affects th e righ t h em ifield of th e righ t
Lesions a long the Visua l Pa thwa y
eye an d th e left h em ifield of th e left eye, w h ile th e
Optic nerve lesions. Th e opt ic n erve can be dam - latter affects th e left h em ifield of th e righ t eye an d
aged at th e p apilla, in its an terior segm en t, or in th e righ t h em ifield of th e left eye.
its retrobulbar segm en t (i.e., beh in d th e eye). Le-
sions of the optic disk (e.g., papilledem a, caused Optic tract lesions, on th e oth er h an d, cau se homo-
by in tracran ial hyperten sion an d by a variety of nymous hemianopsia, in w h ich th e h em ifield of th e
m etabolic disorders) can be seen by op h th alm os- sam e side is affected in each eye. Wh en t h e fibers of
copy. Lesions of the anterior segment of the optic th e righ t optic tract are in terru pted, for exam p le, n o
nerve are often du e to vascu litis (e.g., tem poral visu al im pu lses derived from th e righ t side of eith er
arteritis). Retrobulbar lesions are a cardin al fin d- retin a can reach th e visual cortex. Th e resu lt is
in g in m u ltiple sclerosis (retrobu lbar n eu ritis). Le- blin dn ess in th e left h alf of t h e visu al field of each
sion s at any of th ese sites can cau se lon g-term eye (Figs. 4.9b an d c). Optic tract lesion s are usually
 Cranial Nerves · 87
4
Fig. 4.11 Projection of
the visual fields onto the
retina, lateral geniculate
body, and visual cortex
Right Left Projection onto
Cuneus the left visual cortex
Calcarine
sulcus
Lingual
gyrus

Optic
chiasm Projection on to
the left lateral
Right Left geniculate body

Projection onto the retina

Right Left

Overlapping
visual fields

Fig. 4.12 Position of the

Optic macular bundle in the
tract Optic retina, optic nerve, and
chiasm optic chiasm

Temporal Nasal

Macular
bundle
Retina

Optic n.

Macula
Optic disk

Macular
bundle
4 88 · 4 Brainstem
cau sed by a tu m or or basilar m en in git is, less often
by trau m a.
Because an in terru ption of th e optic tract also
affects t h e optic n erve fibers travelin g to th e sup e-
rior colliculi an d to th e p retectal area (cf. pp . 10 0
an d 101), it im pairs th e p upillary ligh t reflex in re-
spon se to ligh t fallin g on th e side of t h e retin a ip si-
lateral to th e lesion . In t h eory, t h is hem ianopic light
reflex test could be u sed to distin gu ish optic tract
lesion s from lesion s located m ore distally in th e
visu al p ath w ay. In p ractice, h ow ever, it is very diffi-
cu lt to h in e a ligh t on to on e h alf of th e retin a exclu-
sively, an d t h e test is of n o u se in clin ical diagn osis.
Case Presentation 1: Lesion of the Optic Tract in a Pa tient with Multiple Sclerosis
This 19-year-old fem ale high-school senior, previously in ex-
cellent health, noted a visual disturbance in which she had
blurry vision whenever she looked in certain directions.
Within 24 hours, this blurriness spread over the entire right
hem ifield. She consulted her fam ily doctor, who referred
her to hospital.
The adm itting neurologist’s visualfield exam ination revealed
right hom onym ous hem ianopsia sparing the upperm ost por-
tion of the right hem ifield. The rem ainder of the neurological
exam ination was norm al, as were the general physical exam i-
nation and all routine laboratory tests.
a
a b
Fig. 4.13 Inflammatory lesion of the left optic tract in a
patient w ith multiple sclerosis, as revealed by MRI. a The
T2-weighted coronal im age shows a hyperintense lesion
along the course of the left optic radiation above the
choroidal fissure, sparing only the basal portion of the optic
Lesions of the optic radiation. A lesion affectin g th e
p roxim al portion of th e optic radiation also cau ses
homonymous hemianopsia, w h ich , h ow ever, is
often incom plete, becau se th e fibers of th e optic
radiation are spread over a broad area (Fig. 4.9).
Hom onym ou s u pper quadran tan opsia im plies a le-
sion in th e an terior tem poral lobe, affectin g th e
p art of th e radiation kn ow n as Meyer’s loop
(Fig. 4.10). Hom onym ou s low er qu adran tan opsia
im p lies a lesion in th e parietal or occipital portion
of th e opt ic radiation .
Further tests were perform ed, including an MRI scan of the
head, a cerebrospinal fluid exam ination, and recording of
the visual evoked potentials (VEP). All of these tests con-
firm ed the clinical suspicion of an inflam m atory disease af-
fecting the CNS (m ultiple sclerosis) producing a lesion
along the course of the left optic tract. The patient was
given cortisone-bolus therapy and her sym ptom s resolved
within three days.
tract (arrow). b The T1-weighted coronal im age after in-
travenous adm inistration of contrast m aterial reveals en-
hancem ent at this site, indicating a focus of acute inflam -
m ation.

Eye Movements (CN III, IV, and VI)
Th ree cran ial n erves in n ervate th e m u scles of th e
eyes: t h e ocu lom otor n erve (CN III), th e troch lear
n erve (CN IV), an d th e abdu cen s n erve (CN VI)
(Figs. 4.14 an d 4.15).
Th e n u clei of th e ocu lom otor an d troch lear
n erves lie in th e m idbrain tegm en tum , w h ile th e
Cranial Nerves · 89
4
n u cleus of th e abdu cen s n erve lies in th e portion of
th e p on tin e tegm en tu m un derlyin g th e floor of th e
fou rth ven tricle.
Th e discu ssion of eye m ovem en ts in th is ch apter
w ill begin as sim ply as p ossible, i.e., w ith th e
m ovem en ts of a sin gle eye in du ced by im pulses in
each of th e in dividual n erves to th e eye m uscles. It
sh ou ld be born e in m in d from th e ou tset, h ow ever,

Fig. 4.14 Course of the

nerves to the extraocular
Superior oblique m . muscles: lateral view
Levator palpebrae m .
Superior rectus m . Cavernous
Medial rectus m . sinus
Internal carotid a. III

IV

VI

Sphenoid bone
Inferior oblique m .
Superior Clivus
Lateral rectus m . orbital fissure

Inferior rectus m . Tendinous ring

(opened)

Fig. 4.15 Course of the

nerves to the extraocular
muscles: dorsal view
Frontal sinus
Lateral rectus m.

Superior oblique m .

Ethm oid air cells

Abducens n.

Trochlear n.
Sphenoid sinus

Ophthalmic n.

Contour of cavernous Optic chiasm

sinus

Trigem inal ganglion

Clivus
Petrous ridge
(superior margin
of petrous bone) III
VI IV
4 90 · 4 Brainstem
Accessory (autonom ic)
Dorsal Ventral nucleus
Nucleus of Perlia
(parasym pathetic)
ct
u
d
Nucleus of Perlia
e
u
(for convergence)
aq
f
o
Inferior rectus m .
s
xi
A
Inferior oblique m .
Medial rectus m .
Superior rectus m .
Levator palpebrae
superioris m .
th at eye m ovem en ts are usually con ju gate, i.e.,
th ey u su ally occur in th e sam e direction (m ost ly
h orizon tally or vertically) in both eyes at on ce.
Con jugate h orizon t al m ovem en ts, in particu lar, in -
volve sim u ltan eou s m ovem en t of t h e tw o eyes in
op posite sen ses w ith respect to th e m idlin e: on e
eye m oves m edially, w h ile th e oth er m oves later-
ally. Con ju gate m ovem en ts th u s depen d on th e
precisely coordin ated in n ervat ion of t h e tw o eyes,
an d of t h e n uclei of th e m u scles su bservin g eye
m ovem en t on th e tw o sides. Th e com plex cen tral
n ervou s con n ection s en ablin g su ch m ovem en ts
w ill be dealt w ith later in th is ch apter. Fin ally, th e
n erves in n ervatin g th e eye m uscles also take p art
in a n um ber of reflexes: accom m odation , conver-
gen ce, th e pu pillary ligh t reflex, an d th e visu al
defen se reflex. Th ese reflexes w ill also be discu ssed
in th is ch apter.
Oculomotor Nerve (CN III)
Th e nuclear area of t h e oculom otor n erve lies in
th e periaqu eductal gray m atter of th e m idbrain ,
ven tral to t h e aqu educt, at th e level of th e sup erior
collicu li. It h as tw o m ajor com pon en t s: (1) a m edi-
ally situated p arasym path etic n ucleu s, th e so-
called Edinger–W estphal nucleus (or accessory au-
ton om ic n u cleu s), w h ich in n ervates th e in traocu-
lar m u scles (th e sph in cter pu pillae m uscle an d th e
ciliary m uscle); an d (2) a larger an d m ore laterally
situ ated nuclear com plex for four of the six extraocu-
lar m uscles (th e su perior, in ferior, an d m edial rec-
tus m u scles an d th e in ferior obliqu e m uscle). Th ere
is also a sm all nuclear area for the levator palpebrae
m uscle (cf. Warw ick’s diagram of th e sim ian ocu lo-
m otor n u clear com p lex, Fig. 4.16).
Fig. 4.16 Oculomotor nu-
cleus complex (after War-
Ventral
wick).
Dorsal
Th e m otor radicular fibers t h at em erge from
th ese n u clear areas travel ven trally togeth er w ith
th e p arasym path etic fibers; som e of th em cross
th e m idlin e, oth ers do n ot (all of th e fibers for th e
su perior rectu s m u scle cross th e m idlin e). Th e
com bin ed m otor an d p arasym path etic fibers
traverse th e red n u cleu s an d fin ally exit th e brain -
stem in th e in terp edu n cu lar fossa as th e ocu lom o-
tor n erve.
Th e oculomotor nerve first ru n s posteriorly be-
tw een th e sup erior cerebellar an d posterior cere-
bral arteries (Fig. 4.17), in close apposition to th e
ten torial edge, th en pen etrates th e dura m ater,
traverses th e cavern ou s sin u s, an d en ters th e orbit
th rou gh th e su perior orbital fissu re (Figs. 4.15 an d
4.17). Th e parasym path etic portion of th e n erve
bran ch es off at th is poin t an d t ravels to th e ciliary
ganglion , w h ere th e pregan glion ic fibers term in ate
an d th e gan glion cells give off sh ort postgan glion ic
fibers to in n ervate th e in t raocu lar m u scles.
Th e som atic m otor fibers of th e oculom otor
n erve divide in to tw o bran ch es, a sup erior bran ch
su pplyin g th e levator palp ebrae an d su perior rec-
tu s m u scles, an d an in ferior bran ch su pplyin g th e
m edial an d in ferior recti an d th e in ferior oblique
m uscle.
Trochlea r Nerve (CN IV)
Th e nucleus of th e fou rth cran ial n erve lies ven tral
to th e periaqu edu ctal gray m atter im m ediately
below t h e oculom otor n u clear com p lex at th e level
of th e in ferior collicu li. Its radicular fibers run
arou n d th e cen tral gray m atter an d cross to th e op-
posite side w ith in th e su perior m edu llary velum .
Th e trochlear nerve th en exits th e dorsal surface of
 Cranial Nerves · 91
4
a Optic n. Anterior Ophthal-
cerebral a. m ic a.

Internal carotid a.
b

Oculomotor n.
Sella Abducens n.
turcica
Trigem inal ganglion
Posterior
com muni- Trochlear n.
cating a.
Posterior cerebral a.

Posterior Trigem inal n.

petro- Superior cerebellar a. III
clinoidal Superior petrosal
fold VI
sinus V

Vestibular n.
Substantia IV
nigra
Red
nucleus
Nucleus of the
oculomotor n.

Fig. 4.17 a Topographic relationship of the nerves sup- trigem inal nerve in the cavernous sinus, as viewed from
plying the extraocular muscles to the internal carotid above. b Sagittal view.
artery and the trigeminal ganglion with branches of the

th e brain stem (it is th e on ly cran ial n erve th at does
th is), em ergin g from th e m idbrain tectu m in to th e
qu adrigem in al cistern . Its fu rth er course takes it
laterally arou n d th e cerebral pedun cle tow ard th e
ven tral surface of th e brain stem , so th at it reach es
th e orbit th rou gh th e su perior orbital fissu re to-
geth er w it h th e oculom otor n erve. It th en passes to
th e su perior oblique m u scle, w h ich it in n ervates.
Th e eye m ovem en ts subserved by th is m uscle in -
clu de depression of th e eye, in tern al rotation (cy-
cloinversion ), an d sligh t abdu ction .
Abducens Nerve (CN VI)
Th e nucleus of t h e sixth cran ial n erve lies in t h e
cau dal pon tin e tegm en tum , ju st ben eath th e floor
of th e fou rth ven tricle. Th e radicular fibers of th e
seven t h cran ial n erve (t h e facial n erve) loop
arou n d th e n u cleus of th e abducen s n erve at th is
site. Th e radicular fibers of t h e abducen s n erve
traverse th e pon s an d exit from th e brain stem at
th e p on tom edu llary jun ction . Th e abducens nerve
th en ru n s alon g th e ven tral su rface of th e pon s
lateral to th e basilar artery, perforates th e dura,
an d join s th e oth er n erves to th e eye m uscles in t h e
cavern ous sin u s. With in th e sin u s, th e th ird,
fou rth , an d sixth cran ial n erves are in a close spa-
tial relation w ith th e first an d secon d bran ch es of
th e trigem in al n erve, as w ell as w ith th e in tern al
carotid artery (Fig. 4.17). Moreover, th e n erves in
th e cavern ous sin u s lie very n ear th e su perior an d
lateral portion s of th e sph en oid an d eth m oid
sin u ses (Fig. 4.15).
Figu re 4.18 depicts th e action s of th e in dividu al
eye m u scles in t h e six diagn ostic direction s of gaze.
Figure 4.19 sh ow s th e abn orm alities of eye posi-
tion an d th e types of diplopia th at are cau sed by
p alsy of each of th e th ree n erves su bservin g eye
m ovem en ts.
4 92 · 4 Brainstem

Fig. 4.18 Diagram of eye

Superior rectus m . (III Inferior oblique m . (III) uperior rectus m . (III) position in the six diag-
nostic positions of gaze,
in which weakness of one
Right Left
Lateral Medial Lateral or m ore of the extraocular
rectus m. (VI) rectus m. (III) rectus m . (VI) m uscles can be m ost easily
detected

Inferior rectus m . (III) Superior oblique m . (IV) Inferior rectus m . (III)

Gaze upw ard and to the right Gaze upw ard and to the left

Superior Inferior Inferior Superior

rectus m . (III) oblique m. (III) oblique m . (III) rect us m . (III)

Rightw ard gaze Leftw ard gaze

Lateral Medial Medial Lateral

rectus m . (VI) rectus m . (III) rectus m . (III) rectus m . (VI)

Gaze dow nw ard and to the right Gaze dow nw ard and to the left

Inferior Superior Superior Inferior

rectus m . (III) oblique m . (IV) oblique m . (IV) rectus m . (III)

design ated hypertropia an d hypotropia (up w ard

Pa reses of the Eye Muscles
an d dow nw ard deviation , respectively).
Weakn ess of on e or m ore of th e extraocu lar A lesion in th e n ucleu s of on e of th e cran ial
m uscles im pairs m ovem ent of the affected eye and n erves th at subserve eye m ovem en ts causes ap-
restricts its ability to gaze in a particular direction p roxim ately th e sam e deficit as a lesion of th e pe-
or directions. Th e corn eal ligh t reflex test, in riph eral n erve itself. Nu clear lesion s can usually
w h ich th e exam in er n otes th e position of th e be clin ically distin gu ish ed from n erve lesion s be-
ligh t reflex on both corn eas from a poin t source cau se of fu rth er deficits du e to dam age of brain -
h eld in fron t of th e eyes in th e m idlin e, often re- stem stru ctures adjacen t to th e affected n u cleu s.
veals a m ild asym m et ry, in dicatin g a m ild devia-
tion of the visual axis of the eye at rest. A diplop ia
test w ith red–green spectacles, or w ith a ligh t
w an d, reveals th at th e im age arisin g from th e af-
fected eye is th e on e th at lies in th e direction in
w h ich th at eye is n orm ally m oved by th e paretic
m uscle. Th e tw o im ages are farth est apart w h en
th e patien t gazes in th is direction ; th e m ore p e-
riph eral im age is t h e on e arisin g from t h e af-
Fig. 4.19 Eye position and diplopia in various kinds of
fected eye (Fig. 4.19).
extraocular muscle palsy. The clinical effects of right-sided
Horizon tal deviation s of eye p osition are desig- lesions are shown. After Mumenthaler M and Mattle H:
n ated esotropia (inw ard deviation ) an d exotropia Neurology, 4th ed. (transl. E. Taub), Thiem e, Stuttgart/New
(ou tw ard deviation ), w h ile vertical deviation s are York, 2004.
 Cranial Nerves · 93
4
Nerve palsy Position of eyes Compensatory head posture Position of tw o images
(= smallest divergence) depending on direction
of gaze

Oculomotor Straight-ahead gaze None in the presence of ptosis,

nerve palsy (primary position of gaze) because there is no diplopia
Left Right

Largest divergence

Paresis predom inantly

affecting the medial
Fixed and dilated pupil in com - rectus m.
plete oculomotor nerve palsy

Trochlear Straight-ahead gaze Left Right

nerve palsy

Largest divergence Head tilt to unaffected side

Paresis of
superior oblique m .

Left eye

Right eye
Head tilt to side of paretic
muscle (Bielschowsky No diplopia
phenomenon)
Abducens Straight-ahead gaze Left Right
nerve palsy

Largest divergence

Head turn to side of Paresis of

paretic muscle lateral rectus m .
4 94 · 4 Brainstem
Oculom otor Nerve Palsy
A complete oculomotor nerve palsy produ ces th e
follow in g con stellat ion of fin din gs (Fig. 4.19):
¼ Ptosis, caused by p aralysis of th e levator palpe-
brae m u scle an d u n opposed con traction of th e
orbicu laris ocu li m u scle, w h ich is in n ervated by
th e facial n erve (th e lid space m ay be sligh tly
open becau se of con t raction of th e fron talis
m uscle).
¼ Fixed position of the eye, looking dow nw ard and
outw ard, cau sed by u n op posed con traction of
th e lateral rectus an d su perior obliqu e m u scles
(in n ervated by CN VI an d IV, respectively).
¼ Dilation of the pupil, cau sed by loss of con trac-
tion of th e sp h in cter pu pillae m u scle, in n er-
vated by th e p arasym pat h etic portion of th e
ocu lom otor n erve (p. 90); th e pu pillary ligh t
an d accom m odation reflexes are absen t (t h e
latter becau se of sim u ltan eous loss of con trac-
tion of th e ciliary m u scle).
An isolated paralysis of th e in traocular m uscles,
i.e., th e sph in cter pu pillae m uscle an d th e ciliary
m uscle, is called internal ophthalmoplegia. Th e
globe rem ain s fully m obile, bu t th ere is an absolute
paralysis of th e p upil, i.e., both th e direct an d th e
con sen su al ligh t reflexes are absen t, an d loss of ac-
com m odation cau ses blurry vision . In tern al oph -
th alm oplegia is due to selective dam age of th e par-
asym path et ic fibers of th e ocu lom otor n erve.
External ophthalmoplegia is presen t w h en th e
m otility of th e globe is restricted bu t th e au ton -
om ic (parasym pat h etic) in n ervation of th e eye is
preserved.
Ocu lom otor n erve palsies accoun t for abou t 30 %
of all palsies affectin g t h e m u scles of eye m ove-
m en t (abdu cen s n erve palsies are m ore com m on ,
accou n tin g for 40–50 % of cases). Ptosis is m ore
com m on w ith lesion s of th e (periph eral) n erve it-
self, rarer w ith lesion s of its n uclear com plex
w ith in th e brain stem . On ce th e n erve em erges
from th e brain stem , th e pu pillom otor fibers lie in
th e outer portion of th e n erve, directly ben eath th e
epin eu riu m , an d are th u s m ore vu ln erable th an t h e
oth er fibers of th e n erve to com pression by traum a,
tum ors, or an eurysm s. For th e sam e reason , th e
pupillom otor fibers are less com m on ly dam aged
by vascu lar lesion s, su ch as t h ose cau sed by dia-
betes. Th e m ore com m on cau ses of isolated ocu lo-
m otor n erve palsy are an eurysm s (approx. 30 %),
tu m ors (approx. 15 %), an d vascu lar lesion s (in clud-
in g diabetes, app rox. 15–20 %).
Trochlear Nerve Palsy
Troch lear n erve palsy p aralyzes th e superior ob-
liqu e m u scle. Th e affected eye deviates u pw ard
an d sligh tly inw ard, i.e., m edially, tow ard th e side
of th e n orm al eye (Fig. 4.19). Th e deviation is m ost
eviden t, an d th e dip lopia m ost ext rem e, w h en th e
patien t looks dow nw ard an d inw ard. An oth er w ay
of brin gin g ou t th e u pw ard-an d-inw ard deviation
of th e affected eye an d th e resu ltin g diplopia is by
h avin g th e patien t tilt th e h ead to th e affected side
w h ile fixatin g on an object w ith th e n orm al eye
(Bielschow sky test).
Th e m ore com m on cau ses of troch lear n erve
palsy are trau m a (30–60 % of cases), vascular le-
sion s, an d t um ors.
Abducens Palsy
Th e affected eye is deviated inw ard on prim ary
(straigh t-ah ead) gaze an d can n ot be abducted, be-
cau se th e lateral rectu s m u scle is paralyzed. Th e in -
w ard squ in t is also referred to as convergen t stra-
bism us. Wh en lookin g tow ard th e n ose, t h e p aretic
eye rotates u pw ard an d inw ard becau se of th e pre-
dom in an t action of t h e in ferior obliqu e m uscle.
Abdu cen s palsy is u su ally an isolated fin din g
an d is m ost com m on ly cau sed by tu m ors or vascu -
lar lesion s. Am on g all of th e cran ial n erves, th e ab-
du cen s n erve h as th e lon gest cou rse w it h in t h e
subarach n oid space; th u s, abducen s palsies can be
cau sed by m en in gitis an d by subarach n oid h em or-
rh age, as w ell as by elevated in tracran ial pressure
(in tracran ial hyperten sion ). Un ilateral abdu cen s
palsy m ay accom p any gen eralized in tracran ial hy-
perten sion an d is n ot n ecessarily a lateralizin g
sign . Abdu cen s p alsy is also occasion ally produced
by th e tem porary distu rban ce of in tracran ial p res-
sure after a lu m bar pu n ct ure.
Conjuga te Eye Movements
Position in g an d stabilizin g th e im age of an object
exactly on th e fovea of both eyes at th e sam e tim e
requ ires precisely coordin ated act ivity of th e eye
m u scles. Th e agon ist an d an tagon ist m uscles of th e
tw o eyes are alw ays sim ultan eou sly in n ervated
(Hering’s law ), an d each con traction of an agon ist
 Cranial Nerves · 95
4
Case Presentation 2: Nuclea r Lesion of the Trochlea r Nerve due to a Bra instem Infa rct
This 46-year-old m ale com pany em ployee becam e m ildly
nauseated one afternoon while at work. His co-workers
subsequently recalled that he m om entarily seem ed
strangely “distant,” though he had no recollection of this.
The nausea resolved after a short while, only to be im m edi-
ately followed by the onset of diplopia, particularly on
downward gaze, of which he becam e aware while de-
scending a staircase. Concerned about these sym ptom s, he
presented to the hospital for evaluation.
The clinical exam ination (eye position and m ovem ents) indi-
cated paresis of the left superior oblique m uscle as the
cause of diplopia. An MRI scan was obtained to rule out an
intracranial m ass. The T2-weighted im age revealed a m id-
brain lesion affecting the nucleus of the trochlear nerve on
the left (Fig. 4.20). There was no evidence of a diffusion ab-
norm ality or of contrast enhancem ent on the correspond-
ing im ages. The radiological findings and the clinical course
(acute onset of nausea followed by sudden diplopia) were
considered to be m ost consistent with an ischem ic event
(acute lacunar m idbrain stroke). There was no evidence of
inflam m atory disease affecting the CNS. Fig. 4.20 Nuclear lesion of the left trochlear nerve w ith
paresis of the superior oblique muscle due to an acute
midbrain infarct. This T2-weighted im age reveals a hyper-
intense lesion in the m idbrain (arrow).

occu rs in con ju n ct ion w it h relaxat ion of t h e corre-
spon din g an tagon ist (Sherrington’s law ). Con ju gate
m ovem en ts of both eyes in th e sam e direction are
called versive m ovem en ts (from th e Latin for “turn -
in g”), w h ile m ovem en ts of th e tw o eyes in opp osite
direction s are vergence m ovem en ts (eith er conver-
gence or divergence). Movem en ts of a sin gle eye are
called eith er duction or torsion (rotatory m ove-
m en t).
Horizontal and Vertical Gaze
Conjugate horizontal gaze. Th e cen tral relay n u-
cleus of th e ocu lom otor system is fou n d in th e
paramedian pontine reticular formation (PPRF or
“p on tin e gaze cen ter”), w h ich lies adjacen t to th e
n u cleus of th e abducen s n erve. Th e PPRF is th e site
of origin of all of th e n eu ral con n ect ion s part icipat-
in g in con ju gate h orizon tal gaze, in particu lar th e
fibers t h at con n ect th e ipsilateral abdu cen s n u-
cleus to th e portion of th e con tralateral ocu lom o-
tor n ucleu s in n ervatin g th e m edial rectus m uscle.
Th ese fibers ru n in th e medial longitudinal
fasciculus (MLF), a w h ite-m at ter tract th at ascen ds
an d descen ds th e brain stem on both sides n ear t h e
m idlin e. Th e MLF, w h ich exten ds from th e m id-
brain all th e w ay to th e cervical spin al cord, serves
to in tercon n ect all of th e in dividu al n uclei in n er-
vat in g t h e eye m u scles (Fig. 4.21). It also conveys
im pu lses to an d from th e cervical spin al cord
(an terior an d posterior cervical m u sculature), th e
vestibular n u clei, th e basal gan glia, an d th e cere-
bral cortex.
Disturbances of conjugate horizontal gaze. If th e
m edial lon gitu din al fasciculu s is dam aged on th e
left side (for exam p le), th en th e p atien t’s left m e-
dial rectu s m u scle is n o lon ger activated on at-
tem pted con ju gate gaze to th e righ t, an d th e left
eye stays beh in d, i.e., it com es n o furt h er m edially
th an th e m idlin e. At th e sam e tim e, m on ocular
nystagm us is seen in th e righ t eye, w h ose m ove-
m en t to th e righ t (abdu ction ) is su bserved by th e
righ t abdu cen s n erve. Th is com bin ation of fin din gs
is called internuclear ophthalmoplegia (INO,
Fig. 4.22). It is im portan t to realize th at INO in -
volves n eit h er a n u clear n or a periph eral palsy of
th e n erves to th e eye m u scles: in th e patien t ju st
described, th e left m edial rectu s m uscle w ill con -
tract n orm ally on convergen ce of th e tw o eyes.
As m en t ion ed, t h e MLF lies n ear th e m idlin e; th e
tw o m edial lon gitu din al fasciculi in fact lie very
4 96 · 4 Brainstem

Fig. 4.21 The anatomical

Voluntary m ovements basis of conjugate eye
Connections of areas movements: the cranial
18 and 19 to area 8 nerve nuclei controlling the
Area 8 Reflex eye extraocular m uscles, the
Area m ovements m edial longitudinal
19 Medial longitudinal fasciculus, and the vestibu-
18 fasciculus lar nucleus com plex, with
17 Vestibular connections the supranuclear and in-
franuclear pathways for vol-
Pathw ay for
reflex gaze untary and reflex conjugate
movements eye m ovem ents.

Pathw ay for
voluntary
gaze movements

Oculomotor n. Abducens n.
Tectal field for
vertical gaze
movements

Darkshevich’s
nucleus From the retina
III
Interstitial nucleus of
Cajal

Superior colliculus

Inferior colliculus IV Lateral

geniculate
body

Medial longitudinal To the cerebellum

fasciculus
Vestibular nuclei:
Superior nucleus
Lateral nucleus
VI
Medial nucleus
Pontine field for horizontal Inferior nucleus
gaze movements
(nucleus praepositus XII)
From cervical spinal cord
Lateral vestibulospinal
tract

n ear each oth er, an d dam age to th em is usu ally bi-
lateral. Th e above fin din gs of in tern u clear op h th al-
m oplegia are th u s u su ally seen on attem pted gaze
in eith er direction : th e addu ctin g eye com es n o
fu rth er m edially th an th e m idlin e, w h ile t h e ab-
du ctin g (leadin g) eye m an ifests nystagm u s. All
oth er eye m ovem en ts are in tact, an d th e p upillary
reflexes are in t act.
Mu ltiple sclerosis is th e m ost com m on cau se of
in tern uclear oph th alm oplegia. Oth ers in clu de en -
ceph alitis an d (in older patien ts) vascular distu r-
ban ces.
Conjugate vertical gaze. Th e vertical gaze cen ter
lies in th e rostrodorsal portion of the m idbrain retic-
ular form ation (Fig. 4.21) an d con sists of a n um ber
of specialized n u clei: th e prestitial nucleus in th e
rear w all of th e th ird ven tricle for u pw ard gaze; th e
nucleus of the posterior com m issure for dow nw ard
gaze; an d th e interstitial nucleus of Cajal an d Dark-
 Cranial Nerves · 97
4
shevich’s nucleus for con ju gate rotatory m ove-
m en ts.

Other conjugate gaze centers. Vertical gaze m ove-

m en ts can also be gen erated from n eu ron s lyin g at
th e anterior border of the superior colliculi. Distu r-
Medial
ban ces affectin g th is area cau se paresis of u pw ard longitudinal
gaze (Parin au d syn drom e). fasciculus
Im pu lses origin atin g in th e occipital lobes also III
travel to th e con tralateral p on tin e gaze cen ters
IV
(p ara-abducen s n u cleu s) to in itiate con ju gate
lateral gaze m ovem en ts. Exp erim en tal stim u lation Lesion VI
of occipital areas 18 an d 19 h as been foun d to p ro-
voke con jugate gaze m ovem en ts th at are m ost
often lateral, th ou gh som etim es u pw ard or
Para-abducens
dow nw ard (lateral gaze m ovem en ts are certain ly nucleus (nucleus
praepositus XII)
th e m ost im portan t type in h um an bein gs, as th ey
are far m ore frequen t th an th e oth er t w o types) Fig. 4.22 Internuclear ophthalmoplegia due to a lesion
(Fig. 4.21, p. 96). of the m edial longitudinal fasciculus

Case Presentation 3: Internuclea r Ophtha lmoplegia in a Pa tient with a n Acute Bra instem
Stroke
This previously healthy 48-year-old m an was adm itted to The clinical course and radiological findings pointed to an
hospital because of the sudden onset of nausea, vom iting, ischem ic event (lacunar brainstem stroke involving the m e-
and diplopia. Neurological exam ination revealed the typical dial longitudinal fasciculus). There was no evidence of a
findings of internuclear ophthalm oplegia (see p. 94) and no CNS inflam m atory process. No em bolic source was found.
other deficits. The internuclear ophthalm oplegia largely re-
solved over the subsequent course of the patient’s illness.

a b
Fig. 4.23 Internuclear ophthalmoplegia in a patient
w ith an acute midbrain infarct. a The thin-section axial
T2-weighted im age of the m idbrain shows a hyperintense
right param edian lesion adjacent to the aqueduct. b The
axial diffusion-weighted im age shows a fresh lesion at this
site. The two findings, taken together, indicate an ischem ic
event.
4 98 · 4 Brainstem
Volu n tary eye m ovem en ts are in itiated by n eu -
ron s of t h e frontal eye field in Brodm an n area 8 (an d
p erh aps also parts of areas 6 an d 9), an terior to th e
p recen tral gyru s (Fig. 4.21). Th e m ost com m on re-
su lt of st im u lation or irritation in t h is area, e.g.,
du rin g an epileptic seizu re, is a con ju gate lateral
gaze m ovem en t to th e opp osite side (Fig. 4.24). Th is
eye m ovem en t is occasion ally accom pan ied by
tu rn in g of th e h ead to th e opposite side.
Th e pathw ay from the frontal eye field to the
brainstem nuclei subserving eye movements h as
n ot yet been fully traced. It is curren tly th ou gh t
th at fibers of th is path w ay ru n in th e in tern al cap -
su le an d th e cerebral pedu n cle togeth er w ith t h e
corticon u clear tract, but th en do n ot term in ate
directly in th e n u clei subservin g eye m ovem en t,
reach in g t h em in stead th rou gh a n u m ber of “w ay
station s” in clu din g th e superior collicu li, in ter-
n euron s of th e reticular form ation , an d th e m edial
lon gitu din al fascicu lu s (Fig. 4.21).
All volu n tary m ovem en ts are un der th e in -
flu en ce of reflex arcs, n ot on ly visu al, bu t also au di-
tory, vestibu lar, an d prop rioceptive (from th e cer-
vical an d n u ch al m u scu latu re to th e spin otectal
tract an d m edial lon gitu din al fascicu lu s).
Lesions of the gaze centers. Destruction of area 8
on on e side resu lts in a p repon deran ce of im pu lses
com in g from th e correspon din g area of th e op -
p osite h em isph ere, produ cin g con ju gate gaze
tow ard th e side of th e lesion (i.e., déviation con-
juguée lookin g tow ard th e focu s). Th e gaze devia-
tion is occasion ally accom pan ied by turn in g of t h e
h ead to th e side of th e lesion . Th e patien t can n ot
voluntarily look to th e ot h er side, bu t can do so in
reflex fash ion , as w h en visu ally pu rsuin g an object
t h at is slow ly m oved in to t h e con tralateral visu al
field. (Th e opposite is foun d in lesion s of t h e occip-
ital lobe, as discussed below.) Gaze deviation du e
to a lesion of th e fron tal eye field gen erally resolves
after a brief period. In con t rast to a destru ctive le-
sion , stimulation or irritation of area 8 (as in an
ep ileptic seizu re) produces con ju gate gaze aw ay
from th e side of th e focu s.
Th e situation is differen t w ith pontine lesions
becau se th e corticopon t in e pat h w ays are crossed
(Fig. 4.24). Stim u lation or irritation of th e pon tin e
gaze cen ter produ ces ipsilateral gaze deviation ,
w h ile a destru ctive lesion cau ses con tralateral gaze
deviation . Gaze deviation of p on tin e origin rarely
resolves com p letely.
Reflex Conjugate Gaze Movem ents
“Fixation reflex.” Wh en w e direct ou r gaze on to an
object volu n tarily, w e do so w ith very fast, abru pt,
an d precise eye m ovem en ts, called saccades. Most
eye m ovem en ts, h ow ever, occur in reflex fash ion :
w h en an object en ters ou r visu al field, ou r atten -
tion , an d our gaze, are directed to it autom atically.
If th e object m oves, th e eyes pu rsue it involu n tarily
so th at its im age rem ain s on th e fovea, th e portion
of th e retin a in w h ich vision is sh arpest. Th is oc-
cu rs regardless of w h eth er th e observer or th e ob-
ject is in m otion (or both ). All volun tary eye m ove-
m en ts th u s h ave involu n tary reflex com pon en ts. In
th e En glish -lan gu age literature, th e qu asi-reflex
processes th at m ain tain th e visu al im age of an ob-
ject on th e fovea are referred to as th e fixation re-
flex.
Th e afferent arm of th e fixation reflex exten ds
from th e ret in a alon g th e visu al path w ay to t h e
visual cortex (area 17), from w h ich furth er im -
pulses are sen t to areas 18 an d 19. Th e efferen t arm
retu rn s from th ese areas to th e con t ralateral
m esen ceph alic an d pon tin e gaze cen ters, probably
by w ay of th e optic radiation (t h ou gh th e exact lo-
cation of th ese fibers is still u n kn ow n ). Th ese gaze
cen ters th en project to th e cran ial n erve n u clei
subservin g eye m ovem en ts to com p lete th e reflex
arc. Som e of th e efferen t fibers probably run
directly to th e brain stem gaze cen ters, w h ile oth ers
pass first to th e fron tal eye field (area 8).
Lesions affecting the fixation reflex. If th e occipital
areas involved in th e fixation reflex are dam aged,
th e reflex n o lon ger fun ction s properly. Th e patien t
can look volu n tarily in any direction , bu t can n o
lon ger pu rsu e an object visu ally, keepin g its im age
fixed on th e fovea. Th e object im m ediately slips
ou t of t h e zon e of sh arpest vision , an d t h e pat ien t
h as to fin d it again w ith volu n tary eye m ovem en ts.
Optokinetic nystagmus. Wh en a p erson looks
directly at an object, th e im age of th e object on
each retin a falls on th e fovea, an d despite t h e ac-
tu al presen ce of tw o im ages—on e on each retin a—
th e object is perceived as on e (fu sion ). If th e object
sh ou ld th en m ove in any direct ion , eith er closer to
or farth er aw ay from th e observer, vertically, or
h orizon tally, sm ooth pursuit m ovem ents of th e eyes
w ill h old its im age on th e fovea of each eye (cf. th e
above discu ssion of th e fixation reflex). As soon as

Irritation
Area
17
Irritation 1 Lesion 1
(cortical)
Irritation 2
Cortical lesion : gaze away from focus
Pontine lesion: gaze toward focus Pontine lesion: gaze away from focus
Irritatio n
th e im age of th e object m oves out of th e fovea, im -
pu lses travel in a reflex arc from th e retin a alon g
th e visual path w ay to t h e visu al cortex, an d t h en
th rough th e occipitotectal fibers back to th e cran ial
n erve n uclei th at in n ervate th e eye m u scles, cau s-
in g th em to con tract in su ch a w ay as to retrieve th e
im age on to th e fovea (th is is called th e optokinetic
process). Th e jerky eye m ovem en ts produ ced in
th is w ay, kn ow n as optokinetic nystagm us, can be
observed easily in person s w atch in g th e p assin g
scen ery from a train or car w in dow, for exam ple. It
can be reprodu ced in t h e clin ical settin g by h avin g
th e patien t w atch a rotatin g, strip ed dru m : th e
patien t’s gaze pu rsu es on e of th e stripes u n til it
disappears aroun d th e side of t h e drum , t h en sn aps
back to cat ch an ot h er strip e, an d so on , rep eatedly.
Th u s, optokin etic nystagm u s con sists of slow an d
fast ph ases, i.e., relatively slow pu rsuit m ovem en ts
in altern ation w ith faster, corrective jum ps in th e
opposite direct ion . If th e reflex arc for optokin etic
nystagm u s is broken at any poin t, th e reflex is lost.
Absen ce of optokin etic nystagm us is alw ays path o-
logical.
Cranial Nerves · 99
4
Fig. 4.24 Conjugate de-
viation due to cortical
and pontine foci (irritative
or destructive)
Deficit
Lesion 2
(pontine)
Cortical lesion: gaze toward focus
Destructive lesion
Convergence a nd Accommoda tion
Th ese reflexes are evoked by w atch in g an object as
it m oves closer to th e observer in th e visu al field.
Th e so-called n ear respon se actually con sists of
th ree processes th at occur sim u ltan eou sly:
¼ Convergence: t h e m edial rectu s m uscles of th e
tw o eyes are activated so th at th e optical axis of
each con tin u es to poin t directly to th e object
un der observation . Th is keeps th e im age of th e
object on th e fovea of each eye.
¼ Accommodation: con traction of th e ciliary
m uscle slacken s th e su spen din g apparatu s of
th e len s. Because it is in trin sically elastic, th e
len s th en takes on a m ore sph erical sh ape, an d
th us a h igh er refractive p ow er. Th is process
keeps th e retin al im age of an object in focu s as it
is m oved closer to th e eye. Conversely, w h en th e
object is m oved farth er aw ay or th e in dividu al’s
gaze is redirected on to a m ore distan t poin t, re-
laxation of th e ciliary m uscle allow s th e sus-
pen din g apparatus to pu ll th e len s back in to a
flatter sh ape, low erin g it s refractive pow er an d
4 100 · 4 Brainstem

Fig. 4.25 a The anatomi-

Sphincter pupillae m . cal basis of convergence
and accommodation.
Ciliary m .
b The ciliary m uscle in
relaxation (vision at a dis-
tance). c The ciliary m uscle
Medial rectus m . in contraction (near vision).

Oculomotor n.
(parasympathetic
portion)
Optic n.
Ciliary ganglion

Oculomotor n.

Accessory nucleus
(autonom ic)
Oculomotor nucleus
(portion controlling
m edial rectus m .)

Lateral Nucleus of Perlia

geniculate
Pretectal area
body

Optic Ciliary m.
radiation Relaxation

b
a Visual
cortex
Contraction

Area
Area c
19
17

Area 18

on ce again brin gin g th e visual im age in to sh arp
focus (Fig. 4.25).
¼ Pupillary constriction: th e pu pil con stricts to
keep th e retin al im age of th e n ear object as
sh arp as possible. (A cam era sh u tter fu n ction s
sim ilarly: th e closer th e object to be ph oto-
grap h ed, th e n arrow er th e apertu re m u st be to
keep it in focus.)
All th ree of t h ese processes can be brou gh t abou t
volun tarily by fixat in g on a n ear object an d also
occur as reflexes w h en a distan t object m oves
closer to th e observer.
Anatomical substrate of convergence and accom-
modation (Fig. 4.25). Th e afferent im pu lses travel
from th e ret in a to th e visu al cortex, an d th e effer-
ent im pu lses from th e visual cortex to th e pretectal

area an d th en to t h e parasym p ath etic nucleus of
Perlia, w h ich lies m edial an d ven tral to th e
Edin ger–Westph al n u cleus (accessory auton om ic
n u cleus). From th e n u cleu s of Perlia on eit h er side,
im pu lses travel to th e nuclear area of the m edial
rectus m uscle (for ocular convergen ce) an d to th e
Edinger–W estphal nucleus, from w h ich th ey
proceed to th e ciliary gan glion an d m u scle (for ac-
com m odation ) an d to th e pup illary sph in cter (for
pu pillocon st riction ) (Fig. 4.26). Th e n eural path -
w ays to th e ciliary m u scle an d th e pup illary
sph in cter are presu m ably distin ct , becau se t h e ac-
com m odation an d ligh t reflexes can be differen -
tially affected in variou s con dition s. In n eu rosy-
ph ilis, for exam ple, th e p h en om en on of th e Argyll
Robertson pu pil m ay be foun d: t h e ligh t reflex is
absen t , bu t convergen ce an d accom m odat ion are
preserved.
Regula tion of the Pupilla ry Light Reflex
Th e w idth of th e pu pil varies in relation to th e in ci-
den t ligh t: brigh t ligh t in du ces pu pillary con stric-
tion , an d darkn ess in du ces pu pillary dilation . Th e
pu pillary ligh t reflex serves to m odu late th e
am ou n t of ligh t fallin g on t h e retin a, both to pro-
tect th e p h otoreceptors from poten tially dam ag-
in g, excessive illum in ation , an d to keep th e visu al
im ages of objects in th e best possible focu s on th e
ret in a, in an alogou s fash ion to a cam era sh u tter.
Th is reflex is en tirely involu n tary; th e cerebral cor-
tex is n ot involved in th e reflex loop.
Afferent arm of the pupillary light reflex (Fig. 4.26).
Th e afferen t fibers accom pany th e visual fibers in
th e optic n erve an d tract n early to th e lateral
gen icu late body, bu t, in stead of en terin g th e latter,
th ey turn off in th e direction of th e su perior col-
licu li an d term in ate in th e nuclei of the pretectal
area. In tern eu ron s located h ere project fu rth er to
th e parasym p ath etic Edinger–W estphal nuclei (ac-
cessory auton om ic n u clei) on both sides (Fig. 4.26).
Th is bilateral in n ervation of th e Edin ger–Westp h al
n u clei is th e an atom ical basis of th e con sen su al
ligh t respon se: illu m in ation of on e eye in du ces
con striction n ot ju st of th at pu pil, bu t of th e con -
tralateral pu pil as w ell.
Lesions of the afferent pathway. Lesion s of th e optic
radiat ion , visu al cortex, or su perior collicu li h ave
n o effect on th e pu pillary light reflex. A lesion of
Cranial Nerves · 101
4
Sphincter pupillae m.
Ciliary ganglion Optic n.
Autonomic portion
of oculomotor n.
Optic tract
Accessory
nucleus
(autonomic)
Lateral
geniculate body
Medial geniculate body
Pretectal nucleus
Fig. 4.26 The pupillary light reflex
th e pretectal area, h ow ever, abolish es th e reflex.
Th is in dicates th at th e form er stru ctures do n ot
participate in th e reflex arc, an d th at th e afferen t
arm of th e reflex arc m u st traverse th e pretectal
area, th ou gh th e precise an atom ical localization of
th is p ath w ay is n ot yet fu lly clear. Sim ilarly, optic
nerve lesions, w h ich in terrupt th e afferen t arm of
th e reflex arc at a differen t site, im pair th e pu pil-
lary respon se to illum in ation of th e eye on th e side
of th e lesion : n eith er t h e ipsilateral n or th e con -
tralateral pup il w ill con strict n orm ally. Illu m in a-
tion of th e oth er eye is follow ed by n orm al con -
striction of both pu pils. Th ese fin din gs im ply th e
presen ce of an afferent pupillary defect.
Efferent arm of the pupillary light reflex (Fig. 4.26).
Th e efferen t fibers origin ate in th e Edinger–W est-
phal nucleus an d travel in th e oculom otor nerve to
t h e orbit. Th e p arasym path etic pregan glion ic
fibers bran ch off from th e oculom otor n erve w ith in
t h e orbit an d travel to th e ciliary ganglion, w h ose
gan glion cells con stitute a syn aptic relay station .
Th e sh ort postgan glion ic fibers em erge from th e
ciliary gan glion an d th en en ter th e globe to in n er-
vate th e sph in cter p upillae m u scle (Fig. 4.26).
Lesions of the efferent pathway. If th e oculom otor
n erve or ciliary gan glion is dam aged, th e im p ulses
from t h e Edin ger–Westp h al n ucleus can n o lon ger
reach th e sph in cter pu pillae m u scle of th e ip si-
4 102 · 4 Brainstem
lateral eye. Th e resu lt is m ydriasis w ith absen ce of
th e ligh t reflex.
Other stimuli affecting the w idth of the pupils. Th e
w idth of th e p upils varies n ot on ly in respon se to
th e in ciden t ligh t but also in respon se to various
kin ds of stim uli arisin g ou tside th e eye. Very pain-
ful stim uli, su ch as a deep p in ch of th e n u ch al
m uscu latu re, as w ell as heightened em otional
arousal can in du ce pu pillary dilatation . Th e m y-
driasis seen in th ese sit uat ion s w as lon g at-
tribu ted to in creased activity of t h e sym p ath etic
n ervou s system , leadin g to con traction of th e dila-
tor pu pillae m u scle (w h ich is discu ssed fu rth er
below ). Recen t st udies h ave sh ow n , h ow ever, th at
decreased activity of th e parasym p ath etic in n er-
vation of th e pup il is probably th e m ore im portan t
factor.
Anisocoria. Th e w ord “an isocoria” com es from th e
Greek an d m ean s, literally, in equ ality of th e pup ils
(it is th us redu n dan t to state, “Th e pu pils are an iso-
coric”). A m ild disparit y of pu pillary w idth is often
n oted in n orm al p erson s (physiological an iso-
coria), bu t a larger disparity sh ould provoke suspi-
cion of a (u n ilateral) in tracran ial m ass com press-
in g th e oculom otor n erve. In clin ical situ ation s, it is
im portan t to rem em ber th at an isocoria is often
produ ced by th e in stillation of dilatin g or con -
strictin g dru gs in to on e eye (w h ich sh ould be
avoided, for exam ple, in com atose p atien ts).
Sympa thetic a nd Pa rasympa thetic
Innerva tion of the Eye
Parasympathetic innervation of the eye (Fig. 4.27).
Th e parasym path etic in n ervation of th e sph in cter
pup illae m u scle an d of th e ciliary m u scle w as dis-
cu ssed above in con n ection w ith th e pu pillary ligh t
reflex an d th e accom m odation reflex (p. 99 ff.,
p. 101). Activation of th e parasym path etic supp ly
to th e eye is m an ifested by pu pillary con striction
(m iosis) an d accom m odation in respon se to a n ear
object.
Sympathetic innervation of the eye (Fig. 4.27). Th e
n uclear area from w h ich th e sym path etic in n erva-
tion of th e eye arises, th e ciliospinal center, is lo-
cated in th e lateral h orn of th e spin al cord from C8
to T2. Th e pregan glion ic fibers origin ate h ere an d
ascen d to a relay st ation in t h e su perior cervical
gan glion , from w h ich th e postgan glion ic fibers
em erge an d th en ascen d togeth er w ith t h e in tern al
carotid artery an d oph th alm ic artery in to th e orbit,
fin ally reach in g an d in n ervat in g t h e dilator
p upillae, superior an d in ferior tarsal, an d orbitalis
m u scles (Figs. 4.27 an d 4.28). Oth er sym p ath etic
fibers su pply t h e sw eat glan ds an d blood vessels of
th e ip silateral h alf of th e face.
Afferent supply of the ciliospinal center: Afferen t
fibers from th e ret in a travel to t h e hypoth alam u s
(su prach iasm atic n u cleu s), in w h ich th e cen tral
sym p ath et ic pat h w ay arises. Th e path w ay crosses
th e m idlin e at th e level of th e m idbrain an d de-
scen ds t h rou gh th e brain stem an d cervical sp in al
cord to th e ciliospin al cen ter.
Horner syndrome (Fig. 4.28). A lesion affectin g th e
cen tral sym path etic path w ay, th e ciliosp in al
cen ter, th e su perior cervical gan glion , or th e post-
gan glion ic sym path etic fibers on th eir w ay to th e
eye produ ces a ch aracterist ic con stellation of ab-
n orm alities, called Horn er syn drom e. Th e triad of
ocular fin din gs con sists of: narrow ing of the palpe-
bral fissure (due to loss of fu n ction of t h e su perior
t arsal m uscle), m iosis (du e to loss of fun ction of th e
dilator pu pillae m uscle, resultin g in a prepon der-
an ce of th e con strictin g effect of th e sph in cter
pu pillae m uscle), an d enophthalm os (du e to loss of
fu n ction of th e orbitalis m uscle). Anhidrosis an d
vasodilatation in th e ip silateral h alf of th e face are
seen w h en th e sym path etic in n ervation of th e face
is also involved, eith er at th e ciliospin al cen ter or in
th e efferen t fibers th at em erge from it.
Blink Reflex
If an object sudden ly appears before th e eyes, re-
flex eye closu re occu rs (blink reflex). Th e afferen t
im pu lses of th is reflex travel from th e retin a
directly to th e m idbrain tectu m an d th en ru n , by
w ay of th e tecton u clear tract , to th e facial n erve
n uclei of both sides, w h ose efferen t fibers th en in -
n ervate th e orbicu laris oculi m u scles. Furth er im -
pulses m ay descen d in tectospin al fibers to th e
an terior h orn cells of th e sp in al cord, w h ich in n er-
vate th e cervical m u scu latu re to produce aversion
of th e h ead.
 Cranial Nerves · 103
4
Fig. 4.27 The sympa-
From the thetic and parasympa-
diencephalon Pretectal thetic innervation of the
nucleus
Edinger–Westphal intraocular muscles.
Optic n. nucleus

Optic
chiasm
Sphincter
pupillae m .

Dilator
pupillae m . Oculo-
m otor n.
Ciliary
ganglion Central
sym pathetic
Internal pathway
carotid a.
Parasym pathetic
Sym pathetic

Superior
Stroma iridis cervical
ganglion

Sphincter
pupillae m .

Dilator
pupillae m .

Pigm ent epithelium Sym pathetic

trunk T1

Trigeminal Nerve (CN V)

Th e trigem in al n erve is a m ixed n erve. It possesses
a larger com p on en t (portio m ajor) con sistin g of
sensory fibers for th e face, an d a sm aller com -
pon en t (portio m inor) con sistin g of motor fibers for
th e m u scles of m astication .
Trigeminal ganglion and brainstem nuclei. Th e
trigeminal (gasserian) ganglion is th e cou n terpart
of th e spin al dorsal root gan glia for t h e sen sory in -
n ervation of th e face. Like th e dorsal root gan glia, it
con tain s pseudou n ipolar gan glion cells, w h ose
p eriph eral processes term in ate in receptors for
touch , pressu re, tactile discrim in ation , pain , an d
tem p eratu re, an d w h ose cen tral processes p roject
to th e principal sensory nucleus of the trigeminal
nerve (for tou ch an d discrim in ation ) an d to th e spi-
nal nucleus of the trigeminal nerve (for pain an d
tem peratu re). Th e mesencephalic nucleus of the
trigeminal nerve is a special case, in th at its cells
correspon d to sp in al dorsal root gan glion cells
even th ou gh it is located w ith in t h e brain stem ; it
4 104 · 4 Brainstem

Fig. 4.28 The sympa-

thetic innervation of the
From the eye and Horner syn-
Superior diencephalon drome. In the region of
tarsal m. (central the eye, sym pathetic effer-
sym pathetic ents innervate not only the
Internal pathway)
dilator pupillae m uscle (see
carotid a. Fig. 4.27), but also the tar-
sal m uscles and the orbi-
Dilator talis m uscle. The sym pa-
pupillae m. thetic innervation of the
(m iosis) sweat glands of the face
and of its vasculature (va-
Inferior
soconstrictor fibers) is also
tarsal m.
shown.
Superior
cervical
ganglion
Orbitalis m. C8
Vasodilation

Sw eat gland
(anhidrosis)

T1

T2

is, in a sen se, a p erip h eral n ucleu s th at h as been
displaced in to th e cen tral n ervous system . Th e pe-
riph eral processes of n euron s in th is n u cleu s re-
ceive im pu lses from perip h eral receptors in th e
m uscle spin dles in th e m u scles of m astication , an d
from ot h er receptors t h at resp on d to pressu re.
Th e th ree n uclei ju st m en tion ed exten d from th e
cervical spin al cord all th e w ay to th e m idbrain , as
sh ow n in Figu re 4.30. Th e trigem in al gan glion is lo-
cated at th e base of th e skull over th e ap ex of th e
petrou s bon e, ju st lateral to th e posterolateral por-
tion of th e cavern ou s sin us. It gives off th e t h ree
bran ch es of th e t rigem in al n erve to th e differen t
areas of th e face, i.e., t h e ophthalmic nerve (V1 ),
w h ich exits from th e sku ll th rough th e su perior
orbital fissu re; th e maxillary nerve (V2 ), w h ich
exits th rou gh th e foram en rotun dum ; an d th e
mandibular nerve (V3 ), w h ich exits th rough th e
foram en ovale.
Somatosensory trigeminal fibers. Th e periph eral
trajectory of th e trigem in al n erve is sh ow n in
Figure 4.29. Its somatosensory portion su pplies t h e
skin of th e face u p to th e vertex of th e h ead. Figu re
4.30 sh ow s th e cu tan eou s territories supp lied by
each of th e th ree trigem in al bran ch es. Th e cu -
tan eous distribu tion of th e trigem in al n erve
borders th e derm atom es of th e secon d an d th ird
cervical n erve roots. (Th e first cervical n erve root,
C1, is pu rely m otor an d in n ervates th e n uch al
m u scles th at are attach ed to th e sku ll an d th e
u pp er cervical vertebrae.)
Fu rth erm ore, th e m u cou s m em bran es of th e
m ou th , n ose, an d paran asal sin u ses derive th eir so-
m atosen sory in n ervation from th e trigem in al
n erve, as do th e m an dibu lar an d m axillary teeth
an d m ost of th e du ra m ater (in th e an terior an d
m iddle cran ial fossae). Arou n d th e extern al ear,
h ow ever, on ly th e an terior portion of th e p in n a an d
th e extern al au ditory can al an d a part of th e tym -
p an ic m em bran e are sup plied by th e trigem in al
n erve. Th e rest of th e extern al au ditory can al
derives its som atosen sory in n ervation from th e
n ervu s in term ediu s an d th e glossop h aryn geal an d
vagu s n erves.
 Cranial Nerves · 105
4
Fig. 4.29 Peripheral
Nasociliary n. course of the somato-
Tem poralis m . Ciliary ganglion Frontal n. sensory and motor fibers
of the trigeminal nerve
Superficial
tem poral
branch

Ophthalmic n.
Maxillary n.

Mandibular n.
A

Trigeminal g anglion B
C

Auriculotem poral n. 2
Pterygopalatine ganglion
Buccal n.
Lingual n.
Inferior alveolar n.
M
as

A = orbital fissure
se

B = foram en rotundum
te
r

C = foramen ovale
m
.

1 = lateral pterygoid m.
2 = medial pterygoid m .
3 = mylohyoid m . and anterior Mylohyoid n. 3
belly of digastric m . Mental m .

Proprioceptive impulses from th e m u scles of
m astication an d th e h ard palate are tran sm itted by
th e m an dibu lar n erve. Th ese im pu lses are part of a
feedback m ech an ism for th e con t rol of bite
stren gth .
All trigem in al som atosen sory fibers term in ate
in th e principal sensory nucleus of the trigeminal
nerve, w h ich is located in th e dorsolateral portion
of th e p on s (in a posit ion an alogou s to t h at of th e
posterior colum n n uclei in th e m edulla). Th e axon s
of t h e secon d n eu ron s cross th e m idlin e an d as-
cend in th e con tralateral m edial lem n iscu s to th e
ven tral posterom edial n u cleus of th e th alam us
(VPL, Fig. 4.30).
Th e som atosen sory fibers of th e trigem in al n erve
are a com pon en t of several im portan t reflex arcs.
Corneal reflex. Som atosen sory im pu lses from th e
m ucou s m em bran es of th e eye travel in th e op h -
th alm ic n erve to th e prin cipal sen sory n u cleu s of
th e trigem in al n erve (afferent arm ). After a syn -
apse at t h is site, im pulses travel onw ard to t h e fa-
cial n erve n u clei an d th en th rou gh th e facial n erves
to th e orbicularis oculi m uscles on eith er side
(efferent arm ). In terruption of th is reflex arc in
eith er its afferen t com pon en t (trigem in al n erve) or
its efferen t com p on en t (facial n erve) abolish es th e
corn eal reflex, in w h ich touch in g th e corn ea in -
du ces reflex closu re of both eyes.
Sneeze and suck reflexes. Oth er som atosen sory
fibers travel from th e n asal m ucosa to th e trigem i-
n al n u clear area to form the afferent arm of th e
sn eeze reflex. A n u m ber of differen t n erves m ake
up its efferent arm : cran ial n erves V, VII, IX, an d X,
as w ell as several n erves th at are involved in ex-
piration . Th e su ck reflex of in fan ts, in w h ich touch -
in g of th e lip s in du ces su ckin g, is an oth er reflex
4 106 · 4 Brainstem

Fig. 4.30 a Central con-

Meningeal branch
nections of the various
Nerve to tensor Lesser
t ym pani m . petrosal n. trigeminal fibers and
their corresponding nu-
clei (schem atic drawing).
b Motor root of the
trigem inal nerve.

Auriculotem poral n.
Medial and lateral
pterygoid nn.
Nerve to tensor veli palatini m .

Thalam us
Mese ncephalic
nucleus and tract
of the trigeminal n.
Motor nucleus
of the trigeminal n.

Spinal and
trigem inal
lem niscus
(masseter reflex)
(blink reflex, Principal senso ry
corneal reflex) nucleus of the
trige minal n.

Medial Spinal nucle us of the

lem niscus trige - Motor root of
Spinal tract
minal n. the trigem inal n.:
Nucleus Mandibular n. 1 to m uscles of
cuneatus and mastication
nucleus gracilis Maxillary n. 2 mylohyoid m . and
C1 3 anterior belly of
Ophthalm ic n. the digastric m .

C2 Substantia
gelatinosa
Lateral Somatic afferent proprioception
spinothalam ic Somatic afferent touch
Somatic afferent pain, tem perature
tract (body)
Branchial efferent m otor

w ith a trigem in al afferen t arm an d an efferen t arm
th at involves several differen t n erves.
Pain and temperature fibers of the trigeminal
nerve. Fibers su bservin g pain an d tem perature
sen sation travel cau dally in th e spinal tract of the
trigeminal nerve an d term in ate in t h e spinal nu-
cleus of the trigeminal nerve, w h ose low est p or-
tion exten ds in to th e cervical sp in al cord. Th is n u-
cleu s is th e u pper exten sion of th e Lissau er zon e
an d th e su bstan t ia gelatin osa of th e posterior h orn ,
w h ich receive th e pain an d tem perature fibers of
th e upp er cervical segm en ts.
Th e caudal portion (pars caudalis) of th e spin al
n ucleu s of th e trigem in al n erve con tain s an up side-
dow n som atotopic represen tation of th e face an d
h ead: th e n ociceptive fibers of th e oph th alm ic
n erve term in ate m ost cau dally, follow ed from
cau dal to rostral by th ose of th e m axillary an d m an -
dibu lar n erves Th e spin al tract of th e trigem in al
n erve also con tain s n ociceptive fibers from cran ial
n erves VII (n ervus in term edius), IX, an d X, w h ich

subserve p ain an d tem peratu re sen sation on th e ex-
tern al ear, th e posterior th ird of th e ton gu e, an d th e
laryn x an d ph aryn x (see Figs. 4.48 an d 4.49).
Th e m idportion (pars interpolaris) an d rostral
portion (pars rostralis) of t h e sp in al n ucleu s of th e
trigem in al n erve p robably receive afferen t fibers
subservin g tou ch an d p ressu re sen sation (th e
fu n ction al an atom y in t h is area is in com p letely u n -
derstood at presen t). Th e pars in terpolaris h as also
been reported to receive n ocicept ive fibers from th e
pu lp of th e teeth .
Th e secon d n eu ron s th at em erge from th e spi-
n al n u cleus of th e trigem in al n erve project th eir
axon s across th e m idlin e in a broad, fan like t ract.
Th ese fibers traverse th e pon s an d m idbrain , as-
cen din g in close association w ith th e lateral
spin ot h alam ic t ract tow ard th e th alam u s, w h ere
th ey term in ate in th e ven tral posterom edial n u -
cleus (Fig. 4.30). Th e axon s of th e th alam ic (th ird)
n eu ron s in th e trigem in al path w ay th en ascen d in
th e posterior lim b of th e in tern al capsu le to th e
caudal p ortion of th e postcen tral gyru s (Fig. 2.19,
p. 29).
Motor trigeminal fibers. Th e m otor n u cleu s from
w h ich th e m otor fibers of th e trigem in al n erve
arise is located in th e lateral portion of th e pon t in e
tegm en tu m , ju st m edial to th e prin cipal sen sory
n u cleu s of th e trigem in al n erve. Th e portio m in or
exits t h e sku ll t h rou gh th e foram en ovale toget h er
w ith th e m an dibu lar n erve an d in n ervates th e
m asseter, tem p oralis, an d m edial an d lateral ptery-
goid m u scles, as w ell as th e ten sor veli palatin i, th e
ten sor tym pan i, th e m ylohyoid m uscle, an d th e
an terior belly of t h e digastric m uscle (Figs. 4.29
an d 4.30).
Th e m otor n uclei (an d, th rough th em , th e
m uscles of m astication ) are u n der t h e in fluen ce of
cortical cen ters th at project to th em by w ay of th e
corticon u clear tract. Th is su pran uclear path w ay is
m ostly crossed, bu t th ere is also a subst an tial ipsi-
lateral projection . Th is accou n ts for th e fact th at a
un ilateral in terru ption of th e su pran u clear
trigem in al pat h w ay does n ot produce any n ot ice-
able w eakn ess of th e m u scles of m ast ication .
Th e su pran u clear path w ay origin ates in n eu ron s
of t h e cau dal portion of th e precen tral gyrus
(Fig. 3.2, p. 37; Fig. 4.30).
Lesions of the m otor trigem inal fibers. A n u clear or
periph eral lesion of th e m otor trigem in al path w ay
Cranial Nerves · 107
4
produces flaccid w eakness of the muscles of mas-
tication. Th is type of w eakn ess, if un ilateral, can be
detected by palp ation of th e m asseter an d tem -
poralis m u scles w h ile th e p atien t clam p s h is or h er
jaw : th e n orm ally palpable m u scle con traction is
absen t on th e side of t h e lesion . Wh en th e pat ien t
th en open s h is or h er m ou th an d protru des th e
low er jaw, th e jaw deviates to th e side of th e lesion ,
becau se th e force of th e con t ralateral pterygoid
m uscle predom in ates. In such cases, th e m asse-
teric or jaw -jerk reflex is absen t (it is n orm ally eli-
citable by tap pin g th e ch in w ith a reflex h am m er to
stretch th e fibers of th e m asseter m u scle).
Disorders Affecting the Trigem inal Nerve
Trigeminal neuralgia. Th e classic variety of
trigem in al n eu ralgia is ch aracterized by p aroxysm s
of in ten se, ligh tn in glike (sh ootin g or “lan cin atin g”)
pain in t h e dist ribu tion of on e or m ore bran ch es of
th e trigem in al n erve. Th e pain can be evoked by
touch in g th e face in on e or m ore particularly sen si-
tive areas (“trigger zon es”). Typical types of stim uli
th at trigger pain in clu de w ash in g, sh avin g, an d
tooth -bru sh in g. Th is con dition is also kn ow n by
th e tradition al Fren ch design ation , tic douloureux
(w h ich is som ew h at m isleadin g, because any
tw itch in g m ovem en ts of th e face th at m ay be pre-
sen t are a reflex respon se to th e pain , rat h er th an a
tru e tic). Th e n eurological exam in ation is u n re-
m arkable; in particu lar, th ere is n o sen sory deficit
on th e face.
Th e path ophysiology of th is con dition rem ain s
im perfectly u n derstood; both cen tral an d p erip h -
eral m ech an ism s h ave been prop osed. (Th e older
term “idiopathic trigem in al n euralgia” for th e clas-
sic con dition is n o lon ger w idely u sed, because th is
issu e is still u n settled.) Gardn er (1959) an d, later,
Jan n etta (1982) attribu ted trigem in al n eu ralgia to
com p ression of th e trigem in al root by a blood ves-
sel, u su ally th e su perior cerebellar artery, loop in g
arou n d t h e proxim al, un m yelin ated portion of th e
root im m ediately after it s exit from th e pon s
(Fig. 4.31). Th is hypoth esis is sup ported by th e ob-
servation th at a pain -free state can be ach ieved in
up to 80 % of p atien ts w ith a n eurosurgical pro-
cedu re kn ow n as m icrovascu lar decom p ression , in
w h ich th e vascular loop is exposed an d dissected
free of th e n erve, an d a sm all spon ge m ade of syn -
th etic m aterial is in serted betw een th ese tw o
stru ctures to keep th em apart.
4 108 · 4 Brainstem
III
IV
VI
V sensory
(2.0–6.0 m m )
VII
(0.5–4.0 m m )
VIII
IX
(0.1–1.1 m m )
X cerebellar a.
XI
XII
Th e pain can be sign ifican tly dim in ish ed, or
even elim in ated, in 80–90 % of cases by m edical
treatm en t alon e, eith er w ith carbam azep in e,
gabapen tin , or pregabalin , w h ich h as recen tly
com e in to use for th is p urp ose. Neu rosu rgical in -
terven tion is in dicated on ly if th e p ain becom es re-
fractory to m edication . Th e option s for n eu rosu rgi-
cal treatm en t in clu de m icrovascu lar decom pres-
sion (m en tion ed p. 107) an d selective percu-
tan eou s th erm ocoagu lation of th e n ociceptive
fibers of th e trigem in al n erve.
Th e m ost com m on cause of sym ptom atic trigem inal
neuralgia is m ult iple sclerosis: 2.4 % of all MS
patien ts develop trigem in al n eu ralgia; am on g
th ese p atien ts, 14 % h ave it bilaterally.
Ot h er, rarer causes of sym ptom atic pain in th e
distribu tion of th e trigem in al n erve in clude den tal
lesion s, sin u sit is, bony fract ures, an d tu m ors of th e
cerebellopon tin e an gle, th e n ose, or th e m outh .
Pain in th e eye or foreh ead sh ould also arou se su s-
picion of glau com a or iritis. Th e pain of acu te glau -
com a can m im ic th at of classic trigem in al n eu ral-
gia.
Gradenigo syndrome con sist s of pain in th e dis-
tribut ion of th e oph th alm ic n erve accom pan ied by
ipsilateral abducen s palsy. It is cau sed by in fection
in th e air cells of th e petrou s apex.
Fig. 4.31 Unmyelinated
portions of the cranial
Posterior cerebral a.
nerve roots (orange, left)
and nearby vascular loops
(dark red, right) that m ay
Superior cerebellar a.
irritate the nerve roots at
Trigem inal n. these sites. In particular,
the diagram shows a loop
Site of origin of of the superior cerebellar
trigem inal neuralgia artery that may cause
trigeminal neuralgia.
Anterior inferior
cerebellar a.
Posterior inferior
Vertebral a.
Differential Diagnosis: Disorders with Facial
Pain in the Absence of a Trigem inal Lesion
Charlin neuralgia con sists of pain at th e in n er can -
th u s of th e eye an d root of th e n ose accom pan ied
by in creased lacrim ation . It is th ou gh t to be du e to
irritation of th e ciliary gan glion .
Cluster headache is also kn ow n as Bin g–Horton
syn drom e, eryth roprosop algia, an d h istam in e
h eadach e. It is ch aracterized by brief attacks of
pain occurrin g m ain ly at n igh t, in cludin g du rin g
sleep (in distin ction to trigem in al n eu ralgia). Th ese
attacks are accom pan ied by facial eryth em a, lacri-
m ation , w atery n asal secretion , an d often Horn er
syn drom e as w ell. Typical provocative factors in -
clu de h igh altitu de, alcoh ol con su m ption , an d th e
takin g of n itroglycerin (glyceryl trin itrate). Th e at-
tacks occu r repeatedly in periods (clu sters) ch arac-
teristically lastin g a w eek or m ore, separated by
h eadach e-free in tervals of at least tw o w eeks’ du -
ration . Th ere is as yet n o con sen sus on th e
path op hysiology of th is disorder. Its treatm en t is
em pirical, w ith oxygen , triptan es, or ot h er m edica-
tion s.

Facial Nerve (CN VII) and Nervus
Intermedius
Th e facial n erve h as tw o com pon en ts. Th e larger
com p on en t is pu rely m otor an d in n ervates th e
m uscles of facial expression (Fig. 4.32). Th is com -
pon en t is th e facial n erve p roper. It is accom pan ied
by a th in n er n erve, th e n ervu s in term ediu s, w h ich
con tain s visceral an d som atic afferen t fibers, as
w ell as visceral efferen t fibers (Table 4.1, p . 79).
Motor Component of Facial Nerve
Th e nucleus of th e m otor com pon en t of th e facial
nerve is located in th e ven trolateral p ortion of th e
pon tin e tegm en tu m (Figs. 4.2 an d 4.3, an d Fig. 4.33).
Th e n eu ron s of th is m otor n u cleu s are an alogous to
th e an terior h orn cells of th e spin al cord, but are
em bryologically derived from th e secon d bran ch ial
arch . Th e root fibers of th is n ucleu s take a com pli-
cated cou rse. Wit h in t h e brain stem , th ey w in d
Cranial Nerves · 109
4
arou n d th e abdu cen s n ucleu s (form in g th e so-
called internal genu of the facial nerve, Fig. 4.2),
th ereby creatin g a sm all bu m p on th e floor of th e
fou rth ven tricle (facial colliculus) (Fig. 4.1). Th ey
th en form a com p act bu n dle, w h ich travels ven -
trolaterally to th e cau dal en d of th e p on s an d th en
exits th e brain stem , crosses th e subarach n oid space
in th e cerebellopon tin e an gle, an d en ters th e in ter-
n al acoustic m eatus togeth er w ith th e n ervu s in ter-
m edius an d th e eigh th cran ial n erve (th e vestibu lo-
coch lear n erve). With in th e m eatus, th e facial nerve
an d nervus intermedius separate from th e eigh th
n erve an d travel laterally in th e facial can al tow ard
th e gen icu late gan glion . At th e level of th e gan glion ,
th e facial can al takes a sh arp dow nw ard turn (exter-
nal genu of the facial nerve). At th e low er en d of th e
can al, th e facial n erve exits th e sku ll th rou gh th e
stylom astoid foram en . Its in dividu al m otor fibers
are th en distribu ted to all region s of t h e face (som e
of th em first travelin g th rough t h e parotid glan d).
Th ey in n ervate all of th e m u scles of facial expression

Fig. 4.32 Peripheral

Tem poral branches
course of the facial nerve

(VII)
n iu s m.
r a
Ep ic

Occipital
branch
Posterior auricular n.
Geniculate ganglion
Chorda t ym pani
Pterygopalatine ganglion
Zygomatic branches
Buccal branches
Parotid plexus
Mandibular branches
Cervical branches
Branches to the st ylohyoid m .
and the posterior belly
of the digastric m .
4 110 · 4 Brainstem
Precentral gyrus
Cort ical area for
facial expression
Cort iconuclear tract
Nucleus of the
facial n. (VII)
Geniculate
ganglion
Fig. 4.33 Central innervation of the facial nuclear area
in the brainstem. The portion of the nuclear area control-
ling the m uscles of the forehead is innervated by both cere-
bral hem ispheres. Thus, a lesion affecting the corticonu-
clear pathway on one side does not cause weakness of the
forehead m uscles. The rem ainder of the nuclear area,
however, is innervated only by the contralateral hem i-
sphere. A unilateral lesion along the corticonuclear path-
way therefore causes contralateral facial weakness with
sparing of the forehead m uscles.
Fig. 4.34 Facial palsy
a Central facial palsy: the forehead m uscles are not af-
fected.
b Peripheral facial palsy: the forehead m uscles are involved
along with the rest of the face on the affected side.
th at are derived from th e secon d bran ch ial arch , i.e.,
th e orbicu laris oris an d oculi, bu ccin ator, occipitalis,
an d fron t alis m uscles an d th e sm aller m uscles in
th ese areas, as w ell as th e stapediu s, platysm a, sty-
lohyoid m u scle, an d posterior belly of th e digastric
m u scle (Fig. 4.32).
Reflexes involving the facial nerve. Th e m otor n u -
cleu s of th e facial n erve participates in a n um ber of
reflex arcs. Th e corneal reflex is discu ssed above
(p. 105). In th e blink reflex, a stron g visual stim u lu s
in duces th e su perior collicu li to sen d visu al im -
pulses to th e facial n ucleu s in th e pon s by w ay of th e
tectobu lbar tract, w ith th e result th at th e eyes are
im m ediately closed. Sim ilarly, in th e stapedius re-
flex, au ditory im p ulses are t ran sm itted from t h e
dorsal n u cleu s of th e trapezoid body to th e facial
nu cleu s an d cau se eith er con traction or relaxation
of th e stapedius m u scle, depen din g on th e stren gth
of th e au ditory stim u lus.
Motor lesions involving the distribution of the fa-
cial nerve. Th e m uscles of th e foreh ead derive th eir
su pran u clear in n ervation from both cerebral h em i-
sph eres, bu t th e rem ain in g m uscles of facial ex-
pression are in n ervated on ly u n ilaterally, i.e., by
th e con tralateral precen tral cortex (Fig. 4.33). If th e
descen din g supran u clear path w ays are in ter-
ru pted on on e side on ly, e.g., by a cerebral in farct,
th e resu ltin g facial palsy spares th e foreh ead
m u scles (Fig. 4.34a): th e patien t can still raise h is
or h er eyebrow s an d close th e eyes forcefully. Th is
type of facial palsy is called central facial palsy. In a
nuclear or peripheral lesion (see below ), h ow ever,
all of t h e m uscles of facial expression on th e side of
th e lesion are w eak (Fig 4.34b). On e can th u s dis-
tin guish cen tral from n u clear or periph eral facial
palsy by th eir differen t clin ical appearan ces.
Th e m otor n uclei of th e facial n erve are in n er-
vated n ot on ly by t h e facial cortex but also by th e
dien ceph alon , w h ich plays a m ajor role in em o-
tion -related facial exp ression s. Fu rth er inpu t is
derived from th e basal gan glia; in basal gan glia dis-
orders (e.g., Parkin son disease), hyp om im ia or
am im ia can be seen . Th ere are also various dys-
kin etic syn drom es affectin g th e m uscles of facial
expression w ith differen t types of abn orm al m ove-
m en t: h em ifacial spasm , facial dyskin esias, an d
bleph arospasm , am on g oth ers. Th e site of th e
cau sative lesion in th ese syn drom es rem ain s u n -
kn ow n .
 Cranial Nerves · 111
4
Idiopathic facial nerve palsy (Bell palsy). Th is m ost
Internal
com m on disorder affectin g th e facial n erve arises
acoustic m eatus
in abou t 25 per 10 0 0 0 0 in dividu als per year. Its Cochlear n.
cause is still un kn ow n . It is ch aracterized by flaccid Vestibular n.
1
paresis of all m uscles of facial expression (in clu din g Nervus interm edius
th e foreh ead m u scles), as w ell as oth er m an ifesta- Facial n.
tion s depen din g on th e site of th e lesion . Th e Lacrimation and secretion
variou s syn drom es resu ltin g from n erve dam age of intranasal glands
w ith in th e facial can al are depicted in Figu re 4.35, Salivation
an d a t ypical MRI correlate of idiopath ic facial
Geniculate 2
n erve palsy is sh ow n in Figu re 4.36. Differen tial di- ganglion
agn osis is im portan t in cases of acu te facial palsy,
as n ot all cases are idiopat h ic: 10 % are du e to
h erpes zoster oticus, 4 % to otitis m edia, an d 2 % to
tu m ors of variou s types (parotid tu m ors, n euri- Greater
petrosal n.
n om a, an d oth ers). 3
A com plete recovery occu rs w ith out t reatm en t Nerve to the
stapedius m .
in 60–80 % of all p atien ts. Th e adm in istration of
steroids (predn isolon e, 1 m g/kg body w eigh t daily
for 5 days), if it is begu n w ith in 10 days of th e on set
of facial palsy, speeds recovery an d leads to Chorda t ympani
4
com p lete recovery in over 90 % of cases, accordin g
to a n u m ber of pu blish ed stu dies.
Partial or m isdirected rein n ervation of th e af-
fected m uscu latu re after an ep isode of idiopat h ic St ylomastoid
facial n erve palsy som etim es cau ses a facial con - foram en
tractu re or abn orm al accessory m ovem en ts (syn-
Posterior 5
kinesias) of th e m uscles of facial expression . Mis- auricular n.
directed rein n ervation also explain s th e ph en om e-
n on of “crocodile tears,” in w h ich involu n tary lacri-
m ation occurs w h en th e patien t eats. Th e reason is
presum ably th at regen eratin g secretory fibers
destin ed for th e salivary glan ds h ave taken an in - Motor fibers
correct path alon g th e Sch w an n cell sh eath s of Secretory fibers
degen erated fibers in n ervatin g th e lacrim al glan d, Gustatory fibers
so th at som e of th e im pulses for salivation in du ce Somatosensory fibers
lacrim ation in stead.
Fig. 4.35 The components of the facial nerve and typi-
cal deficits caused by lesions at various sites along its
Nervus Intermedius course
1 Peripheral weakness of the m uscles innervated by the
Th e n ervus in term edius con tain s a n u m ber of af- facial nerve (m uscles of facial expression), hearing loss
feren t an d efferen t com pon en t s (Table 4.1, p. 79). or deafness, and dim inished vestibular excitability.
2 Peripheral weakness and im pairm ent of taste, lacrim a-
Gustatory afferent fibers. Th e cell bodies of th e af- tion, and salivation.
3 Peripheral weakness of the m uscles of facial expression,
feren t fibers for taste are located in th e gen icu late
im pairm ent of taste and salivation, and hearing loss.
gan glion , w h ich con tain s p seu dou n ipolar cells re- 4 Peripheral weakness of the m uscles of facial expression
sem blin g th ose of th e spin al gan glia. Som e of th ese and im pairm ent of taste and salivation.
afferen t fibers arise in th e taste buds of th e an terior 5 Peripheral weakness of the m uscles of facial expression.
tw o-th irds of th e ton gu e (Fig. 4.37). Th ese fibers
first accom pany t h e lingual nerve (a bran ch of th e
m an dibu lar n erve, th e low est division of th e
4 112 · 4 Brainstem
a b
Fig. 4.36 MRI in a 73-year-old w oman w ith the acute
onset of painless, total left facial nerve palsy (idiopathic
facial nerve palsy, Bell palsy). a The contrast-enhanced axial
T1-weighted im age shows m arked contrast uptake along
the course of the left facial nerve, as com pared to the nor-
trigem in al n erve), an d travel by w ay of th e chorda
tym pani to th e geniculate ganglion, an d th en in th e
nervus interm edius to th e nucleus of the tractus soli-
tarius. Th is n u cleus also receives gustatory fibers
from th e glossop h aryn geal n erve, rep resen tin g
taste on th e posterior th ird of th e ton gu e an d th e
vallate pap illae, an d from th e vagu s n erve, repre-
sen t in g taste on th e ep iglot tis. Th u s, taste is su p-
plied by th ree differen t n erves (CN VII, IX, an d X)
on both sides. It follow s th at com plete ageusia on
th e basis of a n erve lesion is extrem ely u n likely.
Central propagation of gustatory im pulses. Th e nu-
cleus of the tractus solitarius is th e com m on relay
n ucleu s of all gustatory fibers. It sen ds gustatory
im pu lses to th e con t ralateral thalam us (th eir exact
cou rse is u n kn ow n ) an d onw ard to th e m ost m edial
com pon en t of th e ventral posterom edial nucleus of
th e th alam u s (VPM, p. 173). From th e th alam u s, th e
gu statory path w ay con tin ues to th e caudal precen-
tral region overlyin g t h e in su la (Fig. 4.37).
Afferent somatic fibers. A few som atic afferen t
fibers represen tin g a sm all area of t h e extern al ear
(pin n a), th e extern al au ditory can al, an d th e exter-
n al su rface of th e tym p an u m (eardru m ) travel in th e
facial nerve to th e geniculate ganglion an d th en ce to
th e sensory nuclei of the trigem inal nerve. Th e cu -
m al right side. b Pathological contrast enhancem ent is also
seen along the further course of the nerve in the petrous
bone. Prednisolone was given acutely, and the weakness re-
solved com pletely within three weeks.
tan eous lesion in h erpes zoster oticu s is du e to in -
volvem en t of th ese som atic afferen t fibers.
Efferent secretory fibers (Fig. 4.38). Th e n ervu s in -
term ediu s also con tain s efferen t p arasym path etic
fibers origin atin g from th e superior salivatory nu-
cleus (Fig. 4.38), w h ich lies m edial an d caudal to
t h e m otor n u cleus of th e facial n erve. Som e of th e
root fibers of th is n u cleus leave th e m ain trun k of
t h e facial n erve at th e level of th e gen icu late gan -
glion an d p roceed to th e pterygopalatine ganglion
an d onw ard to th e lacrim al gland an d to th e glands
of the nasal m ucosa. Oth er root fibers take a m ore
cau dal rou te, by w ay of th e ch orda tym pan i an d th e
lin gual n erve, to th e subm andibular ganglion, in
w h ich a syn aptic relay is foun d. Th e postgan glion ic
fibers in n ervate th e sublingual and subm andibular
glands (Fig. 4.38), in ducin g salivation . As m en -
t ion ed above, th e su perior salivatory n u cleu s re-
ceives inp ut from th e olfactory system th rou gh th e
dorsal lon gitu din al fascicu lus. Th is con n ection p ro-
vides th e an atom ical basis for reflex salivation in
resp on se to an ap petizin g sm ell. Th e lacrim al
glan ds receive th eir cen tral inpu t from th e hy-
poth alam u s (em otion ) by w ay of th e brain stem re-
t icu lar form ation , as w ell as from th e spin al n u -
cleu s of th e trigem in al n erve (irritation of th e con -
jun ctiva).
 Cranial Nerves · 113
4
Fig. 4.37 Afferent gus-
To the inferior portion of the tatory fibe rs and the
postcentral gyrus and to the insula
gustatory pathw ay. The
drawing shows the periph-
eral receptors (taste buds),
Taste bud the peripheral course of
the gustatory fibers (along
the nervus interm edius and
the glossopharyngeal and
vagus nerves), and their
central connections with
the corresponding brain-
stem nuclei.

Central
gustatory
pathway (with
m edial lemniscus) Superior
and inferior
salivatory
nuclei

Pterygopalatine
ganglion ?
VII
Greater petrosal n.
Lingual n.
IX
Otic Geniculate
ganglion ganglion

p ani
t ym
o rd a
Ch X
Nucleus of the
tractus solitarius
Pathway to the m uscles
of facial expression,
swallowing, and mastication

VII

Vestibulocochlear Nerve (CN VIII)—
Cochlear Component and the Organ
of Hearing
Th e organ s of balan ce an d h earin g are derived from
a sin gle em bryological precu rsor in t h e petrous
port ion of th e tem poral bon e: t h e u tricle gives rise
to th e vestibular system w ith its th ree sem icircu lar
can als, w h ile th e saccu le gives rise to th e in n er ear
w ith its sn aillike coch lea (Fig. 4.39).
Auditory perception. Sou n d w aves are vibration s
in th e air produ ced by a w ide variety of m ech a-
n ism s (ton es, speech , son g, in stru m en tal m usic,
n atu ral sou n ds, environ m en tal n oise, etc.). Th ese
vibration s are tran sm itted alon g th e extern al audi-
tory can al to th e eardrum (tym pan u m or tym pan ic
m em bran e), w h ich separates th e extern al from
m iddle ear (Fig. 4.39).
4 114 · 4 Brainstem

Fig. 4.38 Parasympa-

Superior and inferior thetic innervation of the
salivatory nuclei
glands of the head
Lacrimal VI
gland
Zygomatic n.

Maxillary n.
VII

Greater petrosal n.

VII
Geniculate
Pterygo- ganglion
Nucleus of
palatine the tractus
ganglion Otic solitarius
Nasal ganglion
glands IX
Chorda Lesser
t ym pani petrosal n.
Lingual n.
Submandibular
ganglion

VII
Parotid gland
Sublingual
gland Submandibular
gland

Th e m iddle ear (Fig. 4.39) con tain s air an d is con -
n ected to th e nasoph aryn geal sp ace (an d th u s to
th e outside w orld) th rough th e au ditory t ube, also
called th e eu stach ian tu be. Th e m iddle ear con sists
of a bony cavity (th e vestibulum ) w h ose w alls are
covered w it h a m u cou s m em bran e. It s m edial w all
con tain s tw o orifices closed up w ith collagen ou s
tissue, w h ich are called th e oval w in dow or fora-
m en ovale (altern at ively, fenestra vestibuli) an d t h e
rou n d w in dow or foram en rotu n du m (fenestra
cochleae). Th ese tw o w in dow s separate th e tym -
pan ic cavity from th e in n er ear, w h ich is filled w ith
perilym ph . In com in g sou n d w aves set th e tym -
pan ic m em bran e in vibration . Th e th ree ossicles
(m alleu s, in cus, an d stap es) th en tran sm it th e
oscillation s of th e tym pan ic m em bran e to th e oval
w in dow, settin g it in vibrat ion as w ell an d produc-
in g oscillation of th e perilym p h . Th e tym p an ic cav-
ity also con tain s tw o sm all m u scles, th e tensor
tym pani m uscle (CN V) an d th e stapedius m uscle
(CN VII). By con tractin g an d relaxin g, th ese
m u scles alter th e m otility of th e au ditory ossicles
in respon se to th e in ten sity of in com in g sou n d, so
th at th e organ of Corti is protected again st dam age
from very lou d stim u li.
Inner ear. Th e au ditory port ion of th e in n er ear h as
a bony com pon en t an d a m em bran ou s com p on en t
(Figs. 4.39, 4.40). Th e bony coch lea form s a spiral
w ith tw o-an d-a-h alf revolu tion s, resem blin g a
com m on garden sn ail. (Fig. 4.39 sh ow s a tru n cated
coch lea for didactic p urposes on ly.) Th e coch lea
con tain s an an tech am ber (vestibule) an d a bony
tube, lin ed w ith epith elium th at w in ds aroun d th e
m odiolu s, a taperin g bony stru cture con tain in g th e
sp iral ganglion . A cross section of th e coch lear du ct
 Cranial Nerves · 115
4
Fig. 4.39 The organ of
anterior hearing and equilibrium:
Sem icircular lateral overview
ducts
posterior

Endo-
Stapes lym phatic
duct
Incus
Malleus Ampullae
with cristae

Utricle
with macula
r
a
Saccule
e
e
with macula
l
d
d
i
M
Cochle a
Tym panic
Helicotrema
m em brane
Vestibular
window
Cochlear
window
Auditory Perilym phatic Scala Scala Cochlear
tube duct t ym pani vestibuli duct

reveals three membranous compartments: th e w h ere a th in m em bran e seals off th e in n er ear

scala vestibuli, th e scala tympani, an d th e scala
media (or coch lear du ct), w h ich con tain s th e organ
of Corti (Fig. 4.40). Th e scala vestibuli an d scala
tympani are filled w ith perilym ph , w h ile th e
cochlear duct is filled w it h endolym ph, a flu id pro-
duced by th e stria vascularis. Th e coch lear du ct ter-
m in ates blin dly at each en d (in th e cecum vestibu -
lare at its base an d in th e cecum cu pulare at its
apex). Th e u pper w all of t h e coch lear du ct is
form ed by th e very th in Reissner’s m em brane,
w h ich divides th e en dolym ph from th e p erilym ph
of th e scala vestibu li, freely tran sm itt in g t h e pres-
su re w aves of th e scala vestibuli to th e coch lear
duct so th at th e basilar m em brane is set in vibra-
tion . Th e pressure w aves of th e perilym ph begin at
th e oval w in dow an d travel th rou gh th e scala vesti-
buli alon g t h e en t ire len gth of t h e coch lea u p to its
apex, w h ere th ey en ter th e scala t ym pan i th rough
a sm all open in g called th e h elicotrem a; th e w aves
th en travel th e len gth of th e coch lea in th e scala
tym pan i, fin ally arrivin g at th e roun d w in dow,
from t h e m iddle ear.
Th e organ of Corti (spiral organ ) rests on th e
basilar m em bran e alon g its en tire len gth , from th e
vestibulu m to th e apex (Fig. 4.41). It is com p osed of
h air cells an d su pportin g cells (Fig. 4.40c an d d).
Th e hair cells are th e receptors of the organ of hear-
ing, in w h ich th e m ech an ical en ergy of sou n d
w aves is tran sdu ced in to electroch em ical poten -
tials. Th ere are abou t 350 0 inner hair cells, ar-
ran ged in a sin gle row, an d 12 0 0 0–19 0 0 0 outer
hair cells, arran ged in t h ree or m ore row s. Each h air
cell h as abou t 10 0 stereocilia, som e of w h ich ex-
ten d in to th e tectorial m em bran e. Wh en th e
basilar m em bran e oscillates, th e stereocilia are
ben t w h ere th ey com e in to con t act w it h th e n on -
oscillatin g tectorial m em bran e; t h is is presu m ed to
be th e m ech an ical stim u lu s th at excites th e au di-
tory receptor cells. In addition to th e sen sory cells
(h air cells), th e organ of Corti also con tain s several
kin ds of supporting cells, su ch as th e Deiters cells,
as w ell as em pty spaces (tu n n els), w h ose fu n ction
4 116 · 4 Brainstem

Fig. 4.40 The micro-

Ham ulus of the spiral lamina scopic architecture of the
organ of hearing.
Helicotrema
a Labyrinth. b Cochlea.
Spiral canal of the m odiolus c and d Organ of Corti.
e Basilar m em brane
Modiolus
(lam ina).
Longitudinal canal of the m odiolus

a Labyrinth Scala vestibuli

Reissner’s m embrane
Cochlear duct
Spiral ligam ent

Scala t ympani

b Cochlea 33 m m

Base 100 µm Apex 500 µm

Spiral limbus
Tectorial
m embrane
Outer e Basilar lamina
tunnel

Stereocilia

Inner Space Basilar

Bony tunnel of Nuel m em brane
spiral lam ina Outer
c Organ of Corti hair
Inner cells
hair
cells

Efferent Basilar outer inner Supporting cells

fibers lam ina Pillar cells of Deiters
d Organ of Corti w ith hair cells

w ill n ot be fu rth er discu ssed h ere (bu t see
Fig. 4.40d). Movem en t of th e footplate of th e
stapes in to th e foram en ovale creates a travelin g
w ave alon g th e stran ds of t h e basilar m em bran e,
w h ich are orien ted tran sversely to th e direction of
m ovem en t of th e w ave. An applied pu re ton e of a
given frequ en cy is associated w ith a particular site
on th e basilar m em bran e at w h ich it produces th e
m axim al m em bran e deviation (i.e., an am p litu de
m axim u m ). Th e basilar m em bran e th u s possesses
a tonotopic organ ization , in w h ich h igh er frequ en -
cies are registered in th e m ore basal portion s of
th e m em bran e, an d low er frequ en cies in m ore
apical portion s. Th is m ay be com pared to a pian o
keyboard, on w h ich th e frequ en cy becom es h igh er
from left to righ t. Th e basilar m em bran e is w ider
at t h e basilar en d th an at th e apical en d
(Fig. 4.40e).
 Cranial Nerves · 117
4
Th e spiral ganglion (Fig. 4.42) con tain s about
25 0 0 0 bip olar an d 5 0 0 0 u n ipolar n eu ron s, w h ich
h ave cen tral an d periph eral p rocesses. Th e periph -
eral processes receive inpu t from t h e in n er h air
cells, an d th e cen tral processes com e togeth er to
form th e coch lear n erve.

Cochlear nerve and auditory pathw ay. Th e

cochlear nerve, form ed by th e cen tral p rocesses of
th e sp iral gan glion cells, passes alon g th e in tern al
auditory can al toget h er w ith th e vest ibu lar n erve,
traverses th e su barach n oid sp ace in th e cerebel-
lopon tin e an gle, an d th en en ters th e brain stem just
beh in d th e in ferior cerebellar pedu n cle. In t h e ven -
tral coch lear n u cleu s, t h e fibers of th e coch lear
n erve split in to tw o bran ch es (like a “T”); each
bran ch t h en proceeds to th e site of t h e n ext relay Fig. 4.41 The course of the basilar lamina
(secon d n euron of th e au ditory path w ay) in th e
ventral or dorsal coch lear n u cleu s. Th e secon d
n euron projects im pu lses cen trally alon g a n um ber
of differen t path w ays, som e of w h ich con tain Vestibulocochlear n.
fu rt h er syn aptic relays (Fig. 4.43). Vestibular Cochlear
root root
Neurites (axon s) derived from th e ventral
Vestibular
cochlear nucleus cross th e m idlin e w ith in th e ganglion
trapezoid body. Som e of th ese n eurites form a syn -
Spiral
ap se w ith a furth er n euron in th e trapezoid body ganglion
itself, w h ile th e rest proceed to oth er relay sta-
tion s—th e su perior olivary n u cleus, th e n ucleu s of
th e lateral lem n iscu s, or th e reticu lar form ation .
Ascen din g auditory im pu lses th en travel by w ay of
th e lateral lem n iscu s to th e in ferior collicu li
(thou gh som e fibers p robably bypass t h e collicu li
an d go directly to t h e m edial gen iculate bodies). Fig. 4.42 The spiral ganglion and the vestibular gan-
glion
Neurites arisin g in th e dorsal cochlear nucleus
cross th e m idlin e beh in d th e in ferior cerebellar
pedu n cle, som e of th em in th e striae m edu llares auditory path w ay from th e organ of Corti all th e
an d oth ers th rou gh th e ret icular form at ion , an d w ay to th e au ditory cortex (Fig. 4.43a an d c), in an
th en ascen d in th e lateral lem n iscu s to th e in ferior an alogous fash ion to th e som atotopic (retin otopic)
colliculi, togeth er w ith th e n eu rites from th e ven - organ ization of th e visu al path w ay.
tral coch lear n ucleu s.
Th e inferior colliculi con tain a fu rt h er syn apt ic Bilateral projection of auditory im pulses. Not all
relay on to t h e n ext n eu ron s in th e pat h w ay, w h ich , au ditory fibers cross th e m idlin e w ith in t he brain -
in turn , project to th e medial geniculate bodies of stem : part of th e path w ay rem ain s ipsilateral, w ith
th e th alam us. From h ere, au ditory im p ulses t ravel th e resu lt th at in jury to a sin gle lateral lem n iscus
in th e auditory radiation, w h ich is located in th e does n ot cause total u n ilateral deafn ess, but rath er
posterior lim b of th e in tern al cap su le (Fig. 3.2, on ly part ial deafn ess on th e opposite side, as w ell
p. 37), to th e prim ary au ditory cortex in th e tran s- as an im paired perception of th e direct ion of
verse tem poral gyri (area 41 of Brodm an n ), w h ich soun d.
are also called t h e tran sverse gyri of Hesch l
(Fig. 9.10, p. 231). A ton otopic represen t ation of Auditory association areas. Adjacen t to th e p ri-
auditory frequen cies is preserved th rou gh ou t th e m ary au ditory areas of th e cerebral cortex, th ere
4 118 · 4 Brainstem

Fig. 4.43 The auditory

pathw ay. Central connec-
tions of the cochlear nerve.
Transverse temporal
gyri (of Heschl)
20 000 Hz

Auditory radiation 200 Hz

(via posterior lim b
of internal capsule)

Lateral
geniculate body

Me dial
geniculate body
Inferior colliculus 200 Hz

Com m issure of the

inferior colliculi

Lateral lemniscus and

lateral lem niscal nuclei 20 000 Hz

Striae m edullares e
an
br
Medial longitu- em
m Tectorial
dinal fasciculus e r’s
Inferior cere- is sn m em brane
Re
bellar peduncle Hair cells
Dorsal coch-
lear nucleus
Ventral coch-
lear nucleus
Dorsal nucleus of the
trapezoid body and
superior olivary nucleus Cochlear n. Basilar lam ina
Nucleus of the
trapezoid body Olivary nucleus Spiral ganglion
Medial lemniscus Corticospinal tract Organ of Corti

are secon dary au ditory areas on t h e extern al su r-
face of t h e tem poral lobe (areas 42 an d 22; Fig.
9.26, p. 247), in w h ich th e auditory stim u li are an a-
lyzed, iden tified, an d com pared w ith au ditory
m em ories laid dow n earlier, an d also classified as
to w h eth er th ey represen t n oise, ton es, m elodies,
or w ords an d sen ten ces, i.e., speech . If th ese corti-
cal areas are dam aged, th e p atien t m ay lose th e
ability to iden tify soun ds or to un derstan d speech
(sensory aphasia, p. 248).
Integration of auditory processing in various reflex
arcs. Th e path w ay from t h e organ of Corti to th e
prim ary au ditory cortex is 4–6 n eu ron s lon g; at
each of th e relay stat ion s in th is path w ay (superior
olivary n u cleu s, reticular form ation , n u cleu s of th e
lateral lem n iscu s, an d in ferior collicu li), collateral
fibers arise th at part icipate in a n u m ber of reflex
arcs.
¼ Som e im p ulses travel to th e cerebellum , w h ile
oth ers p ass in th e m edial lon gitudin al
fasciculu s to t h e nuclei innervating the extraocu-
lar m uscles an d brin g about con ju gate eye
m ovem en ts in th e direction of a sou n d.
¼ Som e im p ulses pass th rou gh th e in ferior an d
superior collicu li to th e pretectal area an d th en ,

by w ay of th e tectobu lbar tract, to variou s brain -
stem n u clei, in clu din g th e nucleus of the facial
nerve (stapedius m u scle), or by w ay of th e tec-
tospin al tract to m otor anterior horn cells in the
cervical spinal cord. Th e im pu lses th at descen d
to th e cervical spin al cord brin g about a reposi-
tion in g of th e h ead tow ard or aw ay from th e
origin of a sou n d.
¼ Oth er im p ulses travel in th e ascen din g reticular
activat in g system to t h e reticular form ation
(arousal reaction , p. 176).
¼ Yet oth ers descen d in th e lateral lem n iscu s an d,
via in tern eu ron s, exert a regu latin g in flu en ce on
th e tension of the basilar lam ina. Som e of t h ese
descen din g im pulses are th ou gh t to h ave an in -
h ibitory effect; th eir fun ction is presu m ably to
im prove th e perception of certain frequ en cies
by su ppressin g oth er, n eigh borin g frequ en cies.
Hea ring Disorders
Conductive and Sensorineural Hearing Loss
Tw o typ es of h earin g loss can be clin ically distin -
guish ed: m iddle ear (con ductive) h earin g loss an d
in n er ear (sen sorin eural) h earin g loss.
Conductive hearing loss is caused by processes af-
fecting the external auditory canal or, m ore com -
m on ly, th e m iddle ear. Vibration s in th e air (sou n d
w aves) are poorly tran sm it ted to th e in n er ear, or
n ot at all. Vibration s in bon e can still be con du cted
to th e organ of Corti an d be h eard (see Rin n e test,
below ).
Th e causes of con du ctive h earin g loss in clu de
defects of th e tym pan ic m em bran e, a serotym -
pan um , m u cotym pan u m , or h em otym pan u m ; in -
terru ption of th e ossicu lar ch ain by trau m a or in -
flam m ation ; calcification of t h e ossicles (otos-
clerosis); destructive processes su ch as ch olestea-
tom a; an d tu m ors (glom u s tu m or, less com m on ly
carcin om a of th e au ditory can al).
Inner ear or sensorineural hearing loss is cau sed by
lesion s affectin g th e organ of Corti, th e coch lear
nerve, or t h e cen tral auditory path w ay.
In n er ear fu n ction can be im paired by con gen i-
tal m alform ation s, m edication s (an tibiotics), in -
du strial poison s (e.g., ben zen e, an ilin e, an d organ ic
solven ts), in fection (m u m ps, m easles, zoster), m e-
tabolic distu rban ces, or traum a (fracture, acou stic
traum a).
Cranial Nerves · 119
4
Diagnostic evaluation of hearing loss. In th e Rinne
test, t h e exam in er determ in es w h et h er auditory
stim u li are perceived better if con ducted th rough
th e air or th rou gh bon e. Th e h an dle of a vibratin g
tu n in g fork is placed on th e m astoid process. As
soon as th e patien t can n o lon ger h ear th e ton e, th e
exam in er tests w h eth er h e or sh e can h ear it w ith
th e en d of th e tu n in g fork h eld n ext to th e ear,
w h ich a n orm al subject sh ou ld be able to do (posi-
tive Rin n e test = n orm al fin din g). In m iddle ear
h earin g loss, th e patien t can h ear th e ton e lon ger
by bon e con du ction th an by air con du ction (n ega-
tive Rin n e test = p ath ological fin din g).
In th e Weber test, th e h an dle of a vibratin g
tu n in g fork is placed on th e vertex of th e patien t’s
h ead, i.e., in th e m idlin e. A n orm al subject h ears th e
ton e in th e m idlin e; a patien t w ith un ilateral con -
du ctive h earin g loss localizes th e ton e to th e dam -
aged side, w h ile on e w ith u n ilateral sen sorin eural
h earin g loss localizes it to th e n orm al side.
Further diagnostic testing. Middle ear lesion s lie in
th e dom ain of th e otorhin olaryn gologist, but le-
sion s of th e coch lear n erve an d th e cen tral auditory
path w ay are th e n eurologist’s con cern .
Th e bedside tests described above for th e differ-
en tiation of con ductive an d sen sorin eural h earin g
loss are in su fficien t for precise diagn ostic assess-
m en t, w h ich requ ires audiometry, a qu an titative
an d rep rodu cible m easu rem en t of h earin g ability.
Th e auditory th resh olds for air an d bon e con duc-
tion are m easu red at differen t frequ en cies. In con -
du ctive h earin g loss, th e th resh old for air con du c-
tion is w orse th an th at for bon e con du ction . In sen -
sorin eu ral h earin g loss, t he fin din g dep en ds on th e
un derlyin g lesion : h igh -frequ en cy h earin g loss is
fou n d in old age (presbycusis) an d in oth er form s of
acute or ch ron ic h earin g loss, bu t a low -frequ en cy
trou gh of auditory perception is fou n d in Mén ière’s
disease.
Neurological disorders causing hearing loss.
Ménière’s disease, m en tion ed briefly above, is a
disorder of th e in n er ear cau sin g h earin g loss an d
oth er n eurological m an ifestation s. It is ch aracter-
ized by th e clin ical triad of rotatory vertigo w ith
n au sea an d vom itin g, flu ctuatin g u n ilateral partial
or total h earin g loss, an d tin n itu s. It is caused by a
distu rban ce of th e osm otic equilibrium of th e en -
dolym ph , resultin g in hydrops of th e en dolym -
ph atic sp ace an d ru pture of th e barrier betw een
4 120 · 4 Brainstem

th e en dolym ph an d th e perilym p h . Th e sym ptom s

are treated w it h an tivertigo m edication s an d in -
Cupula
tratym pan ic perfusion w ith variou s agen ts. Bet a-
h istidin e is given p rophylact ically.
Sudden hearing loss, u su ally accom p an ied by
tin n itus, is presu m ed to be cau sed in m ost cases
eith er by a viral in fection or by isch em ia in th e terri-
tory of th e labyrin t h in e artery (an en d artery).
Th e cen tral auditory con n ection s in th e brain -
stem can be affected by vascu lar processes, in flam -
m ation , in fection , an d tu m ors. Th e resu lt is h earin g
loss. On ly bilateral in terru ption of th e auditory
path w ays in t h e brain stem can cause total bilateral

l
l
e
c
deafn ess.

r
o
t
p
“Acoustic neuroma” is a com m on , t h ou gh in ac-

e
c
e
cu rate, design ation for a t um or t h at act ually arises

R
from th e vestibular n erve an d is, h istologically, a

s
g
l
l
n
e
i
sch w an n om a. Su ch t um ors w ill be described in th e

c
t
r
o
p
n ext section , w h ich deals w ith th e vestibu lar n erve.

p
u
S
Vestibulocochlear Nerve (CN VIII)— Crista
ampullaris
Vestibular Component and Vestibular
System Fig. 4.44 The crista ampullaris

Th ree differen t system s participate in th e regu la-

tion of balan ce (equ ilibriu m ): th e vestibu lar sys-
tem , th e proprioceptive system (i.e., perception of
th e position of m u scles an d join ts), an d th e visu al
system .
Th e vestibular system is com posed of th e laby-
rinth, t h e vestibular p ortion of t h e eigh t h cran ial
n erve (i.e., th e vestibular nerve, a p ortion of th e ves-
tibu lococh lear n erve), an d th e vestibular nuclei of
th e brain stem , w ith th eir cen tral con n ection s.
Th e labyrinth lies w ith in th e petrou s portion of
th e tem poral bon e an d con sists of th e utricle, th e
saccu le, an d th e three semicircular canals
(Fig. 4.39). Th e m em bran ous labyrin th is sepa-
rated from th e bony labyrin th by a sm all sp ace
filled w ith perilym ph ; th e m em bran ou s organ it-
self is filled w ith en dolym ph .
Th e u tricle, th e saccu le, an d th e w iden ed por-
tion s (am pu llae) of t h e sem icircular can als con tain
receptor organ s w h ose fu n ction is to m ain tain
balan ce.
Th e three sem icircular canals lie in differen t plan es.
Th e lateral sem icircu lar can al lies in t h e h orizon tal
plan e, an d th e tw o oth er sem icircular can als are
perpen dicu lar to it an d to each oth er. Th e posterior
sem icircu lar can al is align ed w ith th e axis of t h e
petrou s bon e, w h ile th e an terior sem icircu lar can al
is orien ted tran sversely to it. Sin ce th e axis of th e
petrou s bon e lies at a 45° an gle to th e m idlin e, it
follow s th at t h e an terior sem icircu lar can al of on e
ear is parallel to t h e posterior sem icircu lar can al of
th e opposite ear, an d vice versa. Th e tw o lateral
sem icircu lar can als lie in th e sam e plan e (th e h ori-
zon tal plan e).
Each of th e th ree sem icircu lar can als com m un i-
cates w ith th e u tricle. Each sem icircu lar can al is
w iden ed at on e en d to form an ampulla, in w h ich
t h e receptor organ of th e vestibu lar system , th e
crista am pullaris, is located (Fig. 4.44). Th e sen sory
h airs of th e crista are em bedded in on e en d of an
elon gated gelatin ous m ass called th e cupula, w h ich
con tain s n o otolith s (see below ). Movem en t of en -
dolym ph in th e sem icircular can als stim u lates th e
sen sory h airs of th e cristae, w h ich are th u s kin etic
receptors (m ovem en t receptors).
Th e utricle an d saccule con t ain furth er receptor
organ s, t h e utricular an d saccular m acules
(Fig. 4.45). Th e u tricu lar m acu le lies in th e floor of
th e utricle p arallel to th e base of th e sku ll, an d th e
saccular m acu le lies vertically in th e m edial w all of
t h e saccu le. Th e h air cells of th e m acule are
 Cranial Nerves · 121
4
em bedded in a gelatin ou s m em bran e con tain in g
Gelatinous
calciu m carbon ate crystals, called statolith s. Th ey m em brane Otoliths
are flan ked by su pport in g cells.
Th ese receptors tran sm it static im pu lses, in di-
catin g th e position of th e h ead in sp ace, to th e
brain stem . Th ey also exert an in flu en ce on m u scle
ton e.
Im pu lses arisin g in t h e receptors of th e labyrin t h
Recep -
form th e afferen t lim b of reflex arcs th at serve to tor cell
coordin ate th e extraocu lar, n u ch al, an d body
Suppor-
m uscles so th at balan ce is m ain tain ed w ith every ting cell
position an d every type of m ovem en t of th e h ead.
Acoustic macula Myelinated nerve fibers
to the vestibular ganglion
Vestibulocochlear nerve. Th e n ext station for im -
pu lse tran sm ission in th e vestibular system is th e Fig. 4.45 The acoustic macula
vestibulococh lear n erve. Th e vestibular ganglion is
located in th e in tern al auditory can al; it con tain s to th e vestibular n uclei, w h ich lie in th e floor of th e
bip olar cells w h ose periph eral processes receive fou rth ven tricle.
inpu t from th e receptor cells in th e vestibu lar
organ , an d w h ose cen tral processes form th e vesti- Th e vestibular nuclear complex (Fig. 4.46a) is m ade
bular nerve. Th is n erve join s t h e coch lear n erve, up of:
w ith w h ich it traverses th e in tern al auditory can al, ¼ Th e su perior vestibu lar n u cleus (of Bekh terev)
crosses th e su barach n oid space at th e cerebel- ¼ Th e lateral vestibu lar n u cleu s (of Deiters)
lopon tin e an gle, an d en ters th e brain stem at th e ¼ Th e m edial vestibu lar n u cleu s (of Sch w albe)
pon tom edu llary ju n ction . Its fibers th en proceed ¼ Th e in ferior vest ibu lar n u cleu s (of Roller)

Fig. 4.46 The vestibular

Vestibular nuclei: nuclear complex and its
III Superior nucleus central connections.
(of Bechterew) a Com ponents of the vesti-
Medial longitudinal
IV fasciculus (ascending) Lateral nucleus bular nuclei. b Central con-
(of Deiters) nections of the individual
Vestibulo-
cerebellar fibers
com ponents of the vestibu-
Medial nucleus
(to nodulus (of Schwalbe) lar nuclei.
and flocculus)
Inferior nucleus
(of Roller)

a
VI

Lateral vestibulo-
b spinal tract

Medial longitudinal
fasciculus (descending)
4 122 · 4 Brainstem

Fig. 4.47 Central connec-

tions of the vestibular
nerve

III
Nucleus of
Darkshevich and
interstitial nucleus of Cajal
Red nucleus

Verm is
Fastigial nucleus IV
Globose nucleus

Em boliform
nucleus
Dentate
Uncinate
nucleus
VI fasciculus
(of Russell)

Flocculus

Vesti-
Reticular formation
bular n.
Vestibular ganglion
(of Scarpa)

Vagus n. (nausea, vom iting) X

Accessory n. XI Cristae
Vestibulospinal tract Utricle
Saccule
Reticulospinal tract
Medial longitudinal From the
fasciculus cervical muscles

To the sacral spinal cord

To the cervical spinal cord

Th e fibers of t h e vestibu lar n erve split in to bran ch es
before en terin g th e in dividu al cell grou ps of th e
vestibular n u cleu s com plex, in w h ich th ey form a
syn aptic relay w ith a secon d n eu ron (Fig. 4.46b).
Afferent and efferent connections of the vestibular
nuclei. Th e an atom y of th e afferen t an d efferen t
con n ection s of th e vestibular n uclei is n ot p recisely
kn ow n at presen t. Th e cu rren t state of kn ow ledge
is as follow s (Fig. 4.47):
¼ Som e fibers derived from th e vestibu lar n erve
convey im pu lses directly to th e flocculonodular
lobe of the cerebellum (archicerebellum) by
w ay of th e ju xtarestiform tract, w h ich is adja-
cen t to th e in ferior cerebellar pedun cle. Th e
floccu lon odular lobe projects, in tu rn , to th e
fastigial n ucleu s an d, by w ay of t h e u n cin ate
fasciculu s (of Russell), back to th e vestibu lar n u -
clei; som e fibers retu rn via th e vestibular n erve
to th e h air cells of th e labyrin th , w h ere th ey

exert a m ain ly in h ibitory regu latin g effect .
Moreover, th e arch icerebellu m con tain s sec-
on d-order fibers from th e su perior, m edial, an d
in ferior vestibu lar n uclei (Figs. 4.47 an d 4.48)
an d sen ds efferen t fibers direct ly back to th e
vestibular n u clear com p lex, as w ell as to spin al
m otor n eu ron s, via cerebelloreticular an d reti-
cu lospin al p ath w ays.
¼ Th e im port an t lateral vestibu lospin al tract orig-
in ates in th e lateral vestibu lar n u cleu s (of
Deiters) an d descen ds ipsilaterally in t h e an te-
rior fasciculu s to th e γ and α motor neurons of
the spinal cord, dow n to sacral levels. Th e im -
pu lses conveyed in th e lateral vestibu lospin al
tract serve to facilitate th e exten sor reflexes an d
to m ain tain a level of m u scle ton e th rou gh out
th e body th at is n ecessary for balan ce.
¼ Fibers of th e m edial vestibular n u cleu s en ter
th e m edial lon gitu din al fascicu lu s bilaterally
an d descen d in it to th e anterior horn cells of
the cervical spinal cord, or as th e m edial vesti-
bu lospin al t ract to th e upper thoracic spinal
cord. Th ese fibers descen d in th e an terior p or-
tion of th e cervical spin al cord, adjacen t to th e
an terior m edian fissu re, as th e su lcom argin al
fasciculu s, an d are dist ribu ted to t h e an terior
h orn cells at cervical an d u pper th oracic levels.
Th ey affect n u ch al m u scle ton e in respon se to
th e position of th e h ead an d probably also par-
ticipate in reflexes th at m ain tain equ ilibriu m
w ith balan cin g m ovem en ts of th e arm s.
¼ All of t h e vestibu lar n u clei project to t h e n uclei
in n ervatin g th e extraocular muscles by w ay of
th e m edial lon gitudin al fascicu lu s. An atom ist s
h ave been able to follow som e vestibu lar fibers
to th e n u clear grou ps of Cajal (in terstitial n u -
Autoinduction of Vestibula r Vertigo (a n Experiment)
Instructions: Put a coin or other sm all object on the floor,
stand directly over it, bend the head about 30° forward to
keep the coin in view, and then rotate rapidly 5 or 6 tim es to
the right around the axis of your own body. Stop suddenly,
stand up, and extend both arm s forward.
What happens? The subject suddenly feels as if he or she is
rotating to the left and tends to fall to the right, while the
arm s deviate to the right. This experim ent m ight cause the
subject to fall, so at least one other person should be present
to lend support, if necessary. It m ight also induce nausea or
even vom iting. Nystagm us is observed, in the opposite
direction to the rotation.
Explanation: Keeping the head bent 30° forward during the
rotation puts the horizontal sem icircular canals exactly into
Cranial Nerves · 123
4
cleu s) an d Darksh evich an d fu rth er on in to th e
th alam u s (Fig. 4.47).
Th e com plex of stru ctu res con sistin g of th e vesti-
bu lar n uclei an d t h e flocculon odular lobe of t h e
cerebellu m p lays an im portan t role in th e m ain -
ten an ce of equ ilibrium an d m uscle ton e. Equ i-
libriu m is also served by spin ocerebellar an d cere-
bellocerebellar projection s, w h ich w ill be dis-
cu ssed later in Ch apter 5.
Disturba nces of Equilibrium
Dizziness and dysequilibrium are, after h eadach e,
th e sym ptom s th at m ost com m on ly lead patien ts
to seek m edical atten tion . In colloqu ial speech ,
“dizzin ess” refers to a w ide variety of abn orm al
feelin gs. “Dizzin ess” som etim es m ean s t ru e ver-
tigo, i.e., a sen sation of m ovem en t or rot ation in
som e direction : p atien ts m ay describe feelin g as if
th ey w ere on a carou sel, a sh iftin g boat, or an ele-
vator start in g to m ove or com in g to a h alt . Many
patien ts, h ow ever, use th e w ord loosely for oth er
con dition s, su ch as bein g dazed, feelin g on e is
abou t to fain t, bein g u n steady on on e’s feet (a com -
m on com plain t of th e elderly), or m ild an xiety, as
in claustrop h obia. Patien ts com plain in g of “dizzi-
n ess” sh ould, th erefore, be carefu lly in terview ed to
determ in e th e precise n atu re of th e com plain t. Ver-
tigo is, by defin it ion , th e abn orm al an d distu rbin g
feelin g th at on e is m ovin g w ith respect to th e en -
viron m en t (subjective vertigo), or th at th e en -
viron m en t is m ovin g w h en it is actually station ary
(objective vertigo; n ote th at th e w ords “su bjective”
an d “objective” do n ot h ave th eir com m on m ean -
in gs in th ese tw o expression s). Patien ts w ith
the plane of rotation. Rapid turning sets the fluid (en-
dolym ph) in the canals in m otion. The inertia of the fluid
keeps it m oving in the sam e direction for a little while after
the individual suddenly stops turning. The fluid m oves past
the now stationary cristae, producing the illusion of con-
tinued m ovem ent.
When this experim ent is perform ed, excitatory im pulses
from the sem icircular canals also travel to the nuclei con-
trolling eye m ovem ent (producing nystagm us), to the spi-
nal cord (causing unsteadiness of stance and gait, with a
tendency to fall), and to the autonom ic centers in the retic-
ular form ation.
4 124 · 4 Brainstem
vert igo m ay also h ave oscillopsia, a visu al illu sion
in w h ich objects seem to m ove back an d forth .
On ly w h en “dizzin ess” is truly vertigo, accordin g to
th e strict defin ition of th e term , is it likely to be du e
to a distu rban ce in th e vestibu lar or visual system s,
or bot h , an d to requ ire evalu ation by a n eu rologist.
Non directed feelin gs of u n steadin ess or presyn -
cope, on th e oth er h an d, are m ore likely to be n on -
specific m an ifestation s of a cardiovascular dis-
order, in toxication , or dep ression .
Th e cause of m ost cases of vertigo is presum ed to be
an im balan ce of th e sen sory im p ulses relat in g to
m otion th at reach th e brain th rou gh th ree differen t
percept ual system s—visu al, vestibu lar, an d som a-
tosen sory (proprioceptive). Th is is kn ow n as th e hy-
poth esis of sensory conflict or polysensory m is-
m atch.
Even in n orm al in dividuals, “u n u su al” m ove-
m en t of variou s kin ds can in du ce vertigo. Th e m ost
both ersom e m an ifestation s of m otion sickn ess are
auton om ic (n au sea, pallor, hypoten sion , fat igue,
yaw n in g, diaph oresis, an d vom itin g), w h ile th e
vertigo it self usu ally cau ses less su fferin g for th e
patien t an d m ay be barely n oticed. Norm al person s
can su ffer from severe m otion sickn ess w h en th ere
is a blatan t sen sory con flict, e.g., w h en th e in -
dividu al is below deck on a large sh ip. In t h is situ a-
tion , th e visu al system reports th at th e environ -
m en t is stat ion ary, in con tradiction to t h e con -
tin u al m ovem en t sign aled by th e vestibular sys-
tem . On ce th e in citin g stim u lu s is rem oved, m otion
sickn ess subsides slow ly w ith in th e follow in g 24
hou rs.
Vestibular disorders cau se vertigo rath er th an n on -
specific dizzin ess. Th e respon sible lesion m ay be
anyw h ere in th e vestibular system (a collective
term for th e vestibu lar organ , th e vestibulo-
coch lear n erve, an d th e vestibu lar n u clei, as w ell as
th eir cen tral con n ection s). Vestibu lar vertigo is felt
as eith er rot atory or tran slation al (correspon din g
to th e roles of th e sem icircu lar can als an d th e
otolith s, resp ectively), an d is associated w ith nys-
tagmus. A lesion of th e vestibular organ or th e ves-
tibulococh lear n erve on on e side p rodu ces a differ-
en ce in th e level of act ivity of th e vest ibu lar n u clei
on th e tw o sides, w h ich is in terpreted by t h e cen -
tral vestibu lar apparatus as in dicatin g m ovem en t
to th e side of th e h igh er activity (i.e., th e n orm al
side). Th is, in turn , in du ces th e vestibu lo-ocu lar re-
flex (VOR), i.e., nystagm us, w ith a rapid com pon en t
tow ard th e n orm al ear an d a slow com p on en t
tow ard th e side of th e lesion (but see also vestibu -
lar n europathy, p. 125). Vestibu lar nystagm us often
h as a rotatory (torsion al) com pon en t, w h ich is eas-
iest to see w h en th e fixation of gaze is elim in ated
w ith Fren zel goggles, an d w h ich in creases fu rth er
w h en th e patien t gazes in th e direction of th e rap id
ph ase (Alexander’s law ).
Vestibu lar vertigo cau ses nausea and vomiting,
at least in itially, as w ell as a tendency to fall to the
side of the lesion. Th e accom panyin g nystagm us
in du ces illu sory m otion of th e environ m en t (oscil-
lopsia). Th e p atien t, th erefore, prefers to keep h is
or h er eyes closed, an d to avoid furth er irrit ation of
th e vestibu lar system by keepin g th e h ead in a
fixed position , w it h th e abn orm al ear u pperm ost .
Lesion s affectin g th e vestibu lar n u clei in th e floor
of th e fourth ven tricle can p rodu ce sim ilar sym p-
tom s.
On e can gain som e idea of w h at it feels like to
h ave a vestibu lar lesion by perform in g th e exp eri-
m en t described on p. 123 on on eself.
Proprioceptive vertigo (or, m ore accu rately, pro-
prioceptive un steadin ess) is u su ally m otion -de-
pen den t an d n on -direction al an d is du e to an ab-
n orm ality of th e prop rioceptive im pu lses arisin g in
th e cervical spin al cord. It can also be cau sed by pe-
riph eral n eu ropat hy or by lesion s of th e posterior
colu m n s, eith er of w h ich can im p air cen tral tran s-
m ission of proprioceptive im pu lses from th e low er
lim bs. Proprioceptive u n steadin ess of th e latter
type is ch aracterized by prom in en t un steadin ess of
gait , w ith out nystagm u s. Th e gait dist urban ce
ch aracteristically w orsen s w h en th e eyes are
closed, or in th e dark, because th e in dividu al can
n o lon ger use visu al inpu t to com pen sate for th e
m issin g proprioceptive in form ation .
Periphera l Vestibula r Lesions
Positional Vertigo
Ben ign paroxysm al position al vertigo (BPPV) is th e
m ost com m on cau se of direction al vertigo, ac-
cou n tin g for 20 % of all cases.
Patien ts w ith BPPV typ ically report brief attacks
of intense rotatory vertigo arisin g a sh ort tim e
after rapid movements of the head, u su ally w h en
th e h ead is lean ed backw ard or tu rn ed to on e side,
w ith th e affected ear u pw ard (e.g., w h en th e

patien t tu rn s in bed). Th e vertigo subsides in 10–60
secon ds. Th is typ e of vertigo is caused by detach -
m en t of statolith s from th e statolith m em bran e.
Un der th e in flu en ce of gravity, t h e statolith s m i-
grate to th e low est part of th e labyrin th , w h ere
th ey can easily be sw ept in to th e en tran ce to th e
posterior sem icircular can al w h en th e patien t lies
sup in e. Th e det ach ed statolith s can also (rarely)
en ter t h e lateral sem icircu lar can al.
Movem en t in th e plan e of th e affected sem i-
circular can al sets th e crystals w ith in it in m otion ,
producin g relative m otion of th e en dolym ph
(canalolithiasis; piston effect), w h ich is tran s-
m itted to th e cu pu la. Th e im pu lses th at origin ate
in t h e affected sem icircular can al p rodu ce a sen sa-
tion of m ovem en t an d nystagm u s in th e plan e of
th e stim ulated sem icircular can al, w h ich begin s
after a sh ort laten cy in terval an d su bsides w ith in
60 secon ds. Rep et ition of th e precipit atin g h ead
m ovem en t leads to a tran sien t dim in u tion of th e
sym ptom atic respon se (h abitu ation ).
Th e treatm en t con sists of rap id reposition in g
m an euvers in th e plan e of th e affected sem icircu-
lar can al, by m ean s of w h ich th e statolith s can be
draw n out of th e can al.
In th e differential diagnosis of BPPV, on e m u st con -
sider central positional vertigo du e to lesion s in th e
region of th e floor of th e fou rt h ven t ricle involvin g
th e vestibular n u clei or th eir con n ection s. A lesion
of th e cerebellar n odulus, for exam p le, produces
dow n beat position al nystagm us w h en th e h ead is
bow ed. Cen t ral posit ion al vertigo is som etim es ac-
com p an ied by severe vom itin g, bu t m ore com -
m on ly by relatively m ild n au sea. In cen tral posi-
tion al vertigo, u n like BPPV, nystagm us an d vertigo
are often dissociated: t h e nystagm us is largely in de-
pen den t of th e speed at w h ich th e patien t is reposi-
tion ed, it ten ds to persist for a lon ger tim e, it m ay
ch an ge direction depen din g on th e position of th e
h ead, an d it is u su ally accom pan ied by fu rth er ab-
n orm alities of gaze fixation an d pu rsu it.
Vestibular Neuropathy
An acu te, u n ilateral vestibu lar deficit (vest ibu lar
n eu ropathy or n eu ritis = acute loss of fu n ction of,
usually, a sin gle vestibu lar organ or vestibu lar
n erve) is th e secon d m ost com m on cause of ro-
tatory vertigo. Alth ou gh , in m ost cases, n o cau se
can be defin itively iden tified, m uch eviden ce su g-
Cranial Nerves · 125
4
gests th at su ch episodes are of viral origin, in sim i-
lar fash ion to idiopath ic facial palsy (Bell p alsy)
an d acu te h earin g loss.
Th e m ain sym ptom of vestibular n eu ropathy is
severe rotatory vertigo of acute onset and several
days’ duration, w h ich is exacerbated by m ove-
m en ts of th e h ead. Th is is accom pan ied by h ori-
zon tal torsion al nystagm u s th at beats aw ay from
th e side of th e lesion , as w ell as a ten den cy to fall to
th e affected side, n au sea, vom itin g, an d in ten se
m alaise. A m ild prodrom e in th e form of brief, tran -
sien t sen sation s of vert igo occasion ally precedes
th e acute attack by a few days. Hearin g is m ost
often un affected, bu t if h earin g loss is fou n d, th e
differen tial diagn osis m u st in clu de in fectious ill-
n esses su ch as m u m ps, m easles, m on on u cleosis,
borreliosis, n eu rosyph ilis, an d h erp es zoster ot i-
cu s; an acou stic n eurom a; isch em ia in th e territory
of th e labyrin th in e artery; an d Mén ière’s disease.
Vestibu lar n eu ropathy ten ds to affect person s be-
tw een th e ages of 30 an d 60 years an d does n ot be-
com e m ore com m on in old age, w h ich im plies th at
it is probably n ot du e to isch em ia. Th e diagn osis is
establish ed by a fin din g of im paired excitabilit y of
th e affected labyrin th on caloric testin g in th e ab-
sen ce of oth er n eu rological m an ifestation s (su ch as
oth er cran ial n erve, cerebellar, or brain stem defi-
cits). Th e vertigo an d u n steadin ess im prove slow ly
over 1–2 w eeks, an d all sym ptom s gen erally re-
solve com pletely by t h ree w eeks after th eir on set .
Treatm en t w ith bed rest an d an tivertigo agen ts is
in dicated on ly in th e first tw o or th ree days.
Patien ts sh ou ld start a specific, directed gym n as-
tics p rogram as soon as p ossible, in clu din g balan ce
exercises th at are easy to learn an d to perform at
h om e, to h elp speed th eir recovery.
Acoustic Neurom a
As already stated, th e com m on (in deed alm ost un i-
versal) design ation “acou stic n eu rom a” is act ually
a m isn om er for a sch w an n om a arisin g from th e
vestibular fibers of th e vest ibu lococh lear n erve.
Th e tu m or destroys th ese fibers first, slow ly an d
progressively im p airin g th e excitabilit y of th e ves-
tibu lar organ on th e affected side; patien ts rarely
suffer from vertigo, becau se th is deficit can be
com pen sated for at h igh er levels of vestibu lar pro-
cessin g, bu t th e asym m etric excitability can be de-
m on strated by caloric testin g. Depen din g on
w h eth er th e tum or grow s rapidly or slow ly, irrita-
4 126 · 4 Brainstem
tion an d/or com pression of th e fibers of th e
coch lear n erve leads soon er or later to clin ically
eviden t high-frequency hearing loss. Th e diagn osis
of acou stic n eurom a is sup ported by th e fin din g of
high -frequ en cy h earin g loss by au diom etry, an d of
a prolon ged con du ction tim e by m easu rem en t of
brain stem au ditory evoked p oten t ials (BAEP); it
can be con firm ed by MRI. Th ere is, h ow ever, n o
direct an d reliable relation sh ip betw een th e size of
th e tum or an d t h e severity of th e h earin g loss th at
it cau ses.
Furth er grow th of th e tu m or can com press n eigh -
borin g structu res (brain stem , facial n erve, t rigem i-
nal n erve), leadin g to fu rth er cran ial n erve deficits
(e.g., im paired lacrim ation an d taste du e to dysfu n c-
tion of th e ch orda tym p an i) an d, fin ally, to sym pto-
m atic com pression of th e brain stem an d cerebel-
lum .
Patien ts w ith bilateral acou stic n eu rom a m ost
likely su ffer from n eurofibrom atosis type II (also
called bilateral acou stic n eu rom atosis).
Th e t reatm en t of acou stic n eurom a is cu rren t ly
th e subject of in ten se discu ssion am on g n eu rosu r-
geon s. Many lesion s th at previously cou ld on ly h ave
been t reated by op en su rgery can n ow be treated
w ith as good or better resu lts by stereotactic radio-
surgery (i.e., w it h th e gam m a kn ife or a stereotactic
lin ear accelerator).
Vagal System (CN IX, X, and the
Cranial Portion of XI)
Glossopha ryngea l Nerve (CN XI)
Th e glossoph aryn geal n erve sh ares so m any of its
fu n ction s w ith t h e n ervu s in term ediu s, t h e vagu s
n erve, an d th e cran ial p ortion of th e accessory
n erve th at th ese n erves can be con sidered togeth er
as a sin gle “vagal system ” to avoid m akin g th e pre-
sen t ation u n n ecessarily repetit ive. Th ese n erves
are all m ixed (sen sory an d m otor) n erves, an d
som e of t h eir com pon en ts arise from com m on
brain stem n uclei (th e n u cleu s am bigu us an d n u -
cleu s solitariu s) (cf. Table 4.1 an d Figs. 4.2 an d 4.3).
Anatomical course and distribution (Fig. 4.48). Th e
glossoph aryn geal, vagal, an d accessory n erves exit
th e skull togeth er th rou gh th e ju gular foram en ,
w h ich is also th e site of both gan glia of th e glos-
soph aryn geal n erve, th e superior (intracranial)
gan glion an d th e inferior (extracranial) gan glion .
After leavin g th e foram en , th e glossoph aryn geal
n erve travels betw een th e in tern al carotid artery
an d th e jugu lar vein tow ard t h e styloph aryn geu s
m u scle. It con tin u es betw een th e stylop h aryn geu s
an d styloglossus m uscles an d onw ard to in n ervate
th e root of th e ton gu e, th e ph aryn geal m ucosa, th e
ton sils, an d th e posterior th ird of th e ton gue.
Alon g its course, it gives off th e follow in g
bran ch es:
¼ Th e tym panic nerve ru n s from th e in ferior gan -
glion to th e tym pan ic cavity an d tym pan ic
plexus (of Jacobson ), an d th en onw ard in th e
lesser petrosal n erve, by w ay of th e otic gan -
glion , to th e parotid glan d (Fig. 4.38). It su pplies
sen sation to t h e m u cosa of th e tym pan ic cavit y
an d eustach ian t ube.
¼ Stylopharyngeal branches to th e styloph aryn -
geu s m u scle.
¼ Pharyngeal branches, w h ich , togeth er w ith
bran ch es of th e vagus n erve, form th e ph aryn -
geal plexu s. Th is p lexus su pplies th e striated
m uscles of th e ph aryn x.
¼ Branches to the carotid sinus, w h ich ru n w ith th e
carotid artery to th e carotid sin u s an d carotid
body.
¼ Lingual branches conveyin g gu statory im pu lses
from th e posterior t h ird of th e ton gu e.
Lesions of the Glossopharyngeal Nerve
Isolated lesion s of th e glossoph aryn geal n erve are
rare; th e vagu s an d accessory n erves are usu ally in -
volved as w ell.
Th e causes of glossoph aryn geal n erve lesion s in -
clu de basilar skull fractu re, sigm oid sin us th rom -
bosis, tum ors of th e cau dal portion of th e p osterior
fossa, an eu rysm s of th e vertebral or basilar arter-
ies, iatrogen ic lesion s (caused, e.g., by su rgical pro-
cedures), m en in gitis, an d n eu ritis.
The clinical syndrome of a glossoph aryn geal n erve
lesion is ch aracterized by:
¼ Im p airm en t or loss of taste (ageu sia) on th e
posterior th ird of th e ton gu e
¼ Dim in u tion or absen ce of th e gag an d palatal re-
flexes
¼ An esth esia an d an algesia in th e u pper port ion
of th e ph aryn x an d in t h e area of th e ton sils an d
th e base of th e ton gue
¼ A m ild distu rban ce of sw allow in g (dysph agia)
¼ Im p aired salivation from th e p arotid glan d
 Cranial Nerves · 127
4
Fig. 4.48 Distribution
and central connections
of the glossopharyngeal
and vagus nerves
Motor
Viscerom otor
Corticonuclear Exteroceptive
tract Enteroceptive
Extrapyram idal
tract

Thalam us

To thalam us and cortex

(m edial lem niscus) Mesesncephalic nucleus
Nucleus of the reticular and tract of the trigem inal n.
formation (gag and
swallowing reflex) Principal sensory nucleus
of the trigeminal n.
Somatic
sensation (pain, Nucleus of the tractus solitarius
temperature, touch) Nucleus ambiguus
Superior ganglion
From the Inferior salivatory
ear (t ym panic n.) nucleus to the otic
Nucleus of the IX X X IX ganglion and
spinal tract of parotid gland
the trigeminal n.
Somatic sensation St ylopharyngeus m .
Taste
Constrictor pharyngeus m .
Superior
ganglion
Inferior
ganglion

Carotid body
(glomus caroticum)

Glossopharyngeal neuralgia is app roxim ately 1%as
com m on as trigem in al n eu ralgia; like trigem in al
n eu ralgia, it is ch aracterized by intense, parox-
ysmal pain. Th e p ain fu l att acks gen erally begin
sudden ly in th e pharynx, neck, tonsils, or tongue,
an d last a few secon ds or m in u tes. Th ey can be pro-
voked by sw allow in g, ch ew in g, cou gh in g, or
speakin g. Th e patien t is afraid to eat becau se of th e
pain an d rapidly loses w eigh t. Th is syn drom e u su -
ally resolves sp on tan eou sly w it h in six m on th s of
on set. Persisten ce suggests a possible an atom ical
cau se, su ch as a tum or in th e ph aryn x, w h ich m u st
be ru led out by radiological study. In an alogou s
fash ion to trigem in al n eu ralgia, it is gen erally
treated m edically w ith carbam azep in e, gabapen -
tin , or pregabalin at first. In refractory cases, a n eu -
rosu rgical p rocedu re called m icrovascular decom -
p ression can be con sidered (Jan n etta 1977); th is
involves open in g th e posterior fossa an d m ovin g a
loop of th e vertebral or posterior in ferior cerebellar
artery aw ay from t h e n in th cran ial n erve.
4 128 · 4 Brainstem
Vagus Nerve (CN X)
Like th e glossoph aryn geal n erve, t h e vagus n erve
also possesses t w o gan glia, th e superior (jugular)
ganglion an d th e inferior (nodose) ganglion, both of
w h ich are fou n d in th e region of th e ju gular fora-
m en .
Anatomical course. Th e vagu s n erve is derived
from th e fou rth an d low er bran ch ial arch es. Below
th e in ferior (n odose) gan glion , it follow s th e in ter-
n al carotid an d com m on carotid arteries
dow nw ard, an d th en passes th rou gh th e su perior
th oracic apertu re in to th e m ediastin um . Here, th e
righ t vagal tru n k crosses over th e subclavian
artery, w h ile t h e left t ru n k run s beh in d th e h ilu m
an d past th e aortic arch . Bot h th en becom e applied
to th e esoph agus, w it h t h e fibers of t h e righ t vagal
tru n k ru n n in g on its posterior side, an d th ose of
th e left vagal trun k on its an terior side. Th e term i-
n al vagal bran ch es th en accom pany th e esoph agu s
th rough th e esoph ageal h iatu s of t h e diap h ragm
in to th e abdom in al cavity.
Branches of the vagus nerve. Alon g it s w ay to th e
abdom in al cavit y, th e vagu s n erve gives off th e fol-
low in g bran ch es (Figs. 4.48, 4.49; an d Fig. 6.15,
p. 189):
¼ Dural branch: ru n n in g from t h e su perior gan -
glion back th rou gh th e ju gular foram en to th e
du ra m ater of th e posterior fossa.
¼ Auricular branch: from th e su perior gan glion of
th e vagu s n erve to th e skin on th e posterior su r-
face of t h e extern al ear an d th e in feroposterior
portion of th e extern al auditory can al. Th is is
th e on ly cutan eous bran ch of th e vagus n erve.
¼ Pharyngeal branches: th ese accom pany th e
fibers of t h e glossoph aryn geal n erve an d th e
sym path etic ch ain in to th e ph aryn geal plexus
to sup ply th e m u scles of th e ph aryn x an d soft
palate.
¼ Superior laryngeal nerve: from th e in ferior gan -
glion to th e laryn x. Th is n erve splits in to tw o
bran ch es of its ow n . Th e extern al bran ch gives
off bran ch es to th e ph aryn geal con strictor
m uscle an d th en goes on to in n ervate th e cri-
cothyroid m u scle. Th e in tern al bran ch is a
sen sory n erve su pplyin g th e laryn geal m u cosa
as far dow nw ard as t h e vocal folds, as w ell as
th e m ucosa of th e epiglottis. It also con tain s
gustatory fibers for th e epiglottis an d parasym -
path etic fibers in n ervatin g th e m u cosal glan ds.
¼ Recurrent laryngeal nerve: Th is bran ch run s
arou n d th e su bclavian artery on th e righ t side
an d th e aortic arch on th e left (Fig. 4.49), th en
proceeds upw ard betw een th e trach ea an d th e
esoph agus tow ard t h e laryn x. It su pplies m otor
in n ervation to th e in tern al laryn geal m u scu la-
tu re, w ith th e exception of th e cricothyroid
m uscle, as w ell as sen sory in n ervation to th e
laryn geal m ucosa below th e vocal folds.
¼ Superior cervical cardiac branches and thoracic
cardiac branches: th ese accom pany sym path etic
fibers to th e h eart , by w ay of th e cardiac p lexus.
¼ Bronchial branches: th ese form th e pulm on ary
plexu s in th e w all of th e bron ch i.
¼ Anterior and posterior gastric branches, and he-
patic, celiac, and renal branches: th ese travel, by
w ay of th e celiac an d superior m esen teric plex-
uses, an d togeth er w ith sym path etic fibers, to
th e abdom in al viscera (stom ach , liver, pan creas,
spleen , kidn eys, adren al glan ds, sm all in testin e,
an d proxim al portion of large in testin e). In t h e
abdom in al cavity, th e fibers of th e righ t an d left
vagu s n erves becom e closely associated w ith
th ose of th e sym path etic n ervou s system an d
can n o lon ger be clearly distin guish ed from
th em .
Syndrom e of a Unilateral Lesion of the Vagus
Nerve
¼ Th e soft p alate h an gs dow n on th e side of th e le-
sion , th e gag reflex is dim in ish ed, an d th e
patien t’s speech is n asal because th e n asal cav-
ity can n o lon ger be closed off from th e oral cav-
ity. Paresis of th e p h aryn geal con strictor m uscle
cau ses th e palatal veil to be pu lled over to th e
n orm al side w h en th e patien t ph on ates.
¼ Hoarsen ess results from paresis of th e vocal
folds (lesion of th e recurren t laryn geal n erve
w ith paresis of th e in tern al m u scles of th e
laryn x, w ith th e exception of th e cricothyroid
m uscle).
¼ Fu rth er com pon en ts of th e syn drom e are dys-
ph agia an d occasion ally tachycardia, an d car-
diac arrhyth m ia.
Causes. Many diseases can cau se a cen tral vagal le-
sion , in clu din g m alform ation s (Ch iari m alform a-
tion , Dan dy–Walker syn drom e, etc.), tu m ors,
h em orrh age, th rom bosis, in fection /in flam m ation ,
am yotrop h ic lateral sclerosis, an d an eurysm s. Peri-
 Cranial Nerves · 129
4
Fig. 4.49 Distribution
a and central connections
of the vagus nerve.
Motor a Overview. b Topographic
Viscerom otor relations of the recurrent
Exteroceptive laryngeal nerve.
Enteroceptive

Thalam us

Medial lem niscus Diencephalobulbar

pathway
Pyram idal tract
Nucleus am biguus
Spinal tract of
Dorsal nucleus
the trigem inal n.
of the vagus n.
IX IX Superior ganglion
X Inferior ganglion
Superior ganglion
From the
Inferior ganglion
XI dura mater
XII
Auricular branch
X

b
Superior cervical
ganglion

Recurrent
laryngeal n.

Inhibition
Secretion

Peristalsis

ph eral vagal lesion s can be caused by n euritis,
tu m ors, glan du lar disturban ces, traum a, an d aortic
an eu rysm s.
Common Nuclea r Areas a nd Distribution of
CN IX a nd X
Nucleus Am biguus
Th e n u cleu s am bigu u s is th e com m on m otor n u -
cleu s of th e glossoph aryn geal an d vagu s n erves
an d of t h e cran ial portion of th e accessory n erve
(Figs. 4.48, 4.49, an d 4.50). It receives descen din g
im pu lses from th e cerebral cortex of both h em i-
4 130 · 4 Brainstem
sph eres by w ay of th e corticon uclear t ract. Becau se
of th is bilateral in n ervat ion , u n ilateral in terru ption
of th ese cen tral descen din g fibers does n ot pro-
du ce any m ajor deficit in th e m otor distribu tion of
th e n ucleu s am bigu us.
Th e axon s th at origin ate in th e n u cleu s am -
bigu u s travel in t h e glossop h aryn geal an d vagu s
n erves an d th e cran ial p ortion of th e accessory
n erve to th e m u scles of th e soft palate, p h aryn x,
an d laryn x, an d to th e striated m uscle of th e u pper
portion of th e esoph agu s. Th e n u cleu s am biguu s
also receives afferen t inpu t from th e spin al n u cleu s
of th e trigem in al n erve an d from th e n u cleu s of th e
tractus solitarius. Th ese im p ulses are th e afferen t
lim b of th e im portan t reflex arcs by w h ich m u cosal
irritation in th e respiratory an d digestive tracts
produces cou gh in g, gaggin g, an d vom itin g.
Parasym pathetic Nuclei of CN IX and X
Th e dorsal n u cleu s of th e vagu s n erve an d th e in fe-
rior salivatory n ucleu s are t h e tw o p arasym pa-
th etic n u clei th at sen d fibers in to th e glos-
soph aryn geal an d vagu s n erves. Th e superior sali-
vatory n u cleus is th e parasym path etic n ucleus for
th e n ervu s in term ediu s, as discu ssed above (Figs.
4.48 an d 4.49).
Dorsal nucleus of the vagus nerve. Th e efferent
axon s of th e dorsal n u cleus of th e vagu s n erve
travel as pregan glion ic fibers w ith th e vagu s n erve
to th e p arasym path etic gan glia of th e h ead, th orax,
an d abdom en . After a syn apt ic relay, th e sh ort
postgan glion ic fibers convey viscerom otor im -
pu lses to th e sm oot h m u scu latu re of th e respira-
tory tract an d of th e gastroin testin al tract as far
dow n as th e left colic flexu re, as w ell as to th e car-
diac m u scle. St im u lation of th e vagal parasym pa-
th etic fibers cau ses slow in g of th e h eartbeat, con -
striction of th e bron ch ial sm ooth m uscle, an d
secret ion from th e bron ch ial glan ds. Peristalsis in
th e gastroin testin al tract is prom oted, as is secre-
tion from th e glan ds of th e stom ach an d p an creas.
Th e dorsal n ucleu s of th e vagus n erve receives
afferent inpu t from th e hypoth alam u s, th e ol-
factory system , auton om ic cen ters in t h e ret icular
form ation , an d th e n ucleu s of th e tractu s solitarius.
Th ese con n ection s are im portan t com pon en t s of
th e reflex arcs for th e con trol of cardiovascu lar, res-
piratory, an d alim en tary fu n ction . Im pu lses from
th e baroreceptors in th e w all of th e carotid sin u s,
w h ich reach th e dorsal n u cleus of th e vagu s n erve
th rough th e glossoph aryn geal n erve, serve to regu -
late arterial blood pressu re. Ch em oreceptors in th e
carotid body p articip ate in th e regu lation of th e
partial pressu re of oxygen in th e blood. Oth er re-
ceptors in th e aortic arch an d para-aortic bodies
sen d afferen t im pulses to th e dorsal n u cleus of th e
vagu s n erve by w ay of th e vagu s n erve, an d h ave
sim ilar fu n ction s.
Inferior salivatory nucleus. Th e p arasym path etic
fibers arisin g in t h e in ferior salivatory n ucleus an d
travelin g by w ay of th e glossoph aryn geal n erve to
th e parotid glan d h ave already been discu ssed
(pp . 112 ff. an d 126).
Visceral Afferent Fibers of CN IX and X
Special visceral afferent fibers. Th e perikarya (cell
bodies) of th e afferen t gu statory fibers of th e glos-
soph aryn geal n erve (pseu dou n ipolar n euron s) are
foun d in th e inferior (extracranial) ganglion, w h ile
th ose of th e vagu s n erve are foun d in th e inferior
(nodose) ganglion. Both groups of fibers convey
gu statory im p ulses from th e epiglottis an d th e
posterior th ird of th e ton gu e. Th e glossop h aryn -
geal n erve is th e m ain n erve of taste. Its cen t ral
processes travel in t h e t ractu s solitariu s to th e n u-
cleu s of th e tractu s solitarius, w h ich also receives
gu statory im pu lses from th e an terior tw o-th irds of
th e ton gu e, conveyed by th e n ervus in term ediu s
(Fig. 4.37). From th e n u cleu s of th e tractus solita-
rius, gu statory im pu lses ascen d to th e ven tral pos-
terom edial n u cleus of th e th alam u s (VPM) an d
th en onw ard to th e gu statory cortex at th e low er
en d of th e postcen t ral gyru s (Fig. 4.37).
Visceral afferent fibers of th e glossoph aryn geal
n erve belon g to th e pseudou n ip olar cells of th e su -
perior (in tracran ial) gan glion , w h ile th ose of th e
vagu s n erve are derived from it s in ferior gan glion .
Th ese fibers con du ct sen sory im pu lses from th e
m u cosa of th e posterior th ird of th e ton gu e, th e
ph aryn x (CN IX), an d t h e th oracic an d abdom in al
viscera (CN X) (Figs. 4.48 an d 4.49).
Som atic Afferent Fibers of CN IX and X
Pain and temperature fibers. Nociceptive an d
probably also tem p eratu re-related im pulses from
th e posterior th ird of th e ton gu e, th e upp er portion
of th e ph aryn x, th e eustach ian tube, an d th e
 Cranial Nerves · 131
4
Fig. 4.50 Distribution
Extrapyram idal fibers to the Pyram idal Dorsal nucleus and central connections
nucleus of the accessory n. tract of the vagus n.
of the accessory nerve

Nucleus ambiguus
Jugular foram en
Superior ganglion
Inferior ganglion

Accessory n.
Vagus n.

Foramen
magnum Cranial roots:
with the recurrent
C1
laryngeal n. to the
muscles of the larynx
(except the crico -
Nucleus of the thyroid m .)
C2
accessory n. Spinal roots
to the sterno-
cleidomastoid and
C3 trapezius m m .

C4

C5

C6

Cra nia l Roots of the Accessory Nerve (CN XI)

m iddle ear travel by w ay of th e glossoph aryn geal
n erve an d th e sup erior (in tracran ial) gan glion to
th e n u cleu s of th e spin al tract of th e trigem in al
n erve. Im pu lses of th is type from th e low er portion
of th e ph aryn x, th e skin beh in d th e ear an d in part
of th e extern al au ditory can al, th e t ym pan ic m em -
bran e, an d th e dura m ater of th e posterior fossa ar-
rive at th e sam e brain stem n u cleus by w ay of th e
vagu s n erve an d it s sup erior gan glion (th e jugu lar
gan glion ).
Fibers for touch perception (som atosen sory fibers)
from th e areas ju st n am ed probably term in ate in
th e prin cipal sen sory n u cleu s of th e trigem in al
n erve. Som atosen sory im pu lses ascen d from th is
n u cleus in th e m edial lem n iscu s to th e th alam us,
an d t h en ce to t h e postcen tral cortex.
Th e accessory n erve h as tw o sets of roots, cran ial
an d spin al (Fig. 4.50). Th e n eu ron s givin g rise to th e
cran ial roots lie in th e n u cleu s am bigu u s n ext to
th e n euron s w h ose p rocesses ru n in th e vagu s
n erve. Th is portion of th e eleven th cran ial n erve is
best con sidered a fun ct ion al com p on en t of t h e
vagu s n erve, as its fu n ction s are essen t ially th e
sam e as th ose of th e port ion of th e vagu s n erve
th at arises in th e n u cleu s am bigu u s. (Th e spin al
roots of th e accessory n erve, on t h e oth er h an d,
h ave an en tirely differen t fu n ction .) Th e cran ial
roots sep arate off from t h e spin al roots w ith in t h e
ju gular foram en to join th e vagus n erve. Th is por-
tion of th e accessory n erve th u s belon gs to th e
“vagal system .” Th e sp in al roots an d th eir fu n ction
w ill be discu ssed below.
4 132 · 4 Brainstem

Spina l Roots of the Accessory Nerve (CN XI) (syrin gom yelia, am yotroph ic lateral sclerosis,
poliom yelitis, oth er cau ses).
Th e sp in al portion of th e accessory n erve is purely
m otor an d arises in a cell colu m n in th e ven -
Typical deficits. Un ilateral interruption of the exter-
trolateral p ortion of th e an terior h orn , exten din g
nal branch after its exit from the jugular foram en h as
from C2 dow n to C5 or C6 (Fig. 4.50). Th e root fibers
differen t effects on th e stern ocleidom astoid an d
clim b on e or tw o segm en ts in th e lateral fu n icu lu s
trapezius m uscles: th e stern ocleidom astoid
an d th en exit th e spin al cord bet w een t h e an terior
m uscle is paralyzed (flaccid) in its en tirety, w h ile
an d posterior roots, ju st dorsal to th e den ticu late
th e trapezius m u scle is affected on ly in its u pper
ligam en t. Th ey th en ascen d in th e su barach n oid
h alf, becau se it also receives in n ervation from th e
space an d join w it h root fibers from h igh er levels
spin al n erves of segm en ts C2 th rough C4. Injury to
to form a com m on trun k, w h ich en ters th e skull
the accessory nerve distal to the sternocleidom astoid
th rough th e foram en m agn u m an d un ites, over a
m uscle cau ses w eakn ess of th e trapeziu s m u scle
sh ort stretch , w ith th e cran ial roots of th e acces-
exclu sively; su ch in ju ries som etim es occu r du rin g
sory n erve. As th e accessory n erve passes th rou gh
lym ph n ode biopsies at th e p osterior edge of th e
th e ju gular foram en , th e spin al p ortion splits off
stern ocleidom astoid m uscle. No sen sory deficit
again as th e external branch (ram u s extern u s),
arises, becau se th e spin al port ion of th e accessory
w h ile th e cran ial portion join s th e vagu s n erve. Th e
n erve is pu rely m otor.
extern al bran ch th en descen ds in to th e n uch al re-
In un ilateral w eakn ess of th e stern ocleidom as-
gion to in n ervate th e sternocleidomastoid an d
toid m uscle, th e patien t h as difficulty tu rn in g th e
trapezius muscles. It is join ed alon g its cou rse by
h ead to th e opposite side. Bilateral w eakn ess m akes
sp in al som atic efferen t fibers from C2 th rough C4.
it difficu lt to h old th e h ead erect, or to raise th e h ead
Th e literatu re offers con flictin g view s regardin g
w h en lyin g sup in e. Weakn ess of th e trapeziu s
th e relative im p ortan ce of th e accessory n erve an d
m u scle cau ses a sh ou lder drop w ith dow nw ard an d
sp in al n erves C2 th rou gh C4 in th e in n ervation of
ou tw ard displacem en t of t h e scapu la. Lateral rais-
th e trapezius m uscle. Som e au th ors assert th at th e
in g of th e arm beyon d 90° is im paired, becau se th e
accessory n erve m ain ly su pplies th e low er portion
trapeziu s m u scle n orm ally assists th e serratus
of th e m u scle, oth ers t h at it m ain ly su pplies th e
an terior m uscle w ith th is m ovem en t. Sim ple visu al
upp er portion . Lesion s of th e accessory n erve are
in spection of a p atien t w ith an accessory n erve
follow ed by at rophy m ain ly affectin g th e upp er
p alsy reveals atrop hy of th e stern ocleidom astoid
portion of th e trapezius m u scle.
m u scle as w ell as a droopin g sh ou lder.
Th e extern al bran ch also con tain s a few afferen t
fibers th at con du ct proprioceptive im p ulses
Paresis of central origin. Th e spin al portion of th e
tow ard th e brain stem .
accessory n erve receives cen tral descen din g im -
p ulses by w ay of th e corticon u clear an d corticospi-
Lesions Affecting the Spinal Roots of the
n al tracts. Th ese im pu lses are derived m ain ly, bu t
Accessory Nerve
n ot exclu sively, from th e con tralateral cerebral
Causes. Th e m ost com m on cause of a periph eral h em isph ere. Th u s, a cen tral lesion of th e de-
extracran ial accessory n erve palsy is iatrogen ic in - scen din g pat h w ays som etim es cau ses con -
ju ry as a com p lication of surgical procedu res in th e tralateral w eakn ess of th e stern ocleidom astoid
lateral trian gle of th e n eck (e.g., lym p h n ode bi- an d trapezius m u scles, bu t th e w eakn ess is on ly
op sy), follow ed by pressu re- an d radiation -in - p artial because of th e p reserved ipsilateral in n er-
du ced lesion s. Oth er cau ses in clu de trau m a w ith or vation an d is, th erefore, easily overlooked.
w ith out basilar sku ll fracture, sku ll base tum ors
(particu larly in th e region of th e foram en m ag-
Hypoglossal Nerve (CN XII)
n u m ), an d an om alies of th e cran iocervical ju n c-
tion . Th e nucleus of th e hypoglossal n erve (Figs. 4.2 an d
Intram edullary lesions of th e spin al cord are 4.3, an d Fig. 4.51) is located in th e low er th ird of
rarely exten sive en ou gh to destroy t h e gray m atter th e m edu lla, abu ttin g th e m idlin e an d just below
of th e an terior h orn on on e side from C1 to C4, pro- th e floor of th e fou rth ven tricle (in th e so-called
du cin g a cen t ral extracran ial accessory n erve palsy hypoglossal t rian gle or trigon e). It con sists of a
 Cranial Nerves · 133
4
Fig. 4.51 Distribution
and central connections
of the hypoglossal nerve

Deviation of the tongue due to

paresis of the left genioglossus m .

Corticonuclear tract

Input from the reticular formation,

nucleus of the tractus solitarius
and other nuclear areas (reflex
m ovem ents of swallowing, mastication, sucking)

Hypog lossal canal

and nerve
Vagus n.
Nucleus of the hypog lossal n.

C1

C2

C3

Thyrohyoid m .
Ansa cervicalis
Genioglossus m .
Sternothyroid m .
Om ohyoid m .

Sterno -
thyroid m .

n u m ber of cell grou ps su pplyin g th e in dividu al
m uscles of th e ton gu e. Th e cells are an alogou s to
th e m otor an terior h orn cells of th e spin al cord.
Supranuclear innervation of the nucleus of the hy-
poglossal nerve. Volu n tary m ovem en ts of th e
ton gu e are su bserved by th e corticonuclear tract,
w h ich descen ds th rou gh th e in tern al capsu le in as-
sociation w ith th e corticosp in al t ract an d term i-
n ates in th e n ucleus of th e hypoglossal n erve.
Th e n u cleu s of th e hypoglossal n erve derives its
afferen t inpu t m ain ly from t h e contralateral cere-
bral hem isphere, th ough th ere is som e ip silateral
inpu t as w ell. It derives fu rth er input from th e re-
ticu lar form ation , th e n u cleu s of th e tractus soli-
tariu s (taste), th e m idbrain (tectospin al tract), an d
th e trigem in al n u clei. Th ese con n ection s partici-
pate in reflexes con cern ed w ith sw allow in g, ch ew -
in g, suckin g, an d lickin g.
4 134 · 4 Brainstem

Becau se th e m u scles of th e tw o sides of th e Topographical Anatomy

tongu e con stitu te a fun ction al u n it an d are in n er-
vated by both cerebral h em isp h eres (albeit m ain ly
con tralaterally), a u n ilateral su pran u clear lesion
produces n o sign ifican t deficit of ton gu e m otility.
Course and distribution of the hypoglossal nerve.
Th e hypoglossal n erve is a som atic efferent (m otor)
n erve. Its axon s descen d in th e m edu lla an d
em erge from t h e brain stem as root fibers in th e an -
terolateral su lcu s betw een th e in ferior olive an d
th e pyram id (Fig. 4.1). Th e hypoglossal n erve exits
th e sku ll t h rou gh th e hypoglossal can al (Figs. 4.6
an d 4.51) an d run s in t h e low er cervical region be-
tw een t h e jugu lar vein an d carotid artery togeth er
w ith th e fibers of th e first th ree cervical segm en ts
(an sa hypoglossi). Th ese fibers, w h ich m ake n o
con n ection w ith th e hypoglossal n erve, sep arate
from it again a sh ort distan ce later to su pply th e
m uscles of th e hyoid bon e, i.e., th e thyrohyoid,
stern ohyoid, an d om ohyoid m u scles.
Th e hyp oglossal n erve p roper in n ervates th e
m uscles of the tongue, th e styloglossus m uscle, th e
hyoglossus m uscle, an d th e genioglossus m uscle.
Hypoglossal nerve palsy. In un ilateral hypoglossal
n erve palsy, th e ton gue usually deviates a little
tow ard th e paretic side w h en it is protruded. Th e
gen ioglossus m u scle is respon sible for prot ru sion
(Fig. 4.51). If th e gen ioglossu s m uscle of on e side is
w eak, th e force of th e op posite m u scle prevails an d
pu sh es th e ton gu e to th e side of th e lesion . In
h em iplegia, th e patien t’s speech is dysarth ric at
first, bu t sw allow in g is n ot im paired. Bilateral su -
pran u clear palsy p rodu ces severe dysarth ria an d
dysph agia (pseudobu lbar palsy).
Nuclear lesions affectin g th e hypoglossal n erve
are usually m an ifested by bilateral flaccid paralysis
of th e ton gue w ith atrophy an d fasciculat ion s, be-
cause th e n u clei of th e tw o sides lie so close to each
oth er th at th ey are u su ally affected togeth er. In ad-
van ced cases, th e ton gu e lies lim ply in th e floor of
of the Brainstem
Up to th is poin t, w e h ave discussed th e ascen din g
an d descen din g path w ays of th e spin al cord an d
th e p osition s of th e cran ial n erve n u clei in th e
brain stem , alon g w ith t h eir em ergin g root fibers
an d t h eir cen tral con n ection s. Th is sect ion deals
w ith th e topography of th e pathw ays th at traverse
th e brain stem , as w ell as th e site and function of
other nuclei besides th ose th at h ave already been
described. Kn ow ledge of t h e topograph ical an at-
om y of th e brain stem is essen tial for a p roper u n -
derst an din g of t h e clin ical syn drom es produ ced by
lesion s affectin g th e m edu lla, pon s, an d m idbrain .
Internal Structure of the Brainstem
Th e brain stem con tain s im portan t n uclei, in clu d-
in g th e reticular form ation, th e olives, th e red nu-
cleus, t h e substantia nigra, an d oth ers, each of
w h ich w ill be described in th e su bsection dealin g
w ith th e part of th e brain stem in w h ich it is lo-
cated. Th e connections th at th ese n u clei m ake w ith
each oth er an d w ith th e cerebrum , cerebellu m , an d
spin al cord w ill also be discu ssed.
Figu res 4.52 an d 4.53 con tain lon gitu din al an d
cross-section al diagram s of th e brain stem , sh ow -
in g th e in dividual n u clei, th e ascen din g an d de-
scen din g path w ays, an d th eir spatial relation sh ips.
a Oral
III
IV
Ventral Dorsal
Py
V
m.l.
VI

th e m ou th an d fascicu lates in ten sely. Speech an d

VII 4
sw allow in g are profou n dly im paired. Cau ses in -
3
a
clude progressive bu lbar palsy, am yot roph ic lateral VIII
l
l
u
d
sclerosis, syrin gobu lbia, poliom yelit is, an d vascu- IX XII
e
2
M
X
lar processes.
1
Peripheral lesions of th e hypoglossal n erve h ave
XI
th e sam e con sequ en ces as n u clear lesion s, bu t th e
m .l. = m edial lemniscus
paralysis is usually on ly u n ilateral. Cau ses in clu de Caudal
tu m ors, in fection /in flam m ation , an d vascu lar dis-
ease. Fig. 4.52 Cross-sections of the medulla at four different
levels. a The four planes of section.
Fig. 4.52 b

b
Inferior cerebellar
peduncle
Medial longitudinal
fasciculus
Tectospinal tract
Nucleus of the spinal
tract of the trigem inal n.
Anterior spinocerebellar
tract
Reticular formation
Central tegmental
tract
Topographical Anatom y of the Brainstem · 135
4
Nucleus of the hypoglossal n.
Dorsal nucleus of the vagus n.
Tractus solitarius
Nucleus of the cochlear n.
Nucleus ambiguus
Central sym pathetic pathway
Rubrospinal tract
Lateral spinothalamic tract
Inferior olivary nucleus
Pyram idal tract
4 XII Hypoglossal n.
Medial lem niscus Arcuate nucleus

Roof of the fourth ventricle

Fourth ventricle
Posterior spinocerebellar
tract
Nucleus of the spinal
tract of the trigem inal n.
Anterior spinocerebellar
tract
Reticular formation
Medial longitudinal
fasciculus
Medial lem niscus
3 XII
Nucleus of the spinal
tract of the trigem inal n.
Reticular formation
Posterior spinocerebellar
tract
Medial longitudinal
fasciculus
Medial lem niscus
Anterior spinocerebellar
tract
Tectospinal tract
2 XII
Dorsal nucleus of the vagus n.
Tractus solitarius
Nucleus of the hypoglossal n.
Nucleus ambiguus
Central sym pathetic pathway
Rubrospinal tract
Lateral spinothalamic tract
Inferior olivary nucleus
Hypoglossal n.
Arcuate nuclei
Lemniscal decussation
Gracile nucleus
Accessory cuneate
nucleus
Cuneate nucleus
Tractus solitarius
Nucleus of the hypoglossal n.
Nucleus of the accessory n.
Central sym pathetic pathway
Rubrospinal tract
XI Lateral spinothalamic tract
Inferior olivary nucleus
Hypoglossal n.

Substantia gelatinosa
Nucleus of the spinal tract
of the trigem inal n.
Reticular formation
Posterior spinocerebellar
tract
Anterior horn
Anterior spinocerebellar
tract
Medial longitudinal
fasciculus
Gracile nucleus
Tractus solitarius
Cuneate nucleus
Nucleus of the accessory n.
Lateral pyram idal tract
XI
Central sym pathetic pathway
Lateral spinothalamic
and rubrospinal tracts
Tectospinal tract
Pyram idal decussation
1 Anterior pyram idal tract

Fig. 4.52 Cross-sections of the medulla at four different levels. b Sections in the four planes indicated in a, showing the
im portant nuclei and fiber pathways.
4 136 · 4 Brainstem
Figu res 4.54 an d 4.55 dep ict th e spatial relation -
sh ips of t h e in dividu al fiber pat h w ays in lateral an d
dorsal view s of th e brain stem .
Medulla
Th e spatial arran gem en t of th e gray an d w h ite m at -
ter in th e m edu lla already differs from th at in th e
spin al cord at th e low est m edu llary level, i.e., at th e
level of th e pyram idal decu ssation (Fig. 4.52). Th e
an terior h orn s can still be seen : th ey con tain th e
m otor n uclei for th e first cervical n erve an d for th e
roots of t h e accessory n erve. Th e descen din g fibers
of th e corticospin al tract s are located in th e py-
ram ids; m ost of th ese fibers cross th e m idlin e at
th is level, th en descen d in th e con tralateral lateral
fu n icu lu s of t h e spin al cord. In t h e region of th e
posterior colu m n s, tw o n u clei are fou n d, i.e., th e
cuneate nucleus an d th e gracile nucleus. Th ese are
th e relay n u clei for th e ascen din g posterior colu m n
fibers of th e sp in al cord. Th ey, in t urn , project im -
pulses by w ay of th e m edial lem n iscus to th e con -
tralateral th alam u s. Th ese tw o n u clei possess a so-
m atotopic arran gem en t (poin t-to-poin t projec-
tion ), in w h ich th e cun eate n u cleu s con tain s fibers
for th e upp er lim bs, w h ile th e gracile n ucleu s con -
tain s fibers for th e low er lim bs. Th is som atotopy is
preserved in t h e m edial lem n iscu s, in th e th alam u s,
an d all th e w ay u p to th e prim ary sen sory cortex.
Figure 4.55c sh ow s th e t w istin g cou rse of th e m e-
dial lem n iscu s: th e fibers carryin g im pu lses for th e
low er lim b are m ore lateral, an d th ose carryin g im -
pulses for th e up per lim b are m ore m edial.
Th e lateral spinothalamic tract (pain , tem pera-
tu re), anterior spinothalamic tract (tou ch , pres-
su re), an d spinotectal tract (to th e qu adrigem in al
region ) h ave essen t ially th e sam e position in t h e
cau dal m edu lla as in th e cervical spin al cord.
An exten sive n etw ork of cells, th e lateral reticu-
lar nucleus, receives in com in g fibers from th e re-
ticular form ation of th e spin al cord. Th is n ucleu s
lies dorsal to th e in ferior olivary n ucleus. Th e
sp in oret icular fibers carry sen sory im pu lses from
th e skin an d in tern al organ s. Th ese fibers ru n m ore
diffu sely in th e spin al cord, som e of th em in asso-
ciation w ith th e spin oth alam ic tract.
Th e posterior spinocerebellar tract, w h ich origi-
n ates in Clarke’s colu m n (th e th oracic n ucleu s) an d
ascen ds ipsilaterally in th e sp in al cord, at first
keeps its position in th e caudal m edu lla, th en takes
a p rogressively m ore dorsal position an d fin ally ac-
8
Midbrain
a
III 7
IV
Pons
6
Py
V 5
m .l.
m .l. = m edial lem niscus
Fig. 4.53 Cross-sections of the pons and midbrain at
four different levels. a The four planes of section.
Fig. 4.53 b
com pan ies th e olivocerebellar tract as it travels, via
th e in ferior cerebellar pedu n cle, to th e cerebellum
(Figs. 4.54b an d 4.55b). Th e anterior spinocerebel-
lar tract, p art of w h ich is crossed, traverses th e
m edu lla an d pon s an d fin ally en ters th e cerebel-
lu m by w ay of th e su perior cerebellar p edu n cle
an d th e su perior m edu llary velu m (Figs. 4.54b an d
4.55b).
Th e olivary nuclear complex is located in th e
rost ral portion of th e m edu lla. Th e in ferior olive
(Figs. 4.54 an d 4.55), w h ich resem bles a sh eet of
gray m atter th at h as been folded u p to form a bag,
receives m ost of its afferen t inpu t from th e red n u -
cleu s of th e m idbrain , by w ay of th e cen tral
tegm en tal tract. It receives fu rth er afferen t inpu t
from th e striat um , th e p eriaqu eductal gray m atter,
th e reticular form ation , an d th e cerebral cortex, by
w ay of th e cort ico-olivary tract , w h ich run s to-
geth er w ith th e corticosp in al tract. Efferen t fibers
from th e in ferior olive cross th e m idlin e an d form
th e olivocerebellar tract, w h ich en ters th e cerebel-
lu m th rough th e in ferior cerebellar pedun cle (Figs.
4.54b an d 4.55b) an d conveys im p ulses to th e en -
tire n eocerebellar cortex. Th is olivocerebellar pro-
jection belon gs to th e system for coordin ation of
volu n tary m ovem en t; it w ill be discu ssed furth er
in th e ch apters con cern in g th e cerebellu m (Ch ap-
ter 5) an d basal gan glia (Ch apter 8).
 Topographical Anatom y of the Brainstem · 137
4
b
Nucleus of the superior colliculus Mesencephalic tract of the
Cerebral aqueduct trigem inal n.
Spinotectal tract Lateral spinothalam ic tract
Brachium colliculi Central (periaqueductal)
Reticular formation gray matter
Medial longitudinal Central sym pathetic pathway
fasciculus Nucleus of the oculomotor n.
Medial lem niscus Substantia nigra
Tectospinal tract Red nucleus
Tegm ent al decussation Corticopontine tract
Corticospinal fibers

l
t
III

a
c
d
8

a
i
Corticonuclear fibers

r
m
t
a
Dorsal longitundal fasciculus IV Corticopontine tract

r
y
(of Schütz)

P
Lateral lem niscus Mesencephalic tract of the
Locus ceruleus trigem inal n.
Medial longitudinal Lateral trigem inal
fasciculus lem niscus
Superior cerebellar Lateral spinothalam ic
peduncle tract
Medial cerebellar Rubrospinal tract
peduncle Central sym pathetic pathway
Central tegmental

l
Corticonuclear fibers

t
a
c
d
a
tract

i
Corticospinal fibers

r
m
t
Medial lem niscus

a
Tectospinal tract

r
y
Reticular formation

P
Decussation of the superior 7
cerebellar peduncles Central sym pathetic pathway
Principal sensory nucleus
Posterior spinocerebellar of the trigem inal n.
tract
Nucleus of the spinal tract
Superior cerebellar of the trigem inal n.
peduncle
Motor nucleus of the
Anterior m edullary velum trigem inal n.
Medial longitudinal Rubrospinal tract
fasciculus
Lateral spinothalam ic
Medial cerebellar
tract
peduncle
Tectospinal tract
Reticular formation
Trigem inal n.
Lateral lem niscus V
Pyram idal tract
Central tegm ental tract
Pontine nuclei
Medial lem niscus 6
Fastigial nucleus
Vestibular nuclei Em boliform nucleus
Superior nucleus (of Bekhterev) Dentate nucleus
Medial nucleus (of Schwalbe) Globose nucleus
Lateral nucleus (of Deiters)
Inferior cerebellar
Inferior nucleus (of Roller)
peduncle
Medial longitudinal
Tractus solitarius
fasciculus
Nucleus of the abducens n.
Spinal tract of the trigem inal n.
Central sym pathetic pathway
Central tegm ental tract
Nucleus of the facial n.
Anterior spinocerebellar
tract Trapezoid body
VIII
Lateral lem niscus Rubrospinal tract
VII Lateral spinothalam ic
Medial lem niscus
tract
Superior olivary nucleus
5 VI Corticospinal tract
Pontine nuclei

Fig. 4.53 Cross-sections of the pons and midbrain at four different levels. b Sections in the four planes indicated in a,
showing the im portant nuclei and fiber pathways.
4 138 · 4 Brainstem

a Cort icospinal tract

Cort iconuclear tract
Cort icom esence-
phalic tract
Medial longitudinal
fasciculus
Rubrospinal tract

Thalam us

Anterior cort icospinal

Red nucleus tract
Lateral cort icospinal
tract

b Cerebello-
rubral
Parietopontine tract
Mesencephalic
tract
tract of the
Occipitopontine trigeminal n.
tract
Frontopontine Superior cerebellar peduncle
tract Middle cerebellar peduncle
Tem poropontine
Inferior cerebellar peduncle
tract
Olivocerebellar tract
Posterior spinocerebellar
Cort icopontine tract
tract Anterior spinocerebellar
tract
c Nucleus of the spinal
To the cortex
tract of the
Olive trigeminal n.

Lateral lemniscus
Accessory olivary nucleus

Red Nucleus Nucleus cuneatus

Nucleus gracilis
Medial lem niscus
Spinothalam ic tract
Central tegmental tract
Spino-
olivary tract

Fig. 4.54 Fiber connections in the brainstem, lateral view. a Efferent pathways. b Cerebellar pathways. c Afferent path-
ways.

Th e accessory olive is phylogen etically older
th an th e in ferior olive. It is con n ected to th e ar-
ch icerebellum an d p lays a role in th e m ain ten an ce
of balan ce.
Lesions of the inferior olive or of th e cen tral tegm en -
tal tract produ ce rhyth m ic tw itch in g of th e soft pa-
late, th e ph aryn x, an d som etim es th e diaph ragm
(m yorhyth m ia, m yoclon u s, sin gult us). Isch em ia is
th e usu al cau se.
Th e cou rses of th e corticospinal and corticonu-
clear tracts are depicted in th e cross-section al dia-
gram s of th e brain stem an d in Figures 4.54a an d
4.55a.
Th e rubrospinal tract also passes th rough th e
m edu lla. Th is tract origin ates in th e red n u cleu s of
th e m idbrain an d crosses th e m idlin e a sh ort dis-
tan ce below it in th e ven tral tegm en tal decu ssa-
tion (of Forel). It accom pan ies th e lateral corti-
 Topographical Anatom y of the Brainstem · 139
4
a
Red nucleus
Cort ico-
nuclear
tract
Inferior colliculus
Cort ico-
spinal Rubrospinal tract
tract
Medial longitudinal
fasciculus

Nucleus of
Superior cere- the m esence-
Pyram idal bellar peduncle phalic tract
decussation Middle cere- of the
Lateral cortico- bellar peduncle trigem inal n.
spinal tract Inferior cere-
(crossed) bellar peduncle
Anterior cortico-
spinal tract
(uncrossed)

c
Olivo-
cerebellar tract
Nucleus of
Dentate
Central the spinal tract
nucleus
tegmental of the trigem inal n.
Inferior Anterior spino-
tract
olive cerebellar tract

Posterior spino-
Lateral cerebellar tract
lem niscus
Lateral spinothalam ic
tract
Accessory olivary
Medial nucleus
lem niscus Trapezoid body
Nucleus Inferior olive
cuneatus
Nucleus
gracilis

Fig. 4.55 Fiber connections in the brainstem, dorsal view. a Efferent pathways. b Cerebellar pathways. c Afferent path-
ways.

cosp in al tract as it descen ds in th e lateral fun iculu s
of th e spin al cord (Fig. 4.55).
Th e tectospinal tract origin ates in th e m idbrain
tectu m an d im m ediately crosses th e m idlin e,
sw in gin g aroun d th e periaquedu ctal gray in th e
dorsal tegm en tal decu ssation (of Meyn ert). Th e
tectosp in al tract at first descen ds n ear th e m idlin e
an d th en gradu ally takes a m ore ven t ral an d lateral
position , com in g to lie in th e ven trolateral portion
of th e m edulla, n ear th e ru brospin al tract . Alon g its
w ay in to t h e m edulla, t h e tectosp in al tract gives off
collaterals to th e n u clei in n ervatin g th e extraocu-
lar m u scles, as w ell as to th e n ucleu s of th e facial
n erve an d th e cerebellu m . It en ds in th e cervical
spin al cord. Function: Th e su perior colliculi receive
visu al inpu t from th e retin a an d au ditory inpu t
from th e in ferior collicu li. In ten se visu al an d au di-
tory stim uli evoke reflex closu re of th e eyes, turn -
in g of th e h ead aw ay from th e stim ulu s, an d som e-
tim es also raisin g of th e arm s (defen se position );
4 140 · 4 Brainstem
th ese reflexes are m ediated by th e tecton u clear
an d tectospin al path w ays. Th e fu n ction al in terac-
tion of th e occipit al lobe an d th e su perior collicu lar
plate w as m en t ion ed in an earlier section . Th ese
tw o stru ctures w ork togeth er w ith th e tectospin al
path w ays to en able autom atic pursuit m ovem ents
of the eyes and head w hen the individual looks at a
m oving object.
On th e various cross-section al im ages of th e
m edu lla, pon s, an d m idbrain , on e can see, in th e
sp aces betw een th e larger n u clei an d th e ascen d-
in g an d descen din g path w ays, a n um ber of dif-
fu sely distribu ted n u clei of varyin g size t h at oc-
casion ally clu ster in to n u clear grou ps, w ith an ex-
ten sive n etw ork of fibers con n ectin g th em . Th ese
in tercon n ected grou ps of n eu ron s are kn ow n col-
lectively as th e reticular formation, a stru ctu re
w h ose great im portan ce w as first recogn ized by
Moru zzi an d Magou n (1949). Th e reticu lar form a-
tion exten ds from th e spin al cord (w h ere it lies be-
tw een th e lateral an d posterior fu n icu li) u pw ard,
th rough t h e m edu lla an d p on s, to th e oral part of
th e m idbrain (Figs. 4.52 an d 4.53). We w ill discu ss
its fun ction later (p. 143).
On e of th e im portan t n u clei in t h e m edu lla is th e
dorsal nucleus of the vagus nerve, w h ich lies
ben eath th e floor of th e fou rt h ven tricle (Fig. 4.1b).
It con tain s au ton om ic m otor (i.e., parasym p a-
th et ic) n euron s, w h ich are an alogou s to th e (sym -
path etic) n euron s of th e lateral h orn s of th e spin al
cord from T1 to L2. Th e m ore laterally lyin g nucleus
of the tractus solitarius is a som atosen sory an d
special sen sory n u cleus. Its rostral port ion receives
gu statory inpu t from cran ial n erves VII, IX, an d X.
Its cau dal portion , w h ich receives afferen t fibers
from th e th oracic an d abdom in al viscera, is in ter-
con n ected w ith th e dorsal n u cleus of th e vagus
n erve, w ith visceral cen ters in th e reticu lar form a-
tion , an d w ith n eu ron s projectin g to th e au ton om ic
n u clei in th e lateral h orn s of th e spin al cord. All of
th ese n u clei can th us part icipate in reflex arcs th at
regulate an d con trol cardiovascu lar, respiratory,
an d alim en tary fu n ction , an d oth er vegetat ive
processes (see Fig. 4.56).
Th e nucleus of the hypoglossal nerve an d th e
nucleus ambiguus h ave already been discussed in
th e section dealin g w ith th e cran ial n erves, as h ave
th e vestibular nuclei an d th e nucleus of the spinal
tract of the trigeminal nerve. Th e m edial lon gitu di-
n al fasciculu s is fou n d in a dorsal position n ear th e
m idlin e; ven tral to it lie th e tectosp in al tract an d
th e m edial lem n iscu s (Fig. 4.52).
Pons
Th e pons h as tw o com pon en ts: th e pontine teg-
m entum is dorsal, an d th e ventral portion of the
pons (basis pontis) is ven tral.
Ventral portion of the pons. Many fiber bun dles
traverse th e pon s from on e side to th e oth er in th e
basis pon tis, t h ereby fragm en t in g th e descen din g
corticospin al tracts in to m any little fascicles
(Fig. 4.53). Th ese h orizon tally ru n n in g tracts give
th e p on s its n am e (“bridge”), th ough th ey do n ot, in
fact , con st itu te a bridge. Th ey are pon tocerebellar
fibers, arisin g in n u clei of th e basis pon tis th at con -
tain th e secon d n eu ron s of th e corticopontocere-
bellar path w ay. Th ese n u clei receive inpu t via de-
scen din g cort icopon tin e fibers from th e ipsilateral
fron tal, pariet al, an d tem p oral cerebral cortex
(w h ich are foun d in th e lateral portion of th e cere-
bral pedu n cle on eith er side, accom p anyin g th e
corticospin al an d corticon u clear fibers), an d th ey
receive fu rth er inp ut from collateral fibers of th e
pyram idal t racts. Th e pon tocerebellar fibers pro-
ject across th e m idlin e an d th en en ter th e cerebel-
lum th rough th e m iddle cerebellar p edu n cle.
All cortically derived im pu lses related to volu n -
tary m ovem en t are relayed by th e pon tin e n u clei to
th e cerebellar cortex, w h ich th en projects back to
th e cerebral cortex by w ay of th e den tate n u cleu s,
sup erior cerebellar pedu n cle, an d th alam u s (feed-
back m ech an ism , cf. Fig. 5.6, p. 163). Th is regula-
tory circuit en ables sm ooth an d precise coordin a-
tion of volun tary m ovem en t.
Th e stru cture of th e pon tin e tegmentum is sim ilar
to th at of th e m edullary tegm en tu m . Th e m ost
ven t ral portion of th e tegm en t um con t ain s th e me-
dial lemniscus (Figs. 4.53b an d 4.55c), a tran s-
versely orien ted ban d th at h as tw isted itself
arou n d so th at th e fibers derived from th e cu n eate
n ucleu s are n ow m ore m edial, an d th ose from th e
gracile n ucleu s m ore lateral. Th us, from lateral to
m edial, th e parts of th e body represen ted in th e
m edial lem n iscu s are th e low er lim b, tru n k, up per
lim b, an d n eck. Th e spinothalamic tract abu ts th e
m edial lem n iscus laterally (Fig. 4.55c), as does th e
lateral lem n iscu s (au ditory p ath w ay). Th e last-
n am ed structu re is th e con tin u ation of a fiber
bun dle t h at decu ssates in th e cau dal p on s, th e so-
called trapezoid body (Figs. 4.53b an d 4.55). Th e
trapezoid body con tain s fibers derived from th e
tahir99-VRG & vip.persianss.ir

coch lear n u clei an d t ran sm its au ditory im pu lses to
th e in ferior colliculi, both direct ly an d in directly.
Th e vestibular nuclear complex lies at th e far
lateral en d of th e floor of th e fou rth ven tricle
(Fig. 4.53b). Th e lateral vest ibu lar n ucleus gives off
th e vest ibu lospin al tract to n eu ron s of th e spin al
cord. Th e vestibu lar n u clei are also con n ected,
th rough th e m edial lon gitu din al fascicu lus, to th e
som atom otor an d viscerom otor n u clei of th e
brain stem (Fig. 4.46).
Th e spin al n u cleu s of th e trigem in al n erve en ds
at a m id-pon t in e level, above w h ich t h e principal
sensory nucleus of the trigeminal nerve is fou n d.
Th e motor trigeminal nucleus, w h ich in n ervates
th e m uscles of m astication , is ven trolateral to th e
prin cipal sen sory n u cleu s. Th e secon d n eu ron s of
th e spin al n ucleu s of th e trigem in al n erve (pain
an d tem peratu re) an d th e prin cipal sen sory n u-
cleus of th e trigem in al n erve (epicritic sen sation )
project to th e con tralateral th alam u s th rou gh th e
ventral trigeminothalamic tract. Th e prin cipal
sen sory n u cleus also sen ds u n crossed fibers to t h e
th alam u s th rough th e dorsal trigeminothalamic
tract. Th e nucleus of the mesencephalic tract of the
trigeminal nerve con tin u es rostrally in to th e m id-
brain (Fig. 4.55b). Th is trigem in al n u cleu s differs
from th e rest—as already m en t ion ed—in th at it
con tain s first sen sory n eu ron s, an d can th u s be
th ou gh t of as a sen sory gan glion th at is exception -
ally located w ith in th e brain stem . Th e rem ain der
of th e first sen sory n eu ron s of th e trigem in al sys-
tem are located in th e trigeminal (gasserian) gan-
glion. Th e afferen t fibers of th e n ucleu s of th e
m esen ceph alic tract of th e trigem in al n erve con -
vey prop rioceptive inp ut m ain ly derived from t h e
sen sory receptors of th e m uscles of m astication
an d th e tem porom an dibu lar join t.
Midbra in
Th e m idbrain lies rostral to th e pon s. It s in tern al
stru ctu re is sh ow n in Figure 4.53b (section 8). Th e
m idbrain h as fou r parts: (1) th e tectum (“roof”),
delim ited by an im agin ary h orizon tal lin e t h rou gh
th e aqu educt, w h ich con tain s th e superior an d in -
ferior collicu li (qu adrigem in al plate); (2) th e teg-
mentum, lyin g betw een th e tectu m an d th e su b-
stan tia n igra; (3) th e substantia nigra; an d (4) th e
cerebral peduncles (cru ra cerebri).
Topographical Anatom y of the Brainstem · 141
4
Tectum. Th e quadrigeminal plate con sists of th e
superior and inferior colliculi. Th ese, particularly
th e su perior collicu li, are h igh ly sp ecialized organ s
w ith seven cellu lar layers an d n u m erou s afferen t
an d efferen t con n ection s th at can on ly be dis-
cu ssed h ere in broad ou tlin e.
Th e n uclear area of th e inferior colliculi receives
n um erou s afferen t fibers of th e au ditory path w ay
(lateral lem n iscu s) an d projects onw ard, by w ay of
th e brach ia of th e in ferior collicu li, to th e m edial
gen icu late bodies on eith er side. Th ese, in tu rn ,
project to th e prim ary auditory cortex in th e tem -
poral lobe (tran sverse gyri of Hesch l).
Th e n uclear area of th e superior colliculi receives af-
feren t fibers from t h e visu al path w ay as w ell as
from th e cerebral cortex (occipital lobe), spin al
cord (spin otectal tract), an d in ferior collicu li. It
projects efferen t fibers to th e spin al cord (tectosp i-
n al tract) an d to th e cran ial n erve n uclei (tecton u-
clear tract), as w ell as to th e red n u cleu s an d reticu -
lar form ation .
Reflexes m ediated by the superior and inferior col-
liculi. Fibers project in g from th e in ferior collicu lu s
to th e sup erior collicu lus form p art of a reflex arc
th at tu rn s th e h ead an d eyes tow ard th e sou rce of
an in com in g soun d. Retin al im pu lses th at reach t h e
superior colliculi by w ay of th e lateral gen icu late
body participate in a fu rt h er reflex arc th at m akes
th e eyes close in resp on se to a sudden visu al
st im ulus, an d m ay also cau se th e h ead to tu rn aw ay
from th e stim ulus. Th e tecton u clear an d tectospi-
n al tracts form th e efferen t arm s of th ese reflex
arcs.
The sm all pretectal nuclei are foun d im m edi-
ately an terolateral to th e su perior colliculi on both
sides. Th ese n u clei receive afferen t fibers from th e
ret in a an d p roject efferen t fibers, after a syn aptic
relay, arou n d th e periaqu eductal gray m atter to
th e parasym p ath etic Edin ger–Westph al n u clei
(= accessory [au ton om ic] n u clei). Th ey participate
in th e reflex arc th at regu lates th e size of th e pu pil
in respon se to th e in ten sity of th e in ciden t ligh t
(p. 101).
In th e m iddle of th e tegmentum, betw een th e su b-
stan tia n igra an d th e periaquedu ctal gray m atter,
on e fin ds a large, ellip soidally sh aped n u cleus th at
is red in fresh an atom ical section s, partly because
tahir99-VRG & vip.persianss.ir
4 142 · 4 Brainstem
it is w ell vascularized, an d partly because it con -
tain s iron . Th is is th e red n ucleu s (n ucleu s ruber).
Th e red nucleus h as tw o parts, a cau dal m agnocellu-
lar part an d a rostral parvocellular part. It receives
afferent inpu t from th e em boliform an d dentate nu-
clei of th e cerebellu m by w ay of th e su perior cere-
bellar p edu n cles. Th e fibers th at origin ate in t h e
phylogen etically older em boliform n u cleus p artici-
pate in reflex arcs con trollin g body postu re an d
variou s types of m ovem en t . Th e fibers th at origi-
n ate in th e den tate n ucleu s are especially n u m er-
ous in h um an s an d participate in oth er reflex arcs.
On e regu latory circu it for th e sm oot h an d precise
execu tion of volun tary m ovem en t con sist s of con -
n ection s from th e cortex to th e cerebellum an d
th en back to th e cortex by w ay of th e den tate n u-
cleus, red n u cleus, an d th alam u s (cf. p. 163).
An ot h er grou p of den tatorubral fibers term in ates
prim arily in th e parvocellu lar p art of th e red n u -
cleus. All cerebelloru bral fibers cross th e m idlin e in
th e m idbrain , in th e decu ssation of th e su perior
cerebellar p edun cles. Th e red n u cleu s receives
fu rth er afferen t inp ut from th e cerebral cortex (cor-
ticorubral tract) an d from th e tectum .
Th e m ain efferent projection s of th e red n u cleu s
(th e rubrospinal an d rubroreticular tracts) exert an
in flu en ce on th e spin al m otor n eu ron s; both of
t h ese tracts cross t h e m idlin e, ju st after th ey
em erge from th e red n u cleu s, in th e ven t ral
tegm en tal decussation (of Forel). Fu rth er efferen t
fibers travel by w ay of th e cen tral tegm en tal tract
to th e olive (ru bro-olivary fibers), from w h ich a re-
curren t projection return s to th e cerebellu m .
Other tegm ental nuclei and fiber tracts. Th e lateral
portion of th e tegm en tu m con tain s th e m esen-
cephalic tract of the trigem inal nerve, the trigem inal
lem niscus, th e m edial lem niscus, an d th e
spinothalam ic tract, all of w h ich project to th e
th alam u s. Th e trochlear nerve em erges from th e
brain stem dorsally (it is t h e on ly cranial n erve to
do so); its root fibers cross t h e m idlin e just cau dal
to th e in ferior collicu li, th en circle aroun d th e cere-
bral pedun cle to th e base of th e brain , an d con -
tin u e, below th e ten torial edge, to th e cavern ous
sin u s. Th e nuclear com plex of the oculom otor nerve,
as w ell as th e parasym path etic Edinger–W estphal
nucleus (accessory [auton om ic] n u cleus) an d nu-
cleus of Perlia, lie in th e m idbrain tegm en tu m at
th e level of th e su perior collicu li, an terior to th e
aquedu ct an d periaqu eductal gray m atter an d m e-
dial to th e m edial lon gitu din al fascicu lu s. Som e of
th e root fibers of th e th ird cran ial n erve traverse
th e red n u cleus before th ey em erge from th e brain -
stem in to th e in terpedu n cular fossa. Im pulses from
th e vestibular n u clei are carried dow nw ard tow ard
th e spin al cord in th e m edial longitudinal
fasciculus—a bun dle th at in corp orates a n um ber of
differen t fiber system s an d is presen t alon g th e en -
tire exten t of th e brain stem , as w ell as in th e cervi-
cal spin al cord. Its fibers lie n ear th e m idlin e below
th e floor of th e fourth ven tricle (at m edu llary an d
pon tin e levels), an d ven tral to th e aquedu ct an d
periaquedu ctal gray m atter (at m idbrain levels);
som e of th em term in ate on th e n uclei in n ervat in g
th e extraocu lar m u scles (th e n u clei of th e ocu lo-
m otor, troch lear, an d abdu cen s n erves) an d con -
n ect th ese n u clei w ith on e an oth er. Oth er fibers of
th e m edial lon gitudin al fascicu lus term in ate in n u -
clei of th e reticu lar form ation , in cludin g th e in ter-
st itial n u cleus (of Cajal) an d Darksh evich ’s n u cleus.
Th e central sym pathetic pathway is th ough t to orig-
in ate in m u ltip le n u clei of th e hypoth alam us an d
reticu lar form ation . It passes th rough t h e m idbrain
an d pon s ju st an terior to th e aqu edu ct an d below
th e floor of th e fou rth ven tricle. In th e m edu lla, it
occupies a m ore lateral position , from w h ich it
th en p asses in to th e lateral h orn s of th e spin al gray
m atter. In terruption of th e cen tral sym path etic
path w ay produ ces Horn er syn drom e (pp . 102,
108).
Th e substantia nigra is a large m otor n ucleu s t h at
lies betw een th e tegm en tu m an d th e crus cerebri
on eit h er side. Its dark coloration is du e to a
m elan in pigm en t con tain ed in th e n euron al cell
bodies. Th e su bstan tia n igra is an im portan t com -
pon en t of th e extrapyram idal m otor system an d
th us h as an in tim ate fu n ction al relation sh ip w ith
th e basal gan glia. It w ill be discussed fu rth er, to-
geth er w it h th e basal gan glia, in Ch apter 8.
Th e cerebral peduncles (cru ra cerebri is th e plu ral
form ; sin gular, cru s cerebri) are large fiber bu n dles,
on e on eith er side, m ade u p of corticospin al, corti-
con uclear, an d corticopon tin e fibers (Fig. 3.7, p . 42,
an d Fig. 4.53b). Each cerebral pedun cle is form ed
by fibers from th ese th ree t racts, w h ich tw ist
tow ard th e m idlin e as th ey descen d in th e in tern al
capsule. Th e corticospin al and corticon u clear
tahir99-VRG & vip.persianss.ir
 Topographical Anatom y of the Brainstem · 143
4
Fig. 4.56 The reticular
formation: dorsal (a) and
Nucleus raphe dorsalis lateral (b) view s. a Dia-
Pedunculopontine tegmental gram of the m ajor regula-
nucleus tory centers in the
Superior central nucleus m edulla, pons, and m id-
Locus ceruleus brain. b Additional depic-
Nucleus raphe pontis tion of the raphe nuclei.
Nucleus raphe magnus

Nucleus raphe obscurus

a

Hypothalam ic
nuclei b

Visuospatial orientation,
autonom ic coordination
of food intake (chewing,
licking, sucking)
Pneum otactic nuclear
area, autonomic coordination Dorsal nucleus
of breathing and circulation, of the vagus n.
auditory and vestibular
Area postrema
spatial orientation
Swallowing (“vomiting center”)
Autonomic coordinating areas
Vasom otor
for blood pressure, cardiac function,
control
vasoconstriction/vasodilation,
inspiration/expiration, somatic Nuclear area
swallowing, gag, and for expiration
vom iting reflexes Nuclear area
for inspiration

fibers occupy th e m idport ion of t h e cerebral
pedun cle an d are flan ked, both m edially an d later-
ally, by cort icopon t in e fibers (Fig. 4.53b).
Reticular Form ation
Th e cell group s an d fibers of th e n etlike reticu lar
form ation are fou n d t h rou gh ou t th e en tire len gt h
of th e brain stem , w h ere th ey fill u p th e in terstices
betw een th e cran ial n erve n u clei, olives, an d as-
cen din g an d descen din g n erve p ath w ays (Figs.
4.52b, 4.53b, an d 4.56a). Th e reticu lar form ation
receives afferen t fibers from t h e spin al cord, th e
cran ial n erve n u clei, th e cerebellu m , an d th e cere-
bral h em isph eres, an d projects efferen t fibers back
to th ese sam e stru ctures. Som e of th e n uclei of th e
reticu lar form ation h ave descen din g projection s to
th e spin al cord th at in flu en ce both m otor an d au -
ton om ic fun ction .
Ascending reticular activating system. Oth er n u -
clei of th e reticular form ation , particu larly in th e
m idbrain , project to h igh er cen ters, m ain ly by w ay
of th e in tralam in ar n u clei of th e th alam u s, an d by
w ay of th e subth alam u s. Th ese n u clei receive col-
lateral inpu t from m any differen t ascen din g fiber

tahir99-VRG & vip.persianss.ir

4 144 · 4 Brainstem
tracts (am on g th em th e spin oth alam ic tract , th e
spin al t ract of th e trigem in al n erve, th e tract us soli-
tarius, an d fibers from th e vestibu lar an d coch lear
n u clei, as w ell as from th e visu al an d olfactory sys-
tem s); th ey relay th ese im pu lses u pw ard, over a
polysyn aptic path w ay, to exten sive areas of th e
cerebral cortex, w h ere th ey exert an activatin g
fu n ction . Experim en tal st im u lation of t h ese n u clei
in an im als produces an “arou sal reaction ,” in w h ich
th e sleepin g an im al is aw aken ed. Th e p ion eerin g
st udy of Moru zzi an d Magou n (1949), an d th e su b-
sequen t w ork of n u m erou s oth ers, h ave provided
overw h elm in g eviden ce th at th is system plays an
im portan t role in settin g th e level of consciousness
in h um an s, as w ell as in m ain tain in g th e sleep–
w ake cycle. It h as, th erefore, been n am ed t h e “as-
cen din g reticu lar activatin g system ” (ARAS, cf.
p. 176). Lesion s affectin g th is system can im pair or
abolish con sciou sn ess. Even today, n ot m u ch is
kn ow n abou t th e n euron grou ps th at in flu en ce
ARAS activity; th e m ain ten an ce of w akefu ln ess is
presum ed to depen d, at least in p art, on n eu ron s of
th e reticu lar form ation th at can syn th esize m on o-
am in e n eurotran sm itters su ch as n orepin eph rin e
(n oradren alin e), dopam in e, an d seroton in . Neuron s
syn th esizin g n orepin eph rin e are fou n d in th e
lateral portion of th e reticu lar form ation , w h ich in -
clu des th e locu s ceruleu s. Seroton in is produ ced by
th e n euron s of t h e raph e n uclei (Fig. 4.56b).
Neu ron s of th e basal n u cleus (of Meyn ert) an d of
th e in n om in ate su bstan ce sen d ch olin ergic fibers
to exten sive areas of th e cerebral cortex (Fig. 6.7,
p. 178).
Th e p recise roles p layed by th e ARAS an d th e
ch olin ergic system just m en tion ed in con scious-
ness an d th e sleep–w ake cycle are n ot yet w ell
en ou gh u n derstood to be p resen ted in detail in th is
book. On e th in g th at is certain is th at u n con scious-
ness can be produ ced by lesion s of m ultiple brain
stru ctures.
Th e descending reticular pathw ays (ven t ral an d
lateral reticulospin al tracts) origin ate in th e reticu-
lar form ation an d exert both excitatory an d in h ibi-
tory effects on th e m otor n euron s of th e spin al
cord. Th e cells of origin of th ese path w ays receive
afferen t inp ut from th e cerebral cortex, particularly
th e fron tal lobes, as w ell as from th e cerebellum
an d th e basal gan glia. Excitatory im pulses from th e
brain stem (lateral portion of th e reticu lar form a-
tion , m ain ly in th e p on s bu t also in th e m idbrain )
are carried by bot h th e reticu losp in al an d th e vesti-
bu lospin al t racts in th e an terolateral fu n icu lu s of
th e sp in al cord, w h ile in h ibitory im pu lses, derived
m ain ly from th e ven trom edial portion of th e
m edu lla, reach th e spin al m otor n eu ron s over m u l-
tip le syn aptic relays, m ain ly by w ay of th e lateral
ret iculospin al tract (adjacen t to th e corticosp in al
tract). Both th e excitatory an d th e in h ibitory sys-
tem s im pin ge, th rough in tern euron s, on th e γ m o-
tor n eu ron s of th e spin al cord. Th u s, by regulatin g
th e fu n ction of th e spin al reflex arcs, th e reticu lar
form ation plays an im portan t role in th e m ain -
ten an ce of adequ ate m u scle ton e for stan din g an d
w alkin g, as w ell as in th e m ain ten an ce of balan ce.
Autonomic nuclei and pathw ays. Many n euron s in
th e reticu lar form ation h ave au ton om ic fu n ction s.
Nu clei con tain in g such cells are scattered
th rou gh ou t th e pon s an d m edulla an d receive inpu t
from th e som atic cran ial n erve n u clei (Fig. 4.56,
p. 143). Th ese au ton om ic n u clei receive input from
th e hypoth alam u s an d sen d projection s to th e
cran ial n erve n u clei an d th e spin al cord.
Regulation of salivation. Salivation is con t rolled by
th e superior and inferior salivatory nuclei. It can be
evoked in reflex fash ion by an appetizin g sm ell or
taste. Th e in dividu al’s m en tal state can also in h ibit
salivation un der som e circu m stan ces, causin g a
dry m ou th .
Regulation of blood pressure. Oth er n u clei regu late
blood pressu re. Afferen t im pulses arisin g in t h e
carotid sin us travel over th e glossoph aryn geal an d
vagal n erves to th e correspon din g reticu lar n u clear
areas in t h e m edulla (au tonom ic cen ters for th e
regulation of blood p ressu re, cardiac activity, an d
vasocon striction /vasodilat ion ), w h ich are located
n ear th e n u clei of cran ial n erves IX an d X. Efferen t
im pu lses m ediated by th e vagu s n erve in h ibit car-
diac activity, resu ltin g in slow in g of th e h eart rate
an d a fall in blood pressu re.
Regulation of other autonom ic bodily functions.
Som e descen din g im pu lses from t h e reticular for-
m ation in h ibit th e sym p ath etic n u clei of th e spin al
cord, cau sin g vasodilation . Reticu lar n uclei dorsal
to th e in ferior olive con trol respiration; th ere are
distin ct expiratory an d aspiratory cen ters. Yet
oth er reticular n u clei con trol an d coordin ate
gastrointestinal m otility. Reflex sw allow ing is a
tahir99-VRG & vip.persianss.ir

com p licated process involvin g m any differen t
m uscles, w h ich m u st be activated in th e proper
sequen ce an d at t h e proper in ten sity to propel a
bolu s of food sm ooth ly from th e m ou th in to th e
stom ach ; coordin atin g th e m u ltiple n erves in -
volved in t h is process is t h e fu n ction of t h e so-
called m edu llary sw allow in g cen ter, w h ich lies in
th e vicin ity of th e m otor cran ial n erve n u clei th at it
activates. Nearby, th ere is also a n u cleu s re-
spon sible for gaggin g (th e gag reflex). Th e area
postrem a con tain s an im portan t area for th e regu -
lation of vom iting. Th ere is presum ed to be a h igh er
cen ter for cardiorespiratory fu n ction (a p n eu m o-
Brainstem Disorders · 145
4
tactic n u cleu s) in th e vicin ity of th e locu s ceru leu s,
as w ell as a h igh er cen ter for food intake (ch ew in g,
lickin g, su ckin g) in th e m idbrain (Fig. 4.56a).
Brainstem Disorders
Ischemic Brainstem Syndromes
Th e an atom y of th e arterial blood su pply of th e
brain stem is depicted in Figure 4.57, an d th e terri-
tories of in dividu al arteries su pplyin g th e m edulla,
pon s, an d m idbrain are sh ow n in Figu re 4.58. A

Fig. 4.57 Blood supply of

Anterior cerebral a. the brainstem. a Basal
view. b Lateral view.
Middle cerebral a.

Posterior com m unicating a.

Anterior choroidal a.
Posterior cerebral a.

Superior cerebellar a.
Basilar a.
Anterior inferior cerebellar a.

Labyrinthine a.

Posterior inferior cerebellar a.

Vertebral a.

Anterior spinal a.

Posterior choroidal a.

Posterior cerebral a.

Superior cerebellar a.
s
n
o
p
Short circumferential branch
e
h
t
Long circumferential branch
o
t
s
e
Paramedian branches
h
c
n
a
Basilar a.
r
B
Anterior inferior cerebellar a.

Vertebral aa.
Posterior inferior cerebellar a.

b Anterior spinal a.

tahir99-VRG & vip.persianss.ir

4 146 · 4 Brainstem

Fig. 4.58 Distribution of

a Midbrain
the individual arteries
Superior
supplying the brainstem.
cerebellar a.
a Midbrain. b Pons.
Posterior
c Medulla.
cerebral a.

Posterior
choroidal a.

Posterior Interpeduncular
choroidal a. branches

Posterior Superior Posterior

cerebral a. com m unicating a.
Interpeduncular cerebellar a.
Basilar a. branches (After Murphy)

Superior m edullary velum

Superior cerebellar b Pons
peduncle
Middle Param edian branches
cerebellar
peduncle Short circumferential
branches

Long circumferential
branches

(After Foix and Hillemand)

Trigem inal n.

Basilar a.

c Medulla
Posterior inferior
cerebellar a.

Anterior inferior
cerebellar a.

Anterior spinal a.
and
vertebral param edian aa.

Vertebral a.
Posterior inferior
Anterior spinal a. cerebellar a.

th orou gh discussion of th e arterial blood supp ly
an d ven ous drain age of t h e brain stem is fou n d in
Ch apter 11, on pages 281 ff. Kn ow ledge of th e p at-
tern of blood su pply is essen tial for an u n derstan d-
in g of th e vascu lar syn drom es to be described in
th is sect ion .
Inadequate perfusion of discrete region s of th e
brain stem can be eith er transient (e.g., t h e t ran -
sien t isch em ia of subclavian steal syn drom e, see
p. 147) or permanent (causin g tissu e n ecrosis, i.e.,
brainstem infarction). In farction is u su ally du e to
arterial occlu sion . It produces differen t pat tern s of
clin ical deficits, depen din g on t h e p articu lar vessel
th at h as been occlu ded (vascular syndromes). Be-
cause th e n u clei an d fiber path w ays of th e brain -
stem are n u m erou s, com pactly arran ged, an d
h igh ly diverse in fu n ction , a correspon din gly w ide
variety of vascu lar syn drom es can be observed. To
un derstan d each vascu lar syn drom e, on e m ust first
un derstan d th e com plex top ograp h ical an atom y of
th e brain stem in th e region th at it affects. Th is is
w hy th e brain stem vascu lar syn drom es are pre-
sen ted h ere in th e ch apter on th e brain stem , rat h er
th an in Ch apter 11 togeth er w ith th e vascular dis-
orders of t h e rest of th e brain .
Su bclavian steal syn drom e w ill be discu ssed
first, as an exam p le of a syn drom e w ith tran sien t
brain stem isch em ia. Th e m ajor arterial occlu sion
syn drom es of th e brain stem w ill be presen ted
th ereafter.

Subcla via n Stea l Syndrome
Th is syn drom e occu rs as th e result of occlusion of
the right or left subclavian artery proxim al to th e
origin of t h e vertebral artery. Desp ite th e occlu -
sion , th e cardiovascular system m ain tain s ade-
qu ate perfusion of th e ipsilateral arm by “tapp in g”
th e ipsilateral vertebral artery in retrograde fash -
ion : blood flow s up th e con tralateral vertebral
artery to its ju n ction w it h th e ipsilateral vertebral
artery (w h ere th e t w o arteries join to form th e
basilar artery), an d t h en back dow n th e ipsilateral
vertebral artery in to t h e axillary artery an d onw ard
in to t h e brach ial artery. In rare cases, a situ ation
m ay arise in w h ich exercise of th e arm diverts so
m uch blood from th e vertebrobasilar system th at
clin ically eviden t brain stem isch em ia en su es. Th e
diagn osis of su bclavian steal syn drom e requ ires
both th e ch aracteristic clin ical m an ifestation s and
a clin ically correlated an giograph ic fin din g of ret-
rograde flow in the vertebral artery. Su bclavian
artery occlu sion n eeds to be treated on ly if it
causes isch em ia in th e h an d or fran k su bclavian
steal syn drom e, w ith m an ifestation s of isch em ia in
th e vertebrobasilar territory, su ch as loss of con -
sciou sn ess or vertigo.
Th e t radition al term “vertebrobasilar in su ffi-
cien cy” is n ow obsolete an d sh ou ld n o lon ger be
used.
Individua l Bra instem Vascula r Syndromes
In farction in th e vertebrobasilar distribution , as in
th e carotid distribution , is u su ally du e to embolism
(for a discu ssion , cf. p. 297). Th e respon sible em -
boli m ay arise from th e h eart, from at h erom atous
plaqu es in th e vertebral arteries, or from an arterial
dissection w ith secon dary th rom bosis. Th e on ce-
cu rren t n otion th at kin kin g of th e vertebral arter-
ies durin g sleep m igh t cau se isch em ia is n o lon ger
ten able today.
A n u m ber of differen t brain stem vascu lar syn -
drom es can be iden tified on clin ical an d radiologi-
cal grou n ds. Very recen t ly, h igh -resolu tion m ag-
n etic reson an ce im agin g w ith T2-w eigh ted an d
diffusion -w eigh ted sequ en ces h as en abled th e
direct visu alizat ion of brain stem in farcts in t h eir
acu te ph ase. Alt h ou gh th ere is a degree of variation
am on g in dividu als, t h e vascu lar arch itectu re of th e
brain stem is su fficien tly u n iform th at th e syn -
drom es described h ere are w ell-defin ed clin ical
en t ities.
Brainstem Disorders · 147
4
Brain stem in farction in a n u m ber of differen t lo-
cation s often becom es m an ifest clin ically as alter-
nating hemiplegia (crossed w eakn ess), w h ich is
defin ed as a com bin ation of cran ial n erve deficits
on th e side of t h e lesion w ith w eakn ess of th e op -
posite h em ibody. In Figu re 4.59, t h ree differen t al-
tern atin g h em iplegia syn drom es are sh ow n , each
th e result of isch em ia in a particu lar region of th e
brain stem , w ith correspon din g clin ical deficits.
We n ow list th e in dividu al vascu lar syn drom es
th at can be con sidered, in sim plified term s, to be
“variation s” of th e altern atin g h em iplegia syn -
drom e, albeit w ith extraordin arily diverse m an i-
festation s. To m ake th e presen t ation as clear as
possible, th e discu ssion of each syn drom e is ac-
com pan ied by a draw in g of th e affected structu res
in th e brain stem , an d by a sch em atic diagram of
th e resu ltin g clin ical deficits.
Dorsolateral medullary syndrome (Wallen berg syn -
drom e, Figs. 4.60 an d 4.61). Cause: occlu sion or em -
bolism in th e territory of th e posterior in ferior cere-
bellar artery or vertebral artery. Clinical features:
su dden on set w it h vertigo, nystagm u s (in ferior ves-
tibular n u cleu s an d in ferior cerebellar pedu n cle),
n ausea an d vom itin g (area p ostrem a), dysarth ria
an d dysph on ia (n u cleus am biguu s), sin gult us (res-
piratory cen ter of th e reticular form ation ). For
fu rth er details, see Figure 4.60.
Medial medullary syndrome (Dejerin e syn drom e)
(Fig. 4.62). Cause: occlusion of param edian
bran ch es of th e vertebral or basilar artery
(Fig. 4.58), often bilaterally. Clinical features: ipsi-
lateral flaccid hyp oglossal n erve p alsy, con -
tralateral h em iplegia (n ot spastic) w ith Babin ski’s
sign , con tralateral posterior colu m n hypest h esia
(i.e., hypesth esia to touch an d pressure, w ith im -
paired position sen se), an d nystagm us (if th e m e-
dial lon git udin al fasciculu s is involved by th e le-
sion ).
Syndrome of the caudal basis pontis (Millard–
Gu bler or Foville syn drom e). Cause: occlusion of
th e circum feren tial bran ch es of th e basilar artery,
tu m or, abscess, etc. Clinical features: ip silateral ab-
du cen s palsy (periph eral) an d facial palsy (n u -
clear); con tralateral h em iplegia; con tralateral
an algesia, th erm an esth esia, an d im pairm en t of
tou ch , position , an d vibration sen se (Fig. 4.64).
4 148 · 4 Brainstem

Fig. 4.59 Lesions causing

crossed w eakness (alter-
Leg nating hem iplegia syn-
Arm drom e)

Face

To ngue

Corticonuclear tract
Corticospinal tract
(a) Spastic contralateral
hem iplegia
(b) Ipsilateral peripheral oculomotor
nerve palsy (interruption of infranuclear
oculom otor fibers)
(c) Contralateral supranuclear palsy
of facial and hypoglossal nn.

(a) Contralateral spastic hem iplegia

(b) Ipsilateral supranuclear facial nerve
palsy

(a) Spastic contralateral hem iplegia

(b) Ipsilateral nuclear (flaccid) hypoglossus
palsy

Syndrome of the caudal pontine tegmentum
(Fig. 4.65). Cause: occlu sion of bran ch es of th e
basilar artery (sh ort an d lon g circu m feren t ial
bran ch es). Clinical features: ipsilateral n u clear ab-
du cen s an d facial palsy, nystagm u s (m edial lon gi-
tu din al fasciculu s), gaze paresis tow ard th e side of
th e lesion ; ipsilateral h em iataxia an d asyn ergia
(m edial cerebellar pedun cle); con tralateral an alge-
sia an d th erm an est h esia (lateral spin oth alam ic
tract); con tralateral hypesth esia an d im p airm en t
of position an d vibration sen se (m edial lem n is-
cu s); ipsilateral palatal an d ph aryn geal m yorhyth -
m ia (cen tral tegm en tal tract).
 Brainstem Disorders · 149
4
Fig. 4.60 Dorsolateral
Inferior vestibular nucleus: nystagmus and medullary syndrome
tendency to fall to ipsilateral side
(Wallenberg syndrom e)
Dorsal nucleus of the vagus n.: tachycardia and dyspnea
Inferior cerebellar peduncle: ipsilateral ataxia
and asynergia
Nucleus of the tractus solitarius: ageusia
Nucleus ambiguus: ipsilateral paresis of palate,
larynx, and pharynx; hoarseness
Nucleus of the cochlear n.: hearing loss
Nucleus of the spinal tract of the trigeminal n.:
ipsilateral analgesia and thermanesthesia
of the face; absent corneal reflex
Central sympathetic pathw ay: Horner syndrom e,
hypohidrosis, ipsilateral facial vasodilatation
Anterior spinocerebellar tract: ataxia,
ipsilateral hypotonia
Lateral spinothalamic tract: analgesia and
thermanesthesia of contralateral hem ibody
Central tegmental tract: palatal and
XII pharyngeal myorhythm ia
Reticular formatio n (respiratory center):
singultus (hiccups)

Horner syndrom e,
nystagm us, dysarthria,
dysphagia
III
r.n.
IV

sp.-th.
Analgesia and
V
thermanesthesia

Py m .l. VI
Ataxia and
asynergia
VII
VIII
IX XII r.n. = red nucleus
sp.-th. = spinothalam ic tract
m .l. = m edial lem niscus
Py = pyram idal tract

Syndrome of the oral pontine tegmentum
(Fig. 4.66). Cause: occlusion of th e lon g circu m fer-
en t ial bran ch es of th e basilar artery an d superior
cerebellar artery. Clinical features: ip silateral loss of
facial sen sation (in terruption of all trigem in al
fibers) an d paralysis of th e m u scles of m ast ication
(m otor n ucleu s of th e trigem in al n erve), h em i-
ataxia, in ten t ion trem or, adiadoch okin esia (su pe-
rior cerebellar pedun cle); con tralateral im p airm en t
of all sen sory m odalities.
4 150 · 4 Brainstem

Case Presentation 4: Wa llenberg Syndrome

The MRI findings in this case are typical of Wallenberg syn- sided ataxia and asynergia as well as a deficit of protopathic
drom e. Som e 20 hours before the scan was obtained, this sensation on the right side of the body. A CT scan of the
56-year-old m an suddenly becam e dizzy and unsteady, with head was norm al.
a tendency to fall to the left. Exam ination revealed left-

Fig. 4.61 Wallenberg

syndrome. a The diffusion-
weighted MR im age shows
a lesion in the left dor-
solateral portion of the
m edulla. b Hyperintensity
is seen at this site on the
T2-weighted im age. The
finding was found to be an
infarct in the territory of
the left PICA territory due
to occlusion of the left
vertebral artery.

a b
Fig. 4.62 Medial medul-
lary syndrome (Dejerine
syndrom e)
Medial longitudinal fasciculus: nystagmus
Medial lemniscus: contralateral impairm ent
of touch, vibration, and position sense
Olive: ipsilateral palat al and pharyngeal
myorhythm ia
Hypoglossal n.: ipsilateral hypoglossal palsy
with hem iatrophy of the tongue
Pyramidal tract: contralateral hemiplegia with-
Pyram id out spasticit y but with present Babinski reflex

Hypoglossal
palsy

r.n.

sp.-th.
Nonspastic
paralysis

Py m .l.
Im pairm ent of
touch, position,
and vibration
sense

r.n. = red nucleus

sp.-th. = spinothalam ic
tract
m .l. = m edial lem niscus
Py = pyram idal tract
 Brainstem Disorders · 151
4
Case Presentation 5: Media l Medulla ry Syndrome (Dejerine Syndrome)
The MRI findings in this case are typical of a m edial m edul- left hypoglossal nerve palsy. No infarct was seen on cranial
lary infarct. This 58-year-old wom an suddenly developed CT. The MRI scan was obtained 19 hours later.
flaccid right hem iparesis, a deficit of epicritic sensation, and

Fig. 4.63 Medial medul-

lary syndrome. a The dif-
fusion-weighted im age
shows an abnorm ality of
diffusion in the oral para-
m edian portion of the
m edulla. b The T2-
weighted im age reveals
hyperintensity at this site.

Fig. 4.64 Syndrome of

the caudal basis pontis
(Millard−Gubler syndrom e)
Medial lemniscus: contralateral im pairm ent
of touch, position, and vibration sense
Lateral lemniscus: hearing loss
Nucleus of the facial n.: ipsilateral peripheral
facial nerve palsy
Lateral spinothalamic tract: analgesia and
thermanesthesia of contralateral hem ibody
Pyramidal tract: contralateral spastic
hem iplegia
Abducens n.: ipsilateral peripheral abducens
nerve palsy

Spastic paralysis

r.n.
Flaccid paralysis

sp.-th.
Im pairm ent of
touch, position,
and vibration
Py m .l. sense

Analgesia and
thermanesthesia

r.n. = red nucleus

sp.-th. = spinothalam ic
tract
m .l. = m edial
lem niscus
Py = pyram idal tract
4 152 · 4 Brainstem

Fig. 4.65 Syndrome of

Medial longitudinal fasciculus: nystagmus, the caudal pontine teg-
gaze paresis to side of lesion
mentum
Nucleus of the abducens n.: ipsilateral nuclear
abducens palsy
Middle cerebellar peduncle: hemiataxia, inten-
tion trem or, adiadochokinesia, cerebellar dysarthria
Vestibular nuclei: nystagmus, rotatory vertigo
Central sympathetic pathw ay: Horner syndrome,
hypohidrosis, ipsilateral vasodilatation
Nucleus of the spinal tract of the trigeminal n.:
ipsilateral facial analgesia and thermanesthesia
Nucleus of the facial n.: ipsilateral nuclear facial
palsy (atrophy)
Central tegmental tract: ipsilateral palat al and
pharyngeal myorhythmia
Anterior spinocerebellar tract: ipsilateral
asynergia and hypotonia
Lateral lemniscus: hearing loss
Lateral spinothalamic tract: analgesia and
thermanesthesia of contralateral hemibody
Medial lemniscus: impairment of touch, vibration,
and position sense of the contralateral hem ibody; ataxia

Asynergia

r.n.
Flaccid paralysis

sp.-th.
Impairment of
touch, position,
and vibration
Py m.l. sense

Analgesia and
thermanesthesia
r.n. = red nucleus
sp.-th. = spinothalamic
tract
m.l. = medial
lemniscus
Py = pyram idal tract

Syndrome of the midportion of the basis pontis
(Fig. 4.67). Cause: occlusion of th e param edian an d
sh ort circum feren t ial bran ch es of th e basilar
artery. Clinical features: ipsilateral flaccid paresis of
th e m uscles of m astication , as w ell as facial hy-
pesth esia, an algesia, an d th erm an esth esia; ipsi-
lateral h em iataxia an d asyn ergia; con tralateral
spastic h em iparesis.
Syndrome of the red nucleus (Ben edikt syn drom e)
(Fig. 4.69). Cause: occlusion of t h e in terpedun cu lar
bran ch es of th e basilar an d p osterior cerebral ar-
teries. Clinical features: ipsilateral ocu lom otor
n erve palsy w ith m ydriasis (in terruption of th e
root fibers of CN III); con t ralateral im pairm en t of
touch , position , an d vibration sen se, as w ell as of
tw o-poin t discrim in ation (involvem en t of th e m e-
 Brainstem Disorders · 153
4
Fig. 4.66 Syndrome of
Superior cerebellar peduncle: hem iataxia, inten-
the oral pontine tegmen-
tion trem or, adioadochokinesia, cerebellar dysarthria
tum
Principal senso ry nucleus of the trigeminal n.: im pair-
ed epicritical sensation on the ipsilateral side of the face
Nucleus of the spinal tract of the trigeminal n.:
ipsilateral facial analgesia and thermanesthesia
Motor nucleus of the trig eminal n.: flaccid (nuclear)
paralysis of the ipsilateral muscles of m astication
Central tegmental tract: myorhythm ia of the soft
palate and pharynx
Tectospinal tract: absence of blinking reflex
Lateral spinothalamic tract: analgesia and
thermanesthesia of contralateral hem ibody
Lateral lemniscus: hearing loss
Medial lemniscus: im pairm ent of touch, vibration, and
position sense of the contralateral hem ibody; ataxia
Corticonuclear tract (exiting fibers): facial, glosso-
pharyngeal, vagus, and hypoglossal nerve palsies

r.n.
Flaccid paralysis

sp.-th.
Im pairm ent of
touch, position,
and vibration
m .l. sense
Py

Analgesia and
thermanesthesia

r.n. = red nucleus

sp.-th. = spinothalam ic
tract
m .l. = m edial
lem niscus
Py = pyram idal tract

dial lem n iscu s); con tralateral hyperkin esia
(trem or, ch orea, ath etosis) due to involvem en t of
th e red n u cleu s; con tralateral rigidity (su bstan tia
n igra).
Syndrome of the cerebral peduncle (Weber syn -
drom e) (Fig. 4.70). Cause: occlusion of th e in ter-
pedun cular bran ch es of th e posterior cerebral an d
posterior ch oroidal arteries; rarely also tum or
(gliom a). Clinical features: ipsilateral oculom otor
n erve palsy; con tralateral spastic h em iparesis;
con tralateral p arkin son ian rigidity (su bstan tia
n igra); con tralateral dystaxia (corticopon tin e
tract); p ossible cran ial n erve deficits du e to in ter-
ruption of th e supran uclear in n ervation of CN VII,
IX, X, an d XII.
4 154 · 4 Brainstem

Fig. 4.67 Syndrome of

the midportion of the
basis pontis

Root fibers of the trigeminal n.: ipsilateral hem i-

anesthesia for all sensory m odalities, ipsilateral
flaccid paralysis of the m uscles of mastication
Middle cerebellar peduncle: ipsilateral hem i-
ataxia and asynergia
Corticospinal tract: contralateral spastic hem i-
paresis
Pontine nuclei: ipsilateral dystaxia

Spastic paralysis

Flaccid paralysis
r.n.

sp.-th. Im pairm ent of

touch, position,
and vibration sense,
com bined with
Py m .l. analgesia and
thermanesthesia

Dystaxia
r.n. = red nucleus
sp.-th. = spinothalam ic
tract
m .l. = m edial
lem niscus
Py = pyram idal tract

Case Presentation 6: Pa ra media n Pontine Infa rct

The MRI findings in this case are typical of a param edian com panied by a deficit of both protopathic and epicritic
pontine infarct. Twelve hours before the scan was obtained, sensation.
the patient had suddenly developed left hem iparesis ac-
Fig. 4.68 Paramedian
pontine infarct. a The
axial, diffusion-weighted
im age shows a wedge-
shaped region in the right
param edian area of the
pons sparing the trigem inal
nerve, which exits the
brainstem at this level.
b The sagittal T2-weighted
im age shows a pontine le-
sion of typical configura-
tion, corresponding to the
territory of one of the pon-
tine arteries.

a b
 Brainstem Disorders · 155
4
Fig. 4.69 Syndrome of
the red nucleus (Benedikt
syndrom e)
Medial lemniscus: contralateral im pairm ent of
touch, position, and vibration sense
Red nucleus: contralateral hyperkinesia (chorea,
athetosis)
Substantia nigra: contralateral akinesia
(parkinsonism)
Root fibers of the oculomotor n.: ipsilateral
oculom otor palsy with fixed and dilated pupil

+++++++
r.n. +++++++
+++++++
Im pairm ent of +++++
+++++
touch, position, +++++
sp.-th. +++++
and vibration +++++
+++++
sense +++++
+++++
+++++
+++++ +++++
Py m .l. +++++ +++++ +++++
+++++
Hyperkinesia +++++ +++++
+++++ +++++
+++++
+++++
+++++
+++++
+++++
+++++
r.n. = red nucleus +++++
+++++
sp.-th. = spinothalam ic +++++
tract +++++
+++++
m .l. = m edial ++++
++++
lem niscus ++++
++++
Py ++++
= pyram idal tract ++++

Sm all in farcts of th e oral region of the pons, cau sed
by t h e occlusion of perforatin g arteries, can p ro-
du ce a w ide variety of circum scribed an d often
tran sien t deficits. Arteriosclerosis of th e basilar
artery can cause m u ltip le sm all in farct s on on e or
both sides of t h e brain stem , occu rrin g stepw ise
over tim e an d even tu ally p rodu cin g th e clin ical
pictu re of m icroan giop ath ic p seu dobulbar palsy. In
th is syn drom e, dysarth ria an d dysph agia resu lt
from in terru ption of th e su pran u clear in n ervat ion
of th e m otor cran ial n erve n u clei. Microan -
giopath ic brain stem disease is m ost often due to
gen eralized arterial hyp erten sion ; it is, t h erefore,
usually accom pan ied by fu rth er lesion s above th e
ten torium .
4 156 · 4 Brainstem

Fig. 4.70 Syndrome of

the cerebral peduncle
(Weber syndrom e)

Substantia nigra: akinesia (parkinsonism)

Corticospinal fibers: contralateral spastic
hem iplegia
Corticonuclear fibers: contralateral supranuclear
facial and hypoglossal nerve palsies
Corticopontine tract: contralateral dystaxia
Root fibers of the oculomotor n.: ipsilateral
oculomotor palsy with fixed and dilated pupil

Supranuclear Oculo-
facial and m otor
hypoglossal nerve
nerve palsies palsy
r.n.
++++
++++
++++
++++
sp.-th. ++++
+++++
Spastic paralysis +++++
++++
++++
+++++
+++++ +++++ +
Py m .l. +++++ +++++ ++ +++++
Rigidit y, +++++ +++++
+++++ +++++
parkinsonism , +++++ +++++
+++++ +++++
rest trem or +++++
+++++
+++++
+++++
r.n. = red nucleus +++++
+++++
sp.-th. = spinothalam ic +++++
tract +++++
+++++
m .l. = m edial ++++
++++
lem niscus ++++
++++
Py ++++
= pyram idal tract ++++
 5

5 Cerebellum
Surface Anatomy . . . . . . . . . . . . . . . . . 158
Internal Structure . . . . . . . . . . . . . . . . . 159
Connections of the Cerebellum w ith
Other Parts of the Nervous System . . 162
Cerebellar Function and Cerebellar
Syndromes . . . . . . . . . . . . . . . . . . . . . . . 164
Cerebellar Disorders . . . . . . . . . . . . . . . 167
5 158
5 Cerebellum
Th e cerebellu m is a cen tral organ for fine motor
control. It processes in form ation from m u ltiple
sen sory ch an n els (particu larly vestibu lar an d pro-
priocept ive), togeth er w ith m otor im p ulses, an d
m odu lates th e activity of m otor n u clear areas in
th e brain an d spin al cord.
Anatomically, th e cerebellum is m ade up of tw o
hemispheres an d t h e vermis t h at lies betw een
th em . It is con n ected to th e brain stem by the three
cerebellar peduncles. An an atom ical section re-
veals t h e cerebellar cortex an d t h e u n derlyin g
w h ite m at ter, in w h ich th e deep cerebellar n u clei
are em bedded. Th e cerebellar cortex is prim arily
respon sible for th e in tegration an d processin g of
afferen t im pulses. It p rojects to th e deep cerebellar
nuclei, w h ich th en em it m ost of th e efferen t fibers
th at leave th e cerebellu m .
Surface Anatomy
Th e cerebellum lies in th e posterior fossa. Its su per-
ior surface is covered by th e tentorium cerebelli, a
ten tlike double fold of th e du ra m ater th at sepa-
rates th e cerebellum from th e cerebrum .
Th e surface of th e cerebellu m (Fig. 5.1), u n like
th at of th e cerebru m , displays n u m erous sm all,
h orizon tally run n in g convolu tion s (folia), w h ich
are separated from each oth er by fissures. Th e n ar-
Interm ediate
portion
(paraver- Superior Anterior
Lateral portion m ian zone) vermis lobe
Culmen
Declive
Tuber Folium
Functionally (an d phylogen etically), t h e cere-
bellum is divided in to th ree com pon en t s: th e ves-
t ibu locerebellu m , spin ocerebellu m , an d cere-
brocerebellu m . Th e vestibulocerebellum is p hylo-
gen etically oldest . It receives afferen t inpu t
m ain ly from th e vestibular organ , an d its fun ction
is to regulate balan ce. Th e spinocerebellum
m ain ly p rocesses prop rioceptive im pu lses from
th e spin ocerebellar p ath w ays an d con trols stan ce
an d gait. Th e youn gest com pon en t of th e cerebel-
lu m , th e cerebrocerebellum, h as a close fu n ction al
relation sh ip w it h th e m otor cortex of th e telen -
ceph alon an d is resp on sible for th e sm ooth an d
precise execution of all fin ely con trolled m ove-
m en ts. Cerebellar lesions m an ifest th em selves
clin ically w ith disturban ces of m ovem en t an d
balan ce.
row cen tral portion of th e cerebellu m con n ectin g
th e tw o h em isph eres on eith er side is called th e
verm is becau se of its fan cied resem blan ce to a
w orm .
A view of the cerebellum from below (Fig. 5.2)
reveals th e u pper portion of th e fou rth ven tricle
lyin g betw een th e cerebellar pedun cles. Th e fou rth
ven t ricle com m un icates w ith th e su barach n oid
sp ace th rough a sin gle m edian aperture (foram en
of Magen die) an d tw o lateral apertures (foram in a
of Lu sch ka). Caudal to th e in ferior an d m iddle cere-
Fig. 5.1 The cerebellum,
view ed from above. Left
side: division into verm is,
Primary fissure pars interm edialis, and pars
lateralis. Right side: division
into verm is, anterior lobe,
Posterior and posterior lobe. The
lobe
anterior and posterior
lobes are separated by the
prim ary fissure.

Culmen
Cerebellar peduncles:
superior
m iddle
inferior
Lateral aperture
of fourth
ventricle 4 th
ventricle
Inferior
Flocculo- verm is
Flocculus
nodular
lobe Nodulus Cerebellar tonsil
bral pedu n cles, th ere is a st ru ctu re on eith er side
called th e flocculus; th e tw o floccu li are con n ected
across t h e m idlin e th rough a portion of th e verm is
called th e nodulus. Toget h er, th ese stru ctures con -
stitu te th e flocculonodular lobe.
Th e subdivision s of th e cerebellar verm is an d
h em isph eres w ere given in dividu al n am es by th e
old an atom ists (cu lm en , declive, et c.), w h ich are
in dicated in Figs. 5.1 an d 5.2, alth ough th ey h ave
little fun ction al sign ifican ce an d are gen erally n ot
clin ically relevan t. Today, it is m ore com m on to
dist in gu ish three major components of the cere-
bellum on phylogen etic an d fun ct ion al grou n ds:
Th e archicerebellum (p hylogen etically oldest por-
tion of th e cerebellu m ) is in t im ately related to th e
vestibu lar apparatu s. It receives m ost of its afferen t
inpu t from th e vestibu lar n uclei of th e brain stem
an d is th u s also called th e vestibulocerebellum.
An atom ically, it con sists m ain ly of th e floccu lus
an d n odulus (flocculonodular lobe).
Th e paleocerebellum (n ext oldest portion of th e
cerebellu m , after th e arch icerebellum ) receives
m ost of its afferen t input from th e sp in al cord an d
is, th erefore, also called th e spinocerebellum (th e
term w e w ill u se in t h e follow in g section s). It con -
sists of t h e culm en an d cen tral lobule of th e ante-
rior lobe of th e verm is, as w ell as t h e u vu la an d py-
ram id of its inferior lobe, an d th e parafloccu lus. On e
can state, as a m ild sim p lification , th at th e
spin ocerebellu m is com posed of m ost of th e ver-
m is an d paraverm ian zon e (pars in term edialis).
Internal Structure · 159
5
Fig. 5.2 The cerebellum,
view ed from below
Central lobule
Lingula
Superior m edullary velum
Anterior lobe
Paraflocculus
Posterolateral
Tuber Pyram id Uvula fissure
Th e neocerebellum (you n gest portion of th e cere-
bellu m ) is it s largest p art. Its p hylogen etic develop-
m en t occu rred togeth er w ith th e exp an sion of th e
cerebru m an d th e tran sition to an u prigh t stan ce
an d gait. It is form ed by th e tw o cerebellar h em i-
sp h eres an d h as an in tim ate fun ction al con n ection
to th e cerebral cortex, w h ich projects to it by w ay
of th e pon tin e n u clei. Th u s, th e n eocerebellu m is
also term ed th e pon tocerebellu m or cerebrocere-
bellum, as w e w ill call it in th e follow in g sect ion s.
Internal Structure
Alt h ou gh th e cerebellu m accoun ts for on ly abou t
10 % of th e brain by w eigh t, it con tain s m ore t h an
50 % of all th e brain ’s n eu ron s. Th e n eu ron s of t h e
cerebellu m are located in th e gray m atter of th e
h igh ly convolu ted cerebellar cortex an d in th e fou r
deep cerebellar n u clei on eith er side (see below ).
Cerebellar Cortex
Th e cerebellar cortex is com posed of th ree layers
(Fig. 5.3). Proceedin g from th e outerm ost inw ard,
th ese layers are:
Molecular layer (stratum moleculare). Th is layer
con sists m ain ly of cellular processes, of w h ich th e
m ajority are gran u le cell axon s—parallel fibers, see
below —an d Purkinje cell dendrites.Afew n euron s are
fou n d am on g t h e fibers (stellate cells, basket cells,
5 160 · 5 Cerebellum
Parallel fibers
Granule cell
Purkinje cell Molecular
layer
Purkinje
cell layer
Granular
Basket layer
cell
White
matter
Purkinje Neurons in the
cell axons dentate nucleus
Climbing fiber Mossy fiber
Fig. 5.3 Structure of the cerebellar cortex with its affer-
ent and efferent connections (schem atic drawing)
Golgi cells), w h ich fu n ction as in h ibitory in ter-
n euron s.
Purkinje cell layer (stratum ganglionare). Th is th in
layer con tain s n oth in g bu t th e large cell bodies of
th e Pu rkin je cells, arran ged side by side in row s.
Th e elaborate, h igh ly bran ch ed den dritic trees of
th ese cells are directed ou tw ard in to th e m olecu lar
layer, w h ere th e den dritic tree of each in dividu al
Pu rkin je cell lies in a plan e perpen dicu lar to th e
lon g axis of th e foliu m . Th e Pu rkin je cell axon s are
th e on ly efferen t fibers leavin g th e cerebellar cor-
tex. Th ey p roject m ain ly to th e deep cerebellar n u -
clei an d release th e in h ibitory n eu rotran sm itter
GABA (γ-am in obutyric acid). Efferen t fibers from
th e cortex of th e vestibulocerebellu m bypass th e
deep cerebellar n uclei an d project directly to sites
outside t h e cerebellu m .
Granule cell layer (stratum granulosum). Th is layer
con sists alm ost en tirely of th e den sely packed cell
bodies of t h e sm all gran u le cells, w h ich accou n t for
m ore th an 95 %ofall cerebellar n euron s.Th e axon s of
th ese cells are m ain ly fou n d in th e m olecu lar layer,
w h ere th ey travel alon g in dividual folia as parallel
fibers an d form syn apses w ith th e perp en dicu larly
orien ted den drit ic trees of th e Pu rkin je cells (ap-
proxim ately 20 0 0 0 0 parallel fibers form syn ap ses
w ith a sin gle Pu rkin je cell). Th e cerebellar gran u le
cells are glutam atergic an d are th e on ly n euron s of
th e cerebellar cortex th at exert an excitatory in -
flu en ce on th eir target cells.
Afferent Input to the Cerebella r Cortex
Th e afferen t inpu t to th e cerebellar cortex is m ain ly
derived from th e ipsilateral vestibular nuclei (a
sm all part, in fact, com es directly from th e vestibu-
lar organ, w ith out any in terven in g syn aptic relay),
th e ipsilateral spinal cord, th e contralateral pontine
nuclei (an d th us, in directly, from th e con tralateral
cerebral cortex), an d th e contralateral olivary nu-
clear com plex in th e m edulla (olive, for sh ort). Th e
olivary fibers are th e so-called climbing fibers,
w h ich term in ate on th e Purkin je cells of th e cere-
bellar cortex, clim bin g u p th eir den dritic trees like
ivy. All oth er afferen t fibers term in ate as mossy
fibers on th e gran ule cells of t h e cerebellar cortex,
w h ich th en relay fu rth er im pu lses alon g th eir
axon s (parallel fibers of th e m olecular layer) to th e
Pu rkin je cell den drites. Both m ossy fibers an d
clim bin g fibers give off im portan t collaterals to th e
deep cerebellar n u clei on th eir w ay to th e cortex.
In view of th e fact th at both th e m ossy fibers an d
th e gran u le cells (an d th u s th e overw h elm in g m a-
jority of syn apses in th e cerebellu m ) are gluta-
m atergic, it is n ot surp risin g th at th e administra-
tion of glutamate antagonists cau ses a m arked
w orsen in g of cerebellar fun ction in patien ts w ith
cerebellar lesion s.
Cerebellar Nuclei
A h orizon tal section of th e cerebellum reveals fou r
deep n u clei w ith in each cerebellar h em isph ere
(see Fig. 5.5). Th e fastigial nucleus (“roof n u cleu s”)
is fou n d m ost m edially, in th e roof of th e fou rth
ven tricle. It receives m ost of its afferent fibers from
th e Pu rkin je cells of th e floccu lon odu lar lobe (ves-
tibu locerebellu m ). Its efferent fibers t ravel directly
to th e vestibu lar n uclei (fastigiobulbar tract)
(Fig. 5.5) or cross to th e opposite side of th e cere-
bellu m an d th en con t in u e to t h e ret icu lar form a-
tion an d th e vestibu lar n u clei (uncinate fasciculus).
Lateral to th e fastigial n u cleu s, on e fin ds tw o
sm aller n uclei, th e globose nucleus (u su ally
divided in to tw o or t h ree su bn uclei) an d th e em-
boliform nucleus. Both of th ese n u clei receive affer-
ent inp ut from th e cortex of t h e paraverm ian zon e
 Internal Structure · 161
5
Fig. 5.4 The basic
scheme of neuronal con-
Granule cells nections w ithin the cere-
Purkinje
bellum
Inhibitory cells
interneurons

Afferent
supply to
cerebellum
Neurons
of the
cerebellar
nuclei

Mossy fibers Clim bing fibers Cerebellar

efferent
output
Pontine nuclei Thalam us
Spinal cord Red nucleus
Vestibular nuclei Vestibular nuclei
Olive Reticular formation

Globose and Thalam o-

Fastigial nucleus cortical tract
em boliform
nuclei Dentate nucleus Thalam us

Corticopontine tract
a Red nucleus
Planes of section Central tegm ental tract
Dentatorubral and Em boliform and
Pontine nuclei
dentatothalam ic tracts globose nuclei
Reticular formation
Pontocerebellar Culmen Fastigial
Em boliform nucleus nucleus
tract Central lobule
Dentate nucleus Declive
Lingula Folium

Olive

Anterior and
posterior
spinocere- Vestibular
nuclei
bellar tracts Nodulus Tuber
Spino-olivary Uvula
tract
Pyram id
Rubrospinal
tract Vestibulospinal
Olivocerebellar tract tract
b Pontocerebellar tract Reticulospinal tract

Fig. 5.5 Afferent and efferent connections of the cerebellum (schem atic drawing). (a): The planes of section (left
through the dentate nucleus, right through the verm is).
5 162 · 5 Cerebellum
an d verm is (spin ocerebellum ) an d sen d efferent
fibers to th e con t ralateral red n u cleu s (Fig. 5.5).
Th e largest of th e cerebellar n u clei, th e dentate
nucleus, occu pies a lateral position in th e deep
w h ite m atter of each cerebellar h em isph ere. Its af-
ferent inpu t com es m ain ly from th e cortex of th e
cerebellar h em isph eres (cerebrocerebellum ), an d,
to a lesser exten t, from th e cortex of th e paraver-
m ian zon e. Its efferent fibers travel by w ay of th e
sup erior cerebellar pedu n cle to th e con tralateral
red n u cleu s an d th alam u s (ven tral lateral n u cleus,
VL) (Fig. 5.5). Th e th alam us is th e site of a syn aptic
relay, w ith fu rt h er p rojection to th e m otor areas of
th e cerebral cortex (Brodm an n areas 4 an d 6)
(Fig. 6.4, p. 174).
Afferent and Efferent Projections of
the Cerebellar Cortex and Nuclei
Syn apt ic tran sm ission w ithin th e cerebellu m fol-
low s a un iform sch em e (Fig. 5.4): th e cerebellar af-
feren t path w ays project to th e cerebellar cortex
an d, th rou gh collateral fibers, to th e deep cerebel-
lar n u clei. In th e cortex, afferen t in form ation is
processed in a com plex polysyn aptic path w ay th at
even tu ally converges on to th e Pu rkin je cells. Th e
Pu rkin je cells, in tu rn , tran sm it th e results of th is
processin g to th e deep cerebellar n uclei, in th e
form of in h ibitory, GABAergic im p ulses. In th e deep
n u clei, in tegrative processin g of both prim ary
in form ation (from th e collateral fibers of th e cere-
bellar afferen t path w ays) an d m odu lated in form a-
tion (from th e Pu rkin je cells/from th e cortex) t akes
place an d th e resu lt is th en tran sm it ted, by w ay of
cerebellar efferen t fibers, to th e targets of th e cere-
bellar projection s.
Connections of the Cerebellum
w ith Other Parts of the Nervous
System
All sen sory m odalities th at are im p ortan t for orien -
tation in space (vestibu lar sen se, touch , p roprio-
ception , vision , an d h earin g) convey in form ation to
th e cerebellum . Th e cerebellu m receives inp ut
from w idely diverse sen sory areas of th e n ervous
system by w ay of th e th ree cerebellar pedu n cles,
an d sen ds its ou tpu t by w ay of th e deep cerebellar
n u clei to all m otor areas.
Th is section con cern s th e m any afferen t an d
efferen t con n ection s of th e cerebellu m an d th eir
distribu tion am on g th e th ree cerebellar pedu n cles.
Th e m ore im portan t p ath w ays are sh ow n sch e-
m atically in Fig. 5.5.
Inferior Cerebella r Peduncle
Th e in ferior cerebellar pedu n cle (restiform body)
con tain s th e follow in g afferent path w ays:
¼ Fibers from th e vestibulocochlear nerve an d t h e
vestibular nuclei to th e floccu lon odular lobe an d
fastigial n ucleus (Fig. 5.5).
¼ Axon s from t h e con t ralateral olive in th e olivo-
cerebellar tract, w h ich con tin u e as clim bin g
fibers to th e den drites of th e Pu rkin je cells of all
areas of th e cerebellar cortex (t h e in ferior
olivary n ucleu s projects m ain ly to t h e cere-
brocerebellu m , w h ile th e accessory olivary n u-
clei p roject m ain ly to th e vestibu lo- an d
spin ocerebellu m ).
¼ Th e posterior spinocerebellar tract, w h ose fibers
arise in th e n eu ron s of t h e n u cleu s dorsalis
(th oracic n u cleu s or Clarke’s colu m n ) at th e base
of th e posterior h orn of th e spin al gray m at ter
(Figs. 2.16 an d 2.17, pp. 26, 27); th is tract m ain ly
conveys im pu lses from th e m u scle spin dles of
th e low er lim bs an d tru n k to th e paraverm ian
zon e of th e an terior an d posterior lobes.
¼ A p ath w ay arisin g in n euron s of t h e cervical spi-
n al cord above th e level of th e th oracic n u cleu s,
w h ich ascen ds in th e lateral portion of th e
cu n eate fasciculu s an d u n dergoes a syn aptic
relay in th e accessory cuneate nucleus of t h e
m edu lla; th is path w ay accom p an ies th e poste-
rior spin ocerebellar tract on its w ay in to th e
cerebellu m .
¼ Fibers from th e reticu lar form ation (n ot sh ow n
in Fig. 5.5).
Th e in ferior cerebellar pedun cle con tain s th e fol-
low in g efferent pat h w ays:
¼ Th e fastigiobulbar tract (largest efferen t path -
w ay of th e in ferior cerebellar pedu n cle) to t h e
vestibular n u clei; th is t ract closes a vesti-
bu locerebellar regulatory feedback loop
th rough w h ich th e cerebellu m in flu en ces th e
m otor fu n ction of th e spin al cord.
¼ Fibers from th e fastigial n ucleu s to th e reticular
form ation (cerebelloreticular tract) an d from th e
den tate n ucleu s to th e olive (cerebello-olivary
tract).
 Connections of the Cerebellum with Other Parts of the Nervous System · 163
5
Middle Cerebella r Peduncle
Cerebral cortex
Th e m iddle cerebellar pedu n cle exclusively con -
tain s afferent fibers, of th e follow in g types:
Thalam ocortical
¼ Th e pontocerebellar tract decu ssates in th e pon s tract
an d t h en travels in a th ick bu n dle, by w ay of t h e Cortico-
spinal
m iddle cerebellar pedu n cle, to th e cerebellar
tract
h em isph eres. Th ese fibers origin ate in th e basal
Cortico-
pon tin e n uclei an d are th u s th e con tin uation , pontine
after a syn apt ic relay, of th e cort icocerebellar tract
Dentato-
projection s, w h ich are derived from all of th e
rubral and
lobes of th e cerebru m , bu t in greatest n u m ber dentato-
Pontine
from t h e fron tal lobe. Th e fibers cross th e m id- thalam ic
nuclei
lin e as soon as th ey em erge from th e relay n u- tracts

clei in th e basis p on tis. Dentate

nucleus
¼ Fu rth er afferen t fibers from t h e m on oam in ergic
rap h e n u clei travel by w ay of th e m iddle cere-
bellar pedun cle to th e cerebellu m .

Superior Cerebella r Peduncle

Efferent pathw ays. Th e superior cerebellar pedu n - Neocerebellar
cle con tain s m ost of th e cerebellar efferent fibers. cortex
Th ese fibers origin ate in t h e deep cerebellar n u clei Fig. 5.6 Cerebellar regulatory circuits involving the
an d project m ain ly to th e follow in g st ructu res: pontine nuclei
¼ Th e con tralateral th alam u s (ven t ral lateral an d
cen trom edian n u clei, Figs. 6.4 an d 6.6, p p. 174,
175) Cerebral cortex
¼ Th e con tralateral red n u cleus
¼ Th e reticu lar form ation Thalam o-
cortical tract

Efferent fibers to the thalam us. Efferen t fibers in th e Corticospinal

superior cerebellar p edu n cle t ravelin g to th e and cortico-
rubral tracts
th alam u s arise m ain ly in th e den tate n ucleu s (cere-
Thalamus
brocerebellum ). After a synaptic relay in th e
th alam u s, fu rth er fibers ascen d to t h e m otor an d
Dentato-
prem otor cerebral cortex, w hich , in turn , projects rubral and
back to th e pon tin e n u clei by w ay of th e corticop on - dentato- Red nucleus
thalam ic
tin e tract. A lon g regu latory loop is t h u s created,
tracts
travelin g from th e cerebral cortex to th e pon tin e n u- Central
Dentate tegmental
clei, cerebellar cortex, den tate n ucleu s, th alam u s, nucleus tract
an d fin ally back to th e cortex (Figs 5.5 an d 5.6).

Olive
Efferent fibers to the red nucleus and reticular form a-
tion. A fu rt h er regu latory circu it com p rises th e so- Olivocere-
bellar tract
called trian gle of Gu illain an d Mollaret, travelin g
from t h e red n ucleu s by w ay of th e cen tral tegm en - Neocerebellar
tal tract to th e olive, th en to th e cerebellu m an d cortex
back to th e red n u cleus (Fig. 5.7). Th e cerebellu m Fig. 5.7 Cerebellar regulatory circuits involving the
in fluen ces spin al m otor fun ction by w ay of fibers olive. The triangle of Guillain and Mollaret passes from the
travelin g from th e red n ucleu s an d reticu lar form a- red nucleus by way of the central tegm ental tract, the olive,
tion dow n in to th e spin al cord (cf. Fig. 3.5, p . 40). and the cerebellum back to the red nucleus.
5 164 · 5 Cerebellum
Afferent pathw ays. On e of th e few afferen t path -
w ays in t h e sup erior cerebellar p edu n cle is th e
anterior spinocerebellar tract, w h ich term in ates in
th e sam e area (spin ocerebellum ) as th e posterior
spin ocerebellar tract. Bot h convey proprioceptive
im pu lses from t h e p erip h ery, i.e., from m uscle
spin dles, Golgi ten don organ s, an d join t receptors.
Fibers from th e tectu m travel to th e cerebellar
verm is in th e tectocerebellar tract, w h ich occu pies
a m edial position in th e sup erior cerebellar
pedun cle, at its tran sition to th e superior m edul-
lary velum . Th ese fibers convey au ditory in form a-
tion from th e in ferior collicu li, an d p robably also
visual in form ation from th e su perior collicu li.
Topogra phy of Cerebella r Afferent Pa thwa ys
Each h alf of th e cerebellu m is respon sible for
m otor fun ction on th e ipsilateral h alf of th e body.
Som e of th e efferen t fiber system s are doubly
crossed: th us, th e cerebelloru bral tract crosses th e
m idlin e as soon as it en ters th e brain stem from be-
h in d, an d t h e ru brospin al tract crosses th e m idlin e
again ju st after its origin from th e red n ucleu s (in
th e decussation of Forel). Sim ilarly, th e cerebel-
loth alam ic fibers travel from on e side of th e cere-
bellu m to t h e opp osite side of th e th alam u s an d
th en proceed to th e ipsilateral cerebral cortex,
w h ose efferen t fibers en ter th e pyram idal tract an d
decu ssate on ce m ore before th ey reach th e spin al
cord on th e origin al side.
Cerebellar Function and
Cerebellar Syndromes
Th ree im portan t poin ts m u st be grasped for a
proper u n derstan din g of cerebellar fun ction :
¼ Th e cerebellu m receives a very large am ou n t of
gen eral an d special sen sory input , bu t does n ot
participate to any sign ifican t exten t in con -
scious p erception or discrim in ation .
¼ Alt h ou gh t h e cerebellu m in fluen ces m otor
fu n ction , cerebellar lesion s do n ot p rodu ce par-
alysis.
¼ Th e cerebellu m is u n im portan t for m ost cogn i-
tive processes bu t n on eth eless plays a m ajor
role in m otor learn in g an d m em ory.
Essen t ially, th e cerebellu m is a coordin ation cen ter
th at maintains balance an d controls muscle tone
th rough regulatory circu its an d com plex feedback
m ech an ism s, an d assures the precise , temporally
w ell-coordinated execution of all directed motor
processes. Cerebellar coordin ation of m ovem en t
occu rs u n con sciou sly.
Th e in dividual com p on en ts of th e cerebellum
(vestibu locerebellu m , spin ocerebellu m , an d cere-
brocerebellu m ) h ave differen t fun ction s in th e
coordin ation of m ovem en t. Th ese particular fun c-
tion s can be determ in ed from experim en tal stu -
dies in an im als on t h e on e h an d, an d from clin ical
stu dies of p atien ts w ith cerebellar lesion s on th e
oth er. Th e con stellation s of sign s an d sym ptom s
accom panyin g cerebellar disease th at w ill be de-
scribed h ere are seldom observed in pu re form ,
both becau se it is rare for on ly on e of th e fu n ction al
com pon en ts of th e cerebellu m to be affected in
isolation , an d because slow ly expan din g processes
(su ch as ben ign tu m ors) m ay in du ce fu n ction al
com pen sation . Oth er portion s of th e brain can ap -
paren tly assum e som e of th e fun ction s of th e cere-
bellum , if n ecessary. Yet, if th e distu rban ce affects
n ot ju st th e cerebellar cortex bu t also th e deep
cerebellar n u clei, on ly m in im al recovery is likely to
occu r.
Th is bein g said, it is still best, from th e didactic
poin t of view, to con sider th e fu n ction s an d typical
clin ical syn drom es of each of th e th ree p arts of th e
cerebellu m separately.
Vestibulocerebellum
Function. Th e vestibu locerebellum receives im -
pulses from th e vestibu lar apparatu s carryin g in for-
m ation about th e position an d m ovem en ts of th e
h ead. Its efferen t ou tpu t in flu en ces th e m otor fun c-
tion of th e eyes an d body in such a w ay th at equ i-
libriu m can be m ain tain ed in all p osition s an d w ith
any m ovem en t .
Synaptic connections. Th e follow in g reflex arcs
participate in th e m ain ten an ce of equ ilibriu m
(balan ce). From th e vestibular organ , im p ulses
travel both directly an d in directly (by w ay of th e
vestibu lar n u clei) to th e vestibu locerebellar cortex,
an d onw ard to th e fastigial n u cleus. Th e vest i-
bu locerebellar cortex tran sm its im p ulses back to
th e vestibular n uclei, as w ell as to th e reticu lar for-
m ation ; from th ese sites, th e vestibulospinal an d
reticulospinal tracts an d th e m edial longitudinal
fasciculus en ter th e brain stem an d spin al cord to
 Cerebellar Function and Cerebellar Syndrom es · 165
5
con trol spin al m otor an d ocu lom otor fu n ction Cerebellar lesion s can also p rodu ce variou s
(Fig. 5.5). Th ese reflex arcs assu re stability of types of complex nystagmus, such as opsoclon u s
stan ce, gait, an d eye position an d en able th e fixa- (rapid con ju gate m ovem en ts of th e eyes in m ulti-
tion of gaze. p le plan es) or ocular flutter (op soclon u s in t h e
h orizon tal plan e on ly), w h ose p recise localization
Lesions of the Vestibulocerebellum h as n ot yet been determ in ed.
Fu n ction al im pairm en t of th e flocculon odular lobe
or fastigial n u cleu s ren ders t h e patien t less capable Spinocerebellum
of orien tin g h im self or h erself in t h e earth ’s gravi- Function. Th e spin ocerebellum con t rols m uscle
tation al field, or of keepin g h is or h er gaze fixed on ton e an d coordin ates th e action s of an tagon istic
a station ary object w h en th e h ead is m ovin g. m uscle grou ps th at participate in stan ce an d gait.
Its efferen t output affects th e activity of th e an ti-
Dysequilibrium. Th e patien t h as difficu lty stan din g
gravity m uscles an d con trols th e stren gth of forces
up righ t (astasia) an d w alkin g (abasia), an d th e gait
in du ced by m ovem en t (e.g., in ertia an d cen trifugal
is broad-based an d un steady, resem blin g th e gait
force).
of a dru n ken in dividu al (truncal ataxia). Heel-to-
toe w alkin g can n o lon ger be perform ed. Th e u n -
Connections. Th e cortex of th e spin ocerebellu m re-
steadin ess is n ot du e to a deficien cy of propriocep-
ceives its afferen t inpu t from th e spin al cord by w ay
tive im pulses reach in g con sciou sn ess, bu t rath er to
of th e posterior spinocerebellar tract, th e anterior
fau lty coordin ation of t h e m u sculat ure in resp on se
spinocerebellar tract, an d t h e cuneocerebellar tract
to gravity.
(from th e accessory cu n eate n ucleu s). Th e cortex of
th e paraverm ian zon e m ain ly projects to th e em -
Oculomotor disturbances, nystagmus. Cerebellar
boliform and globose nuclei, w h ile th e verm ian cor-
disturban ces of ocu lom otor fu n ction are m an ifest
tex m ain ly p rojects to th e fastigial nucleus. Th e
as an im paired abilit y to h old on e’s gaze on a sta-
efferen t ou tpu t of th ese n uclei th en proceeds
tion ary or m ovin g target (lesion s of th e floccu lus
th rou gh th e superior cerebellar peduncle to th e red
an d parafloccu lus). Th e resu lt is saccadic pursuit
nucleus an d th e reticular form ation, from w h ich
movements an d gaze -evoked nystagmus: if th e
m odulatin g im pu lses are conveyed over th e ru-
patien t tries to follow a m ovin g object w ith h is or
brospinal, rubroreticular, and reticulospinal tracts to
h er eyes, square-w ave jerks can be observed, i.e.,
th e spin al m otor n eu ron s (Fig. 5.5). Each h alf of th e
th e am p litu de of th e m icrosaccades th at n orm ally
body is served by th e ipsilateral cerebellar cortex,
occur in ocu lar pursu it is abn orm ally in creased, so
bu t t h ere is n o precise som atotopic arran gem en t .
th at th ey becom e visible to t h e exam in er. Gaze-
Recen t stu dies su ggest th at th e n eural organ ization
evoked nystagm u s is m ore p rom in en t w h en th e
of t h e cerebellar cortex resem bles a patch w ork
eyes m ove tow ard th e side of th e cerebellar lesion
rath er th an an exact som atotopic m ap.
an d dim in ish es som ew h at if th e gaze is h eld to t h at
Som e of th e efferen t ou tpu t of th e em boliform
side; if t h e eyes are t h en brou gh t back to th e m id-
n u cleus travels by w ay of th e th alam us to th e
lin e, nystagm us in th e opposite direction m ay be
m otor cortex—m ain ly th e portion of it th at con -
seen (rebound nystagm us).
trols th e p roxim al m u scu latu re of th e lim bs (pelvic
Lesion s of th e vestibulocerebellum m ay im pair
an d sh oulder girdles) an d th e tru n k. By th is m ean s,
th e patien t’s ability to supp ress th e vestibulo-ocu-
th e spin ocerebellum also exerts an in flu en ce on
lar reflex (VOR, p. 124), in w h ich tu rn in g th e h ead
voluntary, directed m ovem ents of t h ese m u scle
produces saccadic jerks of th e eyes. A h ealthy in -
groups.
dividu al can su ppress th is reflex by fixin g th e gaze
upon an object, but a patien t w ith a vestibu locere-
Lesions of the Spinocerebellum
bellar lesion can n ot (impaired suppression of the
VOR by fixation). Furth erm ore, lesion s of th e Th e m ajor m an ifestation s of lesion s of th e cerebel-
n odulu s an d uvu la im pair th e ability of th e VOR lar verm is an d paraverm ian zon e are as follow s.
(rotatory nystagm u s) to h abitu ate an d m ay lead to
th e ap pearan ce of periodic alternating nystagm us Lesion s of th e anterior lobe and of the superior
th at ch an ges direction s every 2–4 m in u tes. portion of the vermis in and near the midline pro-
5 166 · 5 Cerebellum
du ce ataxia of stan ce an d gait. Th e gait ataxia
(abasia) produced by su ch lesion s is w orse th an th e
ataxia of stan ce (astasia). Affected patien ts su ffer
from a broad-based, unsteady gait th at deviates to
th e side of th e lesion , an d th ere is a tendency to fall
to that side. Th e ataxia of stan ce is revealed by th e
Rom berg test: w h en t h e patien t stan ds w ith eyes
closed, a gen tle pu sh on th e stern um causes th e
patien t to sw ay backw ards an d forw ards at a
frequ en cy of 2–3 Hz. If th e lesion is strictly con -
fin ed to th e su perior p ortion of t h e verm is, t h e fin -
ger–n ose test an d t h e h eel–kn ee–sh in test m ay still
be perform ed accurately.
Lesions of the inferior portion of the vermis pro-
du ce an ataxia of stance (ast asia) th at is m ore
severe t h an th e ataxia of gait. Th e patien t h as diffi-
cu lty sittin g or stan din g steadily, an d, in t h e Rom -
berg test, sw ays slow ly back an d forth , w it h ou t
direction al preferen ce.
Cerebrocerebellum
Connections. Th e cerebrocerebellu m receives m ost
of its n eu ral inpu t in directly from exten sive por-
tion s of th e cerebral cortex, m ain ly from Brodm ann
areas 4 and 6 (th e m otor an d prem otor cortex) via
th e corticopontine tract (Fig. 5.6), bu t also, to a
lesser exten t, from th e olive via t h e olivocerebellar
tract (Fig. 5.7). Th e cerebellu m receives advan ce
n otice of any plan n ed volun tary m ovem en t in -
itiated in th e cerebral cortex, so th at it can im m edi-
ately sen d m odu lat in g an d corrective im pu lses
back to th e m otor cortex th rou gh th e denta-
tothalamocortical pathw ay (Fig. 5.5, p. 161, an d
Fig. 5.6). Th e den tate n ucleu s also projects to t h e
parvocellu lar port ion of th e red n u cleus. Un like th e
rest of th e red n u cleu s, th is part does n ot sen d
fibers to th e spin al cord by w ay of th e rubrospin al
tract. Rath er, it projects th rough th e cen tral
tegm en tal tract to th e in ferior olive, w h ich th en
projects back to t h e cerebrocerebellu m . Th is den-
tato -rubro -olivo -cerebellar neural feedback loop
plays an im portan t role in n eocerebellar im pulse
processin g.
Function. Th e com plex con n ection s of th e cere-
brocerebellum en able it to regu late all directed
m ovem en ts sm ooth ly an d precisely. By w ay of th e
very rapidly con ductin g afferen t spin ocerebellar
path w ays, it con tin u ously receives real-tim e in -
form ation about m otor activity in th e periph ery. It
can th u s take action to correct any errors in th e
cou rse of volu n tary m ovem en t to en sure th at th ey
are executed sm oot h ly an d accu rately. Th e execu -
tive p attern s of a large n u m ber of differen t types
of m ovem en t are probably stored in th e cerebel-
lu m , as in a com puter, over th e life of th e in -
dividual, so th at th ey can be recalled from it at
any tim e. Th u s, on ce w e h ave reach ed a cert ain
stage of developm en t, w e can perform difficult
learn ed m ovem en ts rapidly, relatively effortlessly,
an d at w ill by callin g u pon th e precise regu latory
fu n ction of th e cerebellu m .
Th e fu n ction s of th e cerebellu m exten d beyon d
th e coordin ation of m ovem en t to th e processin g of
sen sory stim uli an d of in form at ion t h at is relevan t
to m em ory. A furth er discu ssion of th ese aspects is
beyon d t h e scope of th is book.
Lesions of the Cerebrocerebellum
It follow s from th e discussion of cerebellar fu n c-
tion in th e precedin g section s th at lesion s of th e
cerebrocerebellu m do n ot produ ce paralysis but
n on eth eless severely im pair th e execution of vol-
un tary m ovem en ts. Th e clin ical m an ifestation s are
alw ays ipsilateral to th e cau sative lesion .
Decomposition of voluntary movements. Th e
m ovem en ts of th e lim bs are atactic an d u n coordi-
n ated, w ith dysm etria, dyssyn ergia, dysdiado-
ch okin esia, an d in ten tion trem or. Th ese abn or-
m alities are m ore pron oun ced in th e u pper th an in
th e low er lim bs, an d com plex m ovem en ts are
m ore severely affected th an sim ple on es. Dys-
metria, i.e., th e in ability to stop a directed m ove-
m en t on tim e, is m an ifested (for exam ple) by a
m ovin g fin ger goin g p ast th e location of its target
(past-poin tin g, oversh oot; hyperm etria). Dyssyner-
gia is th e loss of th e precise cooperation of m u lti-
p le m u scle grou ps in th e execu tion of a p articu lar
m ovem en t; each m u scle grou p con tracts, but th e
in dividual grou ps fail to w ork togeth er correctly.
Dysdiadochokinesia is an im pairm en t of rapid al-
tern atin g m ovem en ts cau sed by a breakdow n of
th e precisely tim ed coordin ation of an tagon istic
m u scle groups: m ovem en ts su ch as rap id pron a-
tion an d su pin ation of th e h an d are slow, h altin g,
an d arrhyth m ic. Intention tremor, or—m ore p rop-
erly—action tremor, is seen m ain ly in directed
m ovem en ts an d becom es m ore in ten se th e n earer

th e fin ger com es to its target. Th ere m ay also be a
postu ral trem or at a frequ en cy of 2–3 Hz, part icu-
larly w h en th e patien t tries to h old th e pron ated
h an ds directly in fron t, w ith arm s exten ded.
Rebound phenomenon. Wh en th e p atien t presses
again st th e exam in er’s h an d w ith m axim u m
stren gth an d th e exam in er sudden ly p ulls h is or
h er ow n h an d aw ay, th e p atien t’s m ovem en t fails
to be braked as n orm al, an d th e arm lurch es
tow ard th e exam in er.
Hypotonia and hyporeflexia. In an acute lesion of
th e cerebellar h em isph ere, th e m u scu lar resist an ce
to passive m ovem en t is dim in ish ed, an d abn orm al
postu res (e.g., of th e h an d) m ay resu lt. Th e in trin sic
m uscle reflexes are also dim in ish ed in th e hy-
poton ic m u scles.
Scanning dysarthria and dysarthrophonia. Th ese
m an ifestation s arise m ain ly as a resu lt of paraver-
m ian lesion s an d reflect im paired syn ergy of th e
m u scu latu re of speech . Th e patien t sp eaks slow ly
an d h altin gly, w ith poor articu lation , an d w ith an
abn orm al, u nvaryin g st ress on each syllable.
Cerebellar Disorders
Cerebellar Ischemia and Hemorrhage
Arterial blood reach es th e cerebellu m t h rou gh th e
th ree cerebellar arteries: th e su perior cerebellar,
an terior in ferior cerebellar, an d posterior in ferior
cerebellar arteries. Th e origin an d an atom ical
cou rse of th ese arteries an d th e typ ical clin ical
m an ifestation s of occlu sion s of each of th em are
presen ted in Ch apter 11 on p . 275 ff. Th e typical
m an ifestation s of cerebellar h em orrh age are pre-
sen ted on p . 306.
Cerebellar Tumors
Cerebellar tu m ors are on ly rarely con fin ed to a
sin gle su bdivision of th e cerebellu m .
Benign cerebellar tumors (such as pilocytic
astrocytom a) m ay be problem atic in th at th ey
often grow quite large before produ cin g sym p-
tom s, becau se of th e p lasticity of th e cerebellu m .
Pap illedem a, an in direct sign of an in tracran ial
Cerebellar Disorders · 167
5
m ass, m ay be lackin g for a lon g tim e, particularly in
adults; it is presen t in about 75 % of affected ch ild-
ren . In m ost cases (90 %), cerebellar t um ors
m an ifest th em selves in itially w ith occipitocervical
h eadach e an d n au sea an d vom itin g on an em pty
stom ach (dry h eaves). A forced h ead tilt is a clin ical
sign of im pen din g h ern iation of th e cerebellar ton -
sils t h rou gh t h e foram en m agn u m .
Medulloblastoma is a m align an t tu m or th at prefer-
en tially affects ch ildren an d adolescen ts an d ac-
cou n ts for on e-th ird of all brain tu m ors in th is age
grou p (8 % of all brain tu m ors regardless of age). It
often arises from th e roof of th e fou rth ven tricle an d
th en grow s in to th e verm ian portion of th e floc-
cu lon odu lar lobe, possibly m etastasizin g to oth er
region s of th e brain an d sp in al cord th rou gh th e
cerebrospin al flu id (drop m etastases). Because th is
type of tum or often begin s in th e vestibu lo-
cerebellum , its typical in itial sign is dysequi-
libriu m : th e affected ch ild h as a broad-based, sw ay-
in g, an d staggerin g gait. Fu rth er cerebellar m an i-
festation s in cludin g ataxia, dysm etria, asyn ergia,
adiadoch okin esia, an d in ten tion trem or gradu ally
arise as th e t um or grow s furth er an d begin s to af-
fect th e lateral portion s of t h e cerebellum (th e
h em isph eres). In advan ced stages of tu m or grow th ,
blockage of th e fourth ven tricle or of th e cerebral
aquedu ct cau ses occlu sive hydroceph alus, w ith
clin ical sign s of in tracran ial hyperten sion (Fig. 5.8).
Astrocytoma and hemangioblastoma. Sim ilar
m an ifestation s are produ ced by pilocytic astrocy-
toma, a furth er ch aracterist ic t ype of posterior
fossa t um or arisin g n ear th e m idlin e. On th e oth er
h an d, hemangioblastoma in th e settin g of von Hip-
pel–Lin dau disease an d cystic astrocytoma ten d to
arise in th e cerebellar h em isp h eres an d, t h erefore,
to produ ce appen dicular ataxia an d gaze-evoked
nystagm us as th eir typical m an ifest ation s.
Acoustic neuroma (i.e., vestibular sch w an n om a).
Th is tum or arises from th e Schw ann cells of the
eighth cranial nerve (u su ally its vest ibular portion )
an d is th us fou n d in t h e cerebellopon tin e an gle. It
exp an ds slow ly an d m ay reach a con siderable size,
producin g th e clin ical m an ifestation s described
above on p . 125.
5 168 · 5 Cerebellum

a b
Fig. 5.8 Medulloblastoma, seen in T1-weighted MR im - hydrocephalus, as m anifested by the enlarged tem poral
ages after intravenous adm inistration of contrast m aterial. horns of the lateral ventricles. b The coronal im age shows
a A large, m arkedly and hom ogeneously contrast-enhanc- the origin of the tum or from the superior verm is and re-
ing tum or is seen in the superior portion of the verm is. The veals m arked dilatation of the lateral ventricles.
tum or com presses the fourth ventricle and causes occlusive

Fig. 5.9 Acoustic neuroma, seen in an axial, T1-weighted

MR im age at the level of the internal acoustic m eatus, ob-
tained after intravenous adm inistration of contrast m ate-
rial. Note the typical intram eatal and extram eatal extension
of the left-sided tum or, with expanded extram eatal portion
(“ice-cream cone” appearance).
 6

6 Diencephalon and
Autonomic Nervous
System
Location and Components of the
Diencephalon . . . . . . . . . . . . . . . . . . . . 170
Thalamus . . . . . . . . . . . . . . . . . . . . . . . . 172
Epithalamus . . . . . . . . . . . . . . . . . . . . . . 177
Subthalamus . . . . . . . . . . . . . . . . . . . . . 178
Hypothalamus . . . . . . . . . . . . . . . . . . . . 178
Peripheral Autonomic Nervous
System . . . . . . . . . . . . . . . . . . . . . . . . . . 188
6 170
6 Diencephalon and Autonomic Nervous System
Th e dien ceph alon lies betw een th e brain stem an d
th e telen ceph alon . It h as fou r com pon en ts: th e
th alam u s, epith alam u s, su bth alam us, an d hypo-
th alam u s.
Th e thalamus is fou n d on both sides of th e th ird
ven tricle an d con sists of n um erou s n u clei w it h
differen t fun ct ion s. It is t h e relay stat ion for m ost
of th e afferen t path w ays t h at ascen d to th e cere-
bral cortex. Som e types of im p ulses (e.g., n ocicep-
tive im pulses) m ay already be perceived, in te-
grated, an d given an affective colorin g, in an im -
precise w ay, in th e t h alam u s, bu t actu al con sciou s
exp erien ces do n ot seem to be gen erated u n til
sen sory im pu lses reach th e cerebral cortex.
Moreover, th e th alam u s h as exten sive con n ection s
w ith th e basal gan glia, brain stem , cerebellu m , an d
m otor cortical areas of th e cerebru m an d is th us a
m ajor com pon en t of th e m otor regu latory system .
Th e m ost im portan t n ucleu s of th e subthalamus
is th e subth alam ic n ucleu s, w h ich is closely
fu n ction ally related to th e basal gan glia.
Th e epithalamus is m ain ly com posed of th e
epip hysis (pin eal glan d/pin eal body) an d th e
haben ular n u clei; it plays a role in th e regu lation of
circadian rhyt h m s.
Th e m ost basal portion of th e dien ceph alon is
th e hypothalamus, w h ich coordin ates vital bodily
Location and Components of the
Diencephalon
Location. Th e position of th e dien ceph alon is ju st
oral to th at of th e m idbrain ; th e dien ceph alon does
n ot con tin u e alon g th e brain stem axis, bu t rath er
takes a rostral ben d, so th at it com es to lie n early in
th e lon gitudin al axis of th e cerebru m (Fig. 6.1). It is
located in th e m iddle of th e brain , ven trally an d
cau dally to th e fron tal lobe, an d en closes th e low er
portion of th e th ird ven tricle from both sides
(Fig. 6.2).
Th e thalam us form s th e upper portion of th e
th ird ven tricu lar w all, th e hypothalam us its low er
portion . Dorsally, t h e dien ceph alon is en closed by
th e corpu s callosum , th e lateral ven t ricles, an d th e
fu n ction s su ch as resp iration , circu lation , w ater
balan ce, tem peratu re, an d n u trition al in t ake an d
is th us th e h ierarch ically up perm ost regu latory
organ of t h e au ton om ic n ervous system . It also in -
flu en ces th e activit y of t h e en docrin e glan ds by
w ay of th e hypoth alam ic–pitu itary axis.
Th e autonomic nervous system is respon sible
for th e n erve supply of th e in tern al organ s, blood
vessels, sw eat glan ds, an d salivary an d lacrim al
glan ds. It is called “auton om ic” becau se it fu n c-
tion s largely in depen den tly of con sciou sn ess; it is
altern at ively (less com m on ly) called th e vegeta-
tive n ervous system . Its efferen t arm in th e periph -
ery is com p osed of t w o an atom ically an d
fu n ction ally distin ct parts, t h e sym path etic an d
parasym path etic n ervous system s. Th e afferen t
arm is n ot divided in th is w ay.
Becau se of th e m u ltiplicity of fu n ction s th at th e
dien ceph alon perform s, diencephalic lesions can
h ave very diverse effects, depen din g on th eir site
an d exten t. Th alam ic lesion s p rodu ce h em iparesis
an d h em isen sory deficits, m ovem en t disorders,
distu rban ces of con sciousn ess, an d pain syn -
drom es, w h ile hyp oth alam ic lesion s im pair
various vital fu n ction s sin gly or in com bin ation ,
an d cau se en docrin e dysfu n ction .
cerebral h em isp h eres (Fig. 6.2). Th e roof of th e
th ird ven tricle is form ed by th e th in tela ch oroidea
an d th e att ach ed ch oroid plexu s. Th e rostral exten t
of t h e dien ceph alon is delim ited by t h e lam in a ter-
m in alis an d an terior com m issu re, its caudal exten t
by th e posterior com m issu re, h aben u lar com m is-
sure, an d pin eal body (ep iphysis). Th e in terven tric-
ular foram en of Mon ro, w h ich con n ects th e lateral
ven tricle w ith th e t h ird ven tricle, is fou n d on
eith er side an terior to th e rostral portion of t h e
th alam u s, just below th e gen u of th e forn ix. Th e
basal portion of t h e dien ceph alon is its on ly exter-
n ally visible part: it can be seen on th e u n dersu r-
face of th e brain betw een th e opt ic ch iasm , th e
opt ic t ract, an d th e cerebral p edu n cles. Th e visible
dien ceph alic stru ctu res in th is area are th e m am il-
lary bodies an d th e tu ber cin ereu m , togeth er w ith
 Location and Com ponents of the Diencephalon · 171
6
Fig. 6.1 Sagittal section
Interventricular Septum Crus of
through the diencephalon
foram en (of Monro) pellucidum the fornix
Choroid plexus of third ventricle
and the brainstem show-
ing the m idbrain–dien-
Stria m edullaris thalam i
cephalic junction and the

s
u
m
Habenular nucleus structures surrounding the

a
l
a
Posterior third ventricle

h
t
com m issure

i
p
E
Epiphysis

I
Anterior com m issure
II Thalamus
Tectal
Massa interm edia lamina
Hypothalam ic sulcus
Lam ina term inalis
s
Optic recess
u
m
Optic chiasm
a
l
Aqueduct
a
h
Infundibular recess
t
o
Hypophysis
p
y
H
Neurohypophysis
I
I
I
Tuber cinereum Fourth
ventricle
Mam illary body

Tela choroidea
of third ventricle
Corpus callosum
Choroid plexus of third ventricle
Fornix

Choroid plexus of lateral ventricle

Body of caudate nucleus
Stratum zonale
Reticular nucleus of the thalam us
Internal and external m edullary lam inae
of the thalam us
Thalamus, lateral nuclear group
Thalamus, centrom edian nucleus
Thalam us, m edial nuclear group
Third ventricle, massa interm edia

Globus pallidus
Internal capsule
Optic tract
Zona incerta
Hypothalamus
Mamillothalam ic tract
Nucleus of the
mam illary body Crus cerebri
Subthalamic
nucleus

Fig. 6.2 Coronal section through the diencephalon

6 172 · 6 Diencephalon and Autonom ic Nervous System
its in fu n dibulu m (pitu itary stalk), w h ich leads
dow nw ard to th e pituitary glan d (cf. Fig. 4.8, p. 83.
Th e tw o h alves of th e th alam u s facin g each
oth er across th e th ird ven tricle are con n ected in
70–80 % of cases by th e in terth alam ic adh esion
(m assa interm edia) (Fig. 6.1), w h ich is n ot a fiber
path w ay bu t rath er a secon dary adh esion of th e
gray m atter com in g from eith er side. Laterally, th e
dien cep h alon is delim ited by th e in tern al capsu le.
Th e globu s pallidu s is em bryologically a p art of
th e dien ceph alon , th ou gh it is separated from it by
th e in tern al capsule (Fig. 8.4, p. 216) an d is th us lo-
cated in th e basal gan glia. It w ill be discussed alon g
w ith th e rest of th e basal gan glia in Ch apter 8
(p . 214). Likew ise, a discu ssion of th e hyp ophysis
(p itu itary glan d), w h ich is lin ked to th e hy-
poth alam u s by th e in fu n dibu lu m , w ill be deferred
to th e section on th e periph eral au ton om ic
n ervou s system (p. 188).
Subdivisions. Th e dien ceph alon h as th e follow in g
com pon en ts (Fig. 6.1):
¼ Th e epithalamus, w h ich con sists of t h e
h aben ula an d h aben u lar n uclei, th e h aben u lar
com m issu re, th e epiphysis, an d th e epith alam ic
(p osterior) com m issu re.
¼ Th e thalamus, a large com plex of n eu ron s t h at
accou n ts for fou r-fifth s of t h e volu m e of th e
dien ceph alon .
¼ Th e hypothalamus, w h ich is dem arcated from
th e th alam u s by th e hyp oth alam ic su lcus, an d
con tain s various fu n ction ally distin ct grou ps of
n eu ron s. It is th e h ierarch ically u pperm ost
cen ter (“h ead gan glion ”) of th e auton om ic
n ervou s system ; on each side, th e colu m n of th e
forn ix descen ds th rough th e lateral w all of th e
hyp ot h alam u s to term in ate in th e m am illary
body (see Fig. 6.8).
¼ Th e subthalamus, w h ich m ain ly con sists of t h e
su bth alam ic n ucleus (corpu s lu ysii, Fig. 6.2) an d
is located ben eath th e th alam us an d dor-
solateral to th e m am illary body.
Thalamus
Nuclei
Flan kin g th e th ird ven tricle, on eith er side of th e
brain , t h ere is a large, ovoid com plex of n eu ron s
m easu rin g abou t 3 × 1.5 cm in diam eter. Th is com -
plex, th e th alam us, is n ot a u n iform cluster of cells
bu t rath er a con glom erate of n u m erou s, dist in ct
n uclei, each w ith its ow n fu n ction an d its ow n af-
feren t an d efferen t con n ection s. Each h alf of th e
th alam us (left an d righ t) is divided in to th ree
m ajor region s by sh eetlike layers of w h ite m atter
takin g th e form of a Y (th e in tern al m edu llary
lam in ae, Fig. 6.3). Th e anterior nuclei sit in th e
an gle of th e Y, th e ventrolateral nuclei laterally, an d
th e medial nuclei m edially. Th e ven trolateral n u clei
are fu rt h er su bdivided in to ventral an dlateral nu-
clear groups. Th e ven t ral n u clei in clu de th e ventral
anterior nucleus (VA), th e ventral lateral nucleus
(VL), th e ventral posterolateral nucleus (VPL), an d
t h e ventral posterom edial nucleus (VPM). Th e
lateral n uclei con sist of a lateral dorsal nucleus an d
a lateral posterior nucleus. Fu rth er caudally, on e
fin ds th e pulvinar, w it h th e medial an d lateral
geniculate bodies attach ed to its un derside. Th ere
are a few sm all group s of n euron s w ith in th e in ter-
n al m edullary lam in ae (th e interlaminar nuclei), as
w ell as on e larger, cen trally located cell com p lex,
th e centromedian nucleus (or centre m édian).
Laterally, th e extern al m edullary lam in a separates
th e th alam u s from th e in tern al capsule; th e reticu-
lar nucleus of the thalamus is a th in layer of cells
closely applied to th e extern al m edullary lam in a
(Fig. 6.2).
Th e th ree m ajor n u clear grou ps (an terior, ven -
trolateral, an d m edial) h ave been cytologically an d
fun ct ion ally su bdivided in to abou t 120 sm aller n u -
clei, th e m ost im portan t of w h ich are sh ow n in
Fig. 6.3. Th ere is still n o un iform stan dard for th e
su bdivision an d n om en clat ure of th e th alam ic n u-
clei; th e n om en clature follow ed in Fig. 6.3 is th at
fou n d in Nom ina Anatom ica.
Position of the Thalamic Nuclei in
Ascending and Descending Pathw ays
In th e precedin g ch apters, th e path w ays th at as-
cen d from th e spin al cord, brain stem , an d cerebel-
lu m to th e cerebral cortex h ave been traced u p-
w ard as far as th e th alam u s. Th e t h alam us is t h e
last m ajor relay station for all ascen din g im pu lses
(except olfactory im pu lses) before th ey con tin ue,
via th alam ocortical fibers, to th e cortex. Figure 6.4
sh ow s th e term in ation of variou s afferen t path -
w ays in distin ct th alam ic n uclei, w h ich th en pro-
ject to correspon din g cortical areas (for furth er
details, see p. 173).

Lateral dorsal nucleus
Lateral posterior nucleus
Intralam inar nuclei
Anterior thalam ic nuclei Medial dorsal nucleus
Ventral anterior nucleus (VA) Centromedian
nucleus
Ventral lateral nucleus (VL)
Pulvinar
Thalam us · 173
6
Fig. 6.3 Thalamic nuclei.
The four m ajor nuclear
groups are shown: the
anterior group (green),
the ventrolateral group
(various shades of blue),
the medial group (red),
and the dorsal group,
consisting of the pulvinar
(violet) and the geniculate
bodies (shades of blue).

IV
Ventral interm ediate
nucleus (VI)

Ventral posterolateral
nucleus (VPL)
Medial geniculate
body
Ventral posterom edial
Lateral geniculate
nucleus (VPM)
body

Like th e spin al cord an d brain stem (e.g., t h e m e-
dial lem n iscus), th e th alam ic n u clei an d th e
th alam ocortical projection s m ain tain a strict
point-to -point somatotopic organization.
Specific and nonspecific projections. Th alam ic n u -
clei th at receive inpu t from circum scribed areas of
th e body periph ery an d tran sm it im pu lses to th e
correspon din g circu m scribed cortical areas (pri-
m ary projective fields) are called specific thalamic
nuclei (or prim ary th alam ic n uclei). Th alam ic n u-
clei projectin g to th e u n im odal an d m u ltim odal
cortical association areas (secon dary an d tertiary
th alam ic n u clei) are also coun ted am on g th e
specific n u clei. Th e distin gu ish in g feat ure of th e
specific n u clei is th u s a direct projection to the cere-
bral cortex.
In con trast, nonspecific thalamic nuclei receive
th eir afferen t inpu t from m u ltip le, distin ct sen se
organ s, usually after an in terven in g syn apse in th e
reticu lar form ation an d/or on e of th e prim ary
th alam ic n u clei. Th ey project on ly in directly to th e
cerebral cortex (e.g., by w ay of th e basal gan glia),
in clu din g th e association fields.
Specific Tha la mic Nuclei a nd Their Connections
Nuclei with Connections to Prim ary Cortical
Areas
Ventral posterolateral nucleus (VPL) and ventral
posteromedial nucleus (VPM). All som atosen sory
fibers ascen din g in th e m edial lem n iscus,
spin oth alam ic t ract, t rigem in oth alam ic tract, etc.,
term in ate in a relay station in th e ven troposterior
n u clear com p lex of th e th alam u s. Th e ven tral p os-
terolateral n u cleu s is th e relay station for the m e-
dial lem niscus, w h ile t h e ven tral p osterom edial n u-
cleu s is th e relay station for trigem inal afferents.
Th ese n uclei, in turn , project fibers to circu m -
scribed areas of th e som atosen sory cortex (areas
3a, 3b, 1, an d 2, Fig. 6.4).
Furth erm ore, gustatory fibers from t h e n ucleu s
of th e tractu s solitariu s term in ate in th e m edial tip
of th e ven tral p osterom edial n ucleu s, w h ich , in
tu rn , projects to th e postcen tral region overlyin g
th e in su la (Fig. 6.4).
Medial and lateral geniculate bodies. Th e m edial
an d lateral gen iculate bodies, too, are am on g th e
specific n u clei of th e th alam u s. Th e optic tract ter-
m in ates in th e lateral gen icu late body, w h ich relays
visual im pulses retin otopically, by w ay of th e optic
radiat ion , to th e visu al cortex (area 17). Auditory
im pulses are carried in th e lateral lem n iscus to th e
6 174 · 6 Diencephalon and Autonom ic Nervous System
Globus
pallidus
externus
internus
VI
Pulvinar
Putam en
Dentatothalamic Dentate
tract nucleus
Trigem inal
Medial lem niscus afferents
Spinothalam ic tract
Fig. 6.4 Afferent and efferent connections of the ven-
tral nuclear group
m edial gen icu late body an d relayed ton otopically,
by w ay of th e auditory radiat ion , to th e au ditory
cortex (tran sverse tem poral gyri of Hesch l, area 41)
in th e tem p oral lobe (Fig. 6.5).
Ventral oral nuclei and ventral anterior nucleus.
Th e ven tral oral posterior n ucleu s (V.o.p., a port ion
of th e ven t ral lateral n ucleu s) receives inp ut from
th e dentate nucleus and red nucleus by w ay of th e
den tatoth alam ic tract (Fig. 6.4) an d projects to th e
m otor cortex (area 4), w h ile th e ven tral oral an te-
rior n u cleu s (V.o.a.) an d th e ven tral an terior n u-
cleus (VA), both of w h ich also belon g to th e ven tral
n u clear grou p, receive inp ut from th e globus pal-
lidus an d project to th e prem otor cortex (areas 6aα
an d 6a ) (Fig. 6.4).
Nuclei Projecting to Association Areas of the
Cerebral Cortex
Th e an terior n u cleus, th e m edial n u cleus, an d t h e
pu lvin ar are secon dary an d tertiary th alam ic n u-
clei (Figs. 6.5, 6.6), i.e., specific th alam ic n u clei pro-
jectin g to th e un im odal an d m ultim odal cortical
associat ion fields (pp. 247). Th ese n u clei m ostly re-
ceive th eir inpu t n ot directly from th e p eriph ery
bu t rath er after a syn aptic relay, w h ich is usually
located in on e of th e p rim ary th alam ic n uclei de-
scribed above.
Th e anterior nucleus (Fig. 6.6) is reciprocally con -
n ected to th e m am illary body an d forn ix th rou gh
th e m am illoth alam ic tract (of Vicq d’Azyr); it
possesses bidirection al, p oin t-to-poin t con n ec-
tion s w ith th e cin gu late gyru s (area 24) an d is th u s
an in tegral part of th e lim bic system , w h ose struc-
tu re an d fu n ction are described in Ch apter 7.
Th e medial nucleus of th e th alam u s h as bidir-
ection al, poin t-to-poin t con n ect ion s w ith th e asso-
ciation areas of the frontal lobe an d th e prem otor re-
gion. It receives afferen t inp ut from oth er th alam ic
n uclei (ven tral an d in tralam in ar n u clei), an d from
th e hypoth alam u s, m idbrain n u clei, an d globu s
pallidu s (Fig. 6.5).
Destruction of th e m edial n u cleu s by a t um or or
oth er process cau ses a frontal brain syndrome w ith
a ch an ge of person ality (loss of self-represen tation ,
as described by Hassler), ju st as h as been described
after fron t al leu kotom y—a psych osurgical pro-
cedu re, n ow rarely, if ever, perform ed, in w h ich a
lesion is m ade in th e deep w h ite m atter of th e
fron t al lobe. Th e visceral im p ulses th at reach th is
n ucleus by w ay of th e hypoth alam us exert an in -
flu en ce on t h e affective state of th e in dividual,
leadin g to a sen se of w ell-bein g or u n easin ess,
good or bad m ood, etc.
Th e pulvinar p ossesses reciprocal, poin t-to-poin t
con n ection s w ith th e association areas of th e
p arietal an d occipital lobes (Fig. 6.5). Th ese asso-
ciation areas are su rrou n ded by th e prim ary som a-
tosen sory, visu al, an d auditory cortices an d th u s
probably play a m ajor role in th e bin din g of th ese
differen t typ es of in com in g sen sory in form ation .
Th e pu lvin ar receives n eu ral inpu t from oth er
th alam ic n uclei, especially th e in tralam in ar n u clei.
Lateral nuclei. Th e lateral dorsal n ucleu s an d th e
lateral p osterior n u cleu s do n ot receive any n eu ral
inpu t from ou tside th e th alam u s an d are con -
n ected on ly to oth er th alam ic n u clei. Th ey are th u s
kn ow n as in tegrative n u clei.
 Thalam us · 175
6
Fig. 6.5 Afferent and
efferent connections of
the medial (red), dorsal
(violet/blue), and lateral
(blue) nuclear groups

Medial dorsal nucleus

Oral dorsal nucleus Superficial dorsal
nucleus
Globus pallidus
externus internus

Pulvinar
Putam en

Medial geniculate
body (hearing)
Interm ediate Lateral geniculate
dorsal nucleus body (vision)

Hypothalam us

Fig. 6.6 Afferent and

Cingulate gyrus efferent connections of
Fornix
Corpus the anterior nucleus
callosum (green) and the centrome-
dian nucleus (orange)

Anterior nucleus

Head of caudate
nucleus Centro-
m edian
Globus pallidus nucleus

Putam en
Em boliform
nucleus
Mam illary Mam illo-
body thalam ic
tract

Reticular
formation
6 176 · 6 Diencephalon and Autonom ic Nervous System
Nonspecific Tha la mic Nuclei a nd Their
Connections
Intralaminar nuclei. Th e in tralam in ar n uclei are t h e
m ost im portan t com pon en t of th e n on specific
th alam ic projection system . Th ese n u clei are lo-
cated w ith in th e in tern al m edu llary lam in a, an d
th e largest am on g th em is th e centromedian nu-
cleus. Th ese cell com p lexes receive th eir afferen t
inpu t th rough ascen din g fibers from th e brain stem
reticular form ation an d th e em boliform nucleus of
th e cerebellu m , as w ell as from th e internal pallidal
segm ent an d oth er th alam ic n uclei. Th ey p roject
n ot to th e cerebral cortex bu t rath er to t h e caudate
nucleus, putam en, an d globus pallidus (Fig. 6.6).
Th ey probably also sen d efferen t im pu lses dif-
fu sely to all n u clei of th e th alam us, w h ich th en , in
tu rn , p roject to w idespread secon dary areas of th e
cerebral cortex. Th e cen trom edian n u cleu s is an
im portan t com p on en t of th e in tralam in ar cell
com plex, w h ich con stitu tes th e th alam ic portion of
th e ascen din g reticu lar activatin g system (ARAS or
arousal system ). An oth er p ortion of th is arou sal
system probably involves th e su bth alam u s an d hy-
poth alam us.
Functions of the Thalamus
Th e fun ction s of th e th alam u s are h igh ly com plex
becau se of t h e large n um ber of n u clei it con tain s
an d th eir very diverse afferen t an d efferen t con -
n ection s.
¼ First of all, th e th alam u s is th e largest subcorti-
cal collecting point for all exteroceptive an d
proprioceptive sen sory im pu lses.
¼ Fu rth erm ore, it is a relay station for all im pu lses
arisin g in cu tan eou s an d visceral sen sory recep-
tors, for visu al an d au ditory im pu lses, an d for
im pu lses from th e hypoth alam us, cerebellu m ,
an d brain stem reticular form ation , all of w h ich
are processed in th e th alam us before bein g
tran sm itted onw ard to oth er stru ctures. Th e
th alam u s sen ds a sm all efferen t com pon en t to
th e striatu m , bu t m ost of its outp ut goes to th e
cerebral cortex. All sen sory im p ulses (oth er
th an olfactory im pulses) m ust pass th rou gh th e
th alam us before th ey can be con sciou sly per-
ceived. Th u s, th e th alam u s w as tradition ally
called “th e gatew ay to con sciousn ess,” th ough
th e con sciou s percept ion of sm ell im plies th at
th is con ception is flaw ed an d p erh aps m islead-
in g.
¼ Th e t h alam us, h ow ever, is n ot m erely a relay
station , bu t an im portan t center for integration
and coordination, in w h ich afferen t im pu lses of
differen t m odalities, from differen t region s of
th e body, are in tegrated an d given an affective
coloration . A n eural su bstrate of certain
elem en tary ph en om en a su ch as pain , dis-
pleasure, an d w ell-bein g is already presen t in
th e th alam u s before bein g tran sm itted u pw ard
to th e cortex.
¼ Th rou gh its reciprocal con n ection s (feedback
loops) w ith th e m otor cortex, som e of w h ich
pass th rough th e basal gan glia an d cerebellum ,
th e th alam us modulates motor function.
¼ Som e th alam ic n u clei are also components of
the ascending reticular activating system
(ARAS), a specific arou sal system origin atin g in
n u clei th at are diffu sely located th rou gh out th e
brain stem reticu lar form ation . Activat in g im -
pu lses from th e ARAS are relayed by certain
th alam ic n u clei (ven tral an terior n ucleu s, in -
tralam in ar n u clei [p articu larly th e cen trom e-
dian n u cleu s], reticu lar n uclei) to th e en tire
n eocortex. An in tact ARAS is essen tial for n or-
m al con sciou sn ess.
Syndromes of Thalamic Lesions
Th e clin ical m an ifestation s of th alam ic lesion s de-
pen d on th eir precise location an d exten t becau se
th e fu n ction s of th e in dividu al th alam ic n u clei are
so h igh ly varied.
Lesions of the ventral anterior and intralaminar nu-
clei. Th e ven tral an terior (VA), in tralam in ar, an d re-
ticu lar n u clei are n on specific “activatin g” n u clei.
Th ey project diffusely to th e fron tal lobes (ven tral
an terior n u cleu s, cf. Fig. 6.4, p. 174) an d th e en tire
n eocortex (in tralam in ar n uclei), an d th ey serve to
m odu late cortical resp on ses. Th ese path w ays are
com pon en ts of th e ascen din g reticu lar activatin g
system (ARAS). Lesion s in th is area, particu larly bi-
lateral lesion s, cau se disturbances of consciousness
and attention, an d, if th ey exten d to th e m idbrain
tegm en tum , vertical gaze palsy. Less com m on ly,
param edian lesion s can cau se agitation , dysp h oria,
or acu te con fu sion . Isolated lesion s of th e ven tral
an terior n u clei w ith im paired fron t al cort ical acti-
vat ion h ave been reported to cause distu rban ces of
volun tary beh avior; righ t-sided lesion s in t h is area
h ave also been rep orted to cau se m ore com plex

Case Presentation 1: Tha la mic Pa in Syndrome a fter Hemorrhage in the Basa l Ga nglia
This 51-year-old m ale schoolteacher was attending a
friend’s funeral when he suddenly fell and com plained of
nausea and a pulsatile headache. He had been standing in
the hot sun during the eulogy, and the other funeral at-
tendees at first thought he had sim ply fainted. When he
was still unable to get up unaided and continued to com -
plain of headache ten m inutes later, they called an am bu-
lance. The em ergency physician on the scene found an arte-
rial blood pressure of 220/120 m m Hg and weakness of the
left hand and the entire left lower lim b, and the patient was
transported to the hospital. Exam ination on adm ission re-
vealed central-type left hem iparesis with increased deep
tendon reflexes, as well as hypesthesia and hypalgesia near
the m idline, pallanesthesia, and a m ild deficit of position
sense on the left side of the body. A CT scan revealed an
acute hem orrhage in the right basal ganglia.
disturban ces of m ood, e.g., m an ic state an d logor-
rh ea, or, altern at ively, deliriu m w ith con fabula-
tion s an d in approp riate beh avior. Bilateral m edial
lesion s can cause tran sien t am n esia w ith or
w ith out an osogn osia.
Lesions of the ventral nuclei. As described above,
th e ventral posterior nuclei are relay station s for
specific sen sory im pu lses, w h ich are th en sen t on -
w ard to t h e correspon din g prim ary cort ical areas.
Lesion s of th ese n uclei produ ce specific deficits of
on e or m ore sen sory m odalities, as follow s.
¼ Lesion s of th e ventral posterolateral nucleus
produ ce contralateral im pairm ent of touch and
proprioception, as w ell as paresth esias of th e
lim bs, w h ich m ay feel as if th ey w ere sw ollen or
abn orm ally h eavy.
¼ Lesion s affectin g th e basal portion of the ven-
tral posterolateral an d/or posteromedial nu-
cleus can produce severe p ain syn drom es in ad-
dition to th e sen sory deficit s ju st described
(“th alam ic pain ,” som etim es in an est h etic
areas—“anesthesia dolorosa”; cf. Case Presen ta-
tion 1).
¼ Lesion s of th e ventral lateral nucleus h ave
m ain ly m otor m an ifestation s, as th is n ucleu s is
m ain ly con n ected to th e prim ary an d secon dary
m otor areas of th e cerebral cortex, an d to th e
cerebellu m an d basal gan glia.
¼ Acute lesions of th e ven tral lateral n u cleus an d
th e n eigh borin g subth alam ic region can pro-
du ce severe cen tral “w eakn ess,” in w h ich direct
periph eral testin g reveals n o im pairm en t of raw
m uscle stren gth (e.g., again st resistan ce)
Epithalam us · 177
6
Over the next six m onths, the patient’s hem iparesis and
hem isensory deficit largely resolved, and he was able to re-
sum e playing tennis. In the sam e period of tim e, however,
he began to experience repeated bouts of paroxysm al pain
and dysesthesia in the previously hypesthetic areas on the
left side of the body. These abnorm al sensations were
partly electric in character. An MRI scan of the head at this
tim e revealed only a sm all rem nant of the initial hem or-
rhage, with form ation of a cyst in the right thalam us. The
pain im proved considerably on treatm ent with car-
bam azepine and am itriptyline but returned prom ptly as
soon as the patient tried to stop taking these m edications.
They could finally be discontinued with a slow taper after a
further three years.
(“th alam ic astasia”). Th e patien t falls to th e side
op posite th e lesion an d m ay be un able to sit un -
aided. Such m an ifestation s app ear eith er in
isolation or in con jun ction w ith tran sien t
th alam ic n eglect, in w h ich both sen sory an d
m otor fu n ction is n eglected on th e side op-
posite th e lesion . Th alam ic n eglect, du e to in -
volvem en t of t h alam ocortical fibers project in g
to th e parietal lobe, is u su ally sh ort-lastin g an d
alm ost alw ays resolves com pletely.
¼ Lesion s affectin g th e den tato-ru bro-th alam ic
projection s of th e ventral lateral nucleus (VL.)
produce contralateral hem iataxia w ith action
trem or, dysm etria, dysdiadoch okin esia, an d
path ological rebou n d. Such fin din gs m ay give
th e erron eous im pression of a cerebellar lesion .
Thalamic Vascular Syndromes
Th e th alam u s is supp lied by fou r arteries (p. 277).
In terru ption of th e arterial blood supp ly in each of
th ese distribu tion s causes a ch aracteristic syn -
drom e, as described in Ch apter 11 on p. 299.
Epithalamus
Th e epith alam u s con sists of th e habenula w ith its
habenular nuclei, th e habenular commissure, th e
stria medullaris, an d th e epiphysis. Th e h aben u la
an d th e h aben u lar n u clei con stit ute an im portan t
relay stat ion of th e olfactory system . Afferen t ol-
factory fibers t ravel by w ay of t h e stria m edullaris
6 178 · 6 Diencephalon and Autonom ic Nervous System

th alam i to th e h aben u lar n u clei, w h ich em it effer-

Thalam ic Centromedian nucleus
en t projection s to th e auton om ic (salivatory) n u - fasciculus of the thalam us
clei of th e brain stem , th u s playin g an im portan t
role in n u trit ion al in take.

Th e epiphysis (pineal gland) con tain s specialized Putam en

cells, called pin ealocytes. Calcium an d m agn esiu m

salts are deposited in t h e ep iphysis from approxi-
m ately age 15 years onw ard, m akin g th is stru cture Lenticular
visible in plain radiograp h s of th e sku ll (an im p or- fasciculus

tan t m idlin e m arker before th e era of CT an d MRI). Subthalam ic

fasciculus
Epip hyseal tu m ors in ch ildh ood som etim es cause
Globus pallidus
precocious puberty; it is th u s p resu m ed t h at th is
Basal nucleus
organ in h ibit s sexual m aturat ion in som e w ay, an d of Meynert
th at th e destru ction of epiphyseal tissu e can re- Zona incerta
Ansa lenticularis
m ove th is in h ibition . In low er vertebrates, th e Subthalamic Innom inate
nucleus substance
epiphysis is a light-sensitive organ th at regulates
circadian rhyth m s. In prim ates, ligh t can n ot pen e- Fig. 6.7 Fiber connections in the subthalamus. MD =
trate th e sku ll, bu t th e ep iphysis still in directly re- m edial dorsal nucleus of the thalam us; VL = ventral lateral
ceives visu al inpu t relatin g to th e ligh t–dark cycle. nucleus; IC = internal capsule.
Afferen t im pu lses travel from th e retin a to th e su-
prachiasmatic nucleus of t h e hypot h alam u s, from
w h ich , in tu rn , furth er im pu lses are con du cted to join ed m ore rostrally by th e an sa len ticularis. Th e
th e intermediolateral nucleus an d, via postgan - su bth alam u s also con tain s th e zon a in certa, a ros-
glion ic fibers of th e cervical sym path etic ch ain , to tral con tin u ation of th e m idbrain reticular form a-
th e epiphysis. tion . Th e m ajor con n ection s of th e pu tam en , pal-
lidu m , su bth alam u s, an d th alam u s are depicted in
Fig. 6.7.

Subthalamus Function. Th e su bth alam ic n u cleu s (corpu s Lu ysii)

Location and components. Th e subt h alam us is
fou n d im m ediately caudal to th e th alam us at an
early stage of em bryological developm en t an d
th en m oves laterally as t h e brain develops. It com -
prises th e subthalamic nucleus, part of th e globus
pallidus (cf. p. 217), an d variou s fiber contingents
th at pass th rou gh it on th eir w ay to th e th alam u s,
in clu din g th e m edial lem n iscus, th e sp in oth alam ic
tract, an d th e trigem in oth alam ic tract. All of th ese
tracts term in ate in th e ven troposterior region of
th e th alam u s (Fig. 6.4, p . 174). Th e su bstan tia n igra
an d red n u cleu s border th e subt h alam u s an teriorly
an d p osteriorly. Fibers of t h e den tatoth alam ic tract
travel in th e preru bral field H1 of Forel to term in ate
in th e ven tro-oral posterior n u cleus of th e
th alam u s (a part of th e ven tral lateral n u cleu s, VL);
fibers from th e globu s pallidu s travel in t h e len tic-
u lar fascicu lu s (Forel’s fascicu lus H2) to th e ven tro-
oral an terior n u cleus (an oth er p art of VL) an d th e
ven tral an terior n u cleu s (VA). Th ese tracts are
is, fu n ction ally sp eakin g, a com pon en t of th e basal
gan glia an d h as reciprocal con n ection s w ith th e
globus pallidus (p. 217). Lesion s of th e subth alam ic
n ucleus produce con tralateral hem iballism
(p. 223 f.).
Hypothalamus
Location and Components
Th e hypoth alam us (Fig. 6.8) is com posed of gray
matter in the w alls of the third ventricle from th e
hypoth alam ic su lcus dow nw ard an d in th e floor of
the third ventricle , as w ell as th e infundibulum and
the mamillary bodies. Th e p osterior pituitary lobe,
or neurohypophysis, is also con sidered part of t h e
hypoth alam u s; th is stru cture is, in a sen se, th e en -
larged cau dal en d of th e in fun dibu lum . Th e an te-
rior pitu itary lobe, on th e oth er h an d, is n ot
derived from th e n eu roectoderm at all, but rath er
 Hypothalam us · 179
6
Fig. 6.8 Hypothalamic
nuclei. a Lateral view.
b and c Coronal sections in
two different planes.

Paraventricular nucleus
Preoptic nucleus
Dorsom edial nucleus
Posterior nucleus
Supraoptic nucleus

Ventrom edial nucleus

Mam illary
Infundibular nucleus body
Tuberal nuclei
Neurohypophysis

Fornix

Optic tract
Ventrom edial nucleus
Dorsom edial nucleus
Lateral area
III Dorsal area
Supra-
optic
nucleus
Tuberal nuclei
Lateral area
Paraventricular
Medial area Optic chiasm nucleus

from Rath ke’s pouch , an out cropp in g of th e rostral
en d of th e prim itive alim en tary tract. Th e tw o
pitu itary lobes, th ough adjacen t to each oth er, are
n ot fun ction ally con n ected. Rem n an ts of Rath ke’s
pou ch in th e sellar region can grow in to tu m ors,
e.g., cran iop h aryn giom a.
Th e colu m n s of th e forn ix, as th ey descen d
th rough th e hyp oth alam u s to th e m am illary bodies
on eit h er side, divide th e hypoth alam u s of each
side in to a medial an d a lateral segment (Fig. 6.8).
Th e lateral segm en t con t ain s variou s grou ps of
fibers, in cludin g t h e m edial forebrain bundle, w h ich
run s from basal olfactory areas to th e m idbrain . It
also con tain s th e lateral tuberal n u clei (see p. 180).
Th e m edial segm en t, in con trast, con tain s a n u m -
ber of m ore or less clearly distin gu ish able n u clei
(Fig. 6.8a–c), w h ich are divided in to an anterior
(rostral), a middle (tuberal), an d a posterior
(mamillary) nuclear group.
Hypothalamic Nuclei
Anterior nuclear group. Th e im p ortan t m em bers of
th is grou p are th e preoptic, supraoptic, an d para-
ventricular nuclei (Fig. 6.8). Th e latter tw o n u clei
project , by w ay of th e sup raopt ico-hypop hyseal
tract, to th e n eu rohypophysis (see Figs. 6.10 an d
6.11).
6 180 · 6 Diencephalon and Autonom ic Nervous System
Corpus callosum
Stria terminalis
Fornix
Massa
intermedia
Medial forebrain bundle
(from the paraolfactory region)
Dorsom edial nucleus
Ventromedial nucleus Peduncle
of mamil-
lary body
Amygdala
Hippocampus
Middle nuclear group. Th e im portan t m em bers of
th is group are th e infundibular nucleus, th e tuberal
nuclei, th e dorsom edial nucleus, t h e ventrom edial
nucleus, an d th e lateral nucleus (or tuberom am il-
lary nucleus) (Fig. 6.8).
Posterior nuclear group. Th is grou p in clu des th e
m am illary nuclei (th e su pram am illary n ucleu s, th e
m am illary n u cleu s, th e in tercalate n u cleus, an d
oth ers) an d th e posterior nucleus (Fig. 6.8). Th is
area h as been term ed a dyn am ogen ic zon e (Hess),
from w h ich th e auton om ic n ervou s system can be
im m ediately called in to action , if n ecessary.
Afferent and Efferent Projections of
the Hypothalamus
Th e n eu ral con n ection s of th e hypoth alam u s (Figs.
6.9 an d 6.10) are m u ltifarious an d com plex. In
order to carry ou t its fu n ction as th e coordin atin g
cen ter of all au ton om ic processes in th e body
(p. 190), th e hypoth alam u s m u st com m u n icate via
afferen t an d efferen t pat h w ays w ith very m any
differen t areas of t h e n ervous system . In form ation
from th e ou tside w orld reach es it th rou gh visu al,
olfactory, an d probably also auditory path w ays.
Th e presen ce of cortical afferen ts im p lies th at th e
Fig. 6.9 Major afferent
connections of the hy-
pothalamus (schem atic
drawing)
To the
reticular
formation
hypoth alam u s can also be in flu en ced by h igh er
cen ters. Th e m ajor con n ection s of th e hy-
poth alam u s are to th e cin gu late gyru s an d fron tal
lobe, th e h ippocam pal form ation , th e th alam us,
th e basal gan glia, th e brain stem , an d th e sp in al
cord.
Som e of th e m ore im portan t afferen t con n ec-
tion s (Fig. 6.9) w ill be described in th e follow in g
sect ion .
Afferent Pa thways
Th e medial forebrain bundle origin ates in th e basal
olfactory areas an d th e septal n u clei an d ru n s as a
ch ain of n euron s th rou gh th e hypot h alam u s
(lateral area) u n til it arrives in th e m idbrain reticu -
lar form ation Alon g th e w ay, it gives off collateral
fibers to th e p reoptic n u cleu s, th e dorsom edial n u -
cleus, an d th e ven trom edial n u cleus. Th e m edial
forebrain bun dle con stitutes a recip rocal con n ec-
tion betw een olfactory an d preoptic n uclear areas
an d th e m idbrain . It h as olfacto-visceral an d ol-
facto-som atic fu n ction s.
Th e striae terminales origin ate in th e am ygdala in
th e tem p oral lobe, th en form an arch over th e
th alam u s, term in atin g in th e preoptic area an d to

Anterior nucleus
of the thalam us
Massa
intermedia
Paraventricular
nucleus
Supraoptic nucleus
Supraopticohypo -
physeal tract
Tractus
Tuberohypo -
retroflexus
physeal tract
(fasciculus
of Meynert)
Neuro-
hypophysis
th e an terior hypoth alam ic n u clei. Th ese fiber
bu n dles are th ough t to tran sm it olfactory in form a-
tion , as w ell as im pu lses relatin g to m ood an d drive.
Th e fornix tran sm its corticom am illary fibers origi-
n atin g in th e h ippocam p us an d su bicu lum an d
travelin g to th e m am illary body, w ith collaterals to
th e preoptic n u cleu s, th e an terior n u cleu s of th e
th alam u s, an d th e h aben u lar n u cleu s. Th e forn ix is
an im portan t pat h w ay in th e lim bic system
(p . 203). As it passes over th e dorsal surface of th e
pu lvin ar, som e of its fibers cross th e m idlin e to
join th e con tralateral forn ix (com m issu re of th e
forn ices, psalteriu m ).
At t h e level of th e p salteriu m , th e tw o forn ices
lie un der th e sp len ium of th e corpu s callosu m ,
w h ere th ey are u sually n ot directly visible in an
un cut brain specim en . Lesion s in th e area of th e
psalteriu m often affect both forn ices, because
th ese tw o t h in stru ctu res are close togeth er at th is
poin t. Th e seriou s fun ction al deficits produ ced by
bilateral lim bic lesion s are discu ssed below on
p. 208 ff.
Ascending visceral impulses from th e periph eral
au ton om ic n ervous system , an d from th e n u cleus
of th e tractus solitarius (taste), reach th e hy-
Hypothalam us · 181
6
Fig. 6.10 Major efferent
connections of the hy-
pothalamus (schem atic
Mamillo - drawing)
thalamic tract
Striae m edullares
Dorsal
longitudinal
fasciculus
Mamillo -
tegmental
tract
poth alam us alon g various path w ays: th rou gh relay
n uclei in th e brain stem reticu lar form ation , from
tegm en tal an d in terpedun cu lar n u clei, th rou gh re-
ciprocal con n ection s in th e m edial forebrain
bu n dle, th rou gh t h e dorsal lon gitu din al fascicu lus,
an d th rough t h e pedu n cle of th e m am illary body
(Figs. 6.9 an d 6.10). Som atosen sory in form ation
from th e erogen ous zon es (gen italia an d n ipples)
also reach es th e hypoth alam u s by t h ese p ath w ays
an d in duces au ton om ic react ion s.
Fin ally, further afferent input com es to th e hy-
poth alam us from th e m edial n ucleus of th e
th alam us, th e orbitofron tal n eocortex, an d th e
globus p allidus.
Efferent Pa thwa ys
Efferent fibers to the brainstem. Th e m ost im por-
tan t efferen t p rojection s from th e hypoth alam us to
th e brain stem are th e dorsal longitudinal fasciculus
(of Sch ü tz), w h ich con tain s fibers travelin g in both
direction s, an d th e medial forebrain bundle (Figs.
6.9 an d 6.10). Hypoth alam ic im pu lses travelin g in
th ese path w ays pass th rou gh m u ltiple syn aptic re-
lays, m ain ly in th e reticular form ation , u n til th ey
term in ate in parasym path etic n uclei of th e brain -
6 182 · 6 Diencephalon and Autonom ic Nervous System

stem , in clu din g th e ocu lom otor n u cleus (m iosis),
th e sup erior an d in ferior salivatory n u clei (lacri-
m ation , salivation ), an d th e dorsal n u cleus of th e
vagu s n erve. Oth er im pu lses t ravel to auton om ic
cen ters in th e brain stem th at coordin ate circu la-
tory, respiratory, an d alim en tary fu n ction (etc.), as
w ell as to m otor cran ial n erve n uclei th at play a
role in eat in g an d drin kin g: th e m otor n ucleu s of
th e trigem in al n erve (m astication ), th e n ucleu s of
th e facial n erve (facial expression ), th e n u cleu s
am biguu s (sw allow in g), an d th e n u cleu s of th e hy-
poglossal n erve (lickin g). Yet oth er im p ulses
derived from th e hypoth alam us, relayed to th e spi-
n al cord th rou gh reticu losp in al fibers, affect th e
activit y of spin al n euron s t h at part icipate in
tem peratu re regu lation (sh iverin g).
Th e mamillotegmental fasciculus (Fig. 6.10) ru n s
from th e m am illary body to th e m idbrain tegm en -
tu m , an d th en onw ard to th e reticu lar form ation .
The mamillothalamic tract (of Vicq d’Azyr) recipro-
cally con n ects t h e hypoth alam us w ith t h e an terior
n ucleus of th e th alam u s, w h ich , in tu rn , is recipro-
cally con n ected w ith th e cin gu late gyru s (Fig. 6.6).
Th e an terior th alam ic n u cleu s an d th e cin gu late
gyrus are im portan t com pon en ts of th e lim bic sys-
tem . Th e m ain fu n ction of th e lim bic system is said
to be th e regulation of affective beh avior so as to
prom ote th e su rvival of th e in dividual an d of th e
species (MacLean 1958; cf. p. 202).
Th e supraoptico -hypophyseal tract h as already
been m en tion ed as an efferen t path w ay to th e n eu -
rohypophysis. Neuron s in th e supraoptic an d para-
ven t ricu lar n u clei p rodu ce t h e h orm on es oxytocin
an d vasopressin (an tidiu retic h orm on e), w h ich are
tran sported alon g th e axon s of th e su praoptico-
hypop hyseal tract to th e n eu rohypophysis, an d are
th en released th ere, from th e axon term in als, in to
th e bloodstream (Figs. 6.10 an d 6.11). Th e n euron s
in th ese n uclei are th us com parable to th e h or-
m on e-producin g cells of oth er organ s, an d are re-
ferred to as n eu rosecretory cells. Oxytocin an d
vasop ressin m ain ly exert t h eir effects on cells ou t-
side th e n ervou s system : oxytocin in duces con -

Fig. 6.11 Posterior lobe

Cell of the of the pituitary gland
paraventricular (neurohypophysis). Neu-
nucleus rosecretory fibers reach the
posterior lobe directly by
way of the supraoptico-
hypophyseal tract.
Capillary net work
Cell of the supraoptic nucleus

Supraoptic a.

Optic chiasm
Axons of the
neurosecretory
neurons with
Pars horm ones
interm edia (ADH, oxytocin)

Inferior
hypophyseal a.

Neurohypophysis

Vein

traction of th e sm ooth m u scle of th e uteru s an d th e
m am m ary glan d, w h ile vasop ressin in du ces w ater
reupt ake th rou gh th e ren al t ubu lar ep ith elial cells
(see also p. 184).
Functiona l Connection of the Hypotha la mus
to the Adenohypophysis
Th ere is n o direct n eu ral con n ection betw een th e
hyp ot h alam ic n uclei an d th e aden ohypophysis.
Non eth eless, it h as lon g been recogn ized th at th e
Hypothalam us · 183
6
hypoth alam u s exert s a m ajor in fluen ce on th e ade-
n ohypophyseal en docrin e cells. Fiber bu n dles from
th e tuberal n u clei carry releasing factors an d re-
lease-inhibiting factors to t h e m edian em in en ce by
in tra-axon al tran sport; th e m edian em in en ce, in
tu rn , is con n ected to th e aden ohypophysis th rough
a portal vascu lar n etw ork. Th e hypoth alam us regu -
lates aden ohypophyseal h orm on e secretion by th is
m ech an ism (Fig. 6.12; cf. p. 185).

Fig. 6.12 Anterior lobe of

Anterior com m issure
the pituitary gland (ade-
Afferent nerve fiber nohypophysis). Releasing
horm ones and release-in-
hibiting horm ones are pro-
Capillary net work
around neurosecretory duced by the hypothala-
cells of the hypothalam us m us and travel over neu-
rosecretory fibers to the
Hypophyseal A fiber transporting first capillary network in
portal system releasing factors from the area of the m edian
hypothalam ic cells em inence (neurohem al re-
Optic chiasm gion), where they enter the
bloodstream . They are
transported in the blood-
Superior hypo- Hypothalam ic a.
stream to the adeno-
physeal a.
hypophysis, reaching it by
a second capillary network
im m ediately adjacent to
Adeno-
the horm one-producing
hypophysis
glandular cells (hypophy-
Sinusoids seal portal system ). Thus,
Chrom ophobe (γ-)cells
Basophil (β- and δ -)cells horm one secretion by the
anterior lobe of the pitui-
Eosinophil (α -)cells
tary gland is regulated by
Pars interm edia way of the bloodstream .

Thyrotropin, adrenocorticotropin,
gonadotropin, somatotropin, etc.

Internal secretory glands:

thyroid, adrenal, testes,
ovaries, etc.

Corticosteroids, testosterone,
estrogen, progesterone,
thyroid horm one

Blood circulation
6 184 · 6 Diencephalon and Autonom ic Nervous System
Functions of the Hypothalamus
Th e hyp oth alam u s is th e h ierarch ically u pperm ost
regulatory organ (“h ead gan glion ”) of th e au ton -
om ic n ervou s system . It plays th e leadin g role in a
w ide variety of regu latory circu its for vital bodily
functions such as tem peratu re, h eart rate, blood
pressu re, respirat ion , an d food an d w ater in take.
Th ese regulatory fu n ction s are carried ou t largely
in depen den tly of any con scious th ou gh t on th e
part of th e in dividu al, i.e., au ton om ically. Th e hy-
poth alam us also regu lates im portan t h orm on e
system s th rou gh th e hypot h alam ic–pitu itary axis
an d coordin ates th e in teraction of th e en docrin e
an d au ton om ic n ervou s system s. Th e elem en tary
fu n ction s con trolled by th e hypot h alam u s w ill be
described, briefly an d in dividually, in th is section .
Tempera ture Regula tion
Th e anterior preoptic hypothalam us con tain s
specific receptors for t h e m ain ten an ce of a con -
stan t in tern al tem perature (tem perature hom eosta-
sis). Physiological respon ses to tem perature
changes (vasocon st riction an d sh iverin g at low
tem peratu re, vasodilation an d sw eatin g at h igh
tem peratu re) are regu lated by circu its in th e poste-
rior hypothalam us.
Disturbances of temperature regulation. Dysfu n c-
tion of th e an terior preoptic region of th e hy-
pot h alam u s (cau sed, for exam ple, by trau m atic
brain in ju ry or h em orrh age) can lead to central
hyperthermia. Dysfu n ction of t h e posterior region
can lead to hypothermia or poikilothermia (rapid
flu ct uat ion s of body tem p eratu re by m ore th an
2°C); th e possible cau sat ive lesion s h ere in clu de
hyp oth alam ic tu m ors (cran ioph aryn giom a, glio-
m a), Wern icke’s en cep h alopat hy, an d hydro-
cep h alu s.
Regula tion of Hea rt Ra te a nd Blood Pressure
Th e hypoth alam u s in flu en ces th e au ton om ic
n ervou s system directly th rou gh descen din g path -
w ays th at w ill be discussed below in th e section on
th e periph eral au ton om ic n ervou s system (p. 170).
Th e sym pathetic n ervous system is regulated by
th e ven trom edial an d posterior port ion s of th e hy-
poth alam us (p. 190). St im u lation of t h ese areas in -
du ces a rise in h eart rate an d blood p ressu re, di-
latation of th e pu pils, vasocon striction in th e capil-
lary beds, vasodilation in th e skeletal m u scu latu re,
an d expression s of fear or rage.
Th e parasym pathetic n ervou s system (p. 192), on
th e oth er h an d, is regulated by th e paraven tricular
an d an terior or lateral portion s of th e hypo-
th alam u s. Stim u lation of th ese areas in du ces a fall
in h eart rate an d blood p ressu re an d con striction of
th e pu pils. Stim u lation of posterior parasym pa-
th etic areas in creases blood flow to th e bladder
an d dim in ish es blood flow to skeletal m u scle.
Regula tion of Wa ter Ba la nce
Th e hypothalam ic osm oreceptors are located in th e
supraoptic an d paraventricular nuclei. Th ey are
stim u lated eith er by in tracellu lar dehydration ,
w ith an elevated in tracellu lar sodiu m con cen tra-
tion , or by extracellular dehydration , w ith an ele-
vated con cen tration of an gioten sin II in th e hy-
pot h alam ic cap illary blood; stim ulat ion leads to
th e secretion of ADH (an tidiuretic h orm on e, vaso-
pressin ). Conversely, an in crease of in t ravascular
volum e stim u lates periph eral volum e receptors,
ult im ately leadin g to th e in h ibit ion of ADH secre-
tion .
Disturbances of w ater balance. If 90 % or m ore of
th e n eu ron s of th e su praoptic an d p araven tricu lar
n uclei are destroyed or ren dered dysfu n ction al
(e.g., by a gran u lom atou s process, vascular lesion ,
trau m a, or in fection ), th en ADH is n o lon ger
secreted an d diabetes insipidus resu lts, m an ifested
clin ically by excessive th irst, polyu ria, an d polydip-
sia. Th e diagn osis is establish ed by th e dem on stra-
tion of hypo-osm olar polyuria, i.e., th e excret ion of
at least 3 liters of u rin e per day, w ith an osm olality
bet w een 50 an d 150 m osm /l. ADH su bstit ut ion is
th e treatm en t of ch oice. If th e u rin e osm olality fails
to rise by m ore th an 50 % after th e adm in istration
of 5 IU of ADH, th en th e patien t is sufferin g from
ren al diabetes in sipidu s (in adequ ate respon se of
th e kidn ey to circu latin g ADH), in w h ich substitu -
tion th erapy is of n o h elp.
Many typ es of hyp oth alam ic lesion im p air th e
th irst respon se, an d can th u s cause severe hy-
pon atrem ia.
Th e syndrome of inappropriate ADH secretion
(SIADH or Schw artz–Bartter syndrome), usually
cau sed by abn orm al ectop ic secretion of ADH (e.g.,
by bron ch ial carcin om a or oth er m align an t

tu m ors), is m an ifested by hypervolem ia, hy-
pon atrem ia ( 130 m m ol/l), low serum osm olarity
( 275 m osm /kg), an d h igh ly con cen trated urin e.
Th e clin ical m an ifestation s in clu de w eigh t gain ,
w eakn ess, n au sea, an d disturban ces of con sciou s-
n ess, as w ell as epilept ic seizures. SIADH is treated
by elim in atin g th e un derlyin g cau se, t h ou gh it is
often u sefu l to treat th e hypervolem ia an d hy-
pon atrem ia sym ptom at ically as w ell, by flu id re-
striction an d correction of th e sodiu m balan ce.
Regula tion of Nutritiona l Inta ke
Lesion s of th e ven trom edial hypoth alam ic n uclei
m ay cau se severe obesity th rough hyperph agia
an d poverty of m ovem en t. More lateral lesion s can
cau se an orexia an d abn orm al w eigh t loss.
Neurosecretion a nd Regula tion of the
Endocrine System
As m en tion ed above, th e hypophysis (p itu itary
glan d) h as tw o com pon en ts, th e an terior lobe (ad-
en ohyp ophysis) an d th e posterior lobe (n eu rohy-
pophysis). Th e hypoth alam us con trols each part
differen tly.
Hormone secretion by the posterior lobe.
Secretory n eu ron s in th e supraopt ic an d para-
ven tricu lar n u clei produ ce oxytocin an d ADH,
w h ich are tran sported in tra-axon ally to th e n eu ro-
hyp ophysis an d released th ere in to th e blood-
stream (n eu rosecretion ). Th e fu n ction s of ADH
h ave been described above. Oxytocin is secreted
du rin g th e last few w eeks of pregn an cy; it in duces
th e con traction of u terin e sm ooth m u scle as w ell
as th e secretion of m ilk from th e m am m ary
glan ds. Som atosen sory stim u lation (tou ch in g th e
n ipp le) produ ces afferen t im pu lses th at activate
th e n eu rosecretory n eu ron s of th e hypoth alam u s
(by w ay of th e th alam us an d th e cerebral cortex).
Th e in tim ate con n ection betw een th is regu latory
circu it an d em otion is illu strated by th e fact th at
m ilk p rodu ction decreases sign ifican tly w h en th e
m oth er suffers from fear or stress.
Hormone secretion by the anterior lobe. Th e
parvocellular secretory n euron s fou n d in peri-
ven tricu lar areas of th e hyp ot h alam u s com m un i-
cate w ith th e aden ohypophysis n ot by axon al con -
n ection s (as in th e case of th e n eu rohypophysis)
bu t rat h er th rou gh a p ortal vascu lar system (see
Hypothalam us · 185
6
p. 183). Th ese parvocellu lar n eu ron s secrete th e
“hypophysiotropic” h orm on es gon adotrop in -re-
leasin g h orm on e (Gn RH), thyrotrop in -releasin g
h orm on e (TRH), corticotropin -releasin g h orm on e
(CRH), grow th -h orm on e-releasin g h orm on e
(GHRH), an d factors regu latin g th e secretion of
m elan ocyte-stim u latin g h orm on e (MSH), n am ely
MIF an d MRF. All of th ese h orm on es, in turn , con -
trol th e release of th e corresp on din g pitu itary h or-
m on es from th e aden ohypophysis, on ce th ey arrive
th ere by w ay of th e portal vascu lar n etw ork (cf.
Figs. 6.12 an d 6.13). In th e aden ohypophysis, acid-
ophil cells (α cells) secrete grow th h orm on e (GH,
also called som atot ropic h orm on e or STH) an d pro-
lactin (PRL, also called lu teotropic h orm on e or
LTH). Basophil cells ( cells) secrete thyrotropin
(thyroid-stim u latin g h orm on e, TSH), corticotrop in
(also called adren ocorticotropic h orm on e or
ACTH), m elan ocyte-stim u lat in g h orm on e (MSH),
lutein izin g h orm on e (LH), an d follicle-stim u latin g
h orm on e (FSH). Chromophobe cells (γ cells) are n ot
kn ow n to secrete any h orm on es, but som e auth ors
state th at th ey play a role in ACTH syn th esis.
Th e h orm on es produ ced by th e pitu itary
secretory cells en ter th e bloodst ream an d in du ce
th e respective perip h eral en docrin e organ s to
secrete h orm on es. Th ese periph eral h orm on es cir-
cu late in th e blood, an d th eir con cen tration s, in
tu rn , in flu en ce th e secretion of th e correspon din g
hypot h alam ic an d pit uit ary h orm on es, in a n ega-
tive feedback loop.
Horm onal Disturbances: Disturbances of the
Hypothalam ic–Pituitary Axis
Th e en docrin e fu n ction of th e hypophysis can be
im paired by h orm on e-secretin g tum ors (e.g., p itu i-
tary aden om a) or by destru ction of p itu itary tissue
by n on -h orm on e-secretin g tum ors.
Panhypopituitarism. Th e m ost severe clin ical syn -
drom e con sists of loss of all functions of the hy-
pophysis an d is clin ically m an ifested by lack of
drive, declin e of physical perform an ce, loss of
w eigh t, loss of libido, bradycardia, lessen ed skin
pigm en tation , loss of axillary an d pu bic h air, an d,
som etim es, diabetes in sipidu s (if t h e n eu rohy-
pophysis is involved). Th is syn drom e m ay be
cau sed by large, h orm on ally in active tu m ors of th e
hyp ophysis, in fu n dibu lu m , or hypot h alam u s (e.g.,
aden om a, m etastasis, gliom a, or cran ioph aryn -
6 186 · 6 Diencephalon and Autonom ic Nervous System

Somatostatin Oxytocin
(SRIF) Vasopressin Hypothalamus

Neurosecretion

Pituitary
gland
Adenohypophysis Neurohypophysis

Growth, Lactation Thyroid Gonadal Adrenal Lipolysis Pig- Kidney,

metabolism function function function m enta- uterus, Periphery
tion breast

Inhibitory
Stimulatory

ACTH Adrenocorticotropic hormone (corticotropin) MRF Melanocyte-stim ulating hormone-releasing factor

CRF Corticotropin-releasing factor MSH Melanocyte-stimulating horm one
FSH Follicle-stimulating horm one PIF Prolactin-inhibiting factor (= dopam ine)
GH (STH) Growth hormone (somatotropic hormone) PRL Prolactin
GHRH Growth-hormone-releasing hormone PRF Prolactin-releasing factor
LH Luteinizing hormone SRIF Somatotropin-inhibiting factor
GnRH Gonadotropin-releasing horm one TRH Thyrotropin-releasing hormone
LPH Lipotropin TSH Thyroid-stimulating hormone
MIF Melanocyte-stimulating hormone-inhibiting factor

Fig. 6.13 Endocrine Regulation along the Hypothalamic–Pituitary Axis

giom a). Th e treatm en t of ch oice is su rgical resec-
tion an d h orm on e substitu tion . Hypop itu itarism
m ay also arise in th e afterm ath of trau m a, or as a
com plication of n eu rosu rgical procedures. Sudden
loss of pituitary fu n ction w ith su bsequ en t adren al
failu re (addison ian crisis) is a life-th reaten in g
even t.
an d galactorrh ea. Su rgical resection (e.g., by th e
tran ssph en oidal rou te) is th e treatm en t of ch oice
for prolactin om as w ith m ass effect; for sm aller
tu m ors w ith less severe m an ifestation s, p h ar-
m acological treatm en t w ith a dopam in e agon ist
such as brom ocriptin e can be t ried. Dopam in e ago-
n ists in h ibit prolactin secretion .

Hormone -secreting pituitary tumors. A n eoplasm
arisin g from on e of th e cell types of th e an terior
pitu itary lobe cau ses sym ptom s th rou gh an excess
of the corresponding hormone(s). If th e tum or is
large en ou gh , th e suprasellar mass effect w ill pro-
du ce a ch aracteristic visual field defect (usu ally
bitem poral h em ian opsia, because of com pression
of th e optic ch iasm ; cf. p. 187).
Prolactinom a. Most pit uitary aden om as (60–70 %)
secrete prolactin . In fem ale patien ts, th e resu ltin g
excess of circu latin g prolactin (hyperprolactin e-
m ia) causes secondary amenorrhea th rou gh t h e in -
h ibition of gonadotropin -releasin g h orm on e secre-
tion (w h en th e serum prolactin con cen tration rises
above 40–10 0 n g/m l), as w ell as galactorrhea an d,
less com m on ly, h irsut ism . In m ale patien ts, hyper-
prolactin em ia cau ses impotence, gynecomastia,
Growth-horm one-secreting adenom a. Clin ically, an
excess of circulatin g grow th h orm one ( 5 n g/m l)
cau ses acromegaly: in creased grow th of acral p or-
tion s of th e skeleton (h an ds, feet, h ead circu m fer-
en ce), osteoporosis, hyp erh idrosis, glucose in toler-
an ce, hyperten sion , hypertroph ic cardiom yopathy,
goiter, com p ressive n eu ropath ies such as carpal
tu n n el syn drom e, oth er types of n europathy, pro-
xim al m yopathy, sleep disturban ces (hypersom n ia,
sleep apn ea syn drom e), an d n europ sych iatric dis-
tu rban ces (depression , p sych osis). Th e stan dard
diagn ostic test is an oral glu cose toleran ce test,
w ith a ch aracteristic oversh oot in th e reflex rise of
grow th h orm on e con cen tration . Su rgical resection
is th e treatm en t of ch oice.
ACTH-secreting adenom a cau ses Cushing syndrome
w ith tru n cal obesity, m oon facies, glu cose in toler-

Case Presentation 2: Pituita ry Tumor/Prolactinoma
This 40-year-old m ale office worker com plained to his
fam ily physician of “peculiar” bodily changes that had been
troubling him for som e tim e. He had gained 50 kg in weight
over the previous 2−3 years, and he now needed shoes two
sizes larger than before. His hands also seem ed to have be-
com e “rough.” He had recently had an autom obile accident
caused by his failure to see another car approaching from
the side, and a couple of days previously he had alm ost run
over a pedestrian for the sam e reason. He could no longer
trust him self to drive a car, both because of these occur-
rences and because he was always tired and could not con-
centrate. He had increasing difficulty on the job. He denied
suffering from headache, loss of libido, or im potence.
The physician found his weight to be 132 kg (previously
82 kg), with an unchanged height of 193 cm . His hands and
feet were disproportionately large (acrom egaly), finger per-
im etry revealed severe bitem poral hem ianopsia, and there
was m ild gynecom astia, though no galactorrhea could be in-
duced. Laboratory testing revealed norm al values of all thy-
roid param eters (T3 , T4 , basal TSH, and TRH test) as well as of
ACTH and cortisol. The testosterone level, however, was
very low (50 ng/m l) and the prolactin level extrem ely high
(590 µg/dl). TRH adm inistration caused the prolactin level to
clim b still further to 2020 µg/dl.
Hypothalam us · 187
6
These findings suggested a prolactin-secreting adenom a of
the pituitary gland with partial hypopituitarism affecting the
anterior lobe horm ones, particularly the gonadotropic axis.
A plain radiograph of the head revealed m assive expansion
of the sella turcica with partial destruction of the dorsum
sellae and the sellar floor. An MRI scan revealed a tum or
m easuring 5 × 5 × 4 cm (Fig. 6.14), too large to be rem oved
through a transsphenoidal approach. A frontotem poral
craniotomy was perform ed. Intraoperatively a firm , grayish-
yellow tum or with som e reddish areas was found; it was ad-
herent to the floor of the m iddle cranial fossa, m ade contact
with the term inal portion of the internal carotid artery, and
com pressed the optic chiasm . The histopathological finding
was of a diffusely growing epithelial tum or, without lobular
structure, in which the tum or cells occasionally showed a
papillary organization. Im m m unohistochem ical study re-
vealed an increased expression of prolactin in ca. 30−40 %of
the tum or cells, while a few of them stained positive for
ACTH, LH, or GH. Excessive GH secretion had presum ably
caused the patient’s clinically evident acrom egaly. Post-
operatively, he had transient diabetes insipidus requiring
treatm ent with desm opressin acetate. Anterior pituitary
lobe insufficiency persisted in his subsequent course and he
was treated with hydrocortisone and thyroxine substitution.

a b
Fig. 6.14 A large pituitary tumor (prolacti-
noma) in a 40-year-old m an, seen in coronal
(a, b) and sagittal (c) T1-weighted MR im -
ages. Im ages b and c were obtained after in-
travenous adm inistration of contrast m aterial.
The large intrasellar and suprasellar tum or
places the optic chiasm under tension from
below, stretching it (a). There is m arked con-
trast enhancem ent (b, c). The sella turcica is
m arkedly expanded (c).

c
6 188 · 6 Diencephalon and Autonom ic Nervous System
an ce, hyperten sion , edem a, am en orrh ea, im -
poten ce, a ten den cy to th rom boem bolism , poly-
uria, steroid m yop athy, an d n eu ropsych iatric dis-
tu rban ces. Th e diagn osis is m ade en docrin ologi-
cally by th e dem on stration of an elevated am ou n t
of cortisol in a 24-h our u rin e collection . Su rgical
resection is th e t reatm en t of ch oice.
Peripheral Autonomic Nervous
System
Fundamentals
Th e au ton om ic n ervou s system , w orkin g in con cert
w ith th e en docrin e system (see p . 185 ff.) an d
variou s n uclei in th e brain stem , regu lates vital
fu n ction s t h at are n ecessary for th e m ain ten an ce
of th e in tern al environ m en t (h om eostasis), in clu d-
in g respiration , circu lation , m etabolism , body
tem peratu re, w ater balan ce, digestion , secretion ,
an d rep rodu ctive fu n ction . Th e design ation “au -
ton om ic” is derived from th e fact th at th ese fu n c-
tion s are con trolled by un con sciou s (involun tary)
m ech an ism s, as discu ssed above.
As already m en tion ed, th e hypot h alam us is th e
m ain regulatory cen ter for th e en tire periph eral
au ton om ic system . It exercises its con trol over
m any bodily fun ction s partly th rou gh n erve im -
pu lses an d partly t h rou gh h orm on al path w ays, by
m ean s of th e hypoth alam ic–pitu itary system (see
above an d stan dard w orks on en docrin ology, phys-
iology, an d an atom y).
Th e efferen t arm of th e au ton om ic n ervou s sys-
tem is com posed of tw o com plem en tary system s,
th e sympathetic n ervous system an d th e parasym-
pathetic n ervou s system , w h ose effects are gen er-
ally an tagon ist ic to each oth er. Th e efferen t fibers
of both system s m ain ly in n ervate th e sm ooth
m uscle of th e viscera, blood vessels, an d glan ds
an d are t h u s com m on ly called visceral efferent
(viscerom otor) fibers, to distin gu ish th em from th e
sen sory visceral afferent fibers. Th e latter, u n like
th e visceral efferen t fibers, are n ot divided in to tw o
system s.
General scheme of the sympathetic and parasym-
pathetic nervous systems. Th e fin al efferen t
path w ay of both th e sym path etic an d th e para-
sym path etic n ervous system s con sists of tw o
n eu ron s in series (Fig. 6.15). Th e cell body of th e
first (preganglionic) neuron lies w ith in th e cen -
tral n ervou s system , w h ile th at of th e second
(postganglionic) neuron is fou n d in a periph eral
gan glion .
Th e first n euron s of th e sym path etic n ervou s
system lie in th e th oracic an d lum bar segm en ts of
th e spin al cord (in term ediolateral cell colu m n ,
T1–L2); for th is reason , th e sym path etic n ervou s
system is som etim es called th e thoracolumbar sys-
tem. Som e of th e first n euron s of th e parasym p a-
t h etic n ervou s system are fou n d in th e n u clei of
cran ial n erves III, VII, IX, an d X (see below ), w h ile
th e rem ain der are foun d in th e lateral h orn s of th e
sacral segm en ts of th e spin al cord (pelvic parasym -
path etic system , S2–S4). Th u s, th e parasym p ath etic
n ervous system is som etim es called th e
craniosacral system.
Th e secon d n eu ron s of th e sym path etic n ervous
system are arran ged in p revertebral an d p araverte-
bral ch ain s of gan glia (th e sym path etic ch ain s),
w h ile th ose of th e parasym path etic n ervou s sys-
tem gen erally lie in th e w alls of th e in n ervated or-
gan s (in tram u ral gan glia). Th e first n eu ron s of both
system s u se acetylch olin e as th eir n eurotran sm it-
ter. Th e secon d n eu ron s of th e parasym path etic
n ervous system also u se acetylch olin e as th eir n eu-
rot ran sm itter (a furth er altern ative n am e for t h e
parasym p ath etic n ervou s system is, th erefore, th e
cholinergic system). Th e n eu rotran sm itter of th e
postgan glion ic sym path etic n eu ron s, h ow ever, is
n orepin eph rin e (adrenergic system). Th e sw eat
glan ds are an exception to th is ru le: th e secon d
sym pat h etic n eu ron in n ervatin g th em is ch olin er-
gic, like a secon d n euron in th e parasym path etic
n ervous system .
Hypothalamic control of the sympathetic and para-
sympathetic nervous systems. St im u lation of th e
rostral hypoth alam us in duces increased parasym-
pathetic (trophotropic) activity, in cludin g redu c-
t ion of th e cardiac m in ute volu m e, hypoton ia,
slow in g of th e h eartbeat, redu ct ion of t h e resp ira-
tory volum e, low erin g of th e basal m etabolic rate,
vasodilatation , sw eatin g, salivation , con traction of
t h e bladder, reduced secretion of epin eph rin e, in -
creased peristalsis, an d pu pillary con striction .
Stim ulat ion of t h e caudal hypoth alam us, on th e
oth er h an d, in du ces increased sympathetic (er-
gotropic) activity, in clu din g a rise in blood pres-
su re, acceleration of t h e h eartbeat , in creased blood
su pply to th e skelet al m uscle an d lu n gs, vasocon -
 Peripheral Autonom ic Nervous System · 189
6
Fig. 6.15 The sympa-
Ciliary ganglion thetic and parasympa-
thetic nervous system
Pterygopalatine
Oculomotor n. ganglion (schem atic diagram ). Yel-
N. interm edius low: sym pathetic. Green:
Otic Lacrimal gland
Glossopharyngeal n. ganglion
parasym pathetic.
Parotid gland
Vagus n.
Submandibular Salivary glands
ganglion

Pulm onary nn.

Cardiac nn.

Bronchi
Lung

T1 Heart
Sweat Hair
gland

Stomach
with somatic

nerve to skin
T5

Liver
Celiac Spleen
ganglion Pancreas
Greater
splanchnic n. Adrenal
T10 Lesser
splanchnic n.
Kidney
Superior
m esenteric
ganglion

Inferior m esen-
teric ganglion Small
intes-
tine
Colon
(2 / 3 )

Hypogastric plexus

Colon
(1 / 3 )
and
Pelvic splanchnic nn. Bladder rectum

Genitalia

striction in blood depots such as th e capillary bed
of t h e digestive tract, decreased blood supp ly to
th e abdom in al viscera, in creased respiratory
volu m e, a rise in th e blood glucose level, in h ibition
of peristalsis, u rin ary reten t ion , in creased secre-
tion of epin eph rin e, w iden in g of th e palpebral fis-
sure, an d pup illary dilatation . A m ass react ion th u s
occurs in th e en tire body, directed tow ard physical
exertion an d th erefore en ablin g th e w h ole or-
gan ism to deal optim ally w ith situ ation s of attack
6 190 · 6 Diencephalon and Autonom ic Nervous System
an d st ress. W h ile th e sym path etic, ergotropic reac-
tion is directed tow ard physical exert ion , th e para-
sym path etic, troph otropic react ion is directed
tow ard rest an d recovery. Desp ite th ese gen eral
prin ciples, h ow ever, th e distin ction betw een para-
sym path etic an d sym path et ic activit y is n ot alw ays
clear-cu t.
Neural connections of the hypothalamus to the
peripheral autonomic nervous system. Th e hy-
pot h alam u s exerts its regu latin g an d con trollin g
fu n ction s over th e sym path etic an d parasym pa-
th et ic n ervou s system s by m ean s of descen din g
path w ays in clu din g th e m edial forebrain bundle
(Fig. 6.9), th e m am illotegm ental tract, an d t h e dor-
sal longitudinal fasciculus (of Sch ü tz) (Fig. 6.10).
Th ese th ree fiber p ath w ays con n ect th e hy-
poth alam us to th e descending m idbrain reticular
system , w h ich , in t urn , carries th e cen tral im pu lses
to th e various com p on en ts of th e parasym path etic
an d sym path etic n ervou s system s.
Sympathetic Nervous System
Th e sym p ath etic n ervous system in n ervates th e
sm ooth m u sculatu re of t h e blood vessels, abdom i-
n al viscera, bladder, rectu m , h air follicles, an d
pu pils, as w ell as th e cardiac m u scle, th e sw eat
glan ds, an d th e lacrim al, salivatory, an d digestive
glan ds. Th e sm ooth m u scu latu re of th e abdom in al
viscera, bladder, rectu m , an d digestive glan ds is in -
h ibited, w h ile th at of all oth er target organ s is
stim u lated to con tract.
Th e caliber of th e body’s arteries is m ain ly regu-
lated by th e sym path etic n ervous system . In -
creased sym path etic activity leads to vasocon stric-
tion , an d decreased sym path etic activity to vasodi-
latation .
Anatomy. Th e origin of th e pregan glion ic fibers
from th oracic segm en ts T1 th rou gh T12 an d from
th e first tw o lu m bar segm en ts is sh ow n in Fig. 6.15.
Som e of th e pregan glion ic fibers term in ate on sec-
on d n euron s in t h e righ t an d left sym path etic
ch ain s (on ly th e left sym path etic ch ain is depicted
in th e figu re). Th e rem ain der pass th rou gh th e
sym path etic ch ain w ith ou t a syn apse an d term i-
n ate on a secon d n eu ron in a prevertebral gan glion .
In eith er case, th e postgan glion ic fiber of th e sec-
on d n eu ron tran sm it s th e sym path et ic im pu lses
onw ard to th e target organ .
Sympathetic chain. As sh ow n in Fig. 6.16, t h e pre-
gan glion ic fibers em erge from n eu ron s in th e
lateral h orn of th e spin al cord (in term ediolateral
cell colu m n ) an d th en join th e axon s of th e som atic
m otor n eu ron s to exit from th e sp in al cord in th e
an terior root. At th e level of th e spin al gan glion ,
th e au ton om ic fibers separate from th e som atic
fibers on ce again an d en ter th e sym path etic ch ain
by w ay of th e w hite ram us com m unicans, w h ich is
w h ite becau se its fibers are m yelin ated. Som e pre-
gan glion ic fibers already term in ate on th e secon d
n eu ron in th e path w ay at th e sam e segm en tal
level, but oth ers travel on e or m ore levels u p or
dow n th e sym path etic ch ain before m akin g a syn -
apse on to th eir secon d n eu ron . Yet oth er fibers
traverse th e sym path etic ch ain w ith ou t m akin g a
syn apse an d th en term in ate on a secon d n eu ron in
a p revertebral gan glion . In all cases, th e un m yeli-
n ated p ostgan glion ic fibers leave th e sym path etic
ch ain in th e gray ram us com m unicans, w h ich re-
join s th e sp in al n erve at th e sam e segm en tal level,
so t h at its fibers t ravel to th e correspon din g cu -
tan eou s derm atom e. In th e skin , th e au ton om ic
fibers in n ervate th e cu tan eou s vessels, th e
piloerector m u scles, an d th e sw eat glan ds.
Sympathetic innervation of the head and neck. As
m en tion ed above, som e postgan glion ic fibers
reach th eir t argets in th e periph ery by w ay of th e
segm en tal spin al n erves, but oth ers do so by travel-
in g alon g th e blood vessels an d th eir bran ch es, p ar-
ticu larly in th e h ead an d n eck. Th e cervical spin al
cord con tain s n o sym path etic n u clei; th u s, th e
sym path etic in n ervation of t h e h ead an d n eck is
derived from th e in term ediolateral cell colum n of
th e upp er four or five th oracic segm en ts. Postgan -
glion ic fibers from th ese segm en ts ascen d in th e
sym path etic ch ain , an d term in ate in t h ree gan glia
at its rostral en d: th e superior cervical ganglion, th e
m iddle cervical ganglion, an d th e cervicothoracic
(stellate) ganglion. Th ese gan glia are th e sites of th e
syn aptic relay on to th e secon d n eu ron s, w h ich
em it th e post gan glion ic fibers. Som e of t h ese fibers
travel w ith th e spin al n erves to th e cervical cu -
tan eou s derm atom es. Oth er, u n m yelin ated fibers
from th e sup erior cervical gan glion form th e exter-
nal carotid plexus, w h ich accom pan ies th e extern al
carotid artery an d its bran ch es to th e h ead an d th e
face, in n ervat in g t h e sw eat glan ds, t h e sm ooth
m uscle of th e h air follicles, an d th e blood vessels.
Yet oth er fibers accom pany th e in tern al carotid
tahir99-VRG & vip.persianss.ir

Interm edio- Posterior Sympathetic trunk
lateral nucleus root with paravertebral
ganglia
Anterior
root
Preganglionic fiber Gray ramus
White ramus
ganglionic
Afferent Prevertebral
Intestinal wall fiber ganglion
artery as th e internal carotid plexus, w h ich in n er-
vates th e eye (dilator pu pillae m u scle, orbitalis
m uscle, an d tarsal m uscle) as w ell as th e lacrim al
an d salivary glan ds (Figs. 4.27 an d 4.28 [pp. 103,
104] an d 6.15).
Sympathetic innervation of heart and lungs. Post-
gan glion ic fibers from th e cervical an d upp er four
or five th oracic gan glia ru n in t h e cardiac nerves to
th e cardiac plexus, w h ich in n ervates th e h eart. Pul-
m onary nerves in n ervate t h e bron ch i an d lun gs
(Fig. 6.15).
Sympathetic innervation of the abdominal and pel-
vic organs. Pregan glion ic fibers arise in th oracic
segm en ts T5 t h rou gh T12 an d travel, by w ay of th e
greater an d lesser splanchnic nerves, to t h e u n -
paired prevertebral gan glia (th e celiac, superior
m esenteric, an d inferior m esenteric ganglia), w h ich
are located alon g th e aort a at th e levels of origin of
th e corresp on din gly n am ed aort ic bran ch es.
With in th ese gan glia, th e splan ch n ic fibers m ake
syn apses on to th e secon d sym p ath etic n eu ron s,
w h ich , in tu rn , em it th e p ostgan glion ic fibers for
th e abdom in al an d pelvic viscera. In con trast to th e
parasym path et ic fibers, th e sym path et ic postgan -
glion ic fibers are very lon g an d form variou s plex-
u ses before reach in g th eir target organ s (Fig. 6.15).
Adrenal medulla. Th e adren al m edu lla occupies a
special posit ion in th e sym path etic n ervous sys-
Peripheral Autonom ic Nervous System · 191
6
Fig. 6.16 The sympa-
thetic trunk and the pre-
ganglionic and postgan-
glionic sympathetic fibers
(schem atic diagram )
Spinal
nerve
Cut aneous
vessels
Erector
Post- pili m .
fiber
Sweat
gland
tem . It is an alogou s to a sym p ath etic gan glion , in
th at it is directly in n ervated by pregan glion ic
fibers. Th ese fibers form syn apses on to m odified
secon d n euron s w ith in th e adren al m edu lla,
w h ich , rath er th an possessin g an axon , secrete
epin eph rin e an d n orepin eph rin e in to t h e blood-
stream (Fig. 6.15). Sym path etic activation in duces
th e adren al m edulla to secrete epin ep h rin e an d
n orepin eph rin e, w h ich th en exert sym path etic ef-
fects in th e periph ery. Th is is particu larly im por-
tan t un der con dition s of stress.
Clinica l Symptoms of Sympa thetic Lesions
Horner syndrome. As m en tion ed in Ch apter 4
(p. 102 ff.), lesion s affectin g th e ciliosp in al cen ter,
th e cervical sym path etic ch ain (cervicoth oracic
gan glion ), or th e auton om ic plexu ses alon g th e
blood vessels of th e h ead an d n eck cau se ip silateral
Horn er syn drom e. Th is con sists of th e clin ical triad
of a con stricted pu pil/miosis (du e to loss of con -
traction of th e dilator pu pillae m u scle), a h an gin g
eyelid/ptosis (du e to loss of con traction of th e tar-
sal m uscle), an d an inw ardly su n ken globe/enoph-
thalmos (du e to loss of con traction of th e orbitalis
m uscle). Th ere is also loss of sw eatin g (anhidrosis)
an d vasodilatation (due to loss of th e vasocon stric-
tive effect of th e sym path etic n erves) on t h e ipsi-
lateral h alf of th e face, w h ich th erefore appears dry
an d redden ed.
tahir99-VRG & vip.persianss.ir
6 192 · 6 Diencephalon and Autonom ic Nervous System
Causes of Horner syndrome. In terru ption of t h e
sym path etic p ath w ay to th e h ead an d n eck at any
poin t can cau se Horn er syn drom e. On e com m on
cau se is a bron ch ial carcin om a at th e apex of th e
lu n g (Pancoast tumor) im p in gin g on th e cervical
sym path etic ch ain . Su ch t um ors m ay p resen t w ith
Horn er syn drom e before becom in g oth erw ise
sym ptom atic.
Dissection of the internal carotid artery is
an ot h er im port an t cau se of Horn er syn drom e.
Wh en t h e in tim a of th e artery is torn , blood en ters
th e vessel w all an d th e lu m en is n arrow ed or oc-
clu ded; ru pt ure of t h e artery w ith pseudo-
an eu rysm form ation is rare. Carotid dissection h as
m any possible etiologies; dissection m ay be trau-
m atic or du e to an intrinsic abnorm ality of th e
tissu e of th e vessel w all, e.g., fibrom u scular dys-
plasia, w h ich predisposes to t h e develop m en t of an
in tim al tear. In m ost cases, h ow ever, th e etiology of
carotid dissect ion can n ot be determ in ed.
Th e pat h ogen esis of sym path et ic dysfu n ction in
carotid dissection is n ot yet fu lly un derstood. Ac-
cordin g to on e cu rren t hypoth esis, com pression of
th e sym p ath etic n erve bran ch es by an in tram ural
hem atom a leads to n erve in ju ry an d dysfu n ction .
Accordin g to an ot h er hypoth esis, ischem ia of th e
sym path etic n erve bran ch es is th e m ajor cause of
th eir dysfun ction , as th ese n erve bran ch es are sup-
plied by sm all perforatin g bran ch es of t h e in tern al
carotid artery, w h ich can be displaced or occlu ded
by t h e dissect ion . Neith er hypoth esis is fully satis-
factory.
Horn er syn drom e also arises as a resu lt of brain -
stem lesion s affectin g th e cen tral sym path etic
path w ay, as in Wallen berg syn drom e (p . 147 ff.)
Vasomotor phenomena in sympathetic dysfunc-
tion. Th e vasodilatation th at follow s a sym p ath etic
lesion can be exp loited th erapeu tically: sym pa-
thectom y is som et im es perform ed to in crease re-
gion al blood flow, e.g., in Rayn au d disease.
Th e vasodilatation du e to a sym path etic lesion is
also eviden t after in terruption of th e splan ch n ic
nerves, w h ich leads to a large in crease of in -
travascu lar volum e in th e blood vessels of th e
bow el, i.e., to poolin g of blood in th e splan ch n ic
area, w ith th e risk of in tern al h em orrh age.
Parasympathetic Nervous System
In con trast to th e sym p ath etic n ervou s system , th e
parasym path etic n ervous system does n ot evoke
any system ic resp on ses, but in stead produces its
effects in in dividual, circu m scribed areas, as re-
flected in th e fact th at it s secon d (postgan glion ic)
n eu ron s lie n ear th eir target organ s. Furth erm ore,
acet ylch olin e, w h ich is released as a n eu ro-
tran sm itter at th e parasym path etic n erve term i-
n als, is rapidly broken dow n by ch olin esterases,
an d its effect is th u s relatively sh ort -lived.
Th e pregan glion ic fibers of th e parasym p ath etic
n ervou s system are lon g (u n like th e sh ort pregan -
glion ic fibers of th e sym path etic n ervou s system ).
Th ey em erge from n uclei in th e brain stem an d
sacral spin al cord (S2, S3, S4) (Fig. 6.15).
Cra nia l Portion of the Pa rasympa thetic
Nervous System
Parasympathetic innervation of the head. Th e cell
bodies of th e pregan glion ic n eu ron s lie in variou s
brainstem nuclei, an d th eir axon s are foun d in
cranial nerves III, VII, IX, and X. (Th e an atom y an d
cou rse of th ese n erves w as described in Ch apter 4.)
Th e pregan glion ic fibers travel to a n u m ber of gan -
glia th at lie very close to th eir respective en d or-
gan s (th e ciliary, pterygopalatine, subm andibular,
an d otic ganglia). Th ese gan glia are relay station s in
w h ich th e pregan glion ic fibers form syn apses on to
th e secon d (post gan glion ic) n euron s. Th e p ara-
sym path etic postgan glion ic fibers in th e h ead are
sh ort , as th ey h ave on ly a sh ort distan ce to travel
before th ey reach th eir en d organ s. Like th e sym pa-
th etic p ostgan glion ic fibers, th ey in n ervate sm ooth
m uscle, sw eat glan ds, an d lacrim al an d salivary
glan ds (Fig. 6.15). Th e sm ooth m u scle of th e blood
vessel w alls receives n o parasym pat h etic in n erva-
tion .
Parasympathetic innervation of the thoracic and
abdominal organs. Th e parasym path etic p ortion of
th e vagus nerve (Fig. 4.49, p. 129) origin ates in t h e
dorsal nucleus of the vagus nerve an d carries pre-
gan glion ic fibers for th e in n ervation of th e h eart,
lu n gs, an d abdom in al viscera dow n to th e distal
th ird of th e tran sverse colon (Fig. 6.15). Th e secon d
(postgan glion ic) n eu ron s are fou n d in auton om ic
p lexuses located im m ediately adjacen t to th eir en d
organ s, or else w it h in t h e bow el w all (m yen teric
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 Peripheral Autonom ic Nervous System · 193
6
Fig. 6.17 Innervation of
Somatomotor the bladder
Sym pathetic preganglionic
Sym pathetic postganglionic
Parasym pathetic preganglionic
Parasym pathetic postganglionic
T12
Afferent pathways Inferior L1
m esenteric L2
ganglion

Pelvic
Detrusor m . splanchnic
nn.

Internal sphincter m .
Hypogastric plexus
External sphincter m .

Pudendal n.

plexu s of Au erbach , subm ucosal plexu s of

Meissn er).
Sacra l Portion of the Pa rasympa thetic
Nervous System
Parasympathetic innervation of the pelvic organs
and genitalia. Th e sacral port ion of th e p arasym pa-
th etic n ervou s system carries im p ulses in t h e pel-
vic splanchnic nerves an d th e superior and inferior
hypogastric (pelvic) plexuses to gan glia in th e
m uscu lar w all of th e colon (from th e distal th ird of
th e tran sverse colon onw ard), rectu m , bladder, an d
gen italia (Fig. 6.15). In th e pelvic area, th e para-
sym path etic n ervous system is respon sible for th e
em ptyin g of th e rectu m an d bladder. It also brin gs
abou t p en ile erection , w h ile sym p ath et ic fibers are
respon sible for ejacu lation , w h ich occurs th rou gh
con traction s of th e ductu s deferen s an d th e sem i-
n al vesicles.
Autonomic Innervation and
Functional Disturbances
of Individual Organs
Th e sym path et ic an d p arasym path etic in n ervation
of in dividual organ s is sum m arized in Table 6.1.
Th e in n ervation of th e pelvic organ s w ill be dis-
cu ssed in greater detail in th e follow in g section s,
becau se th e fu n ction of t h ese organ s is com m on ly
im paired in disturban ces of th e auton om ic n ervou s
system . Bladder dysfu n ction is t h e m ost im portan t
problem of th is type.
Innervation of the Bla dder
Parasympathetic innervation. Th e m otor in n erva-
tion of th e u rin ary bladder is m ostly parasym pa-
th etic. Th e pelvic splan ch n ic n erves, derived from
segm en ts S2, S3, an d S4, travel to p arasym path etic
gan glia in th e bladder w all an d to th e sm ooth
m uscle of th e in tern al u reth ral sph in cter (Figs. 6.15
an d 6.17). Parasym path etic stim u lation in du ces
con traction of th e sm ooth detrusor m u scle of th e
bladder w all an d sim u ltan eou s relaxation of th e in -
tern al u reth ral sph in cter. Mictu rition results.
Sympathetic innervation. Th e sym path etic fibers
in n ervatin g th e bladder are derived from n euron s
in th e in term ediolateral cell colu m n of th e low er
th oracic an d u pper lu m bar sp in al cord (segm en ts
T12, L1, an d L2). Th ese fibers travel th rou gh th e
cau dal p ortion of th e sym path etic ch ain an d th e in -
ferior splan ch n ic n erves to t h e in ferior m esen teric
gan glion . Postgan glion ic sym path etic fibers th en
travel, by w ay of th e in ferior hypogastric plexu s, to
th e bladder w all (tu n ica m uscu laris) an d to th e
sm ooth m u scle of t h e in tern al u ret h ral sph in cter
(Fig. 6.15 an d 6.17).
Sensory innervation. Afferen t fibers origin ate in
n ociceptors an d p roprioceptors of th e bladder w all,
w h ich respon d to stretch . As th e bladder fills, th ere
is a reflexive in crease in m uscle ton e in th e bladder
w all an d in tern al sph in cter, w h ich is m ediated by
th e sacral segm en ts (S2–S4) an d th e pelvic

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6 194 · 6 Diencephalon and Autonom ic Nervous System

Table 6.1 The Sympathetic and Parasympathetic Nervous System

Sympathetic Pa rasympa thetic

Organ Pregan- Postganglionic Activit y Pregan- Postganglionic Activit y

glionic neuron glionic neuron
neuron neuron

Eye T1–T2 Superior cervical Mydriasis Edinger– Ciliary ganglion Miosis, contrac-
ganglion Westphal tion of the cili-
nucleus ary m uscle (ac-
(accessory com m odation)
oculom otor
nucleus)

Lacrimal, sub- T1–T2 Superior cervical Vasoconstric- Superior Pterygopalatine Lacrim ation,
lingual, and ganglion tion salivatory ganglion salivation
submandibular Secretion nucleus (watery),
glands (viscous) vasodilation

Parotid gland T1–T2 Superior cervical Vaso- Inferior Otic ganglion Salivation
ganglion constriction salivatory
Secretion nucleus

Heart T1–T4 Superior, m iddle, and Acceleration Dorsal nu- Cardiac plexus Bradycardia,
(T5) inferior cervical gan- Dilation of cleus of constriction of
glia and upper coronary the vagus coronary arter-
thoracic ganglia arteries nerve ies

Small intestine T6–T10 Celiac ganglion, su- Inhibition of Dorsal Myenteric Peristalsis,
and ascending perior m esenteric peristalsis and nucleus of plexus (of Auer- secretion,
colon ganglion secretion the vagus bach), subm u- vasodilation
nerve cosal plexus (of
Meissner)

Pancreas T6–T10 Celiac ganglion — Dorsal nu- Periarterial Secretion

cleus of plexus
the vagus
nerve

Descending L1–L2 Inferior m esenteric Inhibition of S2–S4 Myenteric Secretion, peri-

colon and ganglion, hypogastric peristalsis and plexus (of Auer- stalsis, evacua-
rectum ganglion secretion bach), subm u- tion
cosal plexus (of
Meissner)

Kidney L1–L2 Celiac ganglion, Activation of S2–S4 Hypogastric Relaxation of

Bladder renal and hypogastric internal plexus (vesical the internal
plexuses sphincter plexus) sphincter
m uscle, vaso- m uscle, con-
constriction traction of the
detrusor m uscle,
vasodilation

Adrenal gland T11–L1 Adrenal cells Secretion — — —

(norepine-
phrine, epine-
phrine)

Male genitalia L1–L2 Superior and inferior Ejaculation S2–S4 Hypogastric Erection,
(pelvic hypogastric plexuses Vasoconstric- plexus vasodilation,
splanch- (pelvic plexus) tion (pelvic plexus) secretion
nic
nerves)

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Table 6.1 The Sympathetic and Parasympathetic Nervous System (continued)
Sympa thetic
Skin of head T2–T4 Superior and m iddle Vasoconstric-
and neck cervical ganglia tion
Sweating
Piloerection
Arms T3–T6 Inferior cervical gan-
glion and upper
thoracic ganglia
Legs T10–L2 Lower lum bar and
upper sacral ganglia
splan ch n ic n erves. In creasin g ten sion on t h e blad-
der w all is con sciously perceived, as som e of th e af-
feren t im p ulses t ravel cen t rally, by w ay of th e post-
erior colu m n s, to th e so-called pon tin e m icturition
cen ter, w h ich lies in th e reticular form ation n ear
th e locus ceru leu s. From th e m ictu rit ion cen ter,
im pu lses travel onw ard to th e p aracen tral lobu le
on th e m edial su rface of t h e cerebral h em isp h eres,
an d to oth er brain areas.
Regula tion of Bla dder Function: Continence
and Micturition
Th e bladder perform s its tw o m ajor fu n ction s, th e
continent storage of urine an d periodic, complete
emptying, as follow s.
Urinary continence is ach ieved by activation of the
internal and external urethral sphincters, an d, in
w om en , m ain ly by act ivation of t h e m uscles of the
pelvic floor. Sym path etic efferen t fibers from T11–
L2 activate alph a-receptors of th e in tern al sph in c-
ter an d are also th ou gh t to in h ibit th e detru sor
m uscle by a m ech an ism th at h as n ot yet been de-
term in ed. Th e extern al u reth ral sph in cter is a
striated m u scle th at, like th e m uscles of th e p elvic
floor, receives its som atic in n ervat ion t h rou gh
efferen t fibers of t h e p uden dal n erve (S2–S4, see
p. 193).
As th e bladder is filled an d t h e ten sion on th e
bladder w all in creases, involu n tary reflex con trac-
tion of th e detru sor m uscle is effectively coun tered
by activation of t h e extern al sph in cter by th e sacral
som atic m otor n eu ron s. At th e sam e tim e, lu m bar
sym path etic activation in duces closu re of th e in -
tern al sph in cter as w ell as relaxation of th e detru -
sor m u scle.
Peripheral Autonom ic Nervous System · 195
6
Parasympathetic
— — —
— — —
— — —
Micturition. Th e m ost im portan t stim u lus for m ic-
tu rition is stretching of the bladder w all, w h ich ex-
cites visceral sen sory afferen t n eu ron s, in du ces th e
urge to void, an d, w ith th e cooperation of h igh er
n ervou s cen ters, leads to contraction of the detrusor
m uscle. Th is h ollow m u scle receives its parasym -
path etic in n ervation from th e sacral sp in al cord by
w ay of t h e pelvic n erve. Bladder em ptyin g is
fu rth er p rom oted by som atic, volun tarily con -
trolled abdom inal pressing an d by sim ultaneous re-
laxation of the internal and external urethral sphinc-
ters.
At a supraspin al level, m icturition is con trolled
by th e pontine m icturition center, w h ich projects
descen din g efferen t fibers in th e m edial an d lateral
reticu lospin al t racts to coordin ate th e sim ul-
tan eous relaxation of th e in tern al an d extern al
sph in cters an d con traction of th e det ru sor m u scle.
Th e n eu rotran sm itter glu tam ate m ay play a role in
th is p ath w ay. Th e pon tin e m ictu rition cen ter is an -
atom ically poorly ch aracterized. It can be in h ibited
th rough afferen t fibers from h igh er cen ters, in -
clu din g th e fron tal cortex, cin gulate gyrus, para-
cen tral lobule, an d basal gan glia.
Bla dder Dysfunction
As discu ssed in th e last section , th e regulation of
con tin en ce an d m ictu rition requ ires th e perfect
fu n ction al cooperat ion of n u m erou s an atom ical
structu res, som e of w h ich are very distan t from
oth ers. Lesion s at m any differen t sites in th e cen -
tral or periph eral n ervou s system can h ave far-
ran gin g deleteriou s effects on bladder fu n ction .
Bladder dysfu n ction m ay be du e to stru ctu ral/
an atom ical lesion s of th e bladder or u reth ra (blad-
der dysfunction of urological origin: vesical
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6 196 · 6 Diencephalon and Autonom ic Nervous System
tu m ors, in fravesical obstru ction by ureth ral stric-
tu re or prostatic hypertrop hy), or it m ay be du e to a
lesion of th e n eu ral stru ctures in n ervatin g th e blad-
der (neurogenic bladder dysfunction). Th e re-
spon sible n eu ral lesion m ay lie in t h e periph eral
n erve path w ays, th e au ton om ic plexu ses, th e sp i-
n al cord, or h igh er cen ters.
Im pairm en t of su praspin al con trol m ech an ism s
frequ en t ly cau ses bladder dysfu n ction in patien ts
w ith m ultiple sclerosis, for exam p le. Disturban ces
of th e in teraction betw een th e p on tin e m ictu rit ion
cen ter an d oth er, h igh er cen ters th at m odu late it
play an im portan t role in th e types of n eu rogen ic
bladder dysfu n ction seen in n eu rodegen erative
diseases, in cludin g Parkin son disease.
Neurogenic Bladder Dysfunction
Typical m an ifestation s of n eurogen ic bladder dys-
fu n ction in clu de urinary frequency and urgency, in-
continence, difficult and incom plete bladder em pty-
ing, an d recurrent urinary tract infections.
Th e first step tow ard th e su ccessful treatm en t of
n eu rogen ic bladder dysfu n ction is a correct clin ical
diagn osis. Variou s aspects of u rin ary fu n ction m ust
be taken in to accoun t, in clu din g th e an sw ers to th e
follow in g question s: Wh en an d h ow frequ en t ly is
th e bladder em ptied? Is it em ptied com pletely? Is
th e u rge to void n orm al, dim in ish ed, or abn orm ally
severe (u rin ary u rgen cy)? Has a urin ary t ract in fec-
tion been ru led ou t? Is th e patien t con tin en t?
Detrusor instability and detrusor hyperreflexia are
ch aracterized by p rem atu re detrusor con traction s
du rin g th e vesical fillin g ph ase. Th e term “in stabil-
ity” refers to a lack of th e n orm al in h ibition of
detrusor con t raction ; t h e term “hyp erreflexia” im -
plies th at a n eurological disease is cau sin g th e
bladder em ptyin g disorder. Th us, clin ical en tities
such as un in h ibited n eu rogen ic bladder, autom atic
bladder, an d m otor in stability of th e bladder all
belon g w ith in t h e et iological category of detrusor
hyp erreflexia. In such cases, the lesion lies above the
sacral spinal cord an d im p airs th e fun ction of su -
prasacral in h ibitory projection s to th e detru sor
m uscle. Th e m ajor sym ptom of isolated detrusor
hyp erreflexia is imperative urinary urgency w ith
urge incontinence and low residual volume. Th e
m ore com m on cau ses are m u ltiple sclerosis, cere-
brovascu lar diseases, n orm al pressu re hydro-
cep h alu s, Parkin son disease, spin al cord traum a,
an d t rau m a or tu m or affectin g th e fron tal lobes of
th e brain .
Detrusor–sphincter dyssynergia is defin ed as invol-
un tary detru sor con traction w ith ou t relaxation of
th e extern al u reth ral sph in cter. Th e lesion lies be-
tw een the sacral spinal cord and the pontine m ic-
turition center. Th e m ajor sym ptom is imperative
urinary urgency w ith incomplete emptying of the
bladder. Detru sor–sph in cter dyssyn ergia causes
com plication s (in particu lar, ascen din g u rin ary
tract in fection s) m ore frequ en tly in m en th an in
w om en , becau se w om en h ave a low er bladder ou t-
let resistan ce th an m en . Th e m ore com m on cau ses
are m u ltiple sclerosis, cervical m yelopathy, spin al
tu m ors, vascu lar m alform ation s, an d traum a. Th is
en tity sh ould be dist in gu ish ed from th e rare
functional obstruction of the bladder neck, a dis-
order of u n kn ow n etiology th at is associated w ith
in creased residu al volum e an d can im pair ren al
fu n ction .
Detrusor areflexia result s from deficien t afferen t or
efferen t in n ervation of th e detrusor m u scle. Affer-
en t an d efferen t distu rban ces h ardly ever occu r in
isolation , presu m ably because both afferen t an d
efferen t im p ulses travel t h rou gh t h e p elvic para-
sym path et ic n erves an d th e sacral spin al seg-
m en ts, so th at any lesion im p airin g on e type of im -
pulse n ecessarily im pairs th e oth er. Th e clin ical
m an ifestation s of detru sor areflexia are reduced
urge to void, inability to initiate micturition, and
overflow incontinence w it h an in creased bladder
volum e (u p to 20 0 0 m l). The lesion lies w ithin the
sacral spinal cord or the peripheral nerves that enter
and em erge from it. Cau ses in clude tu m ors involv-
in g th e con us m edullaris an d/or cau da equin a,
lu m bar spin al sten osis an d disk h ern iation , poly-
radiculitis (in clu din g Guillain–Barré syn drom e),
diabetic or alcoh olic p olyn eu ropathy, tabes
dorsalis, pelvic su rgery an d radiation th erapy, m y-
elodysp lasia, an d tet h ered cord syn drom e.
Det ru sor areflexia du e to sacral spin al cord dys-
fun ction is fou n d in 20–30 %of pat ien ts w ith m ult i-
ple sclerosis. Most of th ese patien ts h ave m arkedly
elevated residual volu m es becau se t h e attem pt to
urin ate is fu rth er th w arted by lack of relaxation of
th e extern al u reth ral sph in cter.
Genuine stress incontinence is said to be presen t
w h en detru sor fu n ction is n orm al an d stress in con -
tahir99-VRG & vip.persianss.ir

Case Presentation 3: Tethered Cord Syndrome
This previously healthy 27-year-old nurse com plained to her
fam ily physician of difficulty urinating. She had trouble initi-
ating the flow of urine, needed to strain to urinate, and felt
that her bladder was still full afterward. At other tim es, she
passed sm all am ounts of urine involuntarily. Finally, she had
also had a single episode of stool incontinence. She was
very worried and em barrassed, was afraid to leave the
house, and had stopped going to work. She denied having
pain or any history of traum a.
Neurological exam ination revealed hypesthesia in the sacral
derm atom es (saddle hypesthesia), norm al strength in the
lower lim bs, and m arkedly dim inished sphincter tone. An
MRI scan was ordered to rule out a m ass com pressing the
a b
Fig. 6.18 Tethered cord syndrome. a The sagittal T2-
weighted im age shows an enlarged lum bar spinal canal
with the conus m edullaris lying at an abnorm ally low posi-
tion (L4) im m ediately underlying the dorsal dura m ater. In
this case, there were no associated anom alies such as a der-
tin en ce is due solely to deficien t activation of th e
extern al ureth ral sph in cter. Gen u in e stress in con ti-
n en ce, th e m ost com m on type of bladder em ptyin g
disorder in w om en , occu rs m ain ly after hyster-
ectom y an d in m u ltiparou s w om en w ith u terin e
prolapse. Its in ciden ce rises w ith age. It also occurs
as a m an ifestation of variou s n eu rogen ic bladder
em ptyin g disorders, in clu din g det ru sor hyp er-
reflexia an d detru sor–sph in cter dyssyn ergia.
Peripheral Autonom ic Nervous System · 197
6
conus m edullaris or cauda equina (Fig. 6.18). This study re-
vealed a developm ental anom aly in the lum bosacral spinal
canal, in which the conus m edullaris lay at an abnorm ally
low level (tethered cord syndrom e).
In this disorder, the conus, because it lies im m ediately
under the dorsal dura m ater and adheres to it, cannot as-
cend norm ally to the L1−2 level over the course of develop-
m ent. The resulting neurological deficits m ay not arise until
later in life, and their pathogenesis rem ains incom pletely
understood. Because of her progressive neurological defi-
cits, the patient presented here was treated neurosurgi-
cally, with an operative detachm ent of the conus from the
dura m ater. Her deficits resolved com pletely thereafter.
c
m al sinus, lipom a, or m eningomyelocele. b, c The T2-
weighted axial sections through the spinal canal at T12 (b)
and L2 (c) reveal spinal cord at both levels. Even at the L2
level, the cord has a greater diam eter than the cauda
equina. It adheres to the dorsal dura m ater.
Nonneurogenic Bla dder Dysfunction
Infravesical obstruction usu ally occu rs in m en ,
often as th e resu lt of ben ign prostatic hyperplasia,
an d is m an ifested clin ically w ith urin ary u rgen cy,
pollakiuria, n octu ria, u rin ary reten tion , an d over-
flow in con t in en ce.
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6 198 · 6 Diencephalon and Autonom ic Nervous System
Hypogastric nn.
Inferior
mesenteric
ganglion Pelvic nn.
S2 t o S4
Pudendal n.
Sym pathetic
postganglionic
External sphincter m.
Parasym pathetic
Internal sphincter m preganglionic
Som atomotor Parasym pathetic
Sym pathetic postganglionic
preganglionic Afferent pathways
Fig. 6.19 Innervation of the rectum
Dysfunction of the external urethral sphincter, pre-
ven tin g adequate relaxat ion of th e sph in cter
m uscle, h as been fou n d to be a com m on cau se of
obst ru ct ive bladder em ptyin g dist urban ces in
you n g w om en . It is ch aracterized by m yoton iform
disch arges in th e EMG. Electrom yograp h ic stu dy is
n ecessary to distin guish th is disorder from tw o im -
portan t altern ative diagn oses in you n g w om en
w ith bladder em ptyin g dist urban ces, n am ely, m u l-
tip le sclerosis an d p sych ogen ic bladder dysfun c-
tion .
Enuresis is defin ed as bedw ettin g, by day or n igh t ,
in in dividuals over th e age of 4 years, in th e ab-
sen ce of any dem on strable cau sative lesion . En u re-
sis is t h u s, by defin ition , n ot a n eu rogen ic distu r-
ban ce. Th e im portan t differen tial diagn oses in -
clu de organic n eu rological an d urological cau ses of
bedw ett in g, in clu din g epilepsy, spin a bifida oc-
culta, an d m alform ation s of th e urogen ital tract. A
24-h our EEG recordin g is in dicated in som e cases.
Innerva tion of the Rectum
Em ptyin g of t h e rectu m is an alogous to em pt yin g
of th e bladder in m any respects (Fig. 6.19).
Fillin g of th e rectu m act ivates stretch receptors
in th e rectal w all, w h ich tran sm it im pu lses by w ay
of th e in ferior hypogastric plexu s to segm en ts S2
th rough S4 of th e sacral sp in al cord. Afferen t im -
pu lses th en ascen d th e spin al cord to h igh er con -
trol cen ters, w h ich are probably located in th e pon -
tin e reticu lar form ation an d th e cerebral cortex.
Rectal peristalsis is in du ced by parasym path etic
activation from segm en ts S2 th rough S4, w h ich
also in du ces relaxation of th e in tern al sph in cter.
Th e sym path etic n ervou s system in h ibits peristal-
sis. Th e extern al sph in cter con sists of striated
m u scle an d is un der volun tary con trol.
Rectal em ptyin g is m ain ly accom plish ed volu n -
tarily by abdom in al pressin g.
Recta l Empt ying Disorders
Fecal retention. Tran section of th e spin al cord
above th e lu m bosacral cen ters for defecation leads
to fecal reten tion . In terru ption of th e afferen t arm
of th e reflex path w ay for defecation deprives
h igh er cen ters of in form ation abou t th e fillin g
state of th e rectu m , w h ile in terru ption of de-
scen din g m otor fibers im pairs volun tary abdom i-
n al pressin g. Sph in cter closure is often in adequ ate
becau se of spastic w eakn ess.
Fecal incontinence. Lesion s of th e sacral spin al cord
(S2–S4) abolish th e an al reflex an d produ ce fecal
in con tin en ce. If th e stool is w atery, involu n tary
loss of stool occurs.
Innerva tion of the Ma le Genita lia
Efferen t sym pat h etic fibers from t h e up per lu m bar
spin al cord travel by w ay of a periarterial n ervou s
plexu s (th e hyp ogastric plexu s) to th e sem in al ves-
icles, prostate, an d du ctu s deferen tes. Stim u lation
of th e plexu s causes ejacu lation (Fig. 6.20).
Parasym path etic fibers from segm en ts S2
th rough S4 travel th rou gh th e pelvic splan ch n ic
n erves (th e n ervi erigen tes) to th e corp ora caver-
n osa. Parasym path etically in duced vasodilatation
in th e corpora cavern osa brin gs abou t pen ile erec-
tion (Fig. 6.20). Th e ureth ral sph in cter an d th e
isch iocavern osu s an d bulbospon giosu s m u scles
are in n ervated by th e p uden dal n erve.
Gen it al fu n ction is u ltim ately u n der t h e con trol
of hypoth alam ic cen ters, w h ich exert t h eir effects
partly th rou gh n eu ral con n ection s (reticu lospin al
fibers) an d p artly by h u m oral m ean s (h orm on es).
Genita l Dysfunction
Spin al cord tran section at a th oracic level causes
im poten ce. Reflex priap ism m ay occur, an d oc-
casion al ejacu lation is also possible. Paraplegia h as
tahir99-VRG & vip.persianss.ir
 Peripheral Autonom ic Nervous System · 199
6
been reported to be associated w ith test icular atro-
phy.
Lesion s of th e sacral spin al cord from S2 to S4 L1
also cause im poten ce. In th ese cases, n eith er erec- Hypogastric plexus
tion n or ejacu lation is possible.

Visceral and Referred Pain

Afferen t au ton om ic fibers p articip ate in a large
n u m ber of au ton om ic regu latory circu its. Most of Corpora
Pudendal n. S2 t o
cavernosa
th e im pu lses travelin g in t h ese fibers do not rise to S4
con sciou sn ess.

Sympathetic Parasympathetic
Visceral pain. Th e in dividual can, h ow ever, con - preganglionic preganglionic
sciously perceive th e fillin g state of th e h ollow Sympathetic Parasym pathetic
postganglionic postganglionic
viscera, w h ich is reported to th e cen tral n ervou s Afferent pathways
system t h rou gh afferen t au ton om ic fibers arisin g
from pressu re or stretch receptors in t h e visceral Fig. 6.20 Innervation of the male genitalia (erection and
w all. Overfillin g of a h ollow viscu s is perceived as ejaculation)
pain . Moreover, irritation of t h e w all of a viscu s
can cause reflex sp asm of sm ooth m u scle, w h ich
also gives rise to pain (biliary colic du e to gall-
ston es, ren al colic due to kidn ey ston es). Visceral
C4
in flam m ation or isch em ia is also pain fu l, e.g., Diaphragm (C4 )
C5
T1
an gin a pectoris. T2
Pain origin atin g in th e in tern al organ s is diffu se T3 Heart (T3 – T4 )
an d poorly localizable. Fu rt h erm ore, th e patien t T4
Esophagus (T4 – T5 )
m ay report feelin g pain n ot in th e organ itself bu t T5
T6
in a related zon e of t h e body su rface (th ese are th e T7
Stom ach (T6 – T9 )
T8 Liver, gallbladder
zon es of Head, cf. Fig. 6.21).
T9 (T8 – T11)
T10 Small intestine (T10– L1 )
Referred pain. Th e cell bodies of th e afferen t au - T11 Large intestine (T11– L1 )
T12 Kidney, testes/ovaries
ton om ic fibers, like th ose of th e som atic afferen t (T10– L1 )
fibers, are located in th e spin al gan glia. Th e auton - Bladder (T11– L1 )
om ic fibers en ter th e spin al cord th rough th e post-
erior root togeth er w ith t h e som at ic afferen t fibers
from t h e m yotom e an d derm atom e of each Fig. 6.21 The zones of Head
segm en tal level. Th u s, each in dividu al segm en t of
th e posterior h orn receives convergin g afferen t
inpu t, both from th e in tern al organ s an d from th e ferred. Th e abdom in al w all m ay also becom e rigid.
related m yotom e an d derm atom e. Activation from Th e exact m ech an ism by w h ich referred pain
eith er set of afferen t fibers (visceral or som atic) is arises h as n ot yet been con clu sively explain ed,
tran sm itted cen trally by th e sam e fibers of th e th ough th ere are a n u m ber of hypoth eses.
lateral spin oth alam ic tract (Fig. 6.22). It is th ere- Pain of cardiac origin , for exam ple, is often re-
fore un derstan dable th at pain arisin g in a part icu - ferred elsew h ere. Th e up per th oracic segm en ts on
lar viscu s is som etim es felt elsew h ere, n am ely, in th e left side receive som atic afferen t fibers from
th e derm atom e or m yotom e represen ted by th e th e left side of th e ch est an d th e left arm , as w ell
sam e spin al segm en t. Th is ph en om en on is called as visceral afferen t fibers from th e h eart. Cardiac
referred p ain . It m ay be accom pan ied by a certain disease, particu larly isch em ia, often produ ces pain
degree of hypersen sitivity to som atosen sory in on e of th ese derm atom es (an gin a pectoris). Th e
stim u lation in th e derm atom e to w h ich pain is re- particular zon es to w h ich pain is referred from th e

tahir99-VRG & vip.persianss.ir

6 200 · 6 Diencephalon and Autonom ic Nervous System

Fig. 6.22 The viscerocu-

Common Afferent Afferent
taneous reflex arc with
pool som atic fiber autonomic fiber myotom e, derm atom e, and
enterotom e.
Viscerosensory and som a-
tosensory im pulses con-
verge at the level of the
posterior horn onto a com -
m on neuron, which trans-
m its further im pulses cen-
trally along a single com -
m on pathway. Thus, affer-
Efferent m otor ent signals from the inter-
fiber Myotom e
nal organs can be “m isin-
Autonom ic fiber for vaso- terpreted” as having arisen
constriction, piloerection, in the corresponding cu-
and sweating
taneous or m uscular areas
Viscerosensory (derm atom e or myotom e).
fiber This is the m echanism of
referred pain.
Dermatome

in dividual in tern al organ s are very im p ortan t in
physical diagn osis an d are called th e zon es of
Head (Fig. 6.21). It is also th e case, h ow ever, th at
im pu lses arisin g from th e skin can be projected
(referred) to t h e in tern al organ s. Clearly, t h e so-
m atic afferen t fibers are in tercon n ected w ith
visceral reflex arcs w ith in th e sp in al cord. Th is
m ay explain h ow th erapeu tic m easu res at th e
body su rface (such as th e ap plication of w arm th or
h eat, com presses, ru bbin g, etc.) often relieve pain
arisin g from th e au ton om ically in n ervated viscera.

tahir99-VRG & vip.persianss.ir

 7

7 Limbic System
Anatomical Overview . . . . . . . . . . . . . . 202
Major Components of the Limbic
System . . . . . . . . . . . . . . . . . . . . . . . . . . 203
Functions of the Limbic System . . . . . 206
7 202
7 Limbic System
Th e lim bic system is com posed of both neocortical
an d phylogenetically older cortical areas (portion s
of th e arch icortex an d paleocortex) an d a n u m ber
of nuclei. Th e cellu lar arch itectu re of th e arch icor-
tex an d paleocortex differs from th at of th e n eo-
cortex. Th e m ajor st ru ct ures of th e lim bic system
are th e h ip pocam pal form ation , th e parah ippo-
cam p al gyru s an d en torh in al area, th e den tate
gyru s, t h e cin gu late gyru s, th e m am illary body,
an d t h e am ygdala. Th ese stru ctures are in tercon -
nected in th e Papez circuit an d also m ake exten sive
con n ect ion s w it h ot h er region s of th e brain (n eo-
cortex, th alam u s, brain stem ). Th e lim bic system
th ereby en ables com m un ication betw een m esen -
ceph alic, dien ceph alic, an d n eocortical st ru ct ures.
Anatomical Overview
Broca, in 1878, described th e rin g of brain convolu-
tion s su rroun din g th e corp us callosum , dien -
cep h alon , an d basal gan glia, n am in g it th e “gran d
lobe lim biqu e” (great lim bic lobe, from th e Latin
lim bus, rin g). In som e respects, th is com plex of
stru ctu res can be con sidered a zon e of tran sition
betw een th e brain stem an d th e n eocortex. Th e cor-
tical areas w ith in it are com posed of archicortex
(h ippocam pu s an d den tate gyru s), paleocortex
(piriform cortex), an d mesocortex (cin gu late
gyrus). Fu rth er lim bic stru ctures are th e en torh in al
Commissure Cingulate gyrus
of the fornices Indusium griseum
(medial and lateral
longitudinal striae)
Anterior
comm issure
Fornix
Septal
area
Amygdala
Mamillary body
Hippocam pus Entorhinal area
Fig. 7.1 The limbic cortex
Th rou gh its con n ection w ith th e hypoth alam us,
an d t h u s w ith th e au ton om ic n ervous system , th e
lim bic system participates in th e regulation of
drive and affective behavior. Its m ain fun ction , tel-
eologically speakin g, is said to be th e gen eration of
beh avior t h at prom otes th e survival of th e in -
dividual an d of th e species. Im p ortan t fu n ction s
are ascribed to t h e am ygdala in beh avior as-
sociated w ith fear an d an xiet y. Moreover, th e h ip -
pocam pus plays a very im portan t role in learning
and memory. Lesion s of th e h ip pocam pal form a-
tion , or of oth er stru ctures th at are fu n ction ally as-
sociated w ith it, produce an amnestic syndrome.
Differen t dist urban ces of m em ory can arise, de-
pen din g on th e site of th e lesion .
an d septal areas, th e in du siu m griseum , th e am yg-
dala, an d t h e m am illary bodies (Fig. 7.1). Th e ex-
ten sive fiber con n ection s lin kin g all of th ese struc-
tu res led Papez, in 1937, to prop ose th at a loop , or
circuit, of n eu ral activation (th e Papez circuit, see
Fig. 7.2) m igh t be th e an atom ical su bstrate of
em ot ion al feelin g an d exp ression an d of affect ive
states correspon din g to in stin ctu al drive. Th is
th eory received su pport from th e stu dies of Klü ver
an d Bucy (Klü ver–Bucy syn drom e). Grow in g evi-
den ce of th e an atom ical an d fu n ction al lin kage of
th e variou s lim bic structu res led MacLean to coin
th e term “lim bic system .”
More recen tly, h ow ever, th e con cept of th e lim -
bic system as a discrete fu n ction al u n it h as com e
in to qu estion , as furth er stu dies h ave sh ow n th at
th e lim bic stru ctures p ossess im portan t n eural
con n ection s n ot ju st w ith each oth er bu t w ith ou t-
side st ru ctu res as w ell. Th u s, th e lim bic system
can n ot be regarded as a closed system in eith er an
an atom ical or a fu n ction al sen se. Th e fun ction s as-
sociated w ith th e lim bic system , su ch as in stin ct ual
an d affect ive beh avior, m otivation , an d drive, as
w ell as learn in g an d m em ory (see p. 206 ff.),
sh ou ld n ot be th ou gh t of as th e p reserve of th e lim -
bic system alon e. Th ese fu n ction s depen d on an in -
tact coop eration of th e lim bic system w ith m any
oth er areas of th e brain .
On ce th is h as been u n derstood, th ere is n o
fu rth er objection to th e u se of th e term “lim bic
 Major Com ponents of the Lim bic System · 203
7
system ,” particu larly becau se th e an atom ical con - Thalam ocingulate
n ection s betw een th e variou s lim bic stru ctures, tract (radiation) Cingulum
w h ich origin ally m otivated th is term , are in deed
presen t, robu st, an d fun ction ally im p ortan t. No u n i-
form altern ative term in ology h as yet com e in to
gen eral use. Path ological ch an ges of th e lim bic
stru ctures are still described, in th e clin ical settin g,
as lesion s of th e lim bic system .

Anterior nucleus
Internal and External Connections of the thalam us
Mam illo-
Pa pez Circuit thalam ic tract

A grou p of lim bic st ru ctu res, in clu din g th e h ippo-

cam p us, are con n ected to on e an oth er in th e so-
called Pap ez circu it, w h ich con tain s a n u m ber of
n eu ral relay station s arran ged in a circu it or loop .
Beyon d th e basic w irin g diagram of th e Papez cir-
Fornix, from the hippocampus
cu it, as origin ally described, m uch fu rth er in form a- to the mamillary body
tion h as com e to ligh t regardin g addition al con n ec- Cingulum , back to
tion s an d th e particu lar n eurotran sm itters u sed at the hippocampus

variou s p oin t s in th e circuit .
Th e Papez circuit run s as follow s. From th e hip-
pocam pus (Am m on ’s h orn ), im pu lses travel
th rough th e great arch of th e fornix to t h e m am il-
lary body. Th is n ucleu s, in turn , is th e site of origin
of th e m am illothalam ic tract (of Vicq d’Azyr),
w h ich conveys im pu lses to th e anterior nucleus of
the thalam us. Th e an terior n ucleu s projects to th e
cingulate gyrus by w ay of t h e thalam ocingulate
radiation. From t h e cin gulate gyru s, im pu lses
travel by w ay of th e cingulum back to th e h ip po-
cam pu s, com pletin g th e circu it (Fig. 7.2).
Connections to Other Areas of the Bra in
Th e m am illary body occu pies a key position in th e
Papez circuit becau se it con n ects th e lim bic system
w ith th e m idbrain (n u clei of Gu dden an d Bekh -
terev) an d th e reticular form ation. Th e m am il-
lotegm en tal tract an d th e pedun cle of th e m am il-
lary body (see Figs. 6.9 an d 6.10, pp. 180 an d 181)
form a regu latory circuit of t h eir ow n . Im pulses
arisin g in th e lim bic system can t ravel by w ay of
th e an terior n ucleu s of th e th alam us to th e cin gu -
late gyru s, bu t also, via association fibers, to th e
neocortex. Furth erm ore, im pu lses from th e au to-
n om ic n ervou s system can travel th rough th e hy-
pot h alam us an d th e m edial dorsal n ucleu s of t h e
th alam u s to reach th e orbitofrontal cortex.
Fig. 7.2 The Pape z circuit (hippocam pus—fornix—m am il-
lary body—anterior nucleus of the thalam us—cingulate
gyrus—cingulum —hippocam pus)
Major Components of the Limbic
System
Hippocampus
Th e h ippocam p al form ation is th e cen tral stru cture
of th e lim bic system . Its stru cture an d n eu ral con -
n ection s an d th e clin ical ch an ges observed in
patien ts w ith h ippocam pal lesion s form th e sub-
ject of th is section .
Microanatomy of the Hippocampal
Formation
Th e h ippocam pal cortex con sists of archicortex, a
phylogen etically old type of cerebral cortex, w h ich
possesses on ly three layers in stead of th e u su al six.
Becau se of th is differen t stru ctu re, th e h ippocam -
pu s an d a few oth er cortical areas are called allocor-
tex (as opposed to th e six-layered isocortex). Th e
h ippocam p us proper (Am m on ’s h orn or cornu Am -
m onis) is distin ct from th e den tate gyru s (fascia
dentata, Fig. 7.3a an d b). Th e prin cipal cell type in
th e h ippocam pu s is th e pyramidal cell. Th ere are
differen t typ es of pyram idal cells in t h e in dividu al
region s of Am m on ’s h orn , design ated CA1, CA2, an d
7 204 · 7 Lim bic System

Fig. 7.3 The hippocampal

a Fornix Alveus formation. a Major affer-
ent and efferent projec-
tions of the hippocam pal
Fim bria hippocam pi
Am m on’s form ation: the perforant
Dentate gyrus
horn path and the fornix, respec-
(fascia dentata)
tively. The perforant path
Hippocam pal fissure penetrates the subiculum
to link the entorhinal area
Presubiculum with the dentate gyrus.
Subiculum b Cytoarchitecture of the
Inferior horn of
lateral ventricle hippocam pal form ation.
Parahippo-
c Diagram of the various
cam pal
gyrus cell types of the hippocam -
pal form ation and their
connections. 1–3,
Am m on’s horn regions CA1
Entorhinal Perforant
through CA3. 4, Perforant
area path
(area 28) path.
5, Pyram idal cells.
6, Granule cells of the den-
tate gyrus. 7, Mossy fibers.
8, Alveus. 9, Fim bria hippo-
End plate of Tail of caudate
cam pi. 10, Recurrent Schaf-
b Choroid
Am m on’s horn plexus nucleus fer collaterals of the CA3
pyram idal cells, which form
Lateral geniculate
synapses with the den-
body
Dense band drites of the CA1 pyram idal
of neurons cells. Fig. 7.3c from : Kahle
Fim bria hippocam pi
W and Frotscher M:
Am bient cistern Taschenatlas der Anatom ie,
vol. 3, 8th ed., Thiem e,
Stuttgart, 2002.
Inferior
Dentate gyrus
horn
Parahippo-
cam pal gyrus
Collateral
em inence

Subiculum
Loose band
Entorhinal of neurons
area

Isocortex

Medial Lateral

c
9
3
8
7
2

4
1
6
5
10

CA3 (“CA” stan ds for corn u Am m on is) (Fig. 7.3c);
som e au th ors also describe a fu rt h er CA4 region ad-
jacen t to th e h ilus of th e den tate gyru s. Th e prin ci-
pal cells of t h e den t ate gyru s are th e gran u le cells,
w h ich con n ect th e den tate gyru s w ith th e h ippo-
cam p us p roper (CA4/CA3) th rough th eir axon s,
called m ossy fibers. In addition to th e p rin cipal cell
types (pyram idal cells an d gran u le cells) con stitu t-
in g th e prin cipal cell layers, th e h ipp ocam p us an d
den tate gyrus also con t ain GABAergic interneurons
th at are n ot restricted to any particu lar cellu lar
layer. Th ese cells con tain n ot on ly th e in h ibitory
n eu rotran sm itter GABA bu t also various n europep-
tides an d calcium -bin din g protein s.
Neura l Connections of the Hippoca mpal
Forma tion
Entorhinal afferent fibers. Like th e h ip pocam pu s,
th e entorhinal area, too, is com posed of allocortex.
Recen t stu dies h ave revealed th e im p ortan ce of
th is brain area, w h ich is located lateral to th e h ip-
pocam pu s in th e parah ippocam pal gyru s (Brod-
m an n area 28, Figs. 7.1 an d 7.3) an d borders th e
am ygdala rost rally. Th e collateral sulcu s m arks th e
border bet w een th e en torh in al area an d t h e tem -
poral isocortex (see Fig. 9.9, p. 230). Th e en torh in al
area receives afferent fibers from very w idespread
neocortical areas. It is th ough t to serve as a gatew ay
to the hippocam pus, w h ich in tu rn an alyzes in com -
in g n eocortical in form ation w ith respect to its
n ovelt y. Th e fiber con n ection from th e en torh in al
cortex to th e h ippocam p us is m assive. Most of
th ese fibers belon g to th e perforant path, w h ich
pierces th e su biculu m (Fig. 7.3a).
Septal afferent fibers. Ch olin ergic an d GABAergic
n eu ron s from th e m edial septu m an d th e diagon al
ban d of Broca (septal area, cf. Fig. 7.1) project to th e
h ip pocam pu s. Th e ch olin ergic projection is rath er
diffuse, w h ile t h e GABAergic fibers specifically
form syn apses w it h h ippocam pal GABAergic n eu -
ron s.
Commissural afferent fibers. Axon s of th e CA3 py-
ram idal cells an d certain n eu ron s in th e h ilar re-
gion of th e den tate gyrus (m ossy cells) con n ect th e
tw o h ippocam pi w ith each oth er, term in atin g on
th e proxim al den dritic segm en ts of th e pyram idal
an d gran u le cells of th e con t ralateral h ippocam -
pu s.
Major Com ponents of the Lim bic System · 205
7
Afferent fibers from the brainstem. Variou s brain -
stem n u clei sen d catech olam in ergic fibers to th e
h ipp ocam pus, m ostly in diffuse fash ion .
Sprea d of Activa tion in the Hippoca mpus
As m en tion ed above, t h e projection from th e en -
torh in al cortex is th e m ajor afferen t path w ay to
th e h ippocam pu s. Th e en torh in al fibers are glu -
tam atergic an d term in ate on th e distal den dritic
segm en ts of th e gran ule an d pyram idal cells. Th e
follow in g trisynaptic main pathw ay of excitation
h as been p roposed (Fig. 7.3c): en torh in al cortex
gran u le cells of th e den tate gyrus (first syn-
apse) m ossy fiber system CA3 pyram idal
cells (second synapse) recu rren t Sch affer col-
laterals of th e CA3 pyram idal cell axon s CA1
pyram idal cells (third synapse). At all th ree relay
station s, th e forw ard tran sfer of excitation is
regulated by GABAergic in h ibitory in tern eu ron s.
GABAergic syn apses on to th e n eu ron s of th e
m ain excitatory path w ay are foun d eith er on th e
cell body (basket cells), at th e in itial segm en t of
th e pyram idal an d gran u le cell axon s (axo-axon al
cells or ch an delier cells), or at th e den drites.
Th e CA1 n euron s p roject onw ard to th e sub-
iculum , w h ose efferen t fibers, in tu rn , form th e
fim bria an d fornix, th e m ajor efferen t bu n dle of
th e h ip pocam pal form ation (Fig. 7.3c). Th e forn ix
arch es over t h e dien ceph alon to term in ate in t h e
m am illary body. Th e forn ix is th e m ain con n ec-
tion of th e h ippocam p us w ith th e hypoth alam u s,
an d th u s w it h th e au ton om ic n ervou s system
(Fig. 7.2).
Amygdala
Th e am ygdala is m ade u p of several distin ct com -
pon en ts, som e of w h ich are fu n ction ally m ore
closely related to th e olfactory system , w h ile
oth ers (th e m edial an d cen tral zon es) are con -
sidered to belon g to t h e lim bic system . Th e am yg-
dala is t h e n u cleu s of origin of th e stria term inalis
(Fig. 6.9, p . 180), w h ich form s a large arch u pw ard
an d forw ard in th e groove betw een t h e th alam u s
an d th e caudate n u cleu s u n til it reach es th e level of
th e in terven tricu lar foram en , w h ere it divides in to
several sep arate fiber bu n dles. Som e of its fibers
con tin ue to th e septal area, oth ers to th e rostral
portion of the hypothalam us, an d a few oth ers by
w ay of th e st ria m edu llaris to th e habenular nu-
cleus. Furth erm ore, th e am ygdala is th ou gh t to
7 206 · 7 Lim bic System
m ake con n ection s to th e m idbrain an d, p articu -
larly, to th e m edial dorsal nucleus of the thalam us,
w h ich , in tu rn , projects to th e orbitofrontal cortex.
Th e tw o am ygdalae are also con n ected to each
oth er.
Experim en tal stim u lation of th e am ygdala h as
been fou n d to produ ce affective activation.
Em ot ion al react ion s, su ch as rage, aggression , or
fear, arise an d are accom pan ied by auton om ic re-
action s such as a rise in blood pressure, h eart rate,
an d resp iratory rate. Alterat ion s of at ten tion , of
n utrition al in take, an d of sexu al beh avior occur,
depen din g on w h ich n u clear su bdivision of th e
am ygdala is st im u lated.
Functions of the Limbic System
As explain ed above, th e en torh in al cortex receives
afferen t inpu t from w idespread region s of th e n eo-
cortex an d tran sm its th is in form ation th rough th e
perforan t path to th e h ippocam pu s. Neural pro-
cessin g at th ese levels involves th e testin g of in -
com in g in form ation for its n ovelty. Th is, in tu rn ,
im plies th at th e h ippocam pu s m u st play an im por-
tan t role in th e processes of learning and memory.
Su ch a role h as been abu n dan tly con firm ed by
clin ical observation .
Properly fu n ction in g m em ory depen ds n ot on ly
on an in tact h ippocam pus bu t also on in tact fiber
con n ection s lin kin g th e h ip pocam pu s an d am yg-
dala to oth er region s of th e brain . Th e follow in g
fiber path w ays are particu larly im port an t for
m em ory (m ore specifically, for so-called declara-
tive m em ory, see p. 207):
¼ Projections from the hippocampus by w ay of
th e forn ix
– to th e septal n u clei an d
– to th e m am illary bodies an d onw ard to th e
an terior n u cleus of th e t h alam u s an d cin gu -
late gyru s (Papez circuit)
¼ Projections from the amygdala to t h e dorsom e-
dial n u clear region of t h e th alam u s an d onw ard
to th e orbitofron tal cortex.
Types of Memory
Short-term and long -term memory. A few basic
con cepts of n europsych ology w ill be in trodu ced
h ere as im portan t backgroun d kn ow ledge for an
un derstan din g of th e fu n ction in g of th e lim bic sys-
tem w ith resp ect to m em ory. William Jam es, a
fou n din g fath er of m odern n europsych ology,
divided m em ory in to tw o typ es, w h ich h e called
“primary memory” an d “secondary memory.” Th e
con ten ts of prim ary m em ory are h eld in con sciou s-
n ess for a sh ort tim e after th e sen sory im pression s
th at produ ced th em are n o lon ger presen t (short-
term memory). Secon dary m em ory, on th e oth er
h an d, en ables th e in dividu al to call u p earlier
even ts or st ates th at h ave “disappeared from con -
sciou sn ess” in th e m ean tim e (long -term memory).
Th e distin ction betw een sh ort-term m em ory
(STM) an d lon g-term m em ory (LTM) is n ow an
em pirically w ell-fou n ded m odel in n eu ropsy-
ch ology. Certain illn esses or lesion s of th e brain
can im p air th ese tw o m em ory system s to differen t
exten ts. Both system s m u st fu n ction n orm ally to
en able n orm al cogn itive perform an ce. Dysfu n ction
of eith er system can be revealed by stan dardized
testin g.
Neural substrates of short-term and long -term
memory. Hebb, in th e 1940s, p ostulated th at t h e
tw o form s of m em ory just described h ave differen t
n eu ral su bstrates. Hebb th ou gh t of STM as a circu -
latin g activation in a pool of n eu ron s, an d of LTM as
th e product of lon g-lastin g stru ctural ch an ges at
th e level of syn aptic con n ection s. Accordin g to th e
h ebbian m odel, a process of con solidation , takin g
m in u tes or h ou rs, is required for th is stru ctural
adaptat ion to take place. Later n europsych ological
stu dies in patien ts w ith m em ory disorders re-
vealed th at t h e h ippocam p us in deed plays a cru cial
role in th e con solidation of con scious m em ories.
Diagnostic tests of STM and LTM. A com m on ly u sed
test of STM is perform ed as follow s. Th e subject (or
patien t) is asked to listen to, an d repeat, spoken
sequ en ces of n u m bers of in creasin g len gth . A n or-
m al in dividu al can repeat seven , plu s or m in us
tw o, n u m bers presen ted in th is w ay. Th ese
m em ory traces are very rapidly lost an d fail to
en ter LTM. LTM, on th e oth er h an d, can be tested by
presen tin g certain stim u li (e.g., a list of term s or a
set of objects) an d askin g th e su bject to take n ote
of t h em over a defin ed in terval of tim e, an d th en to
recogn ize or reprodu ce th em som e tim e later. Th is
is a test of volu n tary recall of con scious m em ories.
Subtypes of LTM. Th ere are tw o distin ct su btypes
(su bsystem s) of LTM, called episodic an d semantic

Case Presentation 1: Amnesia a fter Bila tera l Resection of Media l Tempora l Structures
The fam ous and historic case of H.M. illustrates the vitally
im portant role that m edial tem poral structures play in
mem ory. In the decades since this case was described, the
various subtypes of m em ory described have been charac-
terized in detail, and a large num ber of specific neuropsy-
chological tests have been developed to study them .
Medically intractable epilepsy is som etim es treated by neu-
rosurgical resection of the area or areas of the brain from
which the seizures arise. Often, the tissue to be resected is
in the tem poral lobe. In 1953, H.M., a patient with in-
tractable epilepsy, underwent resection of the m edial por-
tions of the tem poral lobe on both sides. (This procedure is
no longer perform ed bilaterally, in large part because of ad-
verse sequelae like those described in H.M.’s case.)
Postoperatively, H.M. m anifested severe disturbances of
mem ory, which have persisted until his death with hardly
any im provem ent. Ever since the operation, he has been
unable to lay down new m em ories, even though his general
level of intelligence, as m easured by standardized tests, is
norm al.
Shortly after the operation, for exam ple, when H.M. con-
versed with the doctor, his cognitive ability appeared to be
unim paired, and he had no trouble answering questions
about how he felt. Yet, if the doctor left the room and re-
turned a few m inutes later, H.M. com pletely forgot ever
having seen him and com plained about having to talk to a
new doctor each tim e. His short-term m em ory was pre-
memory. Ep isodic m em ory deals w ith data th at
belon g to a part icular spatial an d tem poral settin g,
i.e., m em ories of person al exp erien ces (a trip, con -
cert, sportin g even t, et c.). Sem an tic m em ory, on
th e oth er h an d, deals w ith facts belon gin g to
gen eral fields of kn ow ledge (m edicin e, p hysics,
etc.).
Part of LTM can in flu en ce beh avior w ith ou t th e
subject’s con scious kn ow ledge. A basic distin ct ion
is draw n betw een explicit (declarative) an d impli-
cit (nondeclarative) m em ory. Th e form er deals
w ith conscious and verbally com m unicable m em o-
ries, as already described, w h ile th e latter deals
w ith nonverbal m em ory traces, su ch as th ose th at
m ust be learn ed an d recalled du rin g th e perform -
an ce of a m otor task. Im plicit m em ory is also re-
spon sible for classical con dit ion in g (as dem on -
strated in Pavlov’s w ell-kn ow n experim en t w ith
th e dog), as w ell as for perceptual an d cogn itive
skills, an d for th e prim ing effect: in form ation pre-
sen ted in on e con text can be processed later m ore
efficien tly in an oth er con text, even if th e su bject
does n ot con sciou sly rem em ber th e earlier presen -
tation . Th e type of m em ory involved in th e prim in g
Functions of the Lim bic System · 207
7
served, that is, he could still retain new inform ation for peri-
ods of up to about one m inute: he could, for exam ple, cor-
rectly reproduce sequences of num bers or pictures that
were presented to him , but only im m ediately after their
presentation. Thus, his deficit involved the consolidation of
newly laid down m em ories from short-term into long-term
m em ory.
H.M.’s nondeclarative m em ory was not im paired: for ex-
am ple, his perform ance on tasks involving the com pletion of
word or im age sequences im proved over tim e just as m uch
as that of norm al subjects. This im plies that H.M. was able to
learn and retain certain problem -solving strategies, even
though, a short tim e later, he could no longer rem em ber
ever having perform ed the task. He was still able to acquire
new m otor skills postoperatively, and his m etacognitive
functions were also intact, at least in part: he was aware, for
exam ple, that his m em ory was deficient.
This rem arkable case history shows that the m edial tem poral
lobe is necessary for the storage of new inform ation, as well
as for the recall of inform ation that has already been stored.
The m edial tem poral lobe—specifically, the hippocam pus—
can apparently be thought of as a kind of interm ediate or
working storage system , in which explicit m em ory traces are
held for a short tim e before they are transferred to long-term
storage or sent on to other neural centers for further cogni-
tive processing.
effect is stored an d recalled “u n con sciously,” so to
sp eak, an d can on ly be recalled du rin g th e per-
form an ce of t h e relevan t tasks.
Com plex p attern s can also be stored in im p licit
m em ory. Th u s, ch ess players can rem em ber a par-
ticular p attern of ch essm en on a ch essboard better
th an can n onplayers, bu t on ly if th e pattern h as
been draw n from a real ch ess gam e; th ey perform
n o better th an con trol su bjects w h o do n ot play
ch ess if t h e pattern to be rem em bered h as been
gen erated at ran dom .
In su m m ary, m em ory is n ot a sin gle fun ction al
en tity, bu t rath er possesses m ultiple distin ct com -
p on en ts.
Squire’s taxonomy of memory. Squire (1987) pro-
p osed a classification sch em e for th e su btypes of
m em ory. In addition to explicit an d implicit
memory structures, th is sch em e recogn izes oth er
su btypes of m em ory t h at are requ ired to perform
metacognitive tasks, su ch as evalu atin g on e’s ow n
m em ory perform an ce or gen eratin g strategies to
organ ize in form ation storage an d recall. Strategies
of th e latter type are called frontal-lobe -type
7 208 · 7 Lim bic System
memory functions, becau se th ey apparen tly de-
pen d on in tact fu n ction in g of th e fron tal lobes.
Du rin g th e process of m em ory storage, th ere
seem s to be a tran sition from th e con crete to th e
abstract: for exam ple, on e m igh t be able to re-
m em ber th e app roxim ate appearan ce of th e sch ool
on e at ten ded as a ch ild, w ith ou t bein g able to
sketch it in det ail. Yet, w h ile m em ory storage
supp resses som e aspects of experien ce, it accen tu -
ates oth ers. Th e “m em ories” laid dow n by t h e
storage p rocess t h u s bear less resem blan ce to a
docum en tary film th an to a subjectively colored
recon stru ction of even t s. In su m m ary, LTM sh ou ld
be th ou gh t of as a dyn am ic process, w h ich ch an ges
over th e years an d often becom es in creasin gly ab-
st ract, but n on eth eless rem ain s capable of storin g
vivid an d detailed traces of certain experien ces,
particu larly th ose th at are of person al im portan ce.
Memory Dysfunction—the Amnestic
Syndrome and Its Causes
As already m en tion ed on p. 206, n orm ally
fu n ction in g m em ory, particu larly of th e declara-
tive type, depen ds above all on th e in tegrity of th e
h ippocam pu s an d its fiber con n ection s. Fiber p ro-
jection s from th e am ygdala to th e orbitofron tal
cortex also play an im p ortan t role.
Lesion s or illn esses of th e brain involvin g th ese
im portan t stru ctures an d regu latory circu its can
produce an am n estic syn drom e.
General definition of the amnestic syndrome. A
patien t is said to be su fferin g from an am n est ic
syn drom e w h en t h ere is a specific (i.e., isolated or
predom in an t) im p airm en t of th e ability to lay
dow n n ew m em ories an d to recall in form ation
stored before th e on set of th e problem (antero-
grade an d retrograde amnesia, respectively). In an
isolated (p ure) am n estic syn drom e, oth er m en tal
abilities, su ch as lan gu age, logical th in kin g, an d
problem -solvin g beh avior, are n ot im p aired. Am -
nestic syn drom es m ain ly affect LTM an d largely
spare STM, as can be dem on strated by testin g th e
patien t ’s digit or block span ; procedu ral m em ory,
i.e., th e learn in g of beh avioral sequ en ces, also re-
m ain s essen tially in tact. Am n estic syn drom es are
com m on ly accom p an ied by person alit y ch an ges or
abn orm alities of drive, e.g., in th e con text of Kor-
sakoff syn drom e, or after bilateral th alam ic in farc-
tion (cf. Case Presen tation 3, p. 211).
The differential diagnosis of the amnestic syndrome
from dementia is of m ajor clin ical im p ortan ce, e.g.,
w ith respect to Alzh eim er disease, a com m on cause
of dem en tia. Dem en tia involves n ot on ly am n esia
bu t also addit ion al focal n eu ropsych ological defi-
cits, such as aph asia an d agn osia, as w ell as an overall
declin e in cogn itive perform an ce, w h ich is typically
reflected by w orsen in g IQ scores.
Causes of the amnestic syndrome. Mem ory distu r-
ban ces can arise eith er acu tely or slow ly an d pro-
gressively, depen din g on th e n atu re of th e u n derly-
in g brain illn ess.
Mem ory can be im paired by traum atic brain in-
jury, hem orrhage, ischem ia, degenerative processes
such as Alzh eim er disease, an d variou s typ es of
m etabolic encephalopathy, in clu din g th e Wern icke–
Korsakoff syn drom e. Mem ory im pairm en t m ay
also be iatrogen ic, arisin g, for exam ple, after a n eu -
rosurgical procedure in th e tem poral lobe as treat-
m en t for m edically in tractable epilepsy, or after
electroconvu lsive t h erapy for severe depression .
It h as been convin cin gly sh ow n th at un ilateral
dam age of th e stru ctures an d regu latory circu its
subservin g m em ory can p rodu ce “lateralized”
m em ory deficits: left-sided lesion s im p air verbal
m em ory, righ t-sided lesion s im pair visu al
m em ory, an d bilateral lesion s im pair both . Wh en
th e tw o m ajor fiber path w ays involved in m em ory
(cf. p. 206) are sim u ltan eou sly in terrupted in ex-
perim en tal an im als, severe an d persisten t am n esia
resu lts. If on ly on e of t h em is in terru pted, th e en su -
in g am n esia h as been reported to be relatively m ild
an d tran sien t.
Posttraum atic am nesia. Am n esia after a traum atic
brain in ju ry usually con sists of both an terograde
am n esia (th e in ability to rem em ber even ts th at
took place after th e in jury) an d retrograde am n esia
(th e in ability to rem em ber even ts th at took place
before it ). An terograde an d retrograde am n esia af-
fect variable p eriods of tim e after an d before th e
in ju ry, an d th ey can also be in com plete, leavin g so-
called islands of m em ory in betw een am n estic
m em ory gaps. Person s sufferin g from retrograde
am n esia u su ally h ave bet ter recall for even ts th at
took place in th e distan t past. Organ ic disturban ces
of m em ory, u n like psych ogen ic disturban ces, u su -
ally h ave both an terograde an d retrograde com -
pon en ts, w h ich can im prove to a variable exten t,
an d som etim es even recover fu lly. An terograde

an d retrograde am n esia m ay be accom pan ied by
oth er n europsych ological abn orm alities, dep en d-
in g on th eir u n derlyin g cau se.
Other diseases causing amnesia. In prin cip le, any
brain illn ess or in ju ry th at affects th e structu res
subservin g m em ory bilaterally w ill produ ce an
am n estic syn drom e. Th e follow in g con dition s are
of particu lar clin ical im portan ce:
¼ Herpes sim plex encephalitis, w h ich preferen -
tially involves lim bic structu res an d u sually
produ ces bilateral lesion s of th e m esiobasal
tem poral lobes an d cin gulate gyri
Case Presentation 2: Bila tera l Media l Tempora l Dysfunction due to Vira l Infection
This 11-year-old girl suffered from increasingly severe head-
aches, nausea, and vom iting for two weeks, and then be-
cam e confused. At tim es, she could no longer find her way
around the apartm ent in which she lived; she spoke little,
and, when she spoke, she m ade no sense. Her pediatrician
referred her to the hospital, and she was adm itted.
On adm ission, the patient could not rem em ber any new in-
form ation for m ore than a few m inutes. She was thus
suffering from severe anterograde am nesia. No other focal
a b
Fig. 7.4 An 11-year-old girl w ith herpes simple x en-
cephalitis. a and b The coronal T2-weighted im ages reveal
bilateral hyperintense signal abnorm alities in the m edial
portions of the tem poral lobes. The hippocam pal form a-
Functions of the Lim bic System · 209
7
¼ Thalam ic infarction, w h ich , because of th e n a-
tu re of th e th alam ic blood su pply, is often bi-
lateral
¼ Hem orrhage or infarction of the septal nuclei
after ruptu re an d/or n eu rosu rgical treat m en t of
a saccu lar an eu rysm of th e an terior cerebral
artery
¼ Lesions of the splenium of the corpus callosum
(eith er trau m atic or isch em ic), w h ich com -
m on ly also involve th e im m ediately u n derlyin g
com m issu re of th e forn ices (psalteriu m )
Three of th ese con dition s are illustrated in Case
Presen tat ion s 2, 3, an d 4, below.
neurological deficits were noted. The initial m agnetic reso-
nance im ages revealed edem a of the tem poral lobes and
cingulate gyri bilaterally (Fig. 7.4). Later im ages additionally
revealed hem orrhages in these areas. Serological testing
showed the cause of the am nestic syndrom e to be a herpes
sim plex infection of the brain. The patient’s m em ory im -
pairm ent im proved slowly after antiviral treatm ent, but she
nonetheless had to repeat the sixth grade.
tions are swollen bilaterally. The pathological process also
extends into the left thalam us, lateral tem poral cortex, and
insula.
Fig. 7.4 c–e
7 210 · 7 Lim bic System

c d

Fig. 7.4 c–e c and d The axial proton-den-

sity-weighted and T2-weighted im ages re-
veal bilateral m edial tem poral signal abnor-
m alities, as well as very unusual-appearing
abnorm alities in the left thalam us (c) and
splenium of the corpus callosum (d). e The
contrast-enhanced axial T1-weighted
im age reveals an intact blood – brain bar-
rier, as is typically found in the early stage
of herpes sim plex encephalitis.

e

Case Presentation 3: Bila tera l Tha la mic Infa rction
When this 54-year-old businessm an and his wife returned
hom e from a celebration they had attended with friends,
she was surprised to find him sleepy and abnorm ally in-
different. He also seem ed to have suddenly “forgotten”
that it was late at night, repeatedly m um bling questions
such as, “Do I have to get up now?” He asked her where he
was, even though he was sitting in his own living room . He
could no longer rem em ber any individual details of the
evening, or even that a celebration had taken place. He did
not rem em ber having m ade a speech. At first, his wife at-
tributed his strange behavior to the influence of a m oderate
am ount of alcohol, com bined with an oncom ing cold. In
the m orning, however, finding that the problem had only
worsened overnight, she took him to the hospital.
a b
Fig. 7.5 Bilateral thalamic infarction. a The diffusion-
weighted MR im age reveals two acute ischem ic lesions in
the m edial rostral portion of the thalam us on both sides.
b The T2-weighted im age with FLAIR sequence still reveals
the ischem ic lesions, though m uch less clearly than the dif-
Functions of the Lim bic System · 211
7
On adm ission, the m ost rem arkable im m ediate findings
were the patient’s apathy and lack of drive. It was very diffi-
cult to get him to undress for the exam ination or perform
tasks of any other kind. He also fell asleep several tim es
while being exam ined. He could give no m ore than cursory
inform ation about his person, and was not oriented at all to
tim e or place.
The m agnetic resonance im ages revealed bilateral hyperin-
tense lesions in the dorsom edial thalam us, indicating
ischem ia in the territory of the thalam otuberal arteries (ar-
teries of Percheron) bilaterally; these arteries often arise
from a com m on, unpaired trunk (Fig. 7.5). The patient’s
neurological deficits resolved relatively rapidly, and he was
able to return to work a few m onths later.
fusion-weighted im age. The patient was confused and
m oved during the study. A diffusion-weighted im age can
be obtained in 4 seconds, but a T2-weighted im age takes
3 – 5 m inutes.
7 212 · 7 Lim bic System

Case Presentation 4: Bila tera l Lesions Involving the Septa l Nuclei a nd the Frontobasa l Cortex
This 61-year-old housewife had prepared lunch for herself
and her husband as usual. After the m eal, she suddenly
began acting strangely: she could no longer carry on a co-
herent conversation with him , continually changed the sub-
ject, and asked him three tim es whether he had already had
his m idday nap. She seem ed to take no regard of his an-
swers, or to forget them at once. When he tested her by
asking her the date, she could not give the correct day of
the week or the correct m onth, or even rem em ber what
year it was. She also seem ed to have undergone a change of
personality, at tim es reacting aggressively when he ap-
proached her in a friendly way, and at tim es seem ing totally
apathetic. Furtherm ore (he reported), she began m aking
coffee again and again, at brief intervals, even after he ob-
jected, each tim e, that she had just had her coffee a few
minutes before. When he confronted her about her unusual
behavior and her apparent deficits, she said, in stereotypic
fashion, “What do you want from m e? I’m perfectly all
right.” He succeeded with difficulty in bringing her to the
hospital, over her objections.
The adm itting physician diagnosed an am nestic syndrom e,
an affective disturbance with alternating aggressiveness
and apathy, and a lack of insight into the illness (anosog-
nosia). A further finding, on neurological exam ination, was
marked perseveration (i.e., the involuntary and apparently
Fig. 7.6 Bilateral lesions involving the septal nucle i. This
purposeless repetition of actions and behaviors): while
proton-weighted MR im age reveals signal abnorm alities in
being exam ined, for exam ple, the patient could not stop
the anterior portion of the corpus callosum and in both for-
com bing her hair in front of a m irror.
nices. There is also a large signal abnorm ality in the left
Magnetic resonance im aging (Fig. 7.6) and subsequent
basal ganglia.
cerebral angiography revealed acute infarction of part of
the corpus callosum as well as of the fornices, left basal
ganglia, and frontal cortex, caused by occlusion of perforat-
ing branches of the anterior com m unicating artery.
 8

8 Basal Ganglia
Preliminary Remarks on
Terminology . . . . . . . . . . . . . . . . . . . . . 214
The Role of the Basal Ganglia in the
Motor System: Phylogenetic Aspects . 214
Components of the Basal Ganglia and
Their Connections . . . . . . . . . . . . . . . . . 215
Function and Dysfunction of the
Basal Ganglia . . . . . . . . . . . . . . . . . . . . . 219
8 214
8 Basal Ganglia
Th e basal gan glia are a part of th e m otor system .
Th e prin cipal n u clei of th e basal gan glia are t h e
caudate nucleus, th e putamen, an d th e globus pal-
lidus, all of w h ich lie in th e su bcortical w h ite m at-
ter of th e telen cep h alon . Th ese n u clei are con -
n ected to each oth er, an d to th e m otor cortex, in
com p lex regulatory circu its. Th ey exert both exci-
tatory an d in h ibitory effects on th e m otor cortex.
Th ey p lay an im portan t role in th e initiation an d
modulation of movement an d in th e control of
Preliminary Remarks on
Terminology
Th e h ierarch ically upp erm ost cen ter for th e con -
trol of m ovem en t is th e cerebral cortex, w h ose sig-
n als are tran sm itted by th e pyram idal path w ay to
th e m otor cran ial n erve n u clei an d to th e an terior
h orn cells of th e sp in al cord (pyramidal system). A
n u m ber of oth er structu res in th e cen tral n ervou s
system participate in th e in itiation an d m odu lation
of m ovem en t. Th e m ost im p ortan t of t h ese “acces-
sory m otor cen ters” are th e basal gan glia, a set of
subcort ical n uclei located w it h in th e deep w h ite
m atter of th e telen ceph alon . Th e pyram idal system
w as lon g regarded as th e “m ajor” system for th e
con trol of m ovem en t, as it provides th e m ost direct
an d m ost rapid con n ection betw een th e cortex an d
th e m otor n eu ron s of th e brain stem an d spin al
cord. All oth er stru ctu res playin g a role in m ove-
m en t w ere relegated to th e so-called “extrapy-
ramidal system.” Th is term is m isleadin g, h ow ever,
becau se th e pyram idal an d extrapyram idal sys-
tem s do n ot, in fact, operate separately. Rath er,
th ey are subu n its of a single, in tegrated m otor sys-
tem an d, as su ch , are closely lin ked to each oth er,
both st ru ctu rally an d fun ction ally. Th u s, th ere are
exten sive con n ection s, for exam ple, bet w een th e
m otor cortex an d th e striatu m , an im portan t n u -
cleu s w ith in th e basal gan glia. Th e term “extrapy-
ram idal system ” is n ow obsolete an d w ill be u sed
on ly rarely in th is book. In stead, w e w ill speak of
n orm al an d abn orm al fu n ction of th e basal gan glia.
muscle tone. Lesion s of th e basal gan glia, an d of
oth er, fun ction ally related n uclei, su ch as th e su b-
stan tia n igra an d th e su bth alam ic n u cleu s, can
produ ce eith er an excess or a deficien cy of m ove-
m en t-related im pulses, an d/or path ological al-
teration s of m uscle ton e. Th e m ost com m on dis-
ease of th e basal gan glia is Parkin son disease,
w h ich is ch aracterized by th e clin ical triad of rigid-
ity, akin esia, an d trem or.
The Role of the Basal Gang lia in
the Motor System: Phylogenetic
Aspects
Th e corpu s striatu m is an im portan t con trol cen ter
for t h e m otor system . We w ill briefly con sider it s
phylogen etic developm en t in th is sect ion in order
to m ake its fun ction an d an atom ical con n ection s
easier to u n derst an d.
Th e phylogen etically oldest m otor cen ters in
th e cen tral n ervous system are th e spin al cord an d
th e prim itive apparatus of th e reticular form ation
in th e m idbrain tectum . Over th e course of phylo-
geny, th e paleostriatu m (globus pallidus) devel-
op ed n ext, an d th en th e n eostriatu m (caudate nu-
cleus an d putam en), w h ich en larged in parallel
w ith th e cerebral cortex. Th e n eostriatum is par-
ticu larly w ell developed in h igh er m am m als, in -
clu din g h u m an s. As th e phylogen etically m ore re-
cen t stru ctu res grew larger, th e older stru ctures
cam e u n der th eir in fluen ce to an in creasin g ex-
ten t. In phylogen etically older species, th e older
n eu ral cen ters are p rim arily respon sible for th e
m ain ten an ce of n orm al m u scle ton e an d for th e
m ore or less au tom atic con trol of locom otion .
As th e cerebral cortex developed, th e phylo-
gen etically older m otor cen ters (paleostriatu m an d
n eostriatu m ) cam e in creasin gly un der th e con trol
of th e n ew m otor system , i.e., th e pyram idal sys-
tem . Wh ile m ost m am m als, in cludin g th e cat, can
still w alk w ith out m u ch difficu lty after th e cerebral
cortex is rem oved, h u m an s are en tirely depen den t
on an in tact pyram idal system . Hu m an phylo-
gen etic developm en t h as reach ed th e poin t t h at
 Com ponents of the Basal Ganglia and Their Connections · 215
8
th e older n eu ral cen ters can n o lon ger com pen sate
for th e fun ct ion al loss of t h e n ew on es. Yet, even in Thalamus
h u m an s, a spastically p aralyzed lim b can still be
seen to m ake certain involu n tary m ovem en ts, Globus
called associated m ovem en ts, w h ich are gen erated pallidus
by th e older m otor cen ters. Putamen
Caudate
nucleus
Am ygdala
Components of the Basal
Ganglia and Their Connections
Nuclei Fig. 8.1 Topographical relationships of the basal gan-
glia (in red)
Th e basal gan glia in clu de all of th e fun ct ion ally in -
terrelated n u clei w ithin th e deep w h ite m atter of
th e telen ceph alon th at are em bryologically
derived from t h e gan glion ic em in en ce (an terior
port ion of th e telen ceph alic vesicle). Th e m ajor n u -
clei of th e basal gan glia are th e caudate nucleus, th e
putam en, an d p art of th e globus pallidus (Figs. 8.1
an d 8.2); oth er n u clei th at are con sidered part of
th e basal gan glia on em bryological grou n ds are th e
claustrum (Figs. 8.5 an d 8.6) an d th e am ygdala
Head of the
(Figs. 8.1 an d 8.2). Th e am ygdala h as already been caudate nucleus
discu ssed in con n ection w it h th e lim bic system Putam en
Lateral
(p. 205). Like th e claustrum , w h ose fun ction is n ot ventricle
Subthalamic
precisely kn ow n , th e am ygdala h as n o direct nucleus Thalam us

fu n ction al con n ection to th e rem ain der of th e Amygdala

Tail of the
basal gan glia. Th ese tw o structu res w ill n ot be dis- caudate nucleus
cu ssed any fu rth er in th is ch apter.
Fig. 8.2 Late ral view of the basal ganglia and ventricu-
lar system
Th e caudate nucleus form s part of th e w all of th e
lateral ven tricle an d, like it, h as an arch ed sh ap e,
du e to th e rotation of th e telen ceph alon du rin g
Putamen
em bryon ic developm en t (cf. p. 8). Th e h ead of th e
Caudate
cau date n u cleus form s th e lateral w all of th e lateral nucleus
ven tricle; it s tail form s th e roof of th e in ferior h orn
of th e lateral ven tricle in th e tem p oral lobe, ex- X
XX
ten din g as far forw ard as th e am ygdala, w h ich lies
at th e an terior en d of th e in ferior h orn (Fig. 8.2).
Th e caudate n u cleu s can th erefore be seen in tw o Amygdala Thalamus
separate location s on som e coron al section s (cf.
Figs. 8.3 – 8.8, especially Fig. 8.7), in t h e lateral w all
of th e body of th e lateral ven tricle as w ell as in th e Fig. 8.3 Lateral view of the basal ganglia. X, XX: horizon-
roof of t h e in ferior h orn . Th e rost ral portion (h ead) tal planes of section for Fig. 8.4. 1–4: coronal planes of sec-
of th e cau date n ucleu s is con tin uou s w it h th e pu - tion for Figs. 8.5–8.8.
tam en .
som ew h at beyon d it both rostrally an d cau dally.
Th e putamen lies lateral to th e globu s pallidus (or Th e pu tam en an d globu s pallidus are separated by a
pallidu m , so called because of its relatively pale th in layer of w h ite m atter called th e m edial m edu l-
coloration ), coverin g it like a sh ell an d exten din g lary lam in a.
8 216 · 8 Basal Ganglia

Fig. 8.4 Tw o horizontal

Thalam us sections through the
basal ganglia (for planes
Globus pallidor Tail of the caudate nucleus of section, see Fig. 8.3)
Putam en Choroid plexus of
the lateral ventricle
Head of the
caudate nucleus Splenium of the
corpus callosum
Lateral
ventricle
Genu of the
corpus
callosum X

XX
Vermis
Superior
and inferior
colliculi
Pineal body
Inferior horn of
the lateral ventricle

Corpus Lateral
callosum ventricle
Corpus Lateral Head of the Hypothalamus
callosum ventricle caudate nucleus
Body of the
caudate nucleus

Internal
Internal capsule
capsule
Putam en

Claustrum

Putam en
Insula
Insula

Claustrum
Globus
pallidus
Septum Anterior
pellucidum com missure
Septum
pellucidum Optic recess of
the third ventricle Olfactory area
Optic chiasm

Fig. 8.5 Coronal section 1 through the basal ganglia (for Fig. 8.6 Coronal section 2 through the basal ganglia (for
planes of section, see Figs. 8.3 and 8.4) planes of section, see Figs. 8.3 and 8.4)

Th e caudate n ucleus an d p utam en are con n ected altern ative n am e corpus striatum (striped body), or
by n u m erou s sm all bridges of gray m atter, w h ich striatum for sh ort (Fig. 8.2). Th e striation arises
are seen as stripes in an atom ical section s. Th ese du rin g developm en t, w h en th e fibers of th e in ter-
tw o n u clei togeth er h ave, th erefore, been given t h e n al capsu le grow th rou gh th e origin ally un iform
 Com ponents of the Basal Ganglia and Their Connections · 217
8
Splenium of the
Corpus Fornix Choroid plexus of the corpus callosum
callosum lateral ventricle Great cerebral v. (of Galen)

Thalam ostriate v. Tapetum

Body of the
caudate nucleus Posterior horn of
the lateral ventricle
Thalamus

Internal
capsule

Claustrum
Putam en
Globus Nucleus of
pallidus the inferior
colliculus
Tail of
the Superior
caudate cerebellar
nucleus peduncle

Mam illary Cerebellum

body
Hippocam pus; Cerebral aqueduct
inferior horn of
Mam illo- Middle cerebellar
the lateral ventricle
thalam ic tract peduncle
Optic tract
Subthalam ic Periaqueductal Medial
nucleus gray matter lem niscus

Fig. 8.7 Coronal section 3 through the basal ganglia (for Fig. 8.8 Coronal section 4 through the basal ganglia (for
planes of section, see Figs. 8.3 and 8.4) planes of section, see Figs. 8.3 and 8.4)

basal gan glion . Ven t ral segm en ts of t h e striatu m are
also called th e n u cleu s accum ben s.
Globus pallidus. Th e th ird m ajor n u cleus of th e
basal gan glia is m ade u p of an in tern al an d an ex-
tern al segm en t (pars in tern a an d pars extern a). Be-
cau se th e globu s pallidus is phylogen etically older
th an th e oth er n uclei, it is also called th e paleost ri-
atu m . Part of it is, em bryologically speakin g, a
com pon en t of th e dien ceph alon . Th e pu tam en an d
globu s p allidu s are collectively term ed th e len-
tiform or lenticular nucleus (len s-sh aped n u cleu s).
Associated nuclei. Fu rth er n u clei t h at are closely
fu n ction ally related to th e basal gan glia in clu de
tw o m idbrain n u clei—th e substantia nigra (recip-
rocally con n ected to t h e striatum ) an d th e red nu-
cleus—an d on e dien ceph alic n u cleu s, th e sub-
thalamic nucleus (recip rocally con n ected to th e
globus pallidu s). Th e globu s pallidus cau dally
borders th e rostral p ortion (red zon e) of th e su b-
stan tia n igra. Th e pallidu m , substan tia n igra, an d
red n u cleus con t ain large am ou n ts of iron . Th e
dark pigm en tation of th e su bstan tia n igra (“black
substan ce”) is du e to it s h igh m elan in con ten t.
Connections of the Basal Gang lia
Th e n eu ral con n ection s of th e basal gan glia w ith
on e an oth er an d w ith oth er region s of th e brain are
n ot yet com p letely u n derstood. Th e m ajor afferen t
an d efferen t path w ays w ill be described in th is
section .
Afferent Pa thways
Afferent pathw ays to the corpus striatum. Th e cor-
pu s striat um receives afferen t inpu t from exten sive
areas of th e cerebral cortex, particu larly th e motor
areas of the frontal lobe, i.e., Brodm an n areas 4,
6aα, an d 6a . Th ese cortical afferen ts are derived
from project ion n euron s of th e cerebral cortex (py-
ram idal cells of th e fifth layer of th e cortex), are
glutam atergic, run ipsilaterally, an d are topically or-
ganized. Th ere are probably n o reciprocal fibers
8 218 · 8 Basal Ganglia

run n in g from th e corp us striatu m back to th e cor-
tex. A fu rth er poin t-to-poin t afferen t inpu t to th e
corp us striatum is derived from th e centromedian
nucleus of the thalamus, an d is probably excitatory.
Th is afferen t path w ay tran sm its im pu lses from th e
cerebellu m an d th e m idbrain reticular form ation
to th e striatu m . Th e substantia nigra sen ds
dopam inergic afferen t fibers to th e st riat um , w h ose
loss is th e cau se of Parkin son disease (see p. 219 ff).
Fin ally, th e st riatu m also receives a serotonergic
inpu t from th e raphe nuclei.
Other afferent pathw ays. Th e globu s pallidu s
derives its m ajor afferen t input from th e corpu s
striatu m an d receives n o direct afferen t fibers from
th e cerebral cortex. Cortically derived afferen t
fibers do, h ow ever, travel to th e su bstan t ia n igra,
red n ucleu s, an d su bth alam ic n ucleu s.
Efferent Pa thwa ys
Efferent pathw ays of the corpus striatum. Th e
m ajor efferen t p rojection s of th e corpu s striatu m
go to th e external an d internal segments of the
globus pallidus. Fu rth er efferen t fibers travel to th e
pars com p acta an d pars reticu lata of th e substantia
nigra. Th e cells of origin of th e striatal efferen t
fibers are GABAergic spiny n euron s, th e m ost com -
m on cell type in th e striatu m .
Efferent pathw ays of the globus pallidus. Th e
m ajor con tin gen t of efferen t fibers ru n s to th e
thalamus, w h ich , in tu rn , projects to th e cerebral
cortex, com pletin g a feedback loop.
Th e functional interpretation of th e afferen t an d
efferen t projection s of t h e basal gan glia requ ires
con sideration of th e particu lar n eurotran sm itter
su bstan ces an d receptors involved, an d of th e
types of n eurological deficit th at are produ ced
w h en certain path w ays cease to fu n ction n orm ally.
Th us, Parkin son disease is ch aracterized by
degen eration of th e dopam in ergic n euron s of th e
su bstan tia n igra th at p roject to th e corpu s stri-
atu m . Th e clin ical deficits observed in Parkin son
disease provide a clu e to th e probable fu n ction s of
th e n igrostriatal system in n orm al in dividuals.
Pa rticipa tion of the Basa l Ga nglia in
Regula tory Circuits
Th e basal gan glia an d th eir afferen t an d efferen t
con n ection s are in tegral parts of com plex regula-
tory circuits th at excite an d in h ibit th e n eu ron s of
th e m otor cortex. Neu ral tran sm ission w ith in th ese
circuits can be ch aracterized in term s of th e an a-
tom ical course alon g w h ich th e im pulses travel, as
w ell as t h e particu lar n eu rot ran sm itters an d recep-
tors th at are involved at each syn apse. On e of th e
m ore im portan t circuits conveys im pu lses alon g

Fig. 8.9 The dire ct and

indirect basal ganglia
pathw ays. a The norm al
Cortex Cortex Cortex
situation (green = excita-
tion, red = inhibition).
GPe = globus pallidus,
external segm ent.
Striatum Striatum Striatum
STN = subthalam ic nucleus.
GPi = globus pallidus, inter-
nal segm ent. Th = thalam us.
SNg = substantia nigra.
b The situation in Parkinson
disease (untreated). c The
situation in Parkinson dis-
ease during treatm ent with
subthalam ic stim ulation
(i.e., blockage of neural
activity in the STN).
Reproduced with perm ission
from Elsevier. from Bergm an
H, et al. Physiological
aspects of inform ation pro-
cessing in the basal ganglia
of norm al and parkinsonian
prim ates. Trends Neurosci.
1998;21(1):32–38.)

tw o separate pat h s from th e cortex, via th e corpu s
striatum , to th e globu s pallidu s, an d th en to th e
th alam u s an d back to th e cortex (Fig. 8.9). In addi-
tion to th is m ajor regulatory circuit, th ere are oth er
feedback loops th at w ill n ot be explicitly described
in th is book.
Cortico -striato -pallido -thalamo -cortical pathw ay.
Th e m otor an d sen sory cortex sen ds a topograph i-
cally organ ized projection to th e striatum th at u ses
th e excitatory n eu rotran sm itter, glu tam ate. Bey-
on d th e striatu m , th e basal gan glion ic circu it splits
in to tw o parts, w h ich are kn ow n as th e direct an d
in direct path w ays.
Direct pathway. Th e direct path w ay is GABAergic
an d ru n s from th e striatu m to th e internal pallidal
segm ent. Substan ce P is used as a co-tran sm itter.
From th e p allidum , th e path w ay proceeds to th e
glutam atergic projection n eu ron s of th e thalam us,
w h ich com plete th e loop back to the cerebral cortex
(Fig. 8.9).
Indirect pathway. Th e in direct path w ay, w h ich uses
th e n eu rotran sm itters GABA an d en keph alin , run s
from t h e st riat um to th e external pallidal segm ent.
From th is poin t, a fu rth er GABAergic p rojection
proceeds to th e subthalam ic nucleus, w h ich , in
tu rn , sen ds a glutam atergic projection to th e inter-
nal pallidal segm ent. Th e furth er cou rse of th e in -
direct path w ay is iden tical to th at of th e direct
path w ay, i.e., from the thalam us back to the cerebral
cortex (Fig. 8.9).
It follow s from th e com bin ation of in h ibitory an d
excitatory n eu rot ran sm it ters u sed by th ese tw o
path w ays th at the overall effect of stim u lation of
th e direct path w ay on th e cerebral cortex is exci-
tatory, w h ile th at of stim u lation of th e in direct
path w ay is in h ibitory (Fig. 8.9). Th e dopam in ergic
projection from th e substan tia n igra (pars com -
pact a) plays a m odu latin g role in th is system .
Function and Dysfunction of the
Basal Ganglia
Normal functions of the basal ganglia. Th e basal
gan glia participate in m any m otor processes, in -
clu din g th e exp ression of em otion , as w ell as in th e
in tegration of sen sory an d m otor im pu lses an d in
Function and Dysfunction of the Basal Ganglia · 219
8
cogn itive p rocesses. Th e basal gan glia carry out
th eir m otor fu n ction s in directly th rough th e in -
flu en ce th ey exert on th e prem otor, m otor, an d sup-
plem en tary areas of th e cerebral cortex. Th e m ajor
fu n ction al roles of th e basal gan glia con cern t h e ini-
tiation an d facilitation of volun tary m ovem en t, an d
th e sim u ltan eou s su ppression of u nw an ted or in -
volun tary in flu en ces th at m igh t disturb t h e sm ooth
an d effective execu tion of m ovem en t.
Moreover, th e basal gan glia apparen tly u se pro-
p rioceptive feedback from th e periph ery to com -
p are th e m ovem en t pattern s or program s gen erated
by th e m otor cortex w it h t h e m ovem en ts th at are
act ually in itiated, so th at m ovem en t is subject to
on goin g refin em en t by a con tin uous servo-con trol
m ech an ism .
Typical deficits. Lesion s of th e basal gan glia can
p rodu ce com plex m ovem en t disorders an d cogn i-
tive disturban ces of variou s types depen din g on
th eir site an d exten t.
¼ Clin ical disorders involvin g th e basal gan glia
m ay presen t w ith a deficien cy of m ovem en t
(hypokinesia) or
– an excess of m ovem en t (hyperkinesia,
chorea, athetosis, ballism).
¼ Abnormalities of muscle tone com m on ly ac-
com p any abn orm alities of th e above tw o types,
– bu t can also be th e predom in an t or sole
m an ifestation of basal gan glia dysfun ction
(dystonia).
W ilson disease is a good exam p le of a basal gan glia
disorder, w h ere a com bin ation of all of th e above
m an ifestation s can be seen (cf. Case Presen tation 4,
p. 224) becau se of variable an d diffu se affection of
th e differen t n u clei an d subsystem s. In th e re-
m ain der of th is ch apter, w e w ill discu ss th e m ajor
disorders th at m ain ly affect on e particular su bsys-
tem of th e basal gan glia.
Clinical Syndromes of Basal Ganglia
Lesions
Pa rkinsonism
Etiology and pathogenesis. In idiopathic Parkinson
disease, th e dopam in ergic n igrostriatal p rojection
degen erates (see p. 218). Con sequ en tly, th e GABA-
ergic activity of th e striatal n eu ron s is en h an ced,
an d t h ere is th u s an excess of activity in th e in -
direct basal gan glia loop. At th e sam e tim e, th e
8 220 · 8 Basal Ganglia

Table 8.1 Confirmed monogenic forms of Parkinson disease*

Locus Inherita nce Gene Muta tions/Comments

PARK1 AD α-Synuclein Rare, 3 m utations: A53T, A30P, E54K

PARK2 AR Parkin 100 m utations, point m utations, indels, and exon rearrangem ents

PARK4 AD α-Synuclein Duplications and triplications of the SNCA gene

PARK6 AR PINK1 20 m utations, point m utations, indels, and exon rearrangem ents

PARK7 AR DJ-1 Rare, 3-point m utations

PARK8 AD LRRK2 Six confirm ed point m utations: R1441G, R1441C, N1437H, Y1699C, G2019S,
I2020T

PARK9 AR ATP13A2 Com plex phenotype with parkinsonism , spasticity, and dem entia

PARK15 AR FBX07 Rare, com plex phenotype

GBA Multiple rare variants of interm ediate-effect strength

Table 8.2 Risk variants for PD confirmed in GWAS w ith genome -w ide significance*

Locus Gene Varia nts/Comments

PARK1 α-Synuclein REP1 polym orphism , SNPs in 3’-UTR

PARK8 LRK2 Sm all effect in whites, stronger in Asians

MAPT H2 haplotype is protective

PARK16 Stronger effect in Asians

HLA HLA-DRA Noncoding variants m ay act via regulation of expression of HLA-DR and HLA-DQ

GAK Differential expression in SN of PD patients has been observed

* Reproduced with permission from Wiley Online Library, from Gasser T, Hardy J, Mizuno Y. Milestones in PD Genetics. Movement
Disorders 2011;26(6):1042–1048.

subt h alam ic n ucleus also sh ow s in creased activit y
an d th u s excessively in h ibit s th e glutam atergic
n eu ron s of th e th alam u s. Th e overall effect is net
inhibition at the output of the basal ganglia loop
(Fig. 8.9b) an d, th erefore, reduced activation of cor-
tical m otor areas.
A ch aracteristic n europ ath ological h allm ark of
th e disease is in tracytop lasm ic in clusion bodies
called Lew y bodies. A m ajor com p on en t of Lew y bo-
dies is α-syn u clein . It is n ot yet kn ow n w h at role
th is protein p lays, if any, in th e path ogen esis of
sporadic (idiopat h ic) Parkin son disease. How ever,
in familial forms of Parkin son disease, w h ich repre-
sen t a sm all m in orit y of cases, m u tation s in several
differen t gen es h ave been foun d to cau se disease.
More th an 18 m u tation s an d addit ion al subscepti-
bility loci h ave been discovered so far. In terest-
in gly, m u tation s are also foun d in α-syn uclein , sug-
gest in g a direct pat h ological role in t h e degen era-
tion of dopam in ergic n euron s. Fam ilial form s u su -
ally sh ow earlier on set of disease an d specific clin i-
cal sym ptom s (Table 8.1, 8.2).
In addition to idiopath ic Parkin son disease, a
n eu rodegen erative con dition , th ere are also symp-
tomatic forms of parkinsonism th at are cau sed by
structu ral/in flam m atory lesion s of th e cen tral
n ervou s system , or by toxic in fluen ces. Parkin -
son ism can th u s be produ ced, for exam ple, by
m edication s (n euroleptics, an tiem etics, calciu m
an tagon ists, reserp in e-con tain in g an t ihyperten -
sive agen ts) as w ell as by en ceph alitis, isch em ic le-
sion s, in toxication s, an d m et abolic distu rban ces.
If typical parkin son ian m an ifestation s are seen
togeth er w ith oth er n eu rological deficits su ggest-
in g dysfu n ction of oth er cen tral n ervou s stru ctu res
beyon d th e basal gan glia, a Parkinson-plus

Case Presentation 1: Idiopa thic Pa rkinson Disease
A 59-year-old bank teller first realized while counting bank-
notes that he could not use his right hand norm ally. On re-
peated occasions, he counted off several notes at once in-
stead of a single note, so that the tally was incorrect. Mean-
while, his handwriting gradually becam e sm aller and less
legible, so that he could no longer perform his job effec-
tively. He com plained of right shoulder pain and cram ps in
the right arm and was treated unsuccessfully by an or-
thopedist for presum ed arthritis of the shoulder. As tim e
went on, his facial expression becam e sparse (hypom im ia)
and a resting trem or of the right hand developed, at a
frequency of about 8 Hz. None of the patient’s relatives had
ever suffered from sim ilar problem s.
His fam ily physician referred him to a neurologist, whose
exam ination revealed cog-wheel rigidity of the lim bs, worst
in the right arm , a m ildly stooped posture, and a sm all-
stepped gait with reduced arm swing on the right. The
patient took an excessive num ber of steps while turning
around. There were no autonom ic deficits, and his m ental
status was norm al.
ACTscan with intravenous contrast and an EEG were norm al.
The patient was given the diagnosis of idiopathic Parkinson
disease of m ixed type.
syndrome is said to be presen t. Th ere are a n u m ber
of distin ct Parkin son -plu s syn drom es. For ex-
am p le, parkin son ism , vertical gaze palsy, an d
m arked n uch al rigidity m ake u p th e ch aracteristic
clin ical triad of Steele–Richardson–Olszew ski syn-
drom e, also kn ow n as progressive supranuclear
palsy. On t h e oth er h an d, severe au ton om ic dys-
fu n ction , postu ral in stability, an d deficit s involvin g
oth er com pon en ts of th e cen tral n ervou s system
(e.g., pyram idal tract sign s) are seen in m ultiple
system atrophy.
Clinical manifestations. Loss of dopam in ergic affer-
en t s in th e striatu m leads to redu ced volu n tary
m ovem en ts (hypokinesia), con tin u ally elevated,
w axy m u scle ton e (rigidity), an d oscillatin g m ove-
m en ts at a frequen cy of 4 – 6 Hz w h en th e lim bs are
held at rest (restin g tremor) (see Case Presen tat ion
1, p. 221).
Parkin son disease h as three clinical subtypes
th at are defin ed by th e m otor m an ifestation s th at
predom in ate in each type:
¼ Patien ts w ith th e akinetic-rigid type of Parkin -
son disease can be recogn ized at an early stage
by t h eir in creasin g poverty of m ovem en t, in -
clu din g a lack of accessory m ovem ents of the
arm s, slow sh u fflin g gait , a lack of facial expres-
sion (hypom im ia), an d a ch aracteristic stooped
posture. Som e patien ts in itially com p lain of
Function and Dysfunction of the Basal Ganglia · 221
8
Pharm acotherapy with L-dopa and a dopam ine agonist
brought a m arked im provem ent in the patient’s rigidity,
though his trem or rem ained essentially unchanged. He was
able to return to work at the bank, taking up the sam e job
as before.
Som e four years after the onset of sym ptom s, the m ove-
m ent disorder took a turn for the worse, despite an increase
in the dose of m edication. The patient now had difficulty
turning in bed and began to suffer from seborrhea.
Two years later, he began to experience fluctuations in the
effectiveness of L-dopa. The duration of the effect after
each dose becam e shorter, and he occasionally had involun-
tary excessive m ovem ents (dyskinesia). A change of m edi-
cations to controlled-release preparations of L-dopa and
dopam ine agonists with longer half-life brought no m ore
than a transient benefit. The patient finally underwent neu-
rosurgical treatm ent, with stereotactic im plantation of
deep brain electrodes for chronic stim ulation of the sub-
thalam ic nucleus. This resulted in a m arked im provem ent of
rigor and hypokinesia and a definite, but less than
com plete, im provem ent of trem or. These im provem ents
persisted even after the dose of L-dopa was significantly re-
duced.
sh ou lder st iffn ess (“frozen sh ou lder”), w h ich
m ay prom pt erron eous referral to an or-
th op edist before th e progressive cou rse of th e
disease h as revealed th e true diagn osis.
¼ Patien ts w ith tremor-dominant Parkin son dis-
ease su ffer m ain ly from th e low -frequ en cy rest
trem or, w h ich —like th e oth er m otor m an ifesta-
tion s—is often u n ilateral at th e on set of disease.
Parkin son ian trem or is often of th e pill-rollin g
type (see Case Presen tation 1).
¼ Patien ts w ith mixed-type Parkin son disease
sh ow a m ore or less equ al m an ifestation of
akin esia, rigidity, an d trem or.
Chorea —Huntington Disease
Etiology and pathogenesis. Th is disorder of auto-
som al dom in an t in h eritan ce is cau sed by an ex-
pan sion of CAG trin ucleotides w ith in th e h u n tin g-
tin gen e on ch rom osom e 4. Its h istopath ological
h allm ark is degen eration of th e m ediu m -sized
spiny en keph alin ergic/GABAergic n eu ron s of th e
striatum . Loss of th ese n eu ron s leads to in h ibition
of t h e in direct basal gan glia path w ay at its in it ial
stage. Th e en su in g in creased in h ibition of th e su b-
th alam ic n u cleus leads to redu ced in h ibition of th e
th alam ic glutam atergic n eu ron s, so th at th e fin al
resu lt is n et in creased activation of cortical m otor
n eu ron s.
8 222 · 8 Basal Ganglia
Case Presentation 2: Huntington Disease
At the age of 34 years, this skilled worker first noticed un-
controllable m otor restlessness affecting all four lim bs. His
co-workers m ade fun of him for dropping objects re-
peatedly, and eventually suspected him of being an alco-
holic. Within a year, he developed dysarthria: his speech be-
cam e abnorm ally soft, slurred, and hard to understand. He
paid less attention to his surroundings and lost interest in
his regular daily activities, which becam e increasingly slow
and cum bersom e. Ultim ately, he no longer took notice of
even the sim plest things, and forgot tasks that had been as-
signed to him just m inutes before. He was fired from his job
and rem ained unem ployed thereafter. Three m onths later,
at his wife’s urging, he consulted a m edical specialist.
Taking the fam ily history, the specialist learned that the
patient’s father had suffered from a sim ilar m ovem ent dis-
order from age 40 onward. The disease progressed until he
becam e totally dependent on nursing care and finally died
at age 54. No diagnosis was ever m ade.
The m ost prom inent finding on neurological exam ination
was involuntary m ovem ent of all parts of the body, particu-
a b
Fig. 8.10 Huntington disease. The axial T1-weighted (a),
axial T2-weighted (b), and coronal T2-weighted (c) m ag-
netic resonance im ages reveal not only global brain atrophy
(dilatation of the internal and external CSF spaces), but also
a reduction of the volum e of the basal ganglia (i.e., the pu-
Clinical manifestations. Hun tin gton disease is
clin ically ch aracterized by sh ort-lastin g involu n -
tary m ovem en ts th at affect m u ltiple m u scle
grou ps, seem in gly at ran dom (chorea or
choreiform hyperkinesia). Th e patien t at first tries
to in corporate th ese rapid m ovem en ts in to volu n -
tary m otor beh avior, such th at observers m ay n ot
realize t h at t h ese are t ru ly involun tary an d m ay,
in stead, perceive th e patien t as m erely clum sy or
fidgety. As th e disease progresses, h ow ever, hy-
perkin esia becom es in creasin gly severe an d diffi-
cu lt to sup press. Facial tw itch in g appears in th e
form of a grim ace, an d t h e patien t fin ds it ever
m ore difficult to keep th e lim bs at rest, or to keep
larly around the shoulder girdle and in the face. The
patient’s speech was soft, som ewhat slurred, and m ono-
tonous. His sensation and reflexes were norm al.
Ancillary studies were perform ed to rule out a m etabolic
disorder or other system ic cause of sym ptom atic involun-
tary m ovem ents. Magnetic resonance im aging of the head
(Fig. 8.10) revealed a loss of volum e of the head of the cau-
date nucleus on both sides, reflecting neuronal atrophy in
this area. Moreover, global brain atrophy was apparent, to a
degree that would not be expected at the patient’s age.
The diagnosis of Huntington disease was established by a
m olecular-genetic study, which showed an expansion of
CAG trinucleotide repeats in one allele of the huntingtin
gene; 51 repeats were found (norm al up to 38).
Pharm acotherapy with neuroleptic agents brought a tran-
sient im provem ent of the m otor m anifestations, attribu-
table to inhibition of dopam inergic neurotransm ission. The
disease continued to progress, however, so that the patient
rem ained unable to work and depended increasingly on
nursing care.
c
tam en, globus pallidus, and caudate nucleus). The ven-
tricles in c therefore have a boxlike shape, characteristic of
Huntington disease. Although atrophic, the basal ganglia
are of norm al signal intensity (in contrast to Wilson disease,
cf. Fig. 8.12).
th e ton gu e protru ded for m ore th an a few sec-
on ds (so-called ch am eleon or trom bon e ton gu e).
Th ese problem s are accom pan ied by progres-
sively severe dysart h ria an d dysph agia (Case Pre-
sen tat ion 2). Th e distu rbin g involu n tary m ove-
m en ts becom e m ore pron oun ced w ith em otion al
stress an d stop on ly durin g sleep.
At later stages of th e disease, th e hyperkin esia
decreases an d gives w ay to a rigid an d, in som e
cases, dyston ic elevation of muscle tone. Th e
patien t’s cogn itive ability also declin es; i.e., th ere is
progressive dementia (Case Presen tation 2).

Ba llism a nd Dystonia
Ballism. Th is rare m ovem en t disorder is cau sed by
lesion s of th e su bth alam ic n u cleu s. It leads to large-
am p litu de flin gin g/t h row in g m ovem en ts of th e
lim bs, proceedin g from th e proxim al join ts. In th e
vast m ajority of cases it arises on on e side on ly
(h em iballism ) con tralateral to th e lesion . (See Case
Presen tat ion 3.)
Dystonia is ch aracterized by involun tary, lon g-last-
in g m u scle con traction s th at p roduce bizarre
m ovem en ts an d con torted postures of th e lim bs.
Like m any oth er typ es of m ovem en t disorders
cau sed by basal gan glia disease, dyston ia w orsen s
w ith m en tal con cen tration or em otion al stress an d
im proves du rin g sleep. Du rin g th e in tervals w h en
dyston ia is absen t, th e m uscle ton e on passive
Case Presentation 3: Hemiba llism
One evening, while watching television, this 63-year-old re-
tired m ason suddenly could no longer hold his beer bottle
and spilled its contents on the carpet. When he tried to
stand up, he developed uncontrollable flinging m ovem ents
of the left arm and leg. He and his wife were very concerned
about this disturbance, which hit him like a bolt from the
blue, and called a physician on call for em ergencies, who ar-
ranged adm ission to hospital.
The adm itting neurologist observed flinging, choreiform
movem ents of the left arm and leg. The patient was very
distressed by these uncontrollable, excessive m ovem ents,
which rendered him unable to stand or walk unaided. He
a b
Fig. 8.11 Small infarct in the right subthalamic nucleus
causing acute hemiballism. The diffusion-weighted im age
(a) reveals the lesion well. The T2-weighted im age (b)
shows a hyperintensity at the sam e location, which,
Function and Dysfunction of the Basal Ganglia · 223
8
m ovem en t of th e affected lim bs ten ds to be
decreased.
Th ere are differen t varieties of dyston ia. Dys-
ton ia restricted to a sin gle m u scle grou p is called
focal dystonia: exam ples in clu de bleph arospasm ,
an involun tary forced closure of th e eyes due to
con traction s of th e orbicu laris ocu li m u scle, an d
sp asm odic torticollis, i.e., dyston ic w ry n eck.
Generalized dystonias, of w h ich th ere are m u ltiple
types, affect all m u scle grou ps of th e body to vary-
in g degrees. Patien ts sufferin g from gen eralized
dyston ia are often m ost severely distu rbed by th e
dysarth ria an d dysp h agia th at usually form part of
th e syn drom e: th e patien t’s speech is h u rried, an d
often barely in telligible.
Th e precise n atu re of th e fu n ction al abn orm ality
in th e basal gan glia th at gives rise to dyston ia is
p oorly u n derstood at presen t.
was given a variety of objects to hold and dropped all of
them on the floor. The neurologist diagnosed hem iballism .
The patient’s past m edical history was notable for m edically
controlled arterial hypertension, type II diabetes, and obes-
ity. An im aging study revealed the cause of the acute
hem iballism , a fresh ischem ic lesion in the right sub-
thalam ic nucleus. In view of the m ultiple cardiovascular risk
factors, the lesion was considered m ost likely to be a
lacunar (m icroangiopathic) infarct (Fig. 8.11).
Sym ptom atic treatm ent with a neuroleptic agent was fol-
lowed by com plete regression of the m ovem ent disorder
within a few days.
however, is not clear enough to m ake the diagnosis. The
other areas of hyperintensity in the basal ganglia are dilated
perivascular spaces (Virchow–Robin spaces), not infarcts.
The brain is m arkedly atrophic.
8 224 · 8 Basal Ganglia
Case Presentation 4: Wilson Disease
This 17-year-old electrician’s apprentice com plained of pro-
gressive clum siness of the hands, which had been troubling
him for three years and was getting in the way of his work.
He could no longer write cursively and had to resort to a
“printed” handwriting. His hands had also been trem bling
for a year, the right hand worse than the left. The trem or be-
cam e worse whenever he tried to grasp an object. His
speech had becom e slow and ridden with errors.
On neurological exam ination, the ocular pursuit m ovem ents
were m ildly saccadic, but there were no other cranial nerve
abnorm alities. Although the m uscles of m astication and fa-
cial expression were of norm al strength and bulk, m arked hy-
pom im ia was evident. The patient’s speech was slow and la-
bored. He had a fine, high-frequency trem or in both hands.
His gait was som ewhat clum sy, and he had trouble hopping
on one leg (either right or left). He tended to fall in all direc-
tions when his tandem gait was tested, or when he walked
with his eyes closed. Nonetheless, he perform ed finger-
pointing tests accurately. He had bradykinesia and dysdiado-
chokinesia, left worse than right, as well as bilateral m arked
im pairm ent of fine m otor control of the hands and feet. His
deep tendon reflexes were norm al and sym m etric, and there
were no pyram idal tract signs or sensory abnorm alities. His
a b
c d
m ental status was norm al. Split-lam p corneal exam ination
distinctly revealed a Kayser–Fleischer ring.
T2-weighted m agnetic resonance im ages of the brain
(Fig. 8.12) revealed m arked sym m etric signal changes in the
basal ganglia and thalam i (Fig. 8.12a,b,d), the m idbrain
(Fig. 8.12c,d), and the cerebellum (Fig. 8.12d). The MR sig-
nal was bright in the putam en, particularly laterally, but dark
in the globus pallidus on both sides (Fig. 8.12b). Moderate
signal abnorm alities were also seen in the caudate nucleus,
the lateral thalam us, the m idbrain (especially the red nu-
cleus) (Fig. 8.12c), and the m iddle cerebellar peduncle on
both sides (Fig. 8.12d).
This com bination of findings on history, physical exam ina-
tion, and MRI suggested the diagnosis of Wilson disease,
which was confirm ed by further tests: the patient’s urinary
copper excretion was m arkedly elevated and his serum
ceruloplasm in concentration was low.
The MR signal increases in the basal ganglia, lateral thalam i,
m idbrain, and cerebellar peduncles represent toxic changes
of the brain parenchym a caused by the elevated serum cop-
per concentration. The signal decreases in the globus pal-
lidus, on the other hand, are probably due to local copper
deposition.
Fig. 8.12 Wilson disease. T2-
weighted m agnetic resonance im -
ages in axial (a–c) and coronal (d)
planes. The axial im ages are at the
level of the frontal horns (a), the
anterior com m issure (b), and the
red nucleus and substantia nigra
(c). The basal ganglia, lateral
thalam i, and m idbrain gray m atter
appear m uch brighter than usual
(hyperintense com pared to norm al
brain tissue), probably because of
parenchym al injury caused by the
elevated serum copper concentra-
tion. The internal part of the
globus pallidus, however, is hy-
pointense, probably because of
local copper deposition. The white
m atter of the anterior com m issure
has norm al signal characteristics
but is seen m ore distinctly than
usual because of the abnorm al
structures surrounding it. The
coronal im age (d) reveals the sig-
nal abnorm alities in the m idbrain
and the m iddle cerebellar
peduncles.
 9

9 Cerebrum
Development . . . . . . . . . . . . . . . . . . . . . 226
Gross Anatomy and Subdivision
of the Cerebrum . . . . . . . . . . . . . . . . . . 228
Histological Organization of the
Cerebral Cortex . . . . . . . . . . . . . . . . . . . 231
Cerebral White Matter . . . . . . . . . . . . . 235
Functional Localization in the
Cerebral Cortex . . . . . . . . . . . . . . . . . . . 238
9 226
9 Cerebrum
Macroscopically, th e cerebru m is m ade up of th e
cerebral cortex, t h e subcortical w hite matter, an d
th e basal ganglia, w h ich w ere discu ssed in Ch apter
8. Th e gross structu re of t h e cerebru m can be u n -
derstood best w ith referen ce to its em bryological
developm en t. Its m ost im pressive feature is th e
im m en se expan sion of th e cortex, w h ich causes
foldin g (gyration ) of th e brain su rface. Th e in -
dividu al cortical areas are con n ected to each oth er,
an d to deep er brain stru ct ures, by th e n u m erou s
fiber path w ays th at m ake up th e su bcortical w h ite
m atter.
Histologically, m ost of th e cerebral cortex
possesses a six-layered cellular architecture. Th is
basic h istological pattern un dergoes ch aracteristic
variation s from on e location in t h e cortex to
Development
Th e cerebrum or en dbrain (telen ceph alon )
develop s from th e p aired telen ceph alic vesicles at
th e fron t en d of th e n eu ral tube, th e so-called pros-
encephalon. Th e en orm ous grow th of th e telen -
ceph alic vesicles m akes th e en dbrain envelop th e
brain stem like a cloak (p alliu m ) an d leads to th e
developm en t of th e lateral ven tricles, w ith th eir
Parietal
Frontal
Ventricle
Cortex
Occipital
Anterior
horn
Basalganglion
Head of caudate
nucleus Temporal
Tail of caudate
nucleus
Inferior horn
Fig. 9.1 Ontogenetic development of the cerebral cor-
tex. Lateral view of an earlier and a later developm ental
stage of the telencephalon. The telencephalic vesicle ex-
pands m assively (arrows) in the form of an arch, resulting in
sim ultaneous, archlike expansion of the cerebral cortex
(yellow), ventricle (blue), and basal ganglion (orange).
an oth er, givin g rise to n u m erou s, cytoarchitectur-
ally distinct cortical areas. Th e early n eu roan a-
tom ists proposed th at th e sp ecific cellu lar stru c-
tu re of each area corresp on ded to th e sp ecific task
th at it carried out. It h as, in deed, been possible to
assign a sin gle, con crete fun ction to a n um ber of
areas, th e so-called primary cortical fields. Yet th e
greater p art of th e cerebral cortex con sists of asso-
ciation areas, w h ose fu n ction apparen tly con sists
of h igh er-level processin g of in form at ion derived
from , or travelin g to, th e prim ary fields. High er
cortical fun ction s such as lan gu age, in particular,
can n ot be localized to a sin gle cortical area bu t de-
pen d in stead on a com plex in teraction of m u ltiple
areas.
ch aracteristic an atom ical su bdivision s, from ou t-
pou ch in gs of th e fluid-filled lu m en of th e n eu ral
tu be. Th e semicircular extension th at ch aracterizes
th e grow th of th e telen ceph alon (Fig. 9.1) an d th e
lateral ven tricles can also be seen in th e develop in g
fiber p rojection s, in th e forn ices, an d in th e corpu s
callosum , th e great fibrou s con n ection betw een
th e tw o h em isph eres. A few m ore details of telen -
cep h alic developm en t w ill be presen ted h ere as a
useful aid to th e u n derstan din g of cerebral an at-
om y.
Evolution of the endbrain. In th e telen ceph alon , as
elsew h ere in th e cen tral n ervou s system , th e
n eu ral tu be con sists of tw o parts, ven tral an d dor-
Central sal. Th e ventral part gives rise to th e sept al region
portion
m edially an d th e basal gan glion laterally. Th e basal
gan glion , in turn , gives rise to th e cau date (“tailed”)
n u cleus, pu tam en , claustrum , an d am ygdala. Th e
cortex derived from th e dorsal part becom es
differen tiated over t h e cou rse of phylogen etic
Posterior developm en t in to th e m ore laterally lyin g paleo-
horn
cortex, t h e oldest portion of cerebral cortex, an d
th e m ore m edially lyin g an d phylogen etically
you n ger archicortex.
Th e spatial arran gem en t of paleocortex an d ar-
ch icortex is preserved un ch an ged in am ph ibian s.
In reptiles, h ow ever, th e neocortex arises in a
lateral position betw een th e paleocortex an d th e
arch icortex. Th e n eocortex takes on an en orm ous
 Developm ent · 227
9
Indusium Lateral Internal
griseum ventricle capsule

Neocortex
Fibers of
corpus
callosum
Ven- Archi- Paleo- Ventricle Neocortex
tricle cortex cortex Head of
caudate
nucleus

Thalamus
Interthalam ic
adhesion
Basal Septum Hippocam pus
ganglion

Amphibians Reptiles Humans

Fig. 9.2 Phylogenetic development of the cerebral cor-
tex (coronal sections). The neocortex (yellow) arises be-
tween the archicortex (red) and paleocortex (blue). It ex-
pands m arkedly in higher organism s; in hum ans it displaces
the paleocortex to the base of the brain (olfactory cortex,
not shown) and the archicortex to a m edial position overly-
ing the corpus callosum (indusium griseum ). The hippo-
cam pal form ation (archicortex) in the floor of the inferior
horn of the lateral ventricle reaches its basal position
through the archlike expansion of the telencephalon (cf.
Fig. 9.1).

size in h igh er organ ism s, pu sh in g th e paleocortex
an d arch icortex far ap art. In h u m an s, th e paleocor-
tex is ult im ately displaced to t h e base of th e brain ,
w h ere it m akes u p variou s com pon en ts of th e phy-
logen etically an cien t olfactory system (olfactory
bu lb, tract, an d t rigon e, an terior perforated sub-
stan ce, an d lateral olfactory stria; cf. pp . 81, 82).
Meanw h ile, th e arch icortex is displaced m edially;
th e sem icircular grow th of th e telen ceph alic ves-
icle p ush es it in to th e in ferior h orn of th e lateral
ven tricle, w h ere it m akes u p th e m assive hippo-
cam pal form ation. On ly a th in layer of arch icortex
is foun d m ediodorsally on th e ou ter su rface of th e
corpus callosu m : th is is th e indusium griseum , w ith
its m edial an d lateral lon gitu din al striae. By far th e
greatest p art of th e h u m an cerebral cortex is of
n eocortical origin (Fig. 9.2).
Inside -out stratification of the cerebral cortex. Th e
n eu ron s of th e cerebral cortex, as of all parts of th e
cen tral n ervou s system , are in itially form ed in th e
ventricular zone, i.e., n ear th e flu id-filled lu m en
(ven tricle) of th e n eural tu be. Th e cells form ed ear-
liest m ake up t h e so-called preplate, w h ich is later
subdivided in to t h e marginal zone an d th e sub-
plate. Th e cortical plate proper, con sistin g of six
cellu lar layers, develops betw een th ese tw o struc-
tu res. Th e cortical n eu ron s th at are form ed first oc-
cupy th e deep er layers (layers 5 an d 6), an d th ose
form ed later m igrate u pw ard in to th e m ore super-
ficial layers (“in side-ou t” arran gem en t ). Th u s, th e
later n eu ron s m u st travel p ast th eir precu rsor cells
to get to th e su bpial cortical layers (Fig. 9.3), pass-
in g from th e ven tricular zon e to th e cortical plate
alon g radial glial fibers. Th e six cortical layers are
n um bered top ograph ically from ou tside in (th e
tradition al system , as u sed in th is book), or, alter-
n atively, in th e order of th eir form ation , as h as
lately been p roposed (Marin -Padilla, 1998). Ac-
cordin g to th e fin din gs of recen t studies, n orm al
n eu ron al m igration , leadin g to th e ch aracteristic
in side-ou t cortical layerin g, depen ds cru cially on
th e p articip ation of th e Cajal–Retzius cells of th e
m argin al zon e. Th ese cells secrete a protein called
reelin, w h ich apparen tly directs n euron al m igra-
tion alon g th e radial glial fibers (Fig. 9.3). Abn or-
m alities of n euron form ation , m igration , or separa-
tion from th e radial glial fibers are collectively
called neuronal m igration disorders.
9 228 · 9 Cerebrum

Fig. 9.3 Inside -out lamination of the cerebral cortex.

a tervening space (N1–N3). Early cortical neurons (N1) m i-
b c
The earliest neurons form the so-called preplate, which
soon divides into the m arginal zone (M), with its Cajal–Ret-
zius cells (CR), and the “subplate” with its subplate neurons
(S). The neurons of the cortical plate are deposited in the in-
grate upward, from the vicinity of the ventricle (V), along
radial glial fibers (RF) to the m arginal zone of the cerebral
cortex, where it is thought that they are stopped by reelin
(brown), a protein of the extracellular m atrix produced by
the Cajal–Retzius cells. As the cortex thickens, later cortical
neurons (N2, N3) m ust travel longer distances to reach the
reelin-containing m arginal zone. As a result, the neurons
that are laid down earliest form the deeper layers of the
cerebral cortex, while those that are laid down later form its
d m ore superficial layers. P = brain surface with pia m ater.

n eopallium (= n eocortex) ach ieves its greatest ex-

Frontal
ten t in h um an s, envelop in g th e phylogen etically
lobe Parietal older cortical region s in n eocortex. Th u s, m ost of
lobe th e stru ctures derived from th e paleocortex an d
arch icortex can n ot be seen on th e extern al su rface
of th e brain (th e olfactory bu lb an d tract, olfactory
area, paraterm in al gyrus, fasciolar gyrus, in du siu m
griseu m , den tate gyru s, an d h ip pocam pal form a-
tion ).

Frontal
pole
Tem poral Temporal Occipital
pole lobe lobe
Fig. 9.4 The lobes of the cerebrum (left hemisphere,
lateral view )
Gross Anatomy and Subdivision
of the Cerebrum
Th e cerebral longitudinal fissure (in terh em isph eric
fissu re) sep arates th e tw o h em isph eres dow n to
th e corpu s callosum . Each h em isph ere possesses
lateral, m edial, an d basal su rfaces; th e tran sition al
area betw een t h e (dorso-)lateral an d m edial su r-
faces is called th e parasagittal region. Each h em i-
sph ere is also divided in to four lobes, n am ely, th e
frontal, parietal, occipital, an d tem poral lobes (Figs.
9.4–9.6). Th e insula is som etim es coun ted as a fifth
lobe. Th e m assive en largem en t of th e m am m alian
Gyri and Sulci
Th e m assive en largem en t of th e n eocortex cau ses
foldin g of th e brain su rface in to convolu tion s (gyri)
separated by grooves (sulci, fissu res). On ly abou t
on e-th ird of th e cerebral cortex is visible on th e ex-
tern al su rface, w h ile tw o-th irds are h idden in th e
sulci (Figs. 9.7–9.9).
On ly a few su lci h ave a relatively un ch an gin g
an atom ical p osition . Th e lateral sulcus (sylvian fis-
su re) separates th e tem p oral lobe from th e fron tal
an d parietal lobes. Un like oth er n am ed su lci, th e
lateral su lcu s does n ot m erely form th e border be-
tw een tw o adjacen t gyri. It exten ds deep u n der th e
su rface of th e brain , w iden in g ou t in to a broad, flat
space con tain in g cerebrospin al fluid, th e sylvian
cistern , w h ich is n ot visible from th e ou tside. Th e
sylvian cistern is u su ally very n arrow, alm ost a vir-
tual space, except in m arkedly atroph ic brain s. Its
m edial w all is th e in su la (islan d of Reil; cf. Figs.
9.10 an d 9.11), som etim es called th e buried or cen -
tral lobe of th e brain . Th e lateral w all of th e sylvian
cistern is called th e opercu lum (“lid”), becau se it
covers th e cistern like a lid; it con sists of bu ried
portion s of th e th ree lobes of th e brain lyin g
 Gross Anatom y and Subdivision of the Cerebrum · 229
9
Frontal
pole
Tem poral
pole

Frontal
lobe
Parietal
lobe
Frontal Occipital
lobe lobe
Temporal
lobe

Preoccipital
notch

Occipital
Preoccipital
notch lobe
Temporal Occipital
lobe pole

Fig. 9.5 The lobes of the cerebrum (right hemisphere, Fig. 9.6 The lobes of the cerebrum (basal view of the
medial view ) brain after removal of the left cerebellar hemisphere)

Fig. 9.7 Cortical gyri and

Precentral sulci (lateral view )
Inferior frontal
sulcus sulcus Central
Middle frontal sulcus
gyrus Postcentral
sulcus
s
u

Su
s

Superior
yr
u

Parieto-
u

pa pe
yr

yr
g

ri rio
al
lg

frontal
g
s

In e t a r occipital
u

tr

al
ta

yr

tr

p a fe ri l lo b
n

sulcus
lg

ce

sulcus
n
o

rie o r
fr

ce
ta

yr

ul
re

e
r

lg

ta
P

st
o

Supra-
o

l lo
ri

o
ta
fr

P
e

bu
n
le
p

m arginal
o
Su

le
d

fr
id

gyrus
r
M

Angular
ri
fe

gyrus
In

a l g yru s
por
r tem
e rio g yru
s
Su p ra l
te m po
d le
Mid
Pars frontalis
o ra l g yru s
r temp Lunate
Pars In fe rio
sulcus
triangularis
Pars Superior Inferior Lateral sulcus Preoccipital
opercularis temporal tem poral (sylvian fissure) notch
sulcus sulcus
9 230 · 9 Cerebrum

Fig. 9.8 Cortical gyri and

Precentral sulci (me dial view )
gyrus
Cingulate sulcus
Central sulcus

Callosal us
al g yr
sulcus l fr o nt
d ia Pa ra c Parieto-occipital
e e
M lo b u n t ra l
le
Pr
sulcus
Cin gulate e cu
gyrus ne
us
Co r
p us c
a llo
su m Isthm us of
Genu Septum
pellu- - um
the cingu-
Ro s
tr um Sp le o f ca llo s late gyrus
cidum m
n iu co rp u s
th e

Cuneus
Gyrus rectus
Uncus ng u
al g yru s
r us / li Calcarine
Pa ra l gy
Subcallosal area h ip p o c a m p a or al g yru s sulcus
it o tem p
ip
Me d ia l o cc yr us
Paraterm inal La t e p o ra l g
m
gyrus ra l o ccip it o t e

Rhinal sulcus Occipito - Collateral Hippocam pal sulcus

tem poral sulcus and dentate gyrus
sulcus

Longitudinal
Orbital
cerebral fissure
gyri
Orbital
sulci
Fig. 9.9 Cortical gyri and sulci (basal view )
arou n d it, w h ich are called th e tem poral, fron tal,
an d p arietal opercu la. A bu ried portion of th e su-
perior tem poral gyru s con tain s t h e t ran sverse gyri
of Hesch l (prim ary au ditory cortex, Fig. 9.10).
Am on g th e oth er relatively invarian t su lci, th e
central sulcus (rolan dic fissure) defin es th e border
bet w een t h e fron tal an d parietal lobes. Th e precen-
tral gyrus, w h ich lies in fron t of th e cen tral sulcu s
an d is th erefore in t h e fron tal lobe, con tain s th e
prim ary m otor cortex; th e postcentral gyrus, w h ich
lies beh in d it an d is th erefore in th e parietal lobe,
con tain s th e prim ary som atosen sory cortex. On
Olfactory sulcus
th e m edial surface of th e h em isph ere, th e parieto -
Gyrus rectus
occipital sulcus form s th e border betw een th e
Collateral fissure
Uncus
p arietal an d occip ital lobes. Its in ferior en d join s
Parahippocampal th e an terior en d of th e calcarine sulcus, w h ich lies
gyrus
Inferior temporal
en tirely in t h e occipit al lobe an d run s backw ard
gyrus tow ard th e occipital p ole. Most of th e prim ary
Lingual gyrus visu al cortex is located in th e depth s of th is su lcus,
Lateral
occipitotemporal an d th e rem ain der in t h e gyri on eith er side of it.
gyrus
Medial occipito- Fin ally, th e cingulate sulcus separates th e n eocor-
temporal gyrus tex from th e m esocortex of th e cin gu late gyru s.
Fusiform gyrus Th e borders of th e occipital lobe are in -
Calcarine sulcus
com pletely defin ed by th e parieto -occipital sulcus
an d th e preoccipital n otch (Figs. 9.7 an d 9.8).
Th e portion of th e lateral su rface of th e fron tal
lobe th at lies an terior to th e precen tral gyrus is
divided in to th e superior, m iddle, an d in ferior fron -
tal gyri. For th e n am es an d location s of all gyri
m en tion ed in th is section , an d a few oth ers, as w ell
as t h e n am es of th e su lci th at lie betw een th em , see
Figs. 9.7–9.9. Th e an atom y of m any of th e gyri an d
su lci varies greatly from on e in dividu al to an oth er,
an d even betw een th e tw o h em isph eres of th e
sam e in dividual.

Insula
Long gyrus
of insula
Superior tem poral Transverse temporal
gyrus gyri of Heschl
Fig. 9.10 The transverse gyri of Heschl on the superior
aspect of the superior temporal gyrus
Histological Organization of the
Cerebral Cortex
Th e folded su rface of th e brain is m ade u p of th e
gray m atter of th e cerebral cortex, w h ich is gray
becau se of th e very h igh den sit y of n euron s w it h in
it. Th e cortex varies in th ickn ess from 1.5 m m
(visu al cortex) to 4.5–5 m m (precen tral gyru s); it is
gen erally th icker on t h e crow n of a gyrus th an in
th e depth s of th e n eigh borin g su lci.
Laminar Architecture
Th e lam in ar stru ctu re of th e cerebral cortex is vis-
ible to th e n aked eye in on ly a few cortical areas,
m ost clearly in th e visual cortex, w h ere an an atom i-
cal section perpen dicular to th e brain su rface re-
veals t h e w h ite strip e of Gen n ari (or of Vicq d’Azyr)
w ith in th e cortical gray m atter. Microscopic exam i-
n ation of m ost cortical areas reveals th e basic six-
layered structure th at typ ifies th e cerebral cortex
(n eocortex), as described by Brodm an n . Cortical
areas possessin g th is stru ctu re are called isocortex
(after O. Vogt), as opp osed to th e phylogen etically
older allocortex, w h ich , in tu rn , is divided in to th e
paleocortex an d t h e archicortex. Th e paleocortex in -
cludes th e olfactory area, w h ile t h e arch icortex in -
clu des th e fasciolar gyru s, h ipp ocam p us, den t ate
gyru s, an d parah ippocam pal gyru s.
Th e in tern al stru cture of t h e six-layered isocor-
tex is depicted in Fig. 9.12. In an an atom ical sect ion
Histological Organization of the Cerebral Cortex · 231
9
Short gyri of insula
Insula
Central
sulcus of
insula
Long gyrus
Superior tem poral of insula
gyrus
Fig. 9.11 The insula (revealed by dissection)
perpen dicu lar to th e brain su rface, th e follow in g
layers can be distin gu ish ed, from ou tside to in side
(i.e., from th e pial su rface to th e subcortical w h ite
m atter).
1. Molecular layer (zonal layer). Th is layer is rela-
tively poor in cells. In addition to th e distal den -
dritic trees (apical tuft) of low er-lyin g pyram idal
cells an d th e axon s th at m ake syn aptic con tact
w ith th em , th is layer con tain s m ostly sm all n eu -
ron s (Cajal–Retzius cells), w h ose den drites ru n tan -
gen t ially w ith in th e layer. Th e Cajal–Retziu s cells
play an essen tial role in th e develop m en t of th e
cortical lam in ar pattern . Som e of th em degen erate
on ce t h is developm en t is com p lete.
2. External granular layer. Th is layer con tain s m any
granule cells (“n onpyram idal cells”) an d a few py-
ram idal cells w h ose den drites bran ch ou t both
w ith in th e extern al gran ular layer an d u pw ard in to
th e m olecu lar layer. Th e n onpyram idal cells are
m ostly GABAergic in h ibitory n eu ron s, w h ile th e
pyram idal cells are excitatory an d u se glu tam ate as
th eir n eurotran sm itter.
3. External pyramidal layer. As its n am e im plies,
th is layer con tain s m any pyram idal cells, w h ich ,
h ow ever, are sm aller th an th ose of th e deep er cor-
tical layers. Th ese cells are orien ted w ith th eir
bases tow ard th e su bcortical w h ite m atter. Th e
axon of each pyram idal cell arises from t h e cell
base an d t ravels dow n in to th e w h ite m atter. Th e
9 232 · 9 Cerebrum

Fig. 9.12 Cytoarchitec-

Golgi stain Cellular stain Myelin stain ture of the human cere-
bral cortex as revealed by
I. Molecular Tangential three different staining
layer lam ina techniques. (Diagram after
II. External Brodm ann, from Rauber-
granular layer Kopsch: Lehrbuch und Atlas
der Anatom ie des Men-
schen, 19th ed., vol. II,
III. External Thiem e, Stuttgart, 1955.)
pyram idal layer

IV. Internal External

granular layer band of
Baillarger

V. Internal Internal
pyram idal layer band of
Baillarger

VI. Multiform
layer

axon already receives a m yelin sh eath w ith in th e
extern al pyram idal layer. It m ay fu n ction as a pro-
jection fiber or, m ore com m on ly, as an association
or com m issu ral fiber (p. 236 ff.) A den drite em erg-
in g from th e ap ex of th e pyram idal cell travels u p-
w ard in to th e extern al gran u lar an d m olecu lar lay-
ers, w h ere it divides in to it s term in al bran ch es
(ap ical tuft).
corticon u clear an d corticosp in al tracts. Th is layer
also con tain s m any tan gen tially orien ted fibers (in-
ternal band of Baillarger).
6. Multiform layer. Th is layer of p olym orph cells is
subdivided in to an in n er, less den se layer con t ain -
in g sm aller cells, an d an ou ter layer con tain in g
larger cells.

4. Internal granular layer. Like t h e extern al gran u -

lar layer, th is layer con tain s m any n onpyram idal
cells. Th ese granule cells m ain ly receive afferen t
inpu t from th alam ic n eu ron s by w ay of th e
th alam ocortical projection . Th e fibers lyin g in th e
extern al pyram idal layer are m ostly radially
orien ted, but th ose of th e in tern al gran u lar layer
are overw h elm in gly tan gen tial, form in g th e exter-
nal band of Baillarger.
5. Internal pyramidal layer. Th is layer con tain s m e-
diu m -sized an d large pyram idal cells. Th e largest
cells of th is layer (Betz cells) are fou n d on ly in th e
region of th e precen t ral gyru s. Th e especially
th ickly m yelin ated n eurites of th ese cells form th e
Types of Neurons in the Cerebra l Cortex
Th e cerebral cortex th us con tain s tw o m ajor typ es
of n eu ron s: th e excitatory p rojection n eu ron s (py-
ramidal cells) an d t h e oth er nonpyramidal cells
(gran ule cells or in tern eu ron s), w h ich are m ore
com m on ly in h ibitory an d ten d to m ake local rath er
th an lon g-distan ce con n ection s. Bu t th is dich ot-
om y is oversim p lified. Th e in tern euron s, for ex-
am ple, com e in a n u m ber of su btyp es, su ch as
basket cells, chandelier cells (axo-axon al cells), an d
double bouquet cells. Furth erm ore, th e pyram idal
cells also participate in local regu latory circuits
(recu rren t in h ibition : backw ard-ru n n in g local col-
laterals of th e pyram idal cells activate GABAergic

in h ibitory in tern euron s, w h ich , in tu rn , in h ibit th e
pyram idal cells).
Th e pyram idal cells of th e fifth cortical layer give
rise to th e projection pathw ays (Fig. 9.13), w h ich
travel th rou gh th e su bcortical w h ite m atter an d th e
in tern al capsu le to th e th alam u s, striatu m , brain -
stem n uclei, an d spin al cord. Th e association and
com m issural fibers travelin g to oth er ipsilateral an d
con tralateral cortical areas, respectively, are
derived from th e pyram idal cells of th e th ird corti-
cal layer (n u m bered 4 in Fig. 9.13). Th e gran u le cells
of th e secon d an d fou rth cortical layers, as w ell as
th e pyram idal cells, receive p rojection fibers from
th e t h alam us (1), as w ell as association an d com -
m issu ral fibers from oth er cortical areas (2).
Va ria tions of the La mina r Pa ttern
Th e six-layered lam in ar pattern ju st described is
called th e homotypical pattern . In som e cortical
areas, h ow ever, th e fu ll pattern of six layers is barely
discern ible; t h ese areas are called heterotypical.
In th e receptive cortical fields, su ch as th e visu al,
auditory, an d som atosen sory cortices, th e den sity
of gran u le cells is in creased, w h ile th at of py-
ram idal cells is decreased (“granulization”; “granu-
lar cortex”). In th e m otor cortical fields, on th e
oth er h an d, th ere are relatively m ore pyram idal
cells (“pyram idalization”; “agranular cortex”).
Histological Organization of the Cerebral Cortex · 233
9
Fig. 9.13 Simplified dia-
gram of intracortical
neural connections (after
Lorente de Nó and Larsell).
Efferent neurons/neurites
are red, afferent ones are
blue, and interneurons are
black. For details, cf. text,
p. 232.
Cytoarchitectural cortical fields. As w e h ave seen ,
cortical areas vary n ot on ly in th ickn ess bu t also in
h istological stru cture. Th e h eterogen eous distribu-
tion of variou s types of n eu ron s across cortical
areas, an d th e resu ltin g variat ion s in t h e cortical
lam in ar pattern , led th e n eu roan atom ists Brod-
m an n , O. Vogt, an d von Econ om o to su bdivide th e
cerebral cortex in to a large n um ber of cytoarch i-
tectu ral fields. Brodmann’s cytoarchitectural map
of the cerebral cortex, w h ich is som ew h at sim pler
th an von Econ om o’s, is n ow in gen eral use as a sys-
tem for n am in g cortical areas. Agran ular cortex is
fou n d in Brodm an n areas 4 an d 6 (prim ary an d sec-
on dary m otor cortical fields, p. 239); t h e in n er
gran ular layer of th ese areas is rich in pyram idal
cell com pon en ts. Gran u lar cortex (kon iocortex), on
th e oth er h an d, is foun d in Brodm an n areas 3, 1, 2,
41, an d esp ecially 17, th e striate cortex (prim ary re-
ceptive cortical areas, p . 24 4). As sh ow n in
Fig. 9.14, th e cytoarch itectu ral fields do n ot coin -
cide w ith th e gyral pattern of th e brain su rface.
Th ey partly overlap w ith on e an oth er an d vary
across in dividu als in th eir sh ape an d exten t.
It is possible to su bdivide th e cerebral cortex
h istologically, n ot on ly accordin g to cytoarch itec-
tu ral criteria but also on th e basis of local varia-
tion s in m yelin ated fibers, glial cells, or blood ves-
sels (i.e., accordin g to it s m yeloarchitecture, glioar-
chitecture, or angioarchitecture). More recen t brain
9 234 · 9 Cerebrum

Fig. 9.14 Cytoarchitec-

tural fie lds of the human
cerebral cortex. a Lateral
view of left hem isphere.
b Medial view of right
hem isphere. The cortical
fields are num bered.
(From : Brodm ann, from
Bargm ann W: Histologie
und Mikroskopische Anato-
m ie des Menschen, 6th ed.,
Thiem e, Stuttgart, 1967.)

i i i ii i i
i i i
i i i ii
iii i i i i i i ii i i
i i i ii ii i i

m aps h ave also exploited variation s in n eu -
rotran sm it ters, n eu rot ran sm itter-related en zym es,
n eu ropeptides, an d calciu m -bin din g protein s, as
revealed by im m u n oh istoch em ical stu dies u sin g
specific an tibodies again st t h ese su bstan ces.
Plasticity of cortical architecture. Th e m icroscopic
stru cture of th e cerebral cortex is n ot strictly
gen etically determ in ed, n or is it im m u table. Mu ch
cu rren t research con cern s th e qu estion of h ow en -
viron m en tal in fluen ces, by activatin g specific
grou ps of n euron s, can decisively affect th e stru c-
tu ral differen tiation of cortical areas over th e
cou rse of on togen etic developm en t. A furth er
question is w h eth er, an d by w h at m ech an ism s,
lon g-lastin g ch an ges in n eu ron al activity in th e
m ature brain (e.g., th rou gh perturbation s of th e ex-
tern al environ m en t or loss of a sen sory organ ) can
actually brin g about ch an ges in th e m icroarch itec-
tu re of th e cortex, in clu din g a ch an ged an atom y of
syn aptic con n ection s.

Many studies of th is kin d h ave been perform ed
on t h e visual system, becau se th e environ m en tal
condition s affectin g it (visu al stim uli) are relatively
easy to m an ipu late. It h as been fou n d th at certain
“elem en tary com p on en ts” of visu al stim u li, in -
cludin g th eir color, orien tation , an d localization on
th e retin a, are p rocessed separately by dist in ct
grou ps of n eu ron s, w h ich are distribu ted over th e
visu al cortex in sm all, in terspersed areas. Th ese
sp ecialized cortical areas t ake on differen t ch arac-
teristic sh apes, depen din g on th e elem en tary
aspect of visu al processin g w it h w h ich t h ey are
concern ed: color is processed in so-called “blobs,”
w hile th e spatial localization an d orien tation of th e
stim u lus are dealt w ith by ocu lar dom in an ce an d
orien tation colu m n s (cf. p. 243 f.). Experim en tal
m an ipu lation of a given typ e of elem en tary
stim ulus, for a su fficien tly lon g period of tim e, can
be sh ow n to produ ce m orph ological ch an ges in th e
correspon din g processin g un its.
Inpu t-specific differen tiation of cortical m icro-
structu res can be dem on strated in oth er areas as
w ell. Th e cortical barrels of th e roden t som a-
tosen sory cortex, com posed of an n u lar collection s
of cells, are a w ell-kn ow n exam ple: each barrel
represen ts a sin gle w h isker of th e an im al.
Th u s, a large n u m ber of recen t stu dies perm it
th e follow in g gen eral con clu sion s: (1) Certain cor-
tical areas con tain a top ical represen tation of t h e
sensory stim uli th at th ey process. (2) Th is rep re-
sentat ion can un dergo plastic ch an ge.
Th e diversity of h istological stru ctu re am on g corti-
cal fields im m ediately im plies t h at th ey m u st h ave
correspon din gly diverse fun ction s. For w ell over a
h un dred years, m uch research h as focu sed on th e
assign m en t of fu n ction to differen t cort ical fields.
Th e kn ow ledge th at h as been gain ed is of vital
clin ical im portan ce. We w ill discu ss fu n ction al lo-
calization in detail in th e section after n ext, bu t
first, as a n ecessary prerequisite, th e fiber con n ec-
tion s of th e cerebral cortex w ill be presen ted.
Cerebral White Matter
Each h em isp h ere con t ain s a large am oun t of su b-
cortical w h ite m atter, w h ich is com p osed of myeli-
nated nerve fibers of varyin g th ickn ess an d neuro-
glia (m ain ly oligoden drocytes, th e cells th at form
m yelin sh eat h s).
Cerebral White Matter · 235
9
Th e su bcortical w h ite m atter is bou n ded by th e
cerebral cortex, th e lateral ven tricles, an d th e stri-
atu m . It s n erve fibers are of th ree types:
1. Projection fibers
2. Association fibers
3. Com m issu ral fibers
Projection Fibers
Projection fibers con n ect differen t part s of th e cen -
tral n ervou s system w ith each oth er over lon g dis-
tan ces.
Efferent fibers from t h e cerebral cortex traverse th e
subcort ical w h ite m atter an d t h en com e togeth er
to form th e in tern al capsu le. As discussed in Ch ap-
ter 3, th ese are th e corticon u clear, corticosp in al,
an d corticopon tin e fibers, as w ell as th e fibers th at
lin k th e cerebral cortex w ith th e th alam u s, stri-
atu m , reticu lar form ation , subst an tia n igra, sub-
th alam ic n u cleu s, m idbrain tectu m , an d red n u -
cleu s. Th e lon g efferen t corticospin al fibers arise
m ain ly in areas 4, 3, 1, an d 2, an d also in area 6,
w h ile fibers to oth er destin ation s, such as th e cor-
ticopon tin e an d corticoth alam ic fibers, arise from
larger association areas of th e cortex.
Afferent fibers t ravel from th e th alam u s to exten -
sive areas of t h e cerebral cortex. Th ese in clu de
fibers of all som atosen sory m odalities, w h ich
travel to areas 3, 1, 2, an d 4, as w ell as oth er fibers
carryin g im pu lses from th e cerebellum , globu s pal-
lidu s, an d m am illary body by w ay of th e th alam u s
to th e cerebral cortex. Th e th alam u s is th e last
m ajor relay station th at sen sory im p ulses m ust
traverse before reach in g th eir sp ecific prim ary cor-
tical areas an d is th erefore som etim es called th e
“gatew ay to con sciou sn ess.” Olfactory fibers are
th e on ly exception to th is rule: th ey reach th e cor-
tex directly, w ith out any th alam ic relay.
Thalamocortical reciprocity. Most th alam ocortical
projection s are reciprocal (i.e., th ere are fibers run -
n in g in both direction s). Th e cerebral cortex is th u s
presu m ed to m odu late its ow n input by m ean s of a
feedback loop bet w een th e cortex an d th e
th alam u s. Th ese m assive th alam ocortical an d cor-
ticoth alam ic projection s m ake u p th e large w h ite
m atter tracts kn ow n as th e an terior, superior, pos-
terior, an d in ferior th alam ic pedun cles, w h ich are
usually collectively term ed th e corona radiata. Th e
9 236 · 9 Cerebrum

Fig. 9.15 Association

Superior longitudinal fibers of the cerebral
fissure w hite matter (lateral
view ). a After dissection to
the depth of the external
capsule. b After rem oval of
the striatum to expose the
internal capsule.

Uncinate fasciculus

Frontotem poral and

arcuate fasciculi
External capsule
Inferior occipito-
frontal fasciculus

(direction of
view)

Cerebral arcuate
fibers

Corona radiat a

Internal capsule

Inferior occipito-
frontal fasciculus Optic radiation

Uncinate fasciculus
Inferior longitudinal
fissure
Anterior com m issure

topical organ ization of th e th alam ic projection s is
th eir m ost im portan t featu re.
Association Fibers
Th e association fibers (Figs. 9.15 an d 9.16) m ake
up m ost of t h e su bcortical w h ite m atter. Th ese
fibers con n ect n eigh borin g distan t cortical areas
of th e sam e h em isph ere w ith each oth er. Th e cere-
bral cortex is able to carry ou t its diverse associa-
tive an d in tegrative fun ction s on ly becau se all of
its fun ction ally im portan t areas are tigh tly in ter-
con n ected an d n eural im pu lses can travel easily
from on e cortical area to an oth er. Th ese exten sive
fiber con n ect ion s betw een cort ical areas m ay also
be an im portan t an atom ical subst rate for th e par-
tial recovery of fu n ction often seen in th e after-
m ath of cortical in jury (e.g., after traum a or
stroke). Over tim e, as th e in dividu al practices th e
im paired activities, perform an ce m ay im prove be-
cau se th e correspon din g n eu ral im p ulses h ave
been redirected alon g th e rem ain in g, in tact pat h -
w ays.
Th e superior longitudinal fasciculus run s dorsal
to th e in su la an d con n ects th e fron tal lobe w ith
large parts of th e parietal, occipital, an d tem p oral
 Cerebral White Matter · 237
9
Fig. 9.16 The major
Cingulum tracts of association
fibers and commissural
fibers (diagram )

Inferior longitu-
dinal fasciculus

Stria
Cerebral arcuate
term inalis
fibers
Superior longitu-
dinal fasciculus
Vertical occipital
fasciculus

Uncinate
fasciculus

Frontotemporal and
arcuate fasciculi

Superior longitu- Cingulum Corpus

dinal fasciculus callosum
Forceps
m inor

Forceps Anterior
major com m issure
Inferior longitu-
dinal fasciculus

lobes. An exten sion of it, th e arcuate fasciculus,
w in ds arou n d th e posterior en d of th e lateral su l-
cu s (sylvian fissure) in th e depth s of th e su bcortical
w h ite m atter. Th is fiber bu n dle con n ects th e fron -
tal an d tem poral lan gu age areas (of Broca an d
Wern icke, p. 248) w ith each oth er. Lesion s of th e
arcuate fascicu lu s produce con du ct ion ap h asia
(p . 249). Th e inferior longitudinal fasciculus con -
n ects th e tem poral lobe w ith th e occipital lobe. Th e
uncinate fasciculus travels arou n d th e an terior en d
of th e lateral sulcu s like a h ook, con n ectin g th e
orbital fron tal gyri w ith th e an terior p ortion of th e
tem p oral lobe.
Other important bundles of association fibers
are th e superior and inferior occipitofrontal
fasciculi an d th e vertical occipital fasciculus. Th e
cerebral arcuate fibers, also called U fibers, con n ect
n eigh borin g as w ell as distan t gyri. Nerve fibers
th at travel exclu sively w ith in th e cerebral cortex
are called intracortical fibers, in con trast to th e
subcortical fibers th at m ake u p th e cerebral w h ite
m atter.
9 238 · 9 Cerebrum

Th e cingulum is an association bun dle of th e Functional Localization in the

lim bic system . It ru n s from th e su bcallosal area to
th e parah ipp ocam p al gyrus (en torh in al area).
Cerebral Cortex

Commissural Fibers Th e earliest clin ical n eurologists an d n eu roscien -

tists w ere already deeply in terested in th e question
Fibers lin kin g cortical region s w it h th eir cou n ter-
of w h eth er in dividu al fu n ction s of th e brain could
parts in th e opposite cerebral h em isph ere are
be localized to part icu lar brain areas. From th e m id-
called com m issu ral fibers (Fig. 9.16c, d) an d are
n in eteen th cen tury onw ard, research ers an sw ered
fou n d in th e corpus callosum an d th e anterior com-
th is qu estion th rough th e pain stakin g stu dy of brain
missure. Th e fibers of t h e corpu s callosum are
lesion s foun d at au topsy in p atien ts w h o, durin g
derived from very exten sive areas of th e cerebral
th eir lives, h ad suffered from particular types of
cortex; a m idlin e section of th e brain sh ow s th em
n eu rological deficit. Th is patho-anatom ically
tigh tly bu n dled in th e corpu s callosu m . On ce th ey
oriented functional analysis of cortical stru ctu res
h ave crossed over to th e opposite h em isph ere, th e
w as supp lem en ted, from 1870 onw ard, by experi-
callosal fibers fan out again , in th e so-called cal-
m en ts w ith direct electrical or ch em ical stim ulation
losal radiation, to reach t h e cortical location s th at
of th e cerebral cortex, both in an im als an d in
correspon d, in m irror-im age fash ion , to th eir sites
h um an s. Later tech n iqu es, in cludin g stereotaxy,
of origin . Th is sym m etrical lin kage of h om otopic
electroencephalography, an d m icroelectrode record-
cortical areas by com m issural fibers is absen t on ly
ing of poten tials from in dividu al n eu ron s an d n erve
in th e p rim ary visu al cortex (area 17) an d in th e
fibers, yielded ever m ore detailed fun ction al
h an d an d foot areas of th e som atosen sory cortex.
“m ap s” of th e brain (cf. Fig. 9.17). Th e origin al idea
Th e com m issu ral fibers are in terspersed in th e
of th e “localizability” of brain fu n ction rem ain s
subcortical w h ite m atter w ith th e fibers of t h e
valid after a cen tu ry an d a h alf of stu dy, especially
coron a radiata an d th e association bun dles. As th e
w ith respect to th e prim ary cortical areas, w h ich w e
corp us callosu m is sh orter th an th e h em isph eres,
w ill describe furth er below.
th e fibers at its an terior en d (rostru m , gen u ) or
In th e last 20 years, h ow ever, basic n eu robiologi-
posterior en d (splen iu m ) take a U-sh aped cou rse
cal research on th e localization of cortical fun ction
to lin k m irror-sym m etric cortical areas at th e fron -
h as been largely tran sform ed by th e em ergen ce of
tal or occipit al poles. Th ese cu rvin g fibers form th e
n ew er, m ore pow erfu l tech n iqu es of investigation ,
forceps m inor (for th e fron tal pole) an d th e forceps
particu larly fu n ction al n euroim agin g. Curren t
m ajor (for th e occipit al pole).
th in kin g h as tu rn ed aw ay from th e parcelin g out of
fun ction s to in dividu al an atom ical structu res (as
derived from t h e im p ortan t stu dies of Brodm an n ,

Fig. 9.17 Functional

Voluntary m ovem ent areas of the cerebral cor-
Supplem entary Somatic sensation tex as determ ined by elec-
m otor synergies
trical stim ulation of the
cortex during neurosurgical
Eye m ovem ents
Manual procedures. (From : Penfield
dexterit y W and Rasm ussen T: The
Cerebral Cortex of Man,
Language
Macm illan, New York,
Language 1950.)
Language
g Bilateral
a rin
He vision

Mem ory patterns

Contralateral
vision

Pen field, an d m any oth ers) an d tow ard th e con cept
of functional neural netw orks. It is n ow clear th at
cortical fun ction s, particu larly h igh er on es like lan -
guage, cogn ition , an d th e con trol of specific pat-
tern s of beh avior, can n ot alw ays be assign ed to a
sin gle cortical location . Rath er, in dividu al com -
pon en ts of th ese com plex fu n ction s are subserved
by separate parts of t h e n eocortex, w h ich m u st th en
in teract w ith each oth er in m an ifold w ays to pro-
du ce th e correspon din g fu n ction al com peten ce.
In th e p ast, th e stu dy of fu n ction al localization
in th e cerebral cortex relied on exam in ation of th e
sick or in ju red brain (th e “lesion al approach ”), an d
on n onphysiological exp erim en ts involvin g brain
stim u lation . In con trast, research ers n ow try to u n -
derstan d th e physiological basis an d com plexity of
cortical fu n ction s by m ean s of im ages of t h e en tire
norm al brain , obtain ed w h ile th ese fun ct ion s are
bein g carried ou t.
Th e m ajor tech n iques of fu n ction al n eu roim ag-
in g th at are used in th is typ e of research are
m agn etoen ceph alography (MEG), positron em is-
sion tom ography (PET), an d fu n ction al m agn etic
reson an ce im agin g (fMRI).
Magnetoencephalography involves m easu rem en t
of t h e m agn etic fields gen erated in th e cerebral
cortex, rath er th an ch an ges in electrical poten tial,
w h ich are m easured in electroen ceph alograp hy.
Brain tissu e an d th e bony skull severely atten u ate
electric, bu t n ot m agn etic fields, an d MEG is, th ere-
fore, m uch better th an EEG for fu n ction al im agin g.
Th e m agn etic fields th at it detects are stron g
en ou gh th at a th ree-dim en sion al im age of field
sources can be com p uted from th em , in clu din g
sources deep in t h e brain . Fu n ction al im agin g of
th e brain w ith MEG can be perform ed w ith h igh
tem poral resolution bu t relatively low spatial reso-
lution (as com pared to fMRI).
Positron emission tomography, a scan n in g pro-
cedure involvin g radion uclides, is used to investi-
gate m etabolic processes in th e brain . Oxygen an d
glucose con su m ption in th e brain can be directly
m easu red after th e in jection of th e correspon din g
radioactively labeled su bstan ces in to th e body.
Radioactively labeled dru gs can also be u sed to
visualize in tracerebral syn apt ic activity an d recep-
tor distribu tion . Th e disadvan tages of PET in clu de
th e radiation dose to th e p atien t, w h ich is n ot al-
w ays in sign ifican t , an d th e tech n ical difficu lty an d
Functional Localization in the Cerebral Cortex · 239
9
exp en se of th e procedu re. Som e of th e radioactive
isotopes u sed in PET h ave very sh ort h alf-lives an d
m ust be gen erated directly adjacen t to th e scan n er,
in an on -site cyclotron . Fu rth erm ore, th e spatial res-
olu tion an d tem poral resolu tion of PET are rela-
tively low.
Functional magnetic resonance imaging. Most of
th e p roblem s associated w ith MEG an d PET, as ju st
described, do n ot affect fMRI. Th is tech n ique is
based on t h e differen t m agn et ic properties of oxy-
h em oglobin an d deoxyh em oglobin . Region al cere-
bral act ivation is im m ediately follow ed n ot ju st by
a ch an ge in blood flow but also by a ch an ge in th e
relative con cen trat ion s of th e tw o form s of
h em oglobin , w h ich can be detected as a very sm all
ch an ge in t h e MRI sign al. fMRI is n ot kn ow n to
h ave any h arm ful effect on th e body, so th at su b-
jects can be exam in ed at len gth or repeatedly. fMRI
h as n ow largely replaced PET for stu dies of cerebral
activation , bu t it can n ot yet be u sed reliably to
visu alize m etabolic processes.
We w ill n ow describe som e asp ects of th e n ew
con ception of fu n ction al localization in th e cere-
bral cortex th at h as been obtain ed th rou gh th e ap-
plication of th ese n ew tech n iqu es.
Primary Cortical Fields
From th e fun ction al poin t of view, th e cortex can be
divided in to prim ary cortical fields an d u n im odal
(p. 247) an d m u ltim odal association areas (p . 247).
Most of th e prim ary cortical fields h ave a recep -
tive fu n ction : th ey are th e fin al targets of th e so-
m atosen sory an d special sen sory p ath w ays (visual,
au ditory, etc.) in th e CNS, an d th ey receive th eir af-
feren t inp ut by w ay of a th alam ic relay. Th e pri-
m ary cortical fields serve to brin g th e respective
sen sory qu alities to con sciou sn ess in raw form , i.e.,
w ithout interpretation. Th e in dividu al prim ary cor-
tical fields h ave n o distin ctive gross an atom ical
feat ures an d do n ot correspon d precisely to t h e
pattern of convolu tion s on th e brain surface.
Rath er, th e exten t of a prim ary cortical field is de-
fin ed as th e area of cortex in w h ich th e corre-
sp on din g th alam ic projection term in ates.
In addition to th e variou s prim ary receptive
fields, th ere is also a prim ary m otor area, w h ich
sen ds m otor im p ulses th rou gh th e pyram idal path -
w ay to th e spin al cord an d, ultim ately, to th e
m u scles.
9 240 · 9 Cerebrum

eL
T
N
H

r
S
U

pi
u
e

g
E

e
h
p

ck
Fo

n
lb

a d
o
p
W

k
t

u
o
re
o

e
H

ld
Fo

w
ri

r
ar
an

st

ar

e
Li

r
d

m
tt
es

R
To

le
in

fi
g
M

n
a ls

fi
id

g
In

n
n it

er
T

g
h

le
Ge

er
Ey u m

fi
fi

n
e b

g
No

e
s

er

r
e
Fa c
ia l
e xp r
e ssio
Up p n
e r lip
Mo u t h

a Lower lip
Teeth, gum s, and jaw

To ng ue l
in a
x om
h a r y-na b d
P t ra
In

H
S
E

r
h

pi
u

e
lb
W

e
o

u
ri

n
k

K
w

l
st

d
H

e
kl
e
an

n
A
d
s

Li
e
To

tt
R

le
M

in
b

fi
i

g
In d d

n
fi

g
d le

er
Th e x

g
fi

e
u m fin n g

r
Ne g e
ck b er r
E
ye b
Fig. 9.18 Primary cortical fields and premotor and pre- Eye ro ws
lid
and
frontal cortical areas (diagram ). a Lateral view. b Medial Fa c
ia l e e ye
b al
xp re
view. ssio l
n
Mo u t h
n
o
i
t

a
n
o

Ja w
h

e
P

oi

g
n gu in
ta

To w
llo
vi

a
la

Sw
S

ni

eh
w

C
Fig. 9.19 Relative sizes of the cortical representations
of different parts of the body in the hum an prim ary som a-
tosensory (a) and m otor (b) cortical fields. (From : Penfield
W and Rasm ussen T: The Cerebral Cortex of Man, Macm il- b
lan, New York, 1950.)

Prima ry Soma tosensory a nd Motor Cortica l

Areas
Localization and function. Th e primary soma-
tosensory cortex (areas 3, 2, and 1, Fig. 9.18)
rough ly correspon ds to th e postcen tral gyru s of t h e
parietal lobe an d a portion of th e precen tral gyru s.
It exten ds upw ard on to th e m edial su rface of th e
h em isph ere, w h ere it occu pies th e p osterior por-
tion of th e paracen tral lobu le. Th e prim ary som a-
tosen sory cortex is resp on sible for the conscious
perception of pain and tem perature as w ell as so-
m atic sensation and proprioception, m ainly from the
contralateral half of the body and face. Its afferen t
inpu t is derived from th e ven tral posterolateral an d
posterom edial n u clei of th e th alam u s (Fig. 6.4,
p. 174). Even th ou gh som e sen sory stim uli, p articu -
larly pain ful stim u li, m ay already be vagu ely per-
ceived at th e th alam ic level, m ore precise differen -
tiation in term s of localization , in ten sity, an d type
of stim u lu s can n ot occu r un til im pulses reach th e
som atosen sory cortex. Th e con sciou s perception of
vibration an d position is n ot possible w ith ou t th e
participation of th e cortex.
Th e primary motor cortex (area 4) rough ly corre-
spon ds to t h e precen t ral gyru s of t h e fron tal lobe,
in clu din g th e an terior w all of th e cen tral su lcu s, an d
 Functional Localization in the Cerebral Cortex · 241
9
3a = pain including
b = tem perature object
1 = touch recognition
2 = kinesthetic sense by touch
Leg
ts
Motor en
em
e ns
at ion skills ov
rs
m
al
la
bu

u
di
i

iv
st Tu rn in g

d
In
Tr
of trun k

e
V

u
Fa ll e Action

n
k
ons
re s p (sensory) of leg
in g and trunk
Drive, m otivation, Tu rn a d
e
of h th
feeling of strength ng
re

t
fs
Topographical

o
Arm

g
m emory

n
In d i

se
i
a c t iovid u a l

l
e

n
h

se
e
uc ns

c
o
Active ft AA

ti
Eye c tc
((sseennitoionn

e
o

th
thinking Act i ssoorryy Calculation

se

es
Motor move- o n se ))

en

in
Writ q u e n ce

K
S
sequences ments ing s Num ber
Face Ta c t
ile b recognition
Stereo- Rig h o d y im

e
d ist t / le ft a g e Sense

c
Spea- Nam ing Words gnosis

Fa
in c t
io n Reading of place
king in (spon- and
Tones Action Se n
t

n
taneous and (sen- co m e n c

o
sen- h e p re e

ts
ti
m elodies phone- sory) Visual
tences speech) n si -

ep

en
mes io n on
thinking
ept

m
Taste c

er
r
pe ep - Vision:

ve
p
ise c
No e p e r

o
e
Visual bright-

m
s o n
e
n ce T n o n Phonem ic recognition ness,

e
ue es t io Ph

az
e q
S n o is color,
sequences

G
of nes
f t o t io n ) (word shape,

n
Personality, appropriate o
ce s ce p

oi
uen y per com prehension) Name m ove-

t
actions, perseverance q

n
e
S e lo d
com pre-

e
Color m ent

tt
(m
hension

a
perception

la
u
si
V
Listening m ovem ents,
auditory attention

Understanding of
sounds and m usic

Fig. 9.20 Functional localization in the cerebral cortex in relation to cytoarchitecture, after K. Kleist. a Lateral view of
left hem isphere.
Fig. 9.20 b

exten ds u pw ard in to th e an terior p ortion of th e tion s of th e periph ery of th e body, takin g th e form
paracen tral lobu le on th e m edial su rface of th e of a homunculus (a “little m an ,” as it w ere, draw n
h em isph ere. Th e fifth cortical layer in area 4 con - on th e surface of th e brain ; t h e Latin term is th e
tain s th e ch aracteristic Betz pyram idal cells, w h ich dim in u tive of hom o, m an , in th e sen se of h u m an
give off th e rapidly con ductin g, th ickly m yelin ated bein g; cf. Fig. 9.19). Th e con figuration of th ese
fibers of th e pyram idal tract. Area 4 is th u s con - m aps of th e body on th e cortical su rface w as origi-
sidered th e site of origin of voluntary m ovem ent, n ally determ in ed by path oan atom ical study
sen din g m otor im pu lses to th e m u scles by w ay of (Fig. 9.20). Th e fin din gs w ere con firm ed an d re-
th e pyram idal tract an d an terior h orn cells of th e fin ed by th e in traoperative electrical stim u lation
spin al cord. It receives afferen t inpu t from oth er stu dies of Pen field (Fig. 9.21), by th e som a-
areas of th e brain t h at part icipate in th e plan n in g tosen sory evoked p oten tial m appin g stu dies of
an d in it iation of volun tary m ovem en t, particularly Marsh all, an d, m ore recen tly, by PET, fMRI, an d
th e ven tral oral posterior n ucleu s of th e t h alam us MEG stu dies (Fig. 9.22). fMRI en ables visu alization
(cf. p . 174 f.), th e prem otor areas 6 an d 8, an d th e so- of th e region s of th e brain th at are act ivated w h en
m atosen sory areas. norm al, healthy subjects p erform m otor tasks.
Th ese cortical m aps are not metrically propor-
Somatotopy and plasticity. Th e prim ary som a- tional representations of th e body. In th e cortical
tosen sory an d m otor fields of th e n eocortex con - rep resen tation of sup erficial sen sation , for exam ple,
tain som atotop ic, i.e., poin t-to-poin t, represen ta- p arts of th e body th at are den sely in n ervated by
9 242 · 9 Cerebrum

Sensation

Motor skills Indi-

vidual
Turning of trunk m ove-
Foot, m ents A
c t
bladder, i
(s e o
Fall response rectum n so n
r y)

B o d y e g o

Le
Drive (experience of self)

g
T
gr op
ap o -
hi
ca
lm
em
or
Vegetative y
odor
Action

t -
cel c r o -
n es
perception Visu

p
sequen-

ra m
a l fi

Te
ces Vegetative Visu e ld ,
Objective a l fi lo w
(m otor) odor
e ld , er q
reactions uad
upp ra n t
odor er q
Fd uad
perception Up ra n t
CA m wa r

la
Individual and

u
ov d

ac
collective ego em ga

M
e n ze
ts
Color and
Odor object recognition
ts
n

recognition
e

Name
m
ve

o com prehension
ym
ct or
Ob je c t ive o lfa

Understanding of
sounds and m usic

Fig. 9.20 (continued) Functional localization in the cere- fahrungen im Weltkrieg 1914/18, vol. IV, Barth, Leipzig,
bral cortex in relation to cytoarchitecture, after K. Kleist. 1922–1934.)
b Medial view of right hem isphere. (Figs. 9.20a and b from : CA, cornu Am m onis; Am m on’s horn; Fd, fascia dentata.
Kleist K: Gehirnpathologie. In: Handbuch der ärztlichen Er-

sen sory fibers (such as t h e ton gu e, m ou th , an d face)
are m apped to disproportion ately large areas of cor-
tex, an d less den sely in n ervated parts (arm , th igh ,
back) are m apped to sm aller areas (Fig. 9.19).
Furth erm ore, an d despite earlier assum ption s,
th ese m aps are not static: rath er, th e cort ical rep-
resen tation of a given body part can en large or
sh rin k, depen din g on t h e degree to w h ich th at
body p art is put to use. Th u s, if a tact ile discrim in a-
tion task involvin g th e th u m b an d in dex fin ger
(su ch as th e palpation of a die to explore its sur-
face) is carried ou t rep et itively for a lon g en ough
tim e, th e rep resen tation of th ese tw o fin gers in th e
prim ary som atosen sory cortex w ill en large. Sim i-
lar, or even m ore exten sive, ch an ges of cortical rep -
resen tation are foun d after t h e in ju ry or am puta-
tion of a lim b. In such cases, th e som atotopic m ap
of th e body in th e cerebral cortex can be sh ifted by
as m u ch as several cen tim eters. Wh en an arm is
am pu tated, for exam ple, th e cortical area pre-
viou sly respon sible for sen sory im pu lses from th e
(n ow m issin g) h an d can ch an ge its fun ction an d in -
stead process sen sory im pulses from th e face. Th is
ch an ge is brou gh t about by n euron al reorgan iza-
tion in th e brain .
Much cu rren t research con cern s th e poten tial con -
n ection betw een sh iftin g cortical represen tation s
an d th e gen eration of pain ful con dit ion s su ch as
phantom pain. If a con n ection exist s, th en som e
type of th erap eu tic alteration or su ppression of
th is form of cortical “plasticity” m igh t be u sed to
treat, or even preven t, th ese con dition s.
Cortical columns. In addition to th e som atotopic
cortical represen tation of su perficial sen sation
(tou ch an d p ressu re), w h ich involves im pulses th at
are gen erated in cu tan eous m ech an oreceptors an d
 Functional Localization in the Cerebral Cortex · 243
9

D
ia
p
Primary:

h
ra

Fo
To t
sim ultaneous flexion

g
s,

T
;
, e ye it e sid e

m
To

o
b

e
h
e

s
ig
a d Fo s
synergy of the contralateral

Le
o
He p p o s r

h
ot

T ou

m
T

g
h
Le h ig

Sh
o on o

e
o
k to arm and leg, with participa-

n
r
g h
si Ab

ax
t ru n e xt e n gy do

ld m
Se tion of the ipsilateral leg.
n e r ra l

Fo
Th m

er
A ar
y en o f co n

P es
or

e
s

r
re
io n

ri t
te ax
Secondary: turning of

y
Sh co d a
fle x o n t ra la lim b s

m o
ou

m
nt ry

H
ld e

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Ar head, eyes, and

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la t e x

d
5

: t po
th
Eye s
t Fo e ra io trunk to opposite

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oppo o
re a
l li n sy

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th

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g
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b ne

fi

in s
3

er
sit e nd

n
rd
2n rg
s

g id
g
5t
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er
fi
sid e d hf

o e
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g
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Th g 3 h
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e
um rd r

ad
fin g e
b 2 n g r
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an
Up ck Th
d
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d
Lo w r fa c Ne r
er f e b
a c e Up c k
To n p
gue Lo w e r fa Eye s
r f ce
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Ja To e n;
w
Pa la n ac
Ja w g u e e c e p t io t e sid e
te er nk
Ph a r yp u
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te d it o r e s, t r d e
La r yn x Ph u
A d, e y
it e
s i Co m p
a r yn hea ppos n sio n le x
La r yn x x
to o o r e xt e o n t ra - visu a l
Fle xio n h c
e
y o f t a l lim b s p e r ce p
Ch e syn e rg la t e r t io n
p h o win g ,
g ro n a t io lickin
h icc a n in g , n , g ru g , s wa
upi n l
ng scre t in g , lo win g Vi-
am ,
in g su a l
,
p e r- Cen-
ce p -
tral
t io n
sco-
toma

Fig. 9.21 Motor effects induced by electrical stimulation of individual cortical fields: overview. (From : Foerster O:
Grosshirn. In: Handbuch der Neurologie, vol. VI. Ed. by O. Bum ke and O. Foerster, Springer, Berlin, 1936.)

Foot Elbow flexion Thumb tapping

Inde x finger Left fist Lip-pursing

Fig. 9.22 The cortical representation of regions of the this technique, is in perfect accordance with the earlier find-
body as revealed by functional MRI (fMRI) in normal per- ings of Penfield and Foerster (Fig. 9.21). fMRI is thus a non-
sons. fMRI data are shown projected onto a m odel of the invasive m eans of m apping the “hom unculus” very reliably,
brain surface. The data were obtained from 30 subjects either in norm al persons or in patients. The im ages are re-
who perform ed repetitive m ovem ents of the indicated produced with the kind perm ission of Professor Grodd.
body parts. Bright colors correspond to high levels of acti- (From : Lotze M, Erb M, Flor H, et al.: Neuroim age 11 (2000)
vation: i.e., brightly colored brain areas are activated during 473–481.)
the respective m ovem ents. Localization, as determ ined by
9 244 · 9 Cerebrum
Fig. 9.23 Functional localization in the primary visual
cortex as revealed by fMRI. Norm al subjects viewed visual
stim uli in the form of expanding rings, and the associated
cortical activity is depicted, projected onto a m odel of the
brain surface. There is activation of the prim ary visual cor-
tex at the calcarine sulcus, as well as of the secondary visual
th en t ran sm itted to th e cortex alon g th e path w ays
th at h ave been described, th ere are also oth er corti-
cal m aps for th e rem ain in g som atosen sory m odali-
ties (proprioception , tem perature, p ain ), w h ich lie
deeper w it h in t h e cortex bu t h ave a gen erally sim i-
lar con figu ration . Th u s, som atic sen sation as a
w h ole is represen ted by cortical colum ns: each
colu m n deals w ith a p articu lar, sm all region of th e
body surface, an d cells at differen t depth s w ith in
th e colu m n respon d to differen t som atosen sory
m odalities. Th is stru ctu ral property en ables th e
brain to process im p ulses from all som atosen sory
m odalities sim u ltan eou sly an d in parallel, even
th ough th ey h ave reach ed th e cortex th rou gh dis-
tin ct n eu roan atom ical path w ays.
A lesion of the primary somatosensory cortex im -
pairs or abolish es th e sen sat ion s of touch , pres-
sure, pain , an d tem perat ure, as w ell as tw o-poin t
discrim in ation an d position sen se, in a corre-
spon din g area on t h e opp osite side of th e body
(contralateral hemihypesthesia or hemianesthe-
sia).
A lesion in area 4 produ ces contralateral flaccid
hemiparesis. Addition al dam age of th e adjacen t
prem otor area an d th e un derlyin g fiber tract s is
n ecessary to produ ce spastic hemiparesis, w h ich
areas. Im ages obtained by Professor Grodd. (From : Kam -
m er T, Erb M, Beck S, and Grodd W: Zur Topographie von
Phosphenen: Eine Studie m it fMRI und TMS. 3. Tübinger
Wahrnehm ungskonferenz [3rd Tübingen Conference on
Perception, 2000].)
reflect s th e in terru pt ion of n onpyram idal as w ell as
pyram idal path w ays. Focal epileptic seizures re-
stricted to th e som atosen sory cortex are ch aracter-
ized by repetitive m otor ph en om en a, su ch as
tw itch in g, or by paresth esia/dysesth esia on th e op-
posite side of th e body or face (m otor or sen sory
jacksonian seizures).
Prima ry Visua l Cortex
Localization and retinotopy. Th e prim ary visu al
cortex correspon ds to area 17 of t h e occipital lobe
(Figs. 9.17, 9.18). It is located in th e depth s of th e
calcarin e su lcus, an d in th e gyri im m ediately above
an d below th is sulcu s on t h e m edial surface of th e
h em isph ere, an d it exten ds on ly sligh tly beyon d
th e occipital pole (Fig. 9.23). It is also called th e
striate (“striped”) cortex becau se of th e w h ite
st ripe of Gen n ari, w h ich is grossly visible w it h in it
in a p erpen dicular an atom ical section . Th e visu al
cortex receives inpu t by w ay of th e optic radiation
from th e lateral gen iculate body, in orderly, retin o-
topic fash ion : th e visual cortex of on e side receives
visual in form ation from th e tem poral h alf of th e
ipsilateral retin a an d th e n asal h alf of th e con -
tralateral retin a. Th u s, th e righ t visu al cortex su b-
serves th e left h alf of t h e visu al field, an d vice versa
 Functional Localization in the Cerebral Cortex · 245
9
(p p. 86, 87). Visu al in form ation from th e m acu la
lutea is conveyed to th e posterior part of area 17,
i.e., th e area arou n d th e occipital pole.

Columnar structure. Th e n eu ron s of th e prim ary

visu al cortex respon d to stim u li h avin g a particular
Visual cort ex
position an d orien tation in t h e con t ralateral visual
field. Neu ron s respon din g to sim ilarly orien ted Optic
radiation (enlarged)
stim u li are organ ized in vertical colu m n s. Each
colu m n is 30–10 0 m icron s w ide. Neigh borin g
colu m n s are organ ized in “pinw h eels” (Fig. 9.24),
Ocular dominance
in w h ich every direction of th e com pass is repre- colum ns
sen ted on ce. Th e orien tation colu m n s are in ter-
rupted at regu lar distan ces by th e “blobs”
(Fig. 9.24), w h ich con tain n eu ron s p rim arily re-
spon din g to color. Fin ally, t h e ocular dominance Blob

columns are th e th ird m ajor structu ral com pon en t

Pinwheel
of th e prim ary visu al cortex. Each ocu lar dom i-
n an ce colu m n respon ds to visual stim u lation of a
sin gle eye; th e adjacen t colum n respon ds to visu al
stim u lation of th e oth er eye. (pinwheel, enlarged)

Th ese th ree m ajor com pon en ts of th e prim ary

visual cortex togeth er form a hypercolu m n oc-
cu pyin g an area of abou t 1 m m 2 . Th e hyper-
columns, in tu rn , m ake u p a regu larly repeatin g
pattern on th e surface of th e prim ary visu al cortex.
Th ey are in tercon n ected th rou gh h orizon tal cells. Fig. 9.24 Structure of the visual cortex: pinw heels and
Th e st ru ctu ral an d fu n ction al organ ization of th e blobs (diagram )
visu al cortex en ables it to carry ou t an elem en tary
an alysis of visu al stim uli for th eir sh ape an d color.
Direct electrical st im u lation of t h e prim ary visu al im pu lses from both organ s of Corti by w ay of th e
cortex (e.g., in aw ake patien ts u n dergoin g brain lateral lem n isci. Th us, th e prim ary au ditory cortex
surgery) in duces th e perception of flash es of ligh t, of each side processes im pu lses arisin g in both ears
brigh t lin es, an d colors. (bilateral projection ).

Tonotopy. Th e stru cture of th e prim ary au ditory

A unilateral lesion of area 17 produ ces con -
tralateral hemianopsia; a part ial lesion p rodu ces
quadrantanopsia in th e part of th e visu al field th at
correspon ds to th e site of th e lesion . Cen t ral vision
is u n im paired as lon g as th e lesion spares th e post-
erior en d of t h e calcarin e fissu re at th e occipital
pole.
Prima ry Auditory Cortex
Localization. Th e prim ary auditory cortex is lo-
cated in th e tran sverse gyri of Hesch l (area 41),
w h ich form part of t h e u pper su rface of th e sup er-
ior tem poral gyrus (see Figs. 9.10, 9.17, 9.18, an d
9.25). It receives its afferen t inpu t from th e m edial
gen icu late body, w h ich , in t urn , receives au ditory
cortex resem bles th at of th e p rim ary visu al cortex
in m any respects. Its n euron s are fin ely tu n ed for
th e detection an d processin g of ton es of a particu -
lar frequen cy. Th e en tire spectru m of au dible
sou n d is ton otopically represen ted: th e cells for
low er frequen cies are fou n d rostrolaterally, an d
th ose for h igh er frequ en cies caudom edially, alon g
th e sylvian fissure. Th e p rim ary auditory cortex
th u s con tain s isofrequency bands ru n n in g in a m e-
dial-to-lateral direction . Area 41 n eu ron s p referen -
tially respon d n ot on ly to a particu lar frequ en cy
bu t also to a p articu lar in ten sity of sou n d.
Columnar structure. Th e prim ary auditory cortex
also appears to possess a colu m n ar organ ization
9 246 · 9 Cerebrum

Auditory
instruction:
start

Auditory
instruction:
stop

Fig. 9.25 Functional localization of the auditory cortex
and language centers by fMRI. Eighteen subjects were
asked to listen to and repeat spoken words (nam es of
m onths). Listening is associated with activation of the pri-
m ary auditory cortex bilaterally in the area of the transverse
gyri of Heschl. Repetition, on the other hand, is associated
with activity in the left hem isphere only; specifically, in the
angular gyrus of the parietal lobe (Wernicke’s area) and in
the inferior frontal gyrus (Broca’s area). Im ages obtained by
Professor Grodd. (From : Wildgruber D, Kischka U, Acker-
m ann H, et al.: Cognitive Brain Research 7 [1999] 285–294.)

for th e processin g of stim uli from th e tw o ears.
Tw o types of n eu ron s respon d in differen t w ays to
bin au ral stim u li. On e resp on ds m ore stron gly to
stim u li delivered to both ears th an to stim u li in a
sin gle ear (EE neurons), w h ile th e oth er is in h ibited
by sim u ltan eou s bin au ral stim ulat ion (EI neurons).
Colu m n s of cells of th ese tw o types are fou n d in al-
tern ation on th e su rface of th e prim ary au ditory
cortex, like th e ocular dom in an ce colu m n s of th e
prim ary visual cortex (Fig. 9.24). Th ese colum n s lie
tan gen tial to th e isofrequ en cy ban ds. A fu rth er
sp ecial property of n eu ron s of th e prim ary au di-
tory cortex is th at differen t n eu ron s are excited by
au ditory st im u li of th e sam e frequ en cy bu t differ-
en t du rat ion .
Direct elect rical stim u lation of th e auditory cor-
tex in duces th e perception of sim ple sou n ds of
h igh er or low er frequen cy an d greater or lesser
volum e, bu t n ever of w ords.
Unilateral lesions of the primary auditory cortex
cau se on ly subtle h earin g loss because of th e bi-
lateral projection s in t h e au ditory pat h w ay. Th e
im pairm en t m ain ly con cern s directed hearing, an d
th e ability to distin gu ish sim ple from com p lex
soun ds of th e sam e frequ en cy an d in ten sit y.
Prima ry Gusta tory Cortex
Taste-related im p ulses are p rocessed first in th e
rostral n ucleu s of th e t ractu s solitariu s in th e
brain stem an d th en con du cted, by w ay of th e cen -
tral tegm en tal tract, to a relay station in th e ven tral
posterom edial n u cleu s of t h e th alam u s (parvo-
cellu lar p art). Th ey th en travel onw ard th rou gh th e
posterior lim b of th e in tern al cap sule to t h e pri-
m ary gustatory cortex, w h ich is located in th e pars
opercularis of th e in ferior fron tal gyrus, ven tral to
th e som atosen sory cortex an d above th e lateral
sulcu s (area 43, Fig. 9.18).
Prima ry Vestibula r Cortex
Neuron s of th e vestibu lar n uclei in th e brain stem
project bilaterally to th e ven tral posterolateral an d
posteroin ferior n u clei of th e th alam u s, as w ell as to
its posterior n uclear group n ear th e lateral gen icu -
late body. Vestibu lar im p ulses are con du cted from
th ese sites to area 2v in th e parietal lobe, w h ich lies
at th e base of th e in traparietal sulcu s, directly
posterior to th e h an d an d m ou th areas of th e post-
cen tral gyru s. Electrical stim u lation of area 2v in
h u m an s in duces a sen sation of m ovem en t an d ver-
tigo. Area 2v n euron s are excited by h ead m ove-
m en t. Th ey receive visu al an d prop rioceptive as
 Functional Localization in the Cerebral Cortex · 247
9
Fig. 9.26 Association
Hand area areas of the parietal,
(Exner) occipital, and temporal
lobes. These three lobes
Parie tal
associatio n com e together in the re-
area gion of the angular gyrus.
Broca’s and Wernicke’s
Occipital
areas are indicated, along
associatio n
area with the association path-
ways from the secondary
association areas to the
tertiary association area,
and from the latter to the
prem otor cortical fields for
language and for the face
and hand.

Motor
language
area (Broca)
Sensory
Arcuate language area (Wernicke)
Temporal fasciculus
association area

w ell as vestibu lar inpu t. An oth er cortical area re-
ceivin g vestibu lar input is area 3a, at th e base of
th e cen tral su lcu s adjacen t to th e m otor cortex. Th e
fu n ction of area 3a n euron s is probably to in tegrate
som atosen sory, special sen sory, an d m otor in for-
m ation for th e con trol of h ead an d body position .
Large lesions of area 2v in h u m an s can im p air spa-
tial orien tation .
visual w orld. Th e som atosen sory association cor-
tex lies ju st beh in d th e prim ary som atosen sory
cortex in area 5, an d th e au ditory association cor-
tex is part of th e su perior tem poral gyru s (area 22)
(Fig. 9.18). Th e un im odal association areas receive
th eir n eu ral input th rough association fibers from
th e correspon din g prim ary cortical fields. Th ey re-
ceive n o direct inpu t from th e th alam u s.

Multimoda l Associa tion Areas

Association Areas
Unimoda l Associa tion Areas
Th e u n im odal association areas of th e cortex are
located n ext to th e prim ary cortical areas. Th eir
fu n ction , in very gen eral term s, is to provide an in i-
tial interpretation of th e sen sory im pu lses th at are
processed in relatively raw form in t h e prim ary
cortical areas. Sen sory in form ation tran sm itted to
th e association areas is com pared w ith previously
stored in form ation , so th at a m ean in g can be as-
sign ed to it. Th e visu al association areas are areas
18 and 19 (Fig. 9.18), w h ich are adjacen t to th e pri-
m ary visu al cortex (area 17). Th ese areas receive
relatively basic visual in form ation from area 17 an d
use it to perform a h igh er-level an alysis of th e
Un like th e u n im odal association areas, th e m u lti-
m odal association areas are n ot tigh tly lin ked to
any sin gle prim ary cortical field. Th ey m ake affer-
en t an d efferen t con n ection s w ith m any differen t
areas of th e brain an d process in form ation from
m ultiple som atosen sory an d special sen sory m od-
alit ies (Fig. 9.26). Th ey are th e areas in w h ich
m otor an d lin guistic con cepts are first drafted, an d
in w h ich n eural represen tation s are form ed th at do
n ot directly dep en d on sen sory inpu t. Th e largest
m ultim odal association area is th e multimodal
portion of the frontal lobe (to be described fu rth er
on p. 248), accou n tin g for 20 %of th e en tire n eocor-
tex. An oth er im portan t m u ltim odal association
area is fou n d in th e posterior portion of the
9 248 · 9 Cerebrum

parietal lobe. Wh ile th e an terior portion of t h e derstan din g of th ese very com plex fun ction s re-
parietal lobe processes som atosen sory in form a- quires kn ow ledge of certain basic con cepts of n eu -
tion (areas 1, 2, 3, an d 5), its posterior p ortion in te- rop sych ology an d n europsych ological testin g,
grates som atosen sory w ith visual in form ation to w h ich w ill be briefly explain ed w h ere n ecessary.
en able th e perform an ce of com plex m ovem en ts. We w ill discu ss language, aspects of perception, the
planning of com plex patterns of m ovem ent and
Frontal Lobe m otor activities, an d the control of social behavior.
Th ese fu n ction s are m ostly su bserved by th e m ulti-
Th e fron tal lobe can be divided in to th ree m ajor
m odal association cortices, w h ich m ake u p m ore
com pon en ts: th e prim ary m otor cortex (area 4,
th an h alf of th e brain surface an d w h ich receive af-
p. 239), w h ich h as already been described, th e pre-
feren t inpu t from th e p rim ary som atosen sory,
m otor cortex (area 6, see below ), an d th e prefrontal
sp ecial sen sory an d m otor cort ices, th e m ediodor-
region, a large expan se of cortex con sistin g of m u l-
sal an d lateroposterior pu lvin ar p ortion s of th e
tim odal association areas (Fig. 9.18).
th alam us, an d oth er association areas in both
Th e prim ary m otor cortex an d th e p rem otor cor-
h em isph eres (Fig. 9.26).
tex form a fu n ction al system for th e plan n in g an d
con trol of m ovem en t. Th e prefron tal cortex is pri-
m arily con cern ed w ith cogn itive tasks an d th e con - La nguage and La tera lization—Aphasia
trol of beh avior (p. 255).
Lan guage is on e of th e m ore im portan t an d com -
plex activities of th e h um an brain . In m ost in -
Premotor cortex. Th e prem otor cortex (area 6) is a
dividu als (ca. 95 %), lan gu age-related areas are lo-
higher-order center for the planning and selection of
cated in th e fron tal an d tem poroparietal associa-
m otor program s, w h ich are th en execu ted by th e
tion cortices of th e left h em isp h ere, w h ich is u su -
prim ary m otor cortex. Ju st as t h e u n im odal asso-
ally con tralateral to t h e dom in an t (righ t ) h an d.
ciation areas adjacen t to th e p rim ary som a-
Som e im portan t aspects of lan gu age, h ow ever, in -
tosen sory, visual, an d au ditory cort ices are t h ou gh t
clu din g its em otion al (affective) com pon en t, are
to store sen sory im pression s, so too th e prem otor
subserved by th e righ t h em isph ere. Th e m ajor
cortex is th ou gh t to store learn ed m otor processes,
speech cen ters are in t h e basal region of t h e left
actin g in cooperat ion w ith t h e cerebellu m an d
fron tal lobe (Broca’s area, area 44) an d in th e p ost-
basal gan glia. Th e stored “m otor en gram s” can be
erior p ortion of th e tem poral lobe at its jun ction
called u p again for use as n eeded. Even tasks p er-
w ith th e parietal lobe (Wernicke’s area, area 22)
form ed w ith a sin gle h an d activate th e prem otor
(Fig. 9.26).
cortex of both h em isph eres. An oth er im portan t
Th ese areas are spatially distin ct from th e p ri-
fu n ction of t h e p rem otor cortex is th e plan n in g an d
m ary sen sory an d m otor cortical areas respon sible
in itiation of eye m ovem en ts by th e fron tal eye
for p urely au ditory perception (au ditory cortex,
fields (area 8; Figs. 9.17, 9.18, an d 9.21). Un ilateral
tran sverse gyri of Hesch l), p urely visual p erception
stim ulation of area 8 in duces con jugate m ovem en t
(visual cortex), an d th e m otor perform an ce of th e
of both eyes to th e opposite side.
act of speakin g (p rim ary m otor cortex). Experim en -
tal stu dies involvin g th e m easurem en t of region al
Lesions of area 8 th at dim in ish its act ivity produce
cerebral blood flow (rCBF) w ith PET an d fMRI h ave
con jugate gaze deviation to th e side of th e lesion
revealed t h at letter sequ en ces th at do n ot m ake u p
th rough th e prepon deran t activity of th e con -
in telligible w ords m ain ly activate th e visu al cortex,
tralateral area 8 (e.g., in stroke—“th e patien t looks
an d pu re ton es m ain ly activate th e prim ary audi-
tow ard th e lesion ”).
tory cortex (cf. Fig. 9.25), w h ile in telligible w ords or
sen ten ces p resen ted to th e eyes or ears activate
Higher Cortical Functions and Their Wern icke’s area. Th e brain can th u s distin gu ish
w ords from n onw ords after eith er visual or audi-
Impairment by Cortical Lesions
tory p resen tation , an d processes th ese tw o catego-
Th is section con cern s th e m ore im port an t h igh er ries of stim u li in differen t cortical areas.
cortical fu n ction s an d th e typical clin ical fin din gs Broca’s area is activated w h en an in dividu al
associated w ith t h eir im pairm en t. An adequ ate u n - speaks, an d even du rin g “silen t speech ,” i.e., w h en
 Functional Localization in the Cerebral Cortex · 249
9
Table 9.1 Types of Aphasia

Aphasia Spontaneous Repetition Articula - Compre- Sentence Struc- Naming Commonly

Speech tion hension ture, Choice of Associa ted Neu-
Words rologica l Deficits

Broca Markedly Severely Dysarthric Norm al Agram m atism , Mildly Right hem ipare-
aphasia dim inished im paired phonem ic para- im paired sis and left
phasic errors apraxia

Wernicke Norm al Severely Norm al Severely Para- Severely Right hom ony-
aphasia im paired im paired gram m atism , im paired m ous hem i-
sem antic para- anopsia
phasic errors,
neologism s

Conduction Norm al Mildly Norm al Norm al Phonem ic Mildly Right hem i-

aphasia im paired paraphasic im paired hypesthesia and
errors apraxia

Global Severely Severely Dysarthric Severely Single words, Severely Right hem ipare-
aphasia im paired im paired im paired em pty phrases, im paired sis and hem i-
sem antic para- hypesthesia,
phasic errors right hom ony-
m ous hem i-
anopsia

Amnestic Norm al Norm al Norm al Norm al Word substitu- Severely None

aphasia tions, phone- im paired
m ic paraphasic
errors

Transcortical Im paired Norm al Mildly Norm al Sem antic para- Im paired Right hem i-
motor aphasia im paired phasic errors paresis

w ords an d sen ten ces are form ulated w ith out actu-
ally bein g sp oken . Pu re w ord repetition , on t h e
oth er h an d, is associated w ith activation in th e in -
sula. Th is suggests th at tw o path w ays are available
for t h e gen eration of lan gu age. In “automatic lan-
guage,” an in com in g stim u lu s is follow ed by acti-
vation of th e prim ary visu al or au ditory cortex,
th en th e in sular cortex, an d fin ally th e prim ary
m otor cortex. In “nonautomatic language,” activa-
tion of th e p rim ary cortices is im m ediately fol-
low ed by activation of Broca’s area. Wern icke’s
area is p rim arily con cern ed w ith th e an alysis of
h eard sou n ds th at are classified as w ords.
Aphasia. A disturban ce of lan gu age fu n ction is
called aphasia (differen t su btypes of aph asia are
som etim es collectively term ed “th e aph asias”).
Som e typ es of aph asia exclu sively affect speech ,
w ritin g (dysgraphia or agraphia), or readin g (dys-
lexia or alexia). Aph asia is distin ct from im pair-
m en t of th e p hysical act of speakin g, w h ich is
called dysarthria or anarthria (cau sed, for exam ple,
by lesion s of th e pyram idal tract, cerebellar fiber
p ath w ays, th e brain stem m otor n eu ron s in n ervat-
in g th e m u scles of speech , e.g., in bu lbar paralysis,
or th e m u scles th em selves).
Dysarth ria an d an arth ria affect art iculation an d
p h on ation , i.e., speech, rath er th an lan gu age p ro-
duction per se (gram m ar, m orph ology, syn tax, etc.).
Aph asia is called fluent or nonfluent, dep en din g on
w h eth er th e p atien t speaks easily an d rapidly, or
on ly h esitan t ly an d w it h abn orm al effort. Th e m ore
im portan t types of aph asia, th eir distin guish in g
featu res, an d th eir cortical localization are sum -
m arized in Table 9.1.
Broca aphasia. Th e m ost im port an t clin ical fin din g
in Broca aph asia (Case Presen tation 1, p. 250) is
m arkedly reduced or absent language production.
Th e p atien t can still u n derstan d w ords an d n am e
(sim ple) objects, but p rodu ces fau lty sen ten ces
(paragram m atism or agram m atism ) an d m akes
9 250 · 9 Cerebrum
Case Presentation 1: Broca Aphasia
This previously healthy 48-year-old bank em ployee was
dancing and chatting happily at his son’s high school gradua-
tion when his dance partner suddenly noticed that he could
no longer lead properly and had becom e unusually taciturn.
From that m om ent onward, his speech seem ed increasingly
labored, even though he had been telling one joke after
another only m inutes before. He could barely produce even
fragm entary sentences. He left the dance floor to take a
break and, shortly afterward, dropped a glass from of his
hand and began to com plain of a “dim feeling.” His wife took
him to the hospital.
a b
c d
Fig. 9.27 Cerebral infarct in Broca’s area due to dissec-
tion of the left internal carotid artery (MRI).
(a, b) a The axial diffusion-weighted im age reveals the in-
farcted brain tissue, which appears brighter than the sur-
rounding norm al tissue. It lies in the central portion of the
territory of the m iddle cerebral artery, m ainly in the inferior
frontal gyrus (Broca’s area, area 44). This area is supplied by
the prerolandic artery. b The coronal T2-weighted im age
Exam ining him , the neurologist on duty found a m ild, pre-
dom inantly m otor right hem isyndrom e. The patient’s right
lim bs felt heavy to him , his right arm sank when he ex-
tended both arm s in front of his chest, and the deep tendon
reflexes were slightly brisker on the right. He also had
m otor aphasia: he barely spoke at all except in response to
questions, to which he gave telegraphic, m onosyllabic an-
swers. He had difficulty finding words and nam ing objects,
and his sentence construction was faulty.
For the further diagnostic work-up, the neurologist ordered
Doppler ultrasonography of the great vessels of the neck
reveals hyperintense signal, corresponding to infarction, in
Broca’s area. The infarct focally involves this portion of the
inferior frontal gyrus on the upper bank of the sylvian fis-
sure. (c, d) c Axial T2-weighted FLAIR sequence. The in-
farct is hyperintense in com parison to the surrounding
tissue. d Contrast-enhanced MR angiography. Flow is
m arkedly reduced in the left internal carotid artery (arrow).
Fig. 9.27 e–h

and an MRI scan of the head. The form er revealed near-
occlusion of the left internal carotid artery, in which a dis-
section had apparently taken place, in the absence of any
vascular risk factors. The cause was thought m ost likely to
be the patient’s suddenly turning his head while dancing
(Fig. 9.27d, e, f). As a result of the carotid dissection,
ischem ia had developed in Broca’s area in the left, lan-
guage-dom inant hem isphere, as seen in the MRI scan
(Fig. 9.27a, b, c). The scan also showed a sm all area of
ischem ia in the precentral gyrus, which accounted for the
patient’s hem iparesis (Fig. 9.27g, h).
He was fully heparinized at once, and an overlapping treat-
ment with warfarin was initiated. In cases of carotid dissec-
e f
g h
Fig. 9.27 (e, f) Axial im ages at the C2 level, T1-weighted
(e) and T2-weighted (f). Both im ages reveal a hyperintense
mural hem atom a in the left internal carotid artery, indicat-
ing arterial dissection (arrow). (g, h) g The axial diffusion-
weighted im age reveals a second area of infarction in the
Functional Localization in the Cerebral Cortex · 251
9
tion, therapeutic anticoagulation serves to prevent further
m icroem bolism from the dissection site. The blood clot
within the vessel wall is usually resorbed over tim e, and the
defect is covered with new endothelium , so that the internal
carotid artery often regains its norm al patency within 4–6
m onths.
During his stay in the hospital, the patient underwent a
course of regular speech therapy and physical therapy. By
the tim e he was discharged, the hem iparesis had fully re-
solved and his speech had becom e entirely clear and error-
free. Six weeks later, he was asym ptom atic. Warfarin was dis-
continued when norm al patency of the internal carotid
artery was dem onstrated radiologically after five m onths of
treatm ent.
left precentral gyrus, accounting for the patient’s right arm
paresis. This area is supplied by the prerolandic artery.
h The axial T2-weighted FLAIR sequence reveals this second
infarcted area as a sm all zone of hyperintensity.
9 252 · 9 Cerebrum
Case Presentation 2: Wernicke Aphasia
This 54-year-old housewife had been seeing her fam ily doc-
tor regularly because of a persistent cardiac arrhythm ia in
the afterm ath of a bout of myocarditis. On one of these
routine visits, the doctor’s assistant, while perform ing an
ECG, noticed that the patient was not following her instruc-
tions. Instead, she was talking nonstop in an unintelligible
jargon, and she seem ed increasingly anxious and helpless.
The assistant sum m oned the doctor, whose neurological
a b
c d
Fig. 9.28 Infarct in Wernicke’s area (MRI).
(a, b) a The axial diffusion-weighted im age reveals the in-
farct as a zone of hyperintensity in the posterior (i.e.,
parieto-occipital) portion of the territory of the m iddle
cerebral artery, m ainly involving the angular and supra-
m arginal gyri. This area is supplied by the angular and post-
erior parietal arteries. b The coronal T2-weighted im age re-
veals the infarct as a zone of hyperintensity above the syl-
vian fissure. The focal involvem ent of Wernicke’s area is evi-
dent.
exam ination revealed a m ild right hem iparesis in addition
to the evident language disturbance. He arranged the
patient’s urgent adm ission to hospital.
The adm itting physician repeated the neurological exam i-
nation and perform ed a battery of neuropsychological
tests. The patient could easily im itate the exam iner’s m ove-
m ents and shake hands with him when asked to do so by
pantom im e, but linguistic com m unication was practically
(c, d) Axial T2-weighted FLAIRsequences. The infarct, which
is hyperintense in these im ages as well, is m ainly in the cor-
tex rather than the underlying white m atter. It lies m ainly in
the parietal lobe, involving the parietal operculum and the
angular and supram arginal gyri. The apical portion of the in-
farct likewise lies m ainly in the parietal, postcentral region,
but one can see that it also involves a sm all portion of the
precentral gyrus, accounting for the patient’s hem iparesis.
c shows the infarct extending to the wall of the lateral ven-
tricle; it thus presum ably involves the optic radiation. This
would be expected to cause a right visual field defect.

im possible, because of her severe jargon aphasia. When
asked how she was, she replied, “More were m arning”;
when asked her nam e, she replied, “Be give with them dan-
nifer.” She could not nam e objects such as a ball-point pen
(“dadathig”), book (“oughta thissum higher”), or lam p
(“here that sheller”). She answered open-ended questions
(“How are you?”) with long-drawn-out replies (“That from a
fleddra, where is that here, are here, what’s that doing
down though, he says, is too where long”). Requests m ade
with gestures, rather than with spoken language, such as to
write her nam e on the hospital’s adm ission sheet, copy
written sentences and drawings, or perform written calcu-
lations, were com plied with im m ediately and correctly. In-
terestingly, she could copy sentences of any length cor-
rectly, even longer ones, but she could not read them after-
ward, either silently or out loud. [Readers please note: the
phonem ic paraphasic errors (su bstitu tion or ex-
ch an ge of soun ds w ith in w ords, such as “ackle” for
“ap ple,” “parket” for “carp et”).
Wernicke aphasia. In classic Wern icke ap h asia (Case
Presen tat ion 2, p. 252), the understanding of lan-
guage is severely im paired. Th e patien t’s sp eech is
flu en t an d of n orm al prosody (m elody an d rhyt h m )
bu t m arred by frequ en t sem antic paraphasic errors
(substitu tion s or exch an ges of w ords w ith in clauses
or sen ten ces) an d by t h e u se of n eologism s (n on -
w ords) in stead of w ords. Th e patien t’s speech m ay
be so severely distu rbed as to be en t irely un in tel-
ligible (jargon aphasia or w ord salad).
Disconnection Syndromes
Discon n ect ion syn drom es are produ ced by t h e in-
terruption of fiber pathw ays connecting different
cortical areas, w h ile th e cortical areas th em selves
rem ain in t act . Th e respon sible lesion m ay affect
association , project ion , an d/or com m issu ral fibers
(p . 236 ff.).
Major in sigh t in to th e fu n ction of th e com m is-
sural fibers, in particu lar, h as been gain ed from
stu dies of so-called “split-brain” patien ts after su r-
gical tran section of th e corpu s callosu m (callo-
sotom y) for th e treatm en t of m edically in t ractable
epilepsy, as w ell as of person s w h ose corpu s callo-
sum failed to develop n orm ally (agenesis of the cor-
pus callosum ).
For ease of presen tation , w e w ill discu ss th e dis-
con n ection system s h ere in relation to th e variou s
fu n ction al system s of th e brain th at t h ey affect.
Functional Localization in the Cerebral Cortex · 253
9
jargon given here in quotation m arks is an approxim ate Eng-
lish rendition of the patient’s original Germ an jargon.]
An MRI scan showed the cause of the aphasia and m ild
hem iparesis to be a left parietal infarct involving Wernicke’s
area (Fig. 9.28a–d). This, in turn, was thought m ost likely to
be due to em bolism from the heart, in view of the patient’s
known, long-standing cardiac arrhythm ia. Transesophageal
echocardiography indeed revealed throm botic vegetations
in the left atrium . The patient was anticoagulated with he-
parin and an overlapping treatm ent with warfarin was in-
itiated to prevent further em bolization. Her spontaneous
speech gradually becam e m ore intelligible with intensive
speech therapy, though som e aspects of her language defi-
cit persisted until the day of her discharge from the hospital
(sem antic paraphasia and im paired com prehension).
Disconnection in the olfactory system. Th e ol-
factory path w ay is un ique am on g sen sory pat h -
w ays in bein g u n crossed: th e righ t an d left ol-
factory n erves sen d th eir im pu lses to th e olfactory
cortex of th e righ t an d left h em isph eres, respec-
tively (cf. p . 83). Th e tw o prim ary olfactory cen ters
are con n ected by t h e an terior com m issu re. A lesion
in terru ptin g th is fiber tract m akes th e patien t u n -
able to iden tify sm ells presen ted via th e righ t n os-
tril, becau se n o path w ay exists for tran sm ission of
th e olfactory in form ation to th e speech cen ter in
th e left h em isph ere. Th e p atien t can n ot n am e th e
source of th e sm ell (e.g., “cin n am on ”) sp on -
tan eou sly or pick th e appropriate n am e ou t of a
list. Sm ells presen ted via th e left n ostril, h ow ever,
are iden tified im m ediately.
Disconnection in the visual system. Th e decu ssa-
tion of th e fibers from th e n asal h alf of each ret-
in a in th e optic ch iasm (cf. pp . 84, 86) en sures
th at th e righ t an d left h alves of th e visu al field
are separately rep resen ted in t h e left an d righ t
visual cortices, respectively. Th erefore, if th e con -
n ection betw een th e tw o h em isp h eres is in ter-
rupted, visu al stim u li presen ted in th e left h alf of
th e visu al field w ill be cut off from processin g in
th e left h em isph ere: objects sh ow n in th e left
h alf of th e visu al field can n ot be n am ed, n or can
w ords be read (selective aphasia and alexia). Ob-
ject n am in g an d w ord readin g are u n im paired,
h ow ever, in th e righ t h alf of th e visual field. Con -
versely, com p lex spatial con struction s presen ted
in th e righ t h alf of th e visual field are cu t off from
processin g in th e righ t h em isph ere, an d so can -
9 254 · 9 Cerebrum
n ot be correctly an alyzed. Com p lex geom etric
figu res, for exam ple, can n ot be copied (acopia).
Complex Movements—Apra xia
Th e term “ap raxia” w as coin ed in th e 1870s by
Hu gh lin gs Jackson to den ote th e com plete in ability
of som e of h is aph asic pat ien ts to perform certain
volun tary m ovem en ts (e.g., ton gu e p rotrusion ),
despite t h e absen ce of any sign ifican t w eakn ess
an d reten tion of th e ability to m ove t h e sam e part
of th e body au tom atically or involu n t arily (e.g.,
w h en lickin g th e lips). Later, in th e early years of
th e tw en tieth cen tu ry, Liepm an n classified th e
differen t t ypes of apraxia (th e “apraxias”) system -
atically. In h is classificat ion , w h ich rem ain s in use,
ideational an d ideom otor apraxias m ain ly affectin g
th e m otor system are dist in gu ish ed from construc-
tion apraxias m ain ly affectin g th e visu ospatial sys-
tem . Apraxia, in gen eral, is a com p lex distu rban ce
of volu n tary m ovem en t th at does n ot resu lt from
w eakn ess or oth er dysfu n ction of th e prim ary
m otor areas, or from th e patien t’s lack of m otiva-
tion or failure to com preh en d th e task. It m an ifests
itself as an in ability to com bin e in dividu al,
elem en tary m ovem en ts in to com p lex m ovem en t
sequen ces, or to assem ble th ese sequ en ces th em -
selves in to still h igh er-order m otor beh aviors. Th e
in dividual m ovem en ts th em selves, h ow ever, can
still be carried ou t.
Motor apraxia. A patien t w it h severe m otor
apraxia can n ot execu te basic sequ en ces of m ove-
m en ts, su ch as reach in g ou t an d grasp in g an object,
even th ough isolated testin g of th e in dividu al
m uscle group s involved reveals n o w eakn ess in th e
arm or h an d.
Ideom otor apraxia resu lts from lesion s of th e lan -
gu age-dom in an t (left) h em isph ere, eith er in th e
m otor association areas or in th e association an d
com m issu ral fibers by w h ich th ey are in n ervated
an d in tercon n ected. A t ypical clin ical fin din g is th e
om ission , or prem at ure term in at ion , of in dividu al
com pon en ts of a sequ en ce of m ovem en ts. In -
dividu al com pon en ts can also be un n ecessarily re-
peated (m otor perseveration ), so th at th ey start at
in app ropriate tim es an d th ereby im pede or in ter-
rupt th e cou rse of th e n ext m ovem en t.
Patien ts w ith m otor apraxia w h ose lesion s lie in
th e parietal lobe can n ot correctly im itate th e ex-
am in er’s m ovem en ts (e.g., a m ilitary salute). Th ese
patien ts can often still copy facial expression s,
w h ile p atien ts w ith left fron tal lobe lesion s can
copy com plex arm m ovem en ts, bu t n ot facial ex-
pression s.
Ideational apraxia. In th is rarer type of apraxia, a
tem poroparietal lesion in th e lan gu age-dom in an t
(left) h em isph ere im p airs th e plan n in g an d in itia-
tion of com p lex m otor activities. Th e patien t re-
m ain s able, in p rin ciple, to carry out a com plex
sequ en ce of m ovem en ts, but seem s n ot to com p re-
h en d its m ean in g or p urpose. Th e patien t eith er
fails to in itiate th e m ovem en t or term in ates it pre-
m aturely.
Construction apraxia. Patien ts w ith con struction
apraxia h ave difficu lty draw in g spatial con struc-
tion s su ch as geom etrical figu res or objects. Th is
distu rban ce u sually resu lts from a lesion in th e
parietal lobe of th e n on -lan gu age-dom in an t (righ t)
h em isph ere.
Most ap raxic p atien ts are also aph asic. Patien ts
can suffer from ideom otor, ideation al, an d con -
structive apraxia sim u ltan eou sly, depen din g on
th e site an d extent of th e lesion .
Perceptual Integra tion—Agnosia a nd Neglect
Th e an terior portion of th e p arietal lobe, as w e h ave
seen , processes som atosen sory sign als, w h ile its
posterior port ion an d th e visu al association cor-
tices are con cern ed w ith th e in tegration of som a-
tosen sory, visual, an d m otor in form ation . Com p lex
activities, such as pou rin g a drin k w h ile carryin g on
a conversat ion , require th e sim u ltan eou s in tegra-
tion of m any differen t perceptual an d m otor
processes: th e objects h an dled (glass, bottle) m u st
be recogn ized, w h ich requires con ju gate eye m ove-
m en ts an d visual processin g; reach in g, graspin g,
an d pou rin g m ovem en ts m u st be sm ooth ly ex-
ecu ted; an d, at t h e sam e tim e, lan guage m u st be
h eard, u n derstood, form u lated, an d spoken .
In order to perform th ese tasks, th e brain n eeds
in tern al represen tation s of th e body, in form ation
abou t t h e position s of th e lim bs, an d a con ception of
th e ou tside w orld. Th ese represen tation s m ust, in
tu rn , be lin ked to in com in g visual an d auditory sig-
n als, an d to th e brain ’s plan s for in ten ded m ove-
m en t. Th e association cortices an d th e posterior
portion of th e parietal lobe play an essen t ial role in

th ese com plex in tegrative processes. As an illustra-
tion of th is role, th e posterior portion of th e p arietal
lobe is activated n ot on ly by in ten ded graspin g
m ovem en ts in duced by visual stim uli, but also by
palpat ion of an u n seen object.
Lesion s of th e visu al association cortices an d th e
pariet al lobe can produ ce m any differen t types of
agnosia, i.e., com plex disturban ces of perception . A
patien t w it h agn osia can n ot recogn ize object s or
spatiotem p oral con text s despite in tact prim ary
perception (n orm al vision , h earin g, an d som atic
sen sation ) an d m otor fun ct ion (absen ce of w eak-
n ess). Agn osia can be visu al, au ditory, som a-
tosen sory, or spatial.
Visual object agnosia. If th e visual association
areas are dam aged, th e patien t can still com pre-
h en d th e spatial structu re of fam iliar objects, but
can n o lon ger iden tify t h em . A bottle, for exam ple,
can be correctly draw n , bu t can n ot be iden tified as
a bot tle. Oth er, m ore com plex typ es of visual ag-
n osia in clude prosopagnosia (th e in ability to rec-
ogn ize faces) an d alexia (th e in ability to read).
Somatosensory agnosias. Astereognosia is th e in -
ability to recogn ize an object by touch alon e, even
th ough sen sation is in tact an d objects can ot h er-
w ise be n am ed w ith out difficu lty. Asomatognosia
is a gen erally dim in ish ed, or even absen t , ability to
perceive on e’s ow n body. Gerstmann syndrome
con sists of th e in ability to n am e on e’s ow n fin gers
(fin ger agn osia) alon g w ith an im pairm en t of w rit-
in g (dysgraph ia or agraph ia), calcu lation (dyscal-
cu lia or acalcu lia), an d th e ability to distin gu ish
righ t from left. Gerstm an n first described th ese
fin din gs in 1924 in a patien t w ith an isch em ic
stroke in th e territory of th e m iddle cerebral artery
affectin g th e left pariet al lobe.
Balint syndrome. Th is com p lex typ e of agn osia is
cau sed by bilateral p arieto-occipital lesion s. Th e
patien t origin ally described by Balin t cou ld n ot
volun tarily fix h is gaze on a given p oin t in space.
Wh en h is atten tion w as directed to a particular ob-
ject, h e cou ld n ot perceive any oth er visu al stim uli.
He also could n ot follow a m ovin g object w ith h is
eyes (visual ataxia).
Neglect. Patien ts som etim es pay less atten tion to
th e side of th e body or visu al field opp osite a corti-
cal lesion , or ign ore it altogeth er; th is is called neg-
Functional Localization in the Cerebral Cortex · 255
9
lect. Th ere is often an accom panyin g u n aw aren ess
of th e deficit (anosognosia). Neglect u su ally in -
volves vision , h earin g, som atic sen sation , spatial
p erception , an d m ovem en t sim u ltan eou sly. Th e
cau sative lesion is u su ally in th e parietal lobe of th e
n on -lan gu age-dom in an t (righ t) h em isph ere. A
p atien t w ith m otor n eglect m oves on e side of th e
body very litt le, or n ot at all, even t h ou gh it is n ot
p aralyzed. Sen sory n eglect is revealed by th e so-
called extinction phenomenon: w h en th e ex-
am in er sim u ltan eou sly taps th e sam e spot on both
arm s w ith equ al stren gth , t h e patien t reports
h avin g been tou ch ed on ly on on e side, even th ough
all m odalities of tou ch are in tact bilaterally. Th e
p atien t can still perceive a sin gle tap on th e arm on
th e abn orm al side, but m ay report it to h ave been
felt on th e ot h er side (allesthesia). Sim ilarly, sim u l-
tan eous bilateral visual or au ditory stim uli w ill
on ly be perceived on on e side.
Norma l a nd Impa ired Control of Beha vior,
Including Socia l Beha vior
Prefrontal cortex. Cogn ition an d th e con trol of be-
h avior are th e m ain fu n ction s of th e m ultim odal
associat ion areas in th e fron tal lobe th at con stitu te
th e p refron tal cortex (Fig. 9.18). Experim en tal elec-
trical stim u lation of th e prefron tal cortex does n ot
in du ce any m otor respon se. Th is portion of th e
fron tal lobe is extraordin arily en larged in prim ates,
an d particularly in h um an s; th us, it h as lon g been
presu m ed to be th e seat of h igh er m en tal fu n ction -
in g. Th e fron tal cortical fields m ake recip rocal con -
n ection s w ith th e m edial n u cleu s of th e th alam u s
(cf. p. 174), th rou gh w h ich th ey receive inpu t from
th e hypoth alam u s. Th ey also m ake very exten sive
con n ection s w ith all oth er areas of th e cerebral
cortex.
Th e task of th e prefron tal cortex is th e rapid
storage an d an alysis of objective an d tem poral in -
form ation . Th e dorsolateral prefron tal cortex plays
an essen tial role in th e p lan n in g an d con trol of be-
h avior, an d th e orbital prefron tal cortex does th e
sam e in t h e plan n in g an d con trol of sexual be-
h avior.
Lesions of the prefrontal convexity. Patien ts w ith
bilateral prefron tal lesion s can barely con cen t rate
on a task an d are extrem ely easy to distract w ith
any n ew st im u lu s. Th ey can carry ou t com plex
tasks on ly in part, or n ot at all. Th ey h ave n o sen se
9 256 · 9 Cerebrum

Case Presentation 3: Neglect

This 69-year-old retiree, living alone, had had poorly con-
trolled arterial hypertension for a num ber of years and two
brief episodes of left arm weakness in recent m onths. On
another occasion, he had been unable to see anything with
his right eye for a few m inutes. He had paid no further at-
tention to these transient disturbances, because he other-
wise felt well. Getting up from bed one night, he suddenly
fell to the ground and could not stand up again. He shouted
for help, waking a neighbor who had a spare key to his
apartm ent. She notified the em ergency physician on call,
who took him to the hospital.
The adm itting house officer perform ed a thorough neuro-
logical exam ination and found a m ild left hem iparesis, with
sinking of the left arm and leg and im paired fine m otor con-
trol of the left hand. The patient failed to notice a light tap
on the left side of his body when sim ultaneously tapped at
a m irror-im age location on the right side (tactile extinc-
tion). He did not react when spoken to from his left side.
When the doctor asked him to draw a house and a tree, he
drew only the right sides of these objects. He generally
tended to look to the right and appeared to be conscious
only of the right side of space. The cause of these acute
neurological deficits was an approxim ately 80 % stenosis of
the right internal carotid artery, which had led to a right
hem ispheric infarct in the distribution of the m iddle cere-
bral artery (Fig. 9.29).

a b

Fig. 9.29 Infarct in the territory of the

right middle cerebral artery, causing neg-
lect (MRI). a Axial EPI sequence. b Axial T2-
weighted FLAIR sequence. The axial im ages
reveal an infarct affecting the posterior por-
tion of the m iddle cerebral artery territory
on the right, reaching far back into the
occipital lobe and to the wall of the lateral
ventricle. Involved areas include the tem -
poral lobe, the angular and supram arginal
gyri of the parietal lobe, and the occipital
lobe. The patient’s hem ianopsia is due to
involvem ent of the optic radiation and
occipital lobe. c Sagittal T2-weighted
im age. The hyperintense zone of infarction
c is seen behind and under the sylvian fissure.

of advan ce plan n in g an d take n o accoun t of fu tu re
even ts or of possible problem s in th e execu tion of a
task. Th ey often stick rigidly to an idea an d fail to
adapt to ch an gin g circu m stan ces. In extrem e cases,
th ey m an ifest perseveration, i.e., th ey perform th e
sam e task again an d again , alw ays w it h th e sam e
m istakes. Th is deficit is strikin gly brough t ou t by
th e Wiscon sin Card Sortin g Test, in w h ich th e
patien t sorts cards bearin g variou s sym bols an d
colors accordin g to som e criterion (e.g., sh ape),
after seein g th e exam in er do so. Perform an ce in
th e first rou n d is u su ally relat ively n orm al. Th e ex-
am in er con firm s th e patien t’s su ccess, th en
ch an ges th e sortin g criterion (e.g., to color)
w ith out explicitly sayin g so. A patien t w ith a pre-
fron tal lesion realizes abou t as rap idly as a n orm al
in dividual th at th e task h as ch an ged, yet keeps
sortin g accordin g to th e old criterion , despite bein g
im m ediately in form ed of each m istake.
Markedly reduced drive an d lack of spontaneity
are also ch aracteristic clin ical sign s of prefron t al
dysfun ct ion . Th ese deficit s are revealed by very
poor perform an ce on th e Word Flu en cy Test, in
w h ich th e patien t is given a sh ort period of tim e to
say as m any w ords as possible th at begin w ith a
part icular letter of t h e alph abet. Patien t s w ith pre-
fron tal lesion s do badly despite relatively n orm al
verbal m em ory. Th ey do badly on n onverbal tests
Functional Localization in the Cerebral Cortex · 257
9
as w ell: n orm al su bjects can draw about 35 pic-
tu res in five m in utes, patien ts w ith left fron tal le-
sion s 24, patien ts w ith righ t fron tal lesion s 15. Be-
cau se th ey lack spon tan eity in all form s of com -
m un ication , th ese patien ts seem lazy, leth argic,
an d un m otivated. Th ey n eglect m any activities of
daily life, spen d th e m orn in g in bed, fail to w ash or
groom th em selves or to get dressed w ith out h elp ,
an d do n o regular w ork. Non eth eless, th eir form al
IQ an d lon g-term m em ory are largely in tact!
Fronto -orbital lesions. Social an d sexual beh avior
are con trolled an d regulated by h igh ly com p lex
processes. Beh avior of t h ese types, too, is abn orm al
in patien ts w ith fron tal lobe lesion s. Fron to-orbital
lesion s, in particular, p rodu ce tw o ch aracteristic
types of person ality distu rban ce. Pseudo -depres-
sive patien t s are apath etic an d in differen t an d dis-
play m arkedly reduced drive, dim in ish ed sexu al
desire, an d little or n o variation in th eir em otion al
state. Pseudo -psychopathic patien ts, on th e oth er
han d, are hyp om an ic an d restless in th eir m ove-
m en ts, fail to keep an ap propriate distan ce from
oth ers, an d lack n orm al kin ds of in h ibition . Th ey
display m arkedly in creased drive an d sexual
desire. Th ey are u nw illin g or u n able to h old to th e
sam e n orm al conven tion s of beh avior th at th ey
follow ed u n qu estion in gly before becom in g ill.
9 258
 10

10 Coverings of the Brain

and Spinal Cord;
Cerebrospinal Fluid
and Ventricular System
Coverings of the Brain and Spinal
Cord . . . . . . . . . . . . . . . . . . . . . . . . . . . . 260
Cerebrospinal Fluid and Ventricular
System . . . . . . . . . . . . . . . . . . . . . . . . . . 263
10 260
10 Coverings of the Brain and Spinal Cord;
Cerebrospinal Fluid and Ventricular System
Th e brain an d spin al cord are covered by th ree lay-
ers (m en in ges) of m esoderm al origin : th e tough
dura mater is outerm ost , follow ed by th e
arachnoid an d, lastly, th e pia mater. Th e pia m atter
lies directly on th e su rface of th e brain an d sp in al
cord. Betw een th e du ra m ater an d th e arach n oid is
th e (n orm ally on ly virtual) subdural space; be-
tw een th e arach n oid an d th e pia m ater is th e sub-
arachnoid space. Th e subarach n oid space con tain s
th e cerebrosp in al flu id (CSF).
Th e cerebrospinal fluid is form ed in th e ch oroid
plexu ses of th e four cerebral ven tricles (righ t an d
left lateral ven tricles, th ird ven tricle, an d fourth
ven tricle).
Coverings of the Brain and
Spinal Cord
Th e th ree m en in ges (dura m ater, arachnoid, pia
m ater) are depicted in Figs. 10.1 an d 10.2. Th e du ra
m ater is also called th e pachym eninx (“tough m em -
bran e”), w h ile th e arach n oid an d pia m ater are col-
lectively called th e leptom eninges (“delicate m em -
bran es”).
Dura Mater
Th e dura m ater con sists of tw o layers of tou gh ,
fibrous con n ect ive tissue.
Outer and inner layers. Th e ou ter layer of th e
cran ial du ra m ater is th e p eriosteu m of th e in side
of th e sku ll. Th e in n er layer is th e actu al m en in geal
layer; it form s th e ou ter lim it of th e very n arrow
subdu ral sp ace. Th e tw o dural layers separate from
each oth er at th e sites of th e du ral sin uses. Be-
tw een th e su perior an d in ferior sagittal sin uses, a
dou ble fold of th e in n er du ral layer form s th e falx
cerebri, w h ich lies in t h e m idsagittal plan e be-
tw een th e tw o cerebral h em isph eres; th e falx cere-
bri is con tin uou s w ith th e tentorium , w h ich sepa-
rates th e cerebellum from th e cerebru m . Ot h er
structu res form ed by a double fold of in n er dura
It flow s th rough th e ven tricular system (in tern al
CSF space) an d th en en ters th e su barach n oid
space su rroun din g t h e brain an d spin al cord (ex-
tern al CSF space). It is resorbed in th e arach n oid
gran u lation s of th e su perior sagittal sin us an d in
th e perin eural sh eath s of th e sp in al cord. An in-
creased volume of cerebrospinal fluid (because of
eith er dim in ish ed resorpt ion or—less com m on ly—
in creased production ) m an ifests itself in in -
creased CSF p ressu re an d en largem en t of th e ven -
tricles (hydrocephalus).
m ater are th e falx cerebelli separat in g th e tw o cere-
bellar h em isph eres, th e diaphragm a sellae an d th e
w all of Meckel’s cave, w h ich con tain s th e gasserian
(trigem in al) gan glion .
Blood supply of the dura mater. Th e dural arteries
are relat ively large in caliber becau se th ey sup ply
th e bony sku ll as w ell as th e du ra m ater. Th e largest
is th e middle meningeal artery, w h ose bran ch es
are distribu ted over th e en tire lateral convexity of
th e skull. Th is artery is a bran ch of th e m axillary
artery, w h ich is, in tu rn , derived from t h e extern al
carotid artery; it en ters th e sku ll th rou gh th e fora-
m en spin osu m . Th e anterior meningeal artery is
relatively sm all an d sup plies th e m idportion of th e
fron t al dura m ater an d th e an terior portion of th e
falx cerebri. It en ters th e sku ll t h rou gh th e an terior
portion of th e cribriform p late. It is a bran ch of th e
an terior eth m oidal artery, w h ich is, in tu rn , a
bran ch of t h e op h th alm ic artery; it th erefore car-
ries blood from th e in tern al carotid artery. Th e
posterior meningeal artery en ters th e sku ll
th rou gh th e ju gu lar foram en to supp ly th e du ra
m ater of th e posterior cran ial fossa.
Th e m iddle m en in geal artery m akes an an asto-
m otic con n ection in th e orbit to th e lacrim al artery,
a bran ch of th e oph th alm ic artery. Th e oph th alm ic
artery bran ch es off th e in tern al carotid artery n ear
th e in tern al apertu re of th e optic can al. Th u s, in
 Coverings of the Brain and Spinal Cord · 261
10
Fig. 10.1 Meninges of
Superior sagittal Arachnoid the brain (schem atic draw-
sinus granulations ing, coronal view)

Cranial dura mater

Epidural space

Subdural space

Subarachnoid
space

Pia mater of the brain

Cerebral cortex

Cranial
arachnoid

Fig. 10.2 Meninges of

Epidural space with the spinal cord (schem atic
veins and fat drawing, transverse view)
Spinal dura mater

Spinal arachnoid

Subarachnoid
space

Periosteum

Pia mater of
the spinal cord

Denticulate
ligam ent

som e cases, th e cen tral retin al artery can obtain
blood by w ay of t h e m iddle m en in geal artery, even
if th e op h th alm ic artery is proxim ally occlu ded.
Spinal dura mater. Th e tw o layers of th e du ra m ater
adh ere tigh tly to each oth er w it h in t h e cran ial cav-
ity but separate from each oth er at th e ou ter rim of
th e foram en m agn u m . Th e ou ter du ral layer con -
tin u es as th e periosteu m of th e sp in al can al, w h ile
th e in n er layer form s th e du ral sac en closin g th e
spin al cord. Th e space bet w een th e tw o layers is
called th e epidu ral or extradu ral space, even
th ough it is, strictly speakin g, in side th e du ra
m ater. It con tain s loose con n ective tissu e, fat, an d
th e in tern al ven ou s plexu s (Fig. 10.2, Fig. 11.20,
p. 284). Th e tw o layers of th e spin al du ra m ater join
w h ere th e spin al n erve roots exit from th e spin al
can al th rough th e in tervertebral foram in a. Th e
low er en d of th e du ral sac en closes th e cau da
equ in a an d term in ates at th e S2 level (Fig. 3.22,
p. 54). Its con tin uation below th is level is th e filu m
of th e du ra m ater, w h ich is an ch ored to th e sacral
periosteu m by th e fibrous coccygeal ligam en t.
10 262 · 10 Coverings of the Brain and Spinal Cord; Cerebrospinal Fluid and Ventricular System

Orbital dura mater. A sim ilar division of th e t w o

Interventricular
layers of th e dura m ater is fou n d in th e orbit, w h ich foram en
Corpus callosum Fornix
th e du ra m ater reach es from th e cran ial cavity by Suprapineal
recess
exten sion alon g th e optic can al. Th e ou ter du ral
Pineal body
layer is th e periosteal lin in g of th e bony orbit. Th e Collateral
trigone
in n er du ral layer su rrou n ds th e optic n erve, to-
geth er w ith its p ia m ater an d arach n oid, as w ell as
th e perioptic su barach n oid space in betw een . Th is Anterior horn of
lateral ventricle Posterior horn of
space com m un icates w ith t h e subarach n oid sp ace Third ventricle lateral ventricle
Optic recess
of th e cran ial cavity. Th e in n er du ral layer is con -
Infundibular recess
tin uous w ith th e sclera as t h e optic n erve en ters
Inferior horn of
th e globe. lateral ventricle
Cerebral aqueduct
and fourth ventricle
Papilledem a. Th e du ral sh eath of th e optic n erve Lateral recess and
lateral aperture of Median aperture
can be stretch ed if elevated in tracran ial pressure is Lateral fourth ventricle
ventricles of fourth ventricle
tran sm itted to th e perioptic su barach n oid space.
Retrobulbar stretch in g of th e dural sh eath is a
m ajor factor in th e developm en t of papilledem a. b
An ot h er cau se of papilledem a is acu te in tracran ial
subarach n oid h em orrh age (du e to a ru ptu red Third ventricle
an eu rysm or vascular m alform ation ) w ith blood
exten din g in to th e perioptic su barach n oid sp ace. Fourth ventricle

Innervation. Th e du ra m ater above th e ten toriu m is a

in n ervated by bran ch es of t h e trigem in al n erve, its
in fraten torial portion by bran ch es of th e u pper cer- Fig. 10.3 Ventricular system. a Position of the ventricular
vical segm ental n erves an d th e vagu s n erve. Som e system in the brain. b Anatom ical structure.
of t h e du ral n erves are m yelin ated, w h ile ot h ers
are u n m yelinated. Th eir en din gs eviden tly respon d brain , an d m ost of th e cran ial n erves, ru n in th e
to stretch , becau se m ech an ical stim u lation of th e su barach n oid space.
du ra can be con sciou sly felt, an d is often pain ful.
Th e afferen t fibers accom p anyin g th e m en in geal Cisterns. Th e subarach n oid cistern s of th e h ead
arteries are particu larly sen sitive to pain . h ave in dividual n am es, e.g., th e cerebellom edu l-
lary cistern , also called th e cisterna m agna. Th e
m ore im portan t n am ed cistern s are depicted in
Arachnoid
Fig. 10.4, p . 263.
Th e arach n oid of both th e brain an d th e spin al cord
is a th in , delicate, avascu lar m em bran e closely ap- Pia Mater
plied to th e in n er surface of th e du ra m atter. Th e
Th e pia m ater con sists of th in layers of m esoderm al
space betw een th e arach n oid an d th e pia m ater
cells resem blin g en doth eliu m . Un like th e
(th e su barach n oid space) con tain s th e cerebrospi-
arach n oid, it covers n ot ju st th e en t ire extern ally
n al fluid. Th e arach n oid an d th e pia m ater are con -
visible su rface of th e brain an d spin al cord but also
n ected to each oth er across th is sp ace by delicate
all of th e h idden su rfaces in th e depth s of th e sulci
stran ds of con n ective tissu e. Th e pia m ater adh eres
(Figs. 10.1 an d 10.2). It is fixed to th e cen tral n ervou s
to th e su rface of th e brain alon g all of its foldin gs;
tissue ben eath it by an ectoderm al m em bran e con -
th us, th e su barach n oid sp ace is n arrow er in som e
sistin g of m argin al astrocytes (pial-glial m em -
places, an d w ider in oth ers. En largem en ts of th e
bran e). Blood vessels th at en ter or leave th e brain
subarach n oid sp ace are called cisterns. Th e cran ial
an d spin al cord by w ay of th e subarach n oid space
an d spin al subarach n oid spaces com m u n icate
are su rrou n ded by a fu n n el-like sh eath of pia m ater.
directly w ith each oth er across th e foram en m ag-
Th e space betw een a blood vessel an d th e pia m ater
n u m . Most of th e arterial tru n ks sup plyin g th e
arou n d it is called th e Virchow–Robin space.

Choroid plexus of
the lateral ventricle
Interhem ispheric
cistern
Interven-
tricular foramen
Basal Chiasmatic cistern
cistern Interpeduncular cistern
Cerebral aqueduct
Ponto-
medullary cistern
Th e sen sory n erves of th e pia m ater, u n like t h ose
of th e du ra m ater, do n ot respon d to m ech an ical or
th erm al stim u li, bu t th ey are th ough t to resp on d to
vascu lar stretch an d ch an ges in vascu lar w all ton e.
Cerebrospinal Fluid and
Ventricular System
Structure of the Ventricular System
Th e ven tricular system (Fig. 10.3) con sists of th e
tw o lateral ventricles (each of w h ich h as a fron tal
h orn , cen tral portion = cella m edia, posterior h orn ,
an d in ferior h orn ); th e n arrow third ventricle,
w h ich lies betw een th e tw o h alves of th e dien -
cep h alon ; an d th e fourth ventricle, w h ich exten ds
from pon tin e to m edu llary levels. Th e lateral ven -
tricles com m un icate w ith th e th ird ven tricle
th rough th e in terven tricu lar foram in a (of Mon ro);
th e th ird ven tricle, in tu rn , com m un icates w ith th e
fou rth ven tricle th rough th e cerebral aqu educt.
Th e fou rth ven tricle em pties in to th e subarach n oid
Cerebrospinal Fluid and Ventricular System · 263
10
Fig. 10.4 Circulation of
the cerebrospinal fluid
Arachnoid
granulations
Choroid plexus of
the third ventricle
Transverse
cistern
Ambient
cistern
Verm ian cistern
Choroid plexus of the
fourth ventricle
Cerebellomedullary
cistern with median
aperture of the
fourth ventricle
space t h rou gh th ree open in gs: th e sin gle m edian
apertu re (foram en of Magen die) an d th e paired
lateral apertu res (foram in a of Lu sch ka).
Cerebrospinal Fluid Circulation and
Resorption
Properties of the cerebrospinal fluid. Th e n orm al
cerebrospin al fluid is clear and colorless, con tain in g
only a few cells (up to 4/µl) an d relatively little protein
(ratio of CSF albu m in to serum album in = 6.5 ± 1.9 ×
10 -3 ). Its com position differs from th at of blood in
oth er resp ects as w ell. Th e cerebrospin al fluid is n ot
an u ltrafilt rate of blood; rat h er, it is act ively
secreted by th e ch oroid plexu s, m ain ly w ith in th e
lateral ven tricles. Th e blood w ith in th e cap illaries of
th e ch oroid plexu s is separated from th e su b-
arach n oid sp ace by th e so-called blood–CSF barrier,
w h ich con sists of vascu lar en doth eliu m , basal
m em bran e, an d plexus ep ith eliu m . Th is barrier is
perm eable to w ater, oxygen , an d carbon dioxide,
bu t relatively im perm eable to elect rolytes an d
com pletely im perm eable to cells.
10 264 · 10 Coverings of the Brain and Spinal Cord; Cerebrospinal Fluid and Ventricular System

Table 10.1 CSF Findings in Diseases of the Central Nervous System

Diagnosis Appeara nce Pandy Cell Count, Biochemistry Other Findings

Reaction Cytology

Normal lumbar Clear, colorless — Up to 4 cells/µl, Lactate 2.1 m m ol/l. Glucose 50−60 % of
CSF m ainly lym phocytes Album in ratio: blood level
(85 %) Adults over 40 years, 8;
under 40 years, 7;
children under 15 years, 5
Purulent (bacte- Turbid +++ Several thousand/µl, Lactate 3.5 m m ol/l; Dem onstration of
rial) meningitis m ainly neutrophils album in ratio 20 × 10 −3 bacteria
Brain abscess Clear, occasion- +/- A few hundred/µl, Album in ratio norm al or Low glucose,
ally turbid m ononuclear cells m ildly elevated bacteria som etim es
and/or neutrophils dem onstrable, local
IgA synthesis
Encephalitis Clear, colorless +/- Norm al or m ononu- Album in ratio IgG, IgM, IgA ele-
(herpes simplex) clear pleocytosis 10 × 10 -3 vated; dem onstra-
(lym phocytes) tion of specific Ab,
PCR positive for HSV
Viral meningitis Clear + Up to several Album in ratio up to
hundred m ononu- 20 × 10 −3 ;
clear cells, including lactate 3.5 m m ol/l
activated B lym pho-
cytes
Tuberculous Yellow-tinged +++ Up to 1500/µl, m ixed Album in ratio IgG and IgA ele-
meningitis cellular picture, 20 × 10 −3 ; vated; mycobacteria
m ostly m ononuclear glucose 50 % of serum dem onstrated by
cells glucose culture and PCR
Neurosyphilis Clear or turbid +/- Mononuclear pleocy- Im m unoglobulins
tosis elevated, TPHA posi-
tive
Multiple Clear, colorless +/- Up to 40 m ono- Album in ratio Oligoclonal bands
sclerosis nuclear cells/µl 20 × 10 −3 revealed by isoelec-
tric focusing
Acute neuro- Clear Up to a few hundred Album in ratio Im m unoglobulins
borreliosis m ononuclear cells/µl 50 × 10 −3 elevated, dem on-
(Lyme disease) stration of antibody
Fungal Clear Up to a few hundred Im m unoglobulins
meningitis m ononuclear cells/µl elevated, dem on-
stration of fungi by
culture and special
stains
Polyradiculitis Clear No m ore than m ild Album in ratio up to 50 ×
(Guillain–Barré pleocytosis 10 −3 (“album ino-cytologi-
syndrome) cal dissociation”)

Th e circulating CSF volume is gen erally betw een
130 an d 150 m l. Every 24 h ou rs 40 0–50 0 m l of CSF
are produced; t h u s, th e en tire CSF volu m e is ex-
ch an ged th ree or fou r tim es daily. Th e CSF pressure
(n ote th at th e CSF p ressu re is n ot t h e sam e as th e
in tracran ial pressu re) in th e sup in e position is n or-
m ally 70–120 m m H2 O.
In fectiou s or n eoplastic p rocesses affectin g th e
CNS alter th e com position of th e cerebrospin al
flu id in ch aracteristic w ays, as sum m arized in
Table 10.1.
Circulation. Th e CSF is produ ced by th e ch oroid
plexus of th e lateral ven tricles, th ird ven tricle, an d

Case Presentation 1: Norma l Pressure Hydrocepha lus
This retired 80-year-old m an suffered for several m onths
from urge incontinence, which was initially attributed to his
benign prostatic hypertrophy. Over tim e, however, other
sym ptom s developed: he felt unsteady while walking,
walked with his feet wide apart, and fell m ultiple tim es. He
som etim es com plained that he could barely lift his feet off
the ground. His fam ily physician ordered an MRI scan of the
head (Fig. 10.5) and, after viewing the im ages, referred him
for adm ission to hospital. The patient’s wife, in response to
the specific questions of the adm itting neurologist, re-
ported that he had becom e increasingly forgetful and inat-
tentive in recent m onths. Neurological exam ination re-
vealed an unsteady, apraxic gait. The clinical and radiologi-
Cerebrospinal Fluid and Ventricular System · 265
10
cal diagnosis was norm al pressure hydrocephalus (NPH).
Transient im provem ent of gait after rem oval of a large
quantity of cerebrospinal fluid is considered to confirm the
diagnosis of NPH. Even in this 80-year-old patient, a lum bar
puncture and rem oval of 40 m l of cerebrospinal fluid re-
sulted in m arked im provem ent of gait, as well as com plete
resolution of urinary incontinence. His cognitive difficulties
were unchanged, however.
He was transferred to the neurosurgical service for the in-
sertion of a shunt. In the ensuing m onths, his gait becam e
norm al and his urinary incontinence resolved com pletely.
His cognitive difficulties rem ained, but did not progress.

a b

Fig. 10.5 Normal pressure hydrocephalus

(NPH) (com m unicating hydrocephalus), as
seen on MRI. Axial T2-weighted FLAIR im age
(a), coronal im age (b), and sagittal T2-
weighted spin-echo im age (c). The ventricles
are disproportionately enlarged in relation to
the subarachnoid space. The sagittal im age
(c) reveals low signal intensity in the aque-
duct and neighboring portions of the third
and fourth ventricles (arrow) because of
rapid CSF flow (“flow void”). Recent studies
have shown that CSF pulsatility is greater
than norm al, as a rule, in patients with NPH.
The im ages are m ildly blurred because of
patient m ovem ent; persons with NPH and
c other dem enting illnesses are often unable
to cooperate fully with MRI studies.
10 266 · 10 Coverings of the Brain and Spinal Cord; Cerebrospinal Fluid and Ventricular System
fou rth ven tricle (Fig. 10.4). It flow s th rou gh t h e
foram in a of Lusch ka an d Magen die (Figs. 10.3b an d
10.4) in to th e su barach n oid space, circulates
arou n d t h e brain , an d flow s dow n in to th e spin al
subarach n oid space su rrou n din g th e spin al cord.
Som e of th e CSF is resorbed at spin al levels (see
below ). Th e com position of th e CSF is th e sam e at
all poin ts; it is n ot m ore dilu te or m ore con cen -
trated at eit h er en d of th e path w ay.
Resorption. CSF is resorbed (i.e., rem oved from th e
subarach n oid space) in tracran ially an d alon g th e
spin al cord. Som e of th e CSF leaves t h e su b-
arach n oid sp ace an d en ters th e bloodstream
th rough th e m any villous arachnoid granulations
located in th e su perior sagittal sin u s an d in th e di-
ploic vein s of th e sku ll. Th e rem ain der is resorbed
in th e p erin eu ral sh eath s of th e cran ial an d spin al
n erves, w h ere th ese n erves exit th e brain stem an d
spin al cord, respect ively, an d across th e epen dym a
an d capillaries of th e leptom en in ges.
Th u s, CSF is con stan tly bein g produ ced in th e
ch oroid plexu ses of th e ven tricles an d resorbed
again from t h e su barach n oid space at variou s loca-
tion s.
Bottlenecks of the CSF circulation. As it flow s
th rough th e ven tricu lar system , th e CSF m ust
traverse a n u m ber of n arrow passagew ays: t h e in-
terventricular foram ina, th e slen der third ventricle,
th e cerebral aqueduct (n arrow est p oin t), an d th e
exit foram ina of the fourth ventricle an d t h e ten -
torial apertu re.
Disturbances of Cerebrospinal Fluid
Circulation—Hydrocephalus
General aspects of pathogenesis. Many differen t
diseases cau se an im balan ce of CSF production an d
resorption . If too m u ch CSF is produced or too little
is resorbed, th e ven tricu lar system becom es en -
larged (hydroceph alus). Elevated CSF pressu re in
th e ven tricles leads to displacem en t, an d even tu-
ally at rophy, of th e periven t ricular w h ite m atter,
w h ile th e gray m atter is n ot affected, at least at
first. As an im al experim en ts h ave sh ow n , hydro-
cep h alu s cau ses seep age (diaedesis) of CSF
th rough th e ven tricular epen dym a in to th e per-
iven tricu lar w h ite m at ter. Th e elevated hydrostatic
pressure in th e w h ite m atter im p airs tissue perfu -
sion , causin g local tissu e hypoxia, dam age to m y-
elin ated n erve path w ays, an d, u ltim ately, irreversi-
ble gliosis. Th e h istological an d clin ical abn orm ali-
ties caused by hydroceph alus can regress on ly if
th e in traven tricu lar p ressu re is brou gh t back to
n orm al in tim ely fash ion .
Types of Hydrocepha lus
Differen t clin ical varieties of hydroceph alus can be
conven ien tly classified by etiology, by th e site
w h ere CSF flow is blocked, an d by th e dyn am ic sta-
tu s of th e path ological process (e.g., active hydro-
ceph alu s due to con gen ital aqu eductal sten osis).
Classification by etiology and pathogenesis. Hy-
droceph alu s du e to obstruction of th e CSF path -
w ays is called occlusive hydrocephalus, w h ile th at
du e to in adequ ate CSF resorption is called malre-
sorptive hydrocephalus (see Fig. 10.6). Occlusive
hydroceph alu s is typ ically du e to an in tracran ial
space-occupyin g lesion (e.g., tum or, in farct, or
h em orrh age, p articu larly in th e p osterior fossa) or
m alform ation (e.g., aquedu ctal sten osis, colloid
cyst of th e th ird ven tricle). Malresorptive hydro-
ceph alu s often arises in th e afterm ath of su b-
arach n oid h em orrh age an d m en in git is, bot h of
w h ich can produ ce occlu sive adh esion s of th e
arach n oid gran u lation s. Hydroceph alu s can also
resu lt from trau m atic brain in ju ry an d in -
traven tricu lar h em orrh age. Hypersecretory hydro-
cephalus, du e to overp rodu ction of CSF, is m u ch
rarer; it is u su ally caused by a tum or (papillom a) of
th e ch oroid p lexus.
Older, altern at ive, an d essen tially syn onym ous
term s for m alresorptive an d occlusive hydro-
ceph alu s are “com m un icatin g” an d “n on com m un i-
catin g” hydroceph alu s, respectively. In communi-
cating hydrocephalus, th e CSF circulates freely
from th e ven t ricu lar system to th e su barach n oid
cistern s. In noncommunicating hydrocephalus,
th ere is an obstru ction to CSF flow w ith in th e
ven tricu lar system , so th at th e con n ect ion from t h e
ven tricles to t h e CSF-resorbin g st ru ct ures is n o
lon ger paten t, or can on ly be kept open un der ab-
n orm ally h igh pressu re.
Classification by dynamics. Hydroceph alu s is called
active if t h e in t raven tricu lar pressu re is con t in u -
ou sly elevated. Th ere are t w o types of active hydro-
ceph alu s. In com pensated active hydrocephalus, th e
ven t ricu lar size an d th e patien t ’s sym ptom s an d

Case Presentation 2: Ma lresorptive Hydrocepha lus after Suba rachnoid Hemorrhage (SAH)
This 52-year-old m an was adm itted to the hospital because
of an acute, severe headache—the worst headache of his
life—and m ild som nolence. A CT scan of the head revealed
the cause: acute subarachnoid hem orrhage (SAH). Cerebral
angiography showed the source of bleeding to be a rup-
tured aneurysm of the left m iddle cerebral artery. The
a b
Fig. 10.6 Malresorptive hydrocephalus after aneurys-
mal subarachnoid hemorrhage (SAH); CT of head. The
subarachnoid space is filled with hyperdense (bright) blood
(a), which im pairs CSF circulation and resorption. The ven-
tricles are dilated, particularly the tem poral horns (b). The
sign s rem ain con stan t over t im e; in uncontrolled
hydrocephalus, th e patien t ’s con dit ion w orsen s
w h ile th e ven tricles con tin u e to en large. Active hy-
droceph alu s is n ot th e sam e as n orm al pressu re
hydrocep h alu s (see below ), in w h ich t h e CSF p res-
sure is on ly in term itten tly elevated.
Normal pressure hydrocephalus (NPH). NPH is a
special case am on g t ypes of hydrocep h alu s, gen er-
ally involvin g com m u n icatin g hydroceph alus w it h
abn orm al CSF flow dyn am ics an d on ly in term it-
ten tly elevated in traven tricu lar pressure. Th e
ch aracterist ic clin ical t riad of NPH con sists of
apraxic gait disturbance, dem entia, an d urinary in-
continence (Case Presen tation 1, p. 265). Its cause is
un clear; it m ay be th e com m on clin ical expression
of a n u m ber of differen t disease processes (aqu e-
du ctal sten osis, m alresorptive hydroceph alus, etc.).
Cerebrospinal Fluid and Ventricular System · 267
10
blood in the subarachnoid space blocked the outflow and
resorption of CSF, leading to widening of the ventricles (hy-
drocephalus, Fig. 10.6). A tem porary external ventricular
drain was inserted to treat the hydrocephalus, and the
aneurysm was then clipped in an open neurosurgical pro-
cedure.
ventricles are black in the CT scan because they contain
very little blood. A sm all am ount of blood has entered the
ventricular system by reflux and can be seen in the posterior
horns of the lateral ventricles (blood–CSF levels, arrows, b).
Differential diagnosis: “hydrocephalus ex vacuo.”
Degen erative diseases of t h e brain , such as
Alzh eim er disease an d Pick disease, cau se brain
atrop hy, w ith secon dary en largem en t of th e in ter-
n al an d extern al CSF spaces. Th is m ay create th e
im pression of hydroceph alu s. Strictly speakin g,
h ow ever, hydroceph alus is presen t on ly w h en th e
in tern al CSF spaces (i.e., th e ven tricu lar system ) are
en larged out of prop ortion to th e extern al spaces,
an d n ot w h en both are en larged by atrophy. Th e
older term “hydrocep h alu s ex vacuo” for t h e latter
con dition is, th erefore, n ot recom m en ded. Un like
NPH, in w h ich th e ven tricles are en larged but th e
sulci are of relatively n orm al w idth , n eu ro-
degen erative diseases cau se en largem en t of th e in -
tern al an d extern al CSF sp aces to a rou gh ly com -
parable exten t.
10 268 · 10 Coverings of the Brain and Spinal Cord; Cerebrospinal Fluid and Ventricular System
Genera l Aspects of the Clinica l Presenta tion,
Diagnostic Eva luation, and Trea tment of
Hydrocepha lus
Epidemiology. Many types of hydroceph alu s begin
in ch ildh ood, usually accom panyin g oth er abn or-
m alities of developm en t, su ch as th e Ch iari m alfor-
m ation , spin a bifida, or m en in go(m yelo)cele. Th e
prevalen ce of hydroceph alus in th e first th ree
m on th s of postn atal life is 0.1–0.4 %.
Manifestations in children. Th e cran ial su tu res do
n ot close un til on e year after birth ; th rou gh ou t th e
first year of life, th e sku ll bon es can respon d to ele-
vated in t racran ial pressu re by spreadin g w ider
apart. Th u s, th e m ost obvious clin ical sign of ch ild-
h ood hydroceph alus is abnorm al grow th of the
head, w ith disprop ortion ate en largem en t of th e
sku ll in relat ion to th e face. Furth er sign s in clu de
gapin g cran ial su tu res, stasis of th e scalp vein s,
fron t al bossin g, an d tigh tly bulgin g fon tan elles.
Percu ssion of th e h ead produ ces a rattlin g sou n d
(MacEw en sign ). Th e affected ch ildren appear w ell
at first, becau se t h e in tracran ial pressure is on ly
m ildly raised as lon g as th e sutu res are op en an d
th e h ead is still able to expan d. Decom pen sation
occurs later, givin g rise to signs of intracranial hy-
pertension, in clu din g vom itin g (in cludin g projec-
tile vom itin g an d dry h eaves). Th ese ch ildren m ay
also presen t w ith “set tin g su n ” eyes (up w ard gaze
paresis) an d gen eral failure to thrive.
Diagnostic evaluation in children. At presen t, hy-
droceph alus can be diagn osed before birth by
rou tin e pren atal u ltrason ograp hy. Hydroceph alus
arisin g after birth is detected by rout in e serial
m easu rem en t an d docu m en tation of th e ch ild’s
h ead circu m feren ce: if th e h ead grow s faster th an
n orm al (accordin g to th e referen ce cu rves on th e
ch art), th en hydrocep h alu s sh ould be suspected,
an d fu rth er diagn ostic stu dies sh ou ld be don e to
gu ide poten tial treatm en t. After birth , ch ildren
w ith hydrocep h alu s are evalu ated n ot just w ith ul-
trasou n d bu t also w ith CT an d MRI. Th is en ables
th e iden tification of poten tially treatable cau ses of
hydroceph alu s, as w ell as oth er p oten tial cau ses of
disp roportion ate grow th of th e h ead, su ch as su b-
du ral h em atom as an d hygrom as, an d fam ilial m ac-
rocep h aly.
Manifestations in adults. In ch ildren w ith closed
su tu res, an d in adults, hydrocep h alu s p resen ts
w ith m an ifestation s of intracranial hypertension,
in cludin g h eadach e, n au sea, an d vom itin g (p artic-
ularly m orn in g dry h eaves an d p rojectile vom it-
in g), an d sign s of m eningeal irritation, in clu din g
n uch al rigidity, h ead tilt, opisth oton u s, an d ph oto-
ph obia. As th e con dition progresses, fu rth er
m an ifestation s m ay in clude fatigue, cogn itive de-
clin e, un steady gait, cran ial n erve deficits (particu -
larly abdu cen s palsy), Parin aud syn drom e, pap il-
ledem a, an d im pairm en t of con sciou sn ess.
Diagnostic evaluation in adults. CT an d MRI readily
dem on strate ven tricular en largem en t an d often
reveal th e cau se of hydroceph alus.
Treatment. If n o u n derlyin g, treat able cau se of hy-
droceph alus can be iden tified, th e elevated in -
traven tricular pressu re can be relieved by th e in -
sertion of a cerebrospinal fluid shunt. Many differ-
en t t ypes of sh u n ts are available; for fu rth er in for-
m ation , th e reader is directed to textbooks of n eu -
rosu rgery.
 11

11 Blood Supply and

Vascular Disorders
of the Central
Nervous System
Arteries of the Brain . . . . . . . . . . . . . . . 270
Veins of the Brain . . . . . . . . . . . . . . . . . 279
Blood Supply of the Spinal Cord . . . . . 281
Cerebral Ischemia . . . . . . . . . . . . . . . . . 283
Intracranial Hemorrhage . . . . . . . . . . . 305
Vascular Syndromes
of the Spinal Cord . . . . . . . . . . . . . . . . . 312
11 270
11 Blood Supply and Vascular Disorders of the Central
Nervous System
Th e cerebral blood su pply is derived from th e in-
ternal carotid an d vertebral arteries Th e in tern al
carotid artery on eit h er side delivers blood to th e
brain th rou gh it s m ajor bran ch es, th e m iddle an d
an terior cerebral arteries an d th e an terior
ch oroidal artery (anterior circulation). Th e tw o
vertebral arteries u n ite in t h e m idlin e at t h e cau dal
border of th e pon s to form th e basilar artery, w h ich
delivers blood to th e brain stem an d cerebellum , as
w ell as to part of th e cerebral h em isph eres
th rou gh its term in al bran ch es, th e posterior cere-
bral arteries (posterior circulation). Th e an terior
an d posterior circu lation s com m un icate w ith each
oth er th rough th e arterial circle of Willis. Th ere are
also m any oth er an astom otic con n ection s am on g
th e arteries su pplyin g th e brain , an d betw een th e
in tracran ial an d extracran ial circu lation s; th u s,
occlu sion of a m ajor vessel does n ot n ecessarily
lead to stroke, becau se th e brain tissu e distal to th e
occlu sion m ay be adequ ately perfu sed by col-
lateral vessels.
Th e venous blood of th e brain flow s from th e
deep an d sup erficial cerebral vein s in to th e ven ou s
sin uses of t h e dura m ater, an d th en ce in to th e in -
tern al ju gu lar vein s on both sides.
Protracted in terruption of blood flow to a part
of t h e brain cau ses loss of fun ct ion an d, fin ally,
isch em ic n ecrosis of brain tissue (cerebral infarc-
Arteries of the Brain
Extradural Course of the Arteries of
the Brain
Fou r great vessels su pply th e brain w ith blood: th e
righ t an d left internal carotid arteries an d th e righ t
an d left vertebral arteries. Th e in tern al carotid ar-
teries are of th e sam e caliber on both sides, but th e
tw o vertebral arteries are often of very differen t
sizes in a sin gle in dividu al. All of th e arteries sup -
plyin g th e brain are an astom otically in tercon -
n ected at th e base of th e brain th rou gh th e arterial
circle of Willis. Th ey are also in tercon n ected ex-
tracran ially th rou gh sm all bran ch es in th e m u scles
an d con n ective tissu e, w h ich m ay becom e im por-
tan t in certain p ath ological p rocesses affectin g th e
tion). Cerebral isch em ia gen erally p resen ts w ith
th e su dden on set of a n eu rological deficit (h en ce
th e term “stroke”), du e to loss of fu n ction of th e af-
fected part of th e brain . Som etim es, h ow ever, th e
deficit appears gradu ally rath er th an sudden ly.
Th e m ost com m on causes of isch em ia on th e arte-
rial side of th e cerebral circu lation are emboli
(usually arisin g from th e h eart or from an ath ero-
m atou s plaqu e, e.g., in th e aorta or carotid bifu rca-
tion ) an d direct occlu sion of sm all or m iddle-sized
vessels by arteriolosclerosis (cerebral microan-
giopathy, u su ally du e to hyperten sion ). Cerebral
isch em ia can also be du e to im pairm en t of ven ou s
drain age (cerebral ven ou s or ven ous sin us t h rom -
bosis).
An oth er cau se of th e stroke syn drom e is in-
tracranial hemorrhage, w h ich m ay be eith er in to
th e brain paren chym a itself (in tracerebral h em or-
rh age) or in to th e n eigh borin g m en in geal com -
partm en ts (su barach n oid, su bdu ral, an d epidu ral
h em orrh age an d h em atom a).
Th e blood supply of the spinal cord is m ain ly
provided by th e unp aired an terior sp in al artery
an d t h e paired posterolateral spin al arteries. Th e
an terior sp in al artery receives con t ribu tion s from
m any segm en tal arteries. Like th e brain , th e spin al
cord can be dam aged by h em orrh age or by
isch em ia of arterial or ven ou s origin .
vascu latu re, but w h ich are n orm ally too sm all to be
dem on strated.
Th e stru ctu res of th e an terior an d m iddle cran ial
fossae are m ain ly su pplied by th e in tern al carotid ar-
teries (th e so-called anterior circulation), w h ile th e
structu res of th e posterior fossa an d th e posterior
portion of th e cerebral h em isp h eres are m ain ly su p-
plied by th e vertebral arteries (th e so-called poste-
rior circulation).
Common carotid artery. Th e in tern al carotid artery
is on e of th e tw o term in al bran ch es of th e com m on
carotid artery, w h ich , on th e righ t side, arises from
th e aortic arch in a com m on (brach ioceph alic) trun k
th at it sh ares w ith th e righ t subclavian artery
(Fig. 11.1). Th e left com m on carotid artery u su ally
arises directly from t h e aortic arch , bu t t h ere are

Basilar a.
Posterior cerebral a.
Superior cerebellar a.
Arteries of the Brain · 271
11
Fig. 11.1 Extracranial
course of the major arter-
ies supplying the brain
Posterior
com m unicating a.
(com m on carotid artery,
vertebral artery)
Middle cerebral a.

Anterior inferior Anterior cerebral a.

cerebellar a.
Ophthalm ic a.
Cavernous sinus
Internal carotid a.
Superficial
temporal a.
Maxillary a.
Facial a.
Lingual a.
Posterior inferior
cerebellar a.

Vertebral a.

Superior
thyroid a.

Com m on carotid a.

Subclavian a.

Brachiocephalic
trunk

Aorta

frequ en t an atom ical varian ts. In 20 %of in dividu als,
th e left com m on carotid artery arises from a left bra-
ch ioceph alic tru n k.
Th e internal carotid artery origin ates at th e bifu rca-
tion of th e com m on carotid artery at th e level of
th e thyroid cartilage an d ascen ds to th e sku ll base
w ith out givin g off any m ajor bran ch es. It passes
th rough th e carotid canal of th e petrou s bon e,
w h ere it is separated from th e m iddle ear on ly by a
th in , bony w all, an d th en en ters th e cavernous sinus
(Fig. 11.1). For its fu rth er in tracran ial course, see
p. 273.
Anastom otic connections of the arteries of the brain
with the external carotid artery. Th e secon d bran ch
of th e com m on carotid artery, th e extern al carotid
artery, su pplies th e soft tissues of the neck and face.
It m akes n um erous an astom otic con n ection s w ith
th e opposite extern al carotid artery, as w ell as w ith
th e vertebral arteries (see Fig. 11.11, p. 278) an d th e
in tracran ial territory of th e in tern al carotid artery
11 272 · 11 Blood Supply and Vascular Disorders of the Central Nervous System
(e.g., th rough th e oph th alm ic artery [Fig. 11.11] or
th e in ferolateral trun k, see p. 278). Th ese con n ec-
tion s can dilate in t h e sett in g of slow ly progressive
sten osis or occlu sion of th e in tern al carot id artery,
th ereby assu rin g con tin u ed delivery of blood to th e
brain .
Vertebral artery. Th e vertebral arteries arise from
th e su bclavian arteries on eith er side an d are often
of differen t caliber on th e tw o sides. Th e left verte-
bral artery rarely arises directly from th e aortic
arch . Th e vertebral artery travels up th e n eck in t h e
bony can al form ed by th e t ran sverse foram in a of
th e cervical vertebrae, w h ich it en ters at th e C6
level (i.e., it does n ot p ass th rou gh th e tran sverse
foram en of C7). At t h e level of th e atlas (C1), it
leaves th is bony can al an d curves arou n d th e
lateral m ass of th e atlas dorsally an d m edially, sit-
tin g in th e sulcus of the vertebral artery on th e
up per su rface of th e posterior arch of C1. It th en
Fig. 11.2 Arteries of the
base of the skull
Ant erior cerebral a.
Int ernal carot id a.
Mid d le cereb ral a.
Post erio r
com m unicat ing a.
Ant erior cho ro idal a.
Po st erior
cereb ral a.
Sup erio r cerebellar a.
Basilar a.
Ant erior inferior
cerebellar a.
Labyrint hine a.
Po st erior inferio r
cerebellar a.
Vert ebral a.
Ant erior sp inal a.
run s ven trally betw een th e occip ut an d th e atlas
an d passes th rough t h e atlan to-occipit al m em -
bran e. It u su ally p en et rates th e du ra m ater at th e
level of th e foram en m agn um .
In th e subarach n oid space, th e vertebral artery
cu rves ven trally an d cran ially arou n d th e brain stem ,
th en join s th e con tralateral vertebral artery in fron t
of t h e caudal portion of th e pon s to form t h e basilar
artery. Th e vertebral artery gives off m any bran ch es
to th e m u scles an d soft tissu es of th e n eck; its m ajor
in tracran ial bran ch es are th e posterior inferior cere-
bellar artery (PICA) an d th e anterior spinal artery
(Fig. 11.2). Th e origin of th e PICA (cf. also p. 275) is
ju st distal to th e poin t w h ere th e vertebral artery
en ters th e su barach n oid space; a ru pt ured
an eurysm at th e origin of th e PICAm ay, th erefore, be
ext racran ial an d n on eth eless produ ce a su b-
arach n oid h em orrh age. Th e branches of the verte-
bral artery to the spinal cord h ave a variable an at-
om y. Th ey su pply blood to th e u pper cervical spin al

cord an d form an astom oses w ith segm en tal spin al
arteries arisin g from th e proxim al port ion of th e
vertebral artery, an d w ith t h e n u ch al arteries.
Arteries of the Anterior and Middle
Cranial Fossae
Interna l Ca rotid Artery (ICA)
After it exits th e carotid can al, th e in tern al carot id
artery cou rses rostrally, n ext to th e clivu s an d
ben eath th e du ra m ater, to t h e cavern ou s sin us. It
cu rves u pw ard an d backw ard w ith in th e cavern ou s
sin u s, form in g a loop th at is op en p osteriorly (th e
carotid siph on , Fig. 11.1). Fin e extradural bran ch es
of t h e in tern al carotid artery su pply th e floor of th e
tym p an ic cavity, t h e dura m ater of th e clivu s, th e
sem ilun ar gan glion , an d th e pitu it ary glan d.
In ju ry or ruptu re of th e in tern al carotid artery
w ith in th e cavern ou s sin u s produces a “sh ort-cir-
cu it” con n ection betw een its arterial blood an d th e
ven ou s blood of t h e sin u s (carotid-cavernous
fistula). If an intracavernous aneurysm of the inter-
nal carotid artery ru ptu res, exoph th alm os develops
bu t t h ere is n o su barach n oid h em orrh age, becau se
th e an eu rysm is extradural. Th e patien t’s vision in
th e ip silateral eye deteriorates th ereafter because
of ou tflow obstruction an d con gestion of th e reti-
n al vein s.
Ophthalmic artery. Th e in tern al carot id artery en -
ters th e su barach n oid space m edial to th e an terior
clin oid process. Th e op h th alm ic artery arises at
th is poin t from th e in tern al carotid artery; it is th u s
already in tradural at its site of origin (Fig. 11.1). It
en ters th e orbit togeth er w ith th e opt ic n erve an d
sup plies n ot on ly th e contents of the orbit, bu t also
th e sphenoid sinus, th e ethm oid air cells, t h e nasal
m ucosa, th e dura m ater of the anterior cranial fossa,
an d th e skin of the forehead, root of the nose, and
eyelids. Th e cu tan eou s bran ch es of th e oph th alm ic
artery form an astom oses w ith bran ch es of th e ex-
tern al carotid artery, w h ich can be an im portan t
path for collateral circu lation arou n d a sten osis or
occlu sion of th e in tern al carotid artery (oph t h al-
m ic collaterals). Ruptu red an eu rysm s or in ju ries of
th e ICA distal to th e origin of th e oph th alm ic artery
cause subarach n oid h em orrh age.
Posterior communicating artery. Th e n ext an gio-
grap h ically visible artery arisin g from th e in tern al
Arteries of the Brain · 273
11
carotid artery alon g its in tradural course is th e
posterior com m un icatin g artery (Figs. 11.1 an d
11.2). In th e early stages of em bryon ic develop-
m en t, th is artery is th e p roxim al segm en t of th e
posterior cerebral artery, w h ich is at first a bran ch
of th e in tern al carotid artery an d on ly later com es
to be su pplied by th e basilar artery. In som e 20 %of
cases, th e p osterior com m u n icatin g artery rem ain s
th e m ain sou rce of blood for th e posterior cerebral
artery; th is is equivalen t to a direct origin of th e
posterior cerebral artery from th e ICA, or fetal
origin of the posterior cerebral artery, as it is tradi-
tion ally called. Th e fetal pattern , if presen t, is usu-
ally seen on ly on on e side, w h ile th e con t ralateral
posterior cerebral artery arises from an asym -
m etric basilar tip. Som etim es, h ow ever, both post-
erior cerebral arteries arise directly from th e ICA
th rough un usually large posterior com m u n icatin g
arteries. In su ch cases, th e basilar tip is sm aller
th an u su al, an d th e basilar artery app ears to term i-
n ate w h ere it gives off th e tw o su perior cerebellar
arteries.
Th e posterior com m u n icatin g artery en ds
w h ere it join s th e p roxim al segm en t of th e poste-
rior cerebral artery som e 10 m m lateral to th e
basilar tip. It is a com pon en t of th e circle of Willis
an d the m ost im portant anastom otic connection be-
tw een the anterior and posterior circulations.
Th e p osterior com m un icatin g artery gives off
fin e p erforatin g bran ch es to th e tuber cinereum ,
m am illary body, rostral thalam ic nuclei, sub-
thalam us, an d part of the internal capsule.
Th e origin of th e posterior com m u n icatin g
artery from t h e ICA is a preferred site for t h e for-
m ation of an eu rysm s (so-called PCom m an eu -
rysm s; see above). Such an eu rysm s u su ally arise
from th e side w all of th e in tern al carotid artery,
an d on ly rarely from th e posterior com m un icatin g
artery itself.
Anterior choroidal artery. Th is artery arises from
th e in tern al carotid artery im m ediately distal to
th e posterior com m u n icatin g artery (Fig. 11.2),
run s tow ard th e occipu t parallel to th e optic tract,
an d th en en ters th e ch oroidal fissure to su pply th e
choroid plexus of the tem poral horn of the lateral
ventricle. Alon g its cou rse, it gives off bran ch es to
th e optic tract, uncus, hippocam pus, am ygdala, part
of the basal ganglia, an d part of the internal capsule.
It is clin ically sign ifican t th at th e an terior ch oroidal
artery also sup plies part of t h e pyram idal tract. It
11 274 · 11 Blood Supply and Vascular Disorders of the Central Nervous System

Middle Cerebral Artery

Th e m iddle cerebral artery (MCA) is th e largest
Lateral posterior bran ch of th e in tern al carot id artery (Fig. 11.2).
choroidal a.
Anterior
After its origin from t h e ICA above th e an terior
choroidal a. clin oid process, it travels laterally in th e sylvian fis-
St riate branches
of the m iddle sure (lateral su lcus). Th e m ain tru n k of th e m iddle
ce re bral a. cerebral artery gives off n u m erou s perforating
Middle
cerebral a. branches to the basal ganglia an d to t h e anterior
Posterior thala- lim b and genu of the internal capsule, as w ell as to
mo-perforating a.
Posterior th e external capsule and claustrum (Fig. 11.3).
cerebral a.
Th e m iddle cerebral artery divides in to its m ajor
a
cortical bran ch es w ith in th e in su lar cistern . Th ese
bran ch es su pply large areas of the frontal parietal,
Anterior and tem poral lobes.
cerebral a.
Middle
cerebral a.
Posterior
Th e major branches of the middle cerebral artery
cerebral a. (Fig. 11.4) are th e orbitofron tal (I), prerolan dic (II),
Anterior
choroidal a. rolan dic (III), an terior p arietal (IV), an d posterior
pariet al (V) arteries, t h e artery of th e an gu lar gyru s
(VI), an d th e tem p oro-occipital, posterior tem poral
(VII), an d an terior tem poral (VIII) arteries. Th e cor-
tical areas su pplied by th e m iddle cerebral artery
in clude, am on g oth ers, th e prim ary sen sory an d
m otor cortices (except for th eir p arasagittal an d
b
m edial portion s), th e lan gu age areas of Broca an d
Fig. 11.3 Arterial supply of the interior of the brain. a Wern icke, th e prim ary au ditory cortex, an d th e
Coronal section. b Horizontal section. prim ary gu statory cortex.
Th e m iddle cerebral artery h as cortical an asto-
m otic con n ection s w ith th e an terior an d p osterior
An terior cerebral arteries.
cerebral a.
Middle
cerebral a. Anterior Cerebral Artery
Th e an terior cerebral artery (ACA) origin ates from
th e bifu rcation of th e in tern al carotid artery an d
th en courses m edially an d rostrally. Th e an terior
cerebral arteries of th e tw o sides com e to lie adja-
cen t to each oth er across th e m idlin e in fron t of th e
Posterior lam in a term in alis; from th is location , th e tw o ar-
cerebral a.
teries cou rse in parallel u pw ard an d posteriorly.
Fig. 11.4 Territory and branches of the middle cerebral Th is is also th e site of th e an astom otic con n ection
artery on the convexity of the brain. betw een t h e tw o an terior cerebral arteries th rough
th e anterior com m unicating artery, a fu rth er im -
port an t com pon en t of t h e circle of Willis (see
h as an astom otic con n ection s w ith th e lateral pos- Fig. 11.12, p. 279). Th e an terior com m u n icatin g
terior ch oroidal artery (see Fig. 11.10, p. 277). artery an d t h e n eigh borin g segm en ts of th e an te-
rior cerebral arteries are preferred sites for th e for-
Terminal branches. Th e in tern al carotid artery bi- m ation of an eu rysm s (so-called ACom m an eu -
fu rcates above th e clin oid p rocess, givin g rise to rysm s, p. 307).
th e anterior cerebral artery m edially an d th e
middle cerebral artery laterally.

Branches of the anterior cerebral artery. Th e p roxi-
m al (basal) segm en t of th e an terior cerebral artery
gives off n u m erou s sm all perforatin g bran ch es th at
sup ply t h e paraseptal region, rostral portion of the
basal ganglia an d diencephalon, an d th e anterior
lim b of the internal capsule (Fig. 11.3). Th e recurrent
artery of Heubner is a large bran ch of th e proxim al
segm en t of th e an terior cerebral artery th at su p-
plies th e basal gan glia; it is som etim es visible on
an an giogram (see Fig. 11.12, p . 279).
In th eir fu rth er course, th e an terior cerebral ar-
teries w in d arou n d th e gen u of th e corp us callo-
sum an d th en course p osteriorly u n til t h ey reach
th e cen tral region , w h ere th ey m ake an astom otic
con n ection s w ith th e p osterior cerebral arteries
Alon g t h e w ay, th ey give off bran ch es to th e corpus
callosum , th e m edial surfaces of the cerebral hem i-
spheres, an d t h e parasagittal region. Areas of th e
brain receivin g th eir blood sup ply from t h e an te-
rior cerebral artery in clu de th e leg areas of the pri-
m ary sensory and m otor cortices an d th e cingulate
gyrus. Th e an terior cerebral artery m akes an asto-
m otic con n ection s w ith th e m iddle cerebral artery
as w ell as th e posterior cerebral artery.
Th e major cortical branches of t h e an terior cere-
bral artery (Fig. 11.5) are th e orbital (I), fron topolar
(II), fron tal, pericallosal (III), callosom argin al (IV),
an d in tern al parietal (V) arteries.
Arteries of the Posterior Fossa
Vertebra l Artery
Ju st after it en ters t h e du ra m ater, th e vertebral
artery gives off bran ch es to th e cervical sp in al cord.
Th e vascular an atom y in th is area is variable, but
th e anterior spinal artery alm ost alw ays arises
from th e in tradural p ortion of th e vertebral artery.
Posterior inferior cerebellar artery (PICA). Th e PICA
is th e largest bran ch of th e vertebral artery (Figs.
11.1, 11.2, an d 11.6–11.8) an d likew ise arises from its
in tradu ral portion , ju st before th e vertebral artery
join s its coun terp art from th e opposite side to form
th e basilar artery. Th e PICA sup plies t h e basal por-
tion of the cerebellar hem ispheres, th e low er portion
of the verm is, p art of th e cerebellar nuclei, an d th e
choroid plexus of the fourth ventricle, as w ell as th e
dorsolateral portion of the m edulla. It m akes
n u m erou s an astom otic con n ection s w ith th e re-
m ain in g cerebellar arteries.
Arteries of the Brain · 275
11
An terior
cerebral a.
IV
III V
,
V
II
IV
,
I
,
III
II
,
Middle
cerebral a. Posterior cerebral a.
Fig. 11.5 Territories and branches of the anterior cere-
bral, posterior cerebral, and middle cerebral arteries on
the medial surface of the brain. I’, anterior tem poral
artery; II’, posterior tem poral artery; III’, posterior occipital
artery; IV’, calcarine artery; V’, parieto-occipital artery. For
labels I–V, see text, pp. 274–275.
Th e size of th e PICA territory is inversely related
to th at of th e an terior in ferior cerebellar artery
(AICA) territory; fu rth erm ore, th e PICA an d its
territory m ay be of very differen t sizes on th e tw o
sides. If on e PICA is particularly sm all, th e basal
portion of th e cerebellu m w ill be su pplied by th e
AICA ipsilaterally an d th e larger PICA con tralater-
ally. A con gen itally sm all (“hypoplastic”) vertebral
artery m ay term in ate as t h e PICA an d give off n o
con tribu tion to th e basilar artery, w h ich , in su ch
cases, is sim ply a con tin u ation of th e con tralateral
vertebral artery. Th is is a fairly com m on n orm al
varian t.
Basila r Artery
Th e basilar artery arises from th e un ion of th e righ t
an d left vertebral arteries in fron t of th e brain stem
at a low er pon tin e level (Fig. 11.2). Its m ajor
bran ch es are th e tw o pairs of cerebellar arteries
an d th e p osterior cerebral arteries. Th e basilar
artery also gives off n um erous sm all p erforatin g
bran ch es to th e brain stem —th e param edian
branches as w ell as t h e short an d long circum feren-
tial branches (Fig. 4.58, p . 146). Occlu sion s of th ese
bran ch es produce th e brain stem syn drom es de-
scribed in Ch apter 4 (p. 145 ff.).
Anterior inferior cerebellar artery (AICA). Th e first
m ajor bran ch of th e basilar artery is th e AICA (Figs.
11.1, 11.2, an d 11.6–11.8), w h ich su pp lies th e floc-
culus an d th e anterior portion of the cerebellar
hem isphere. Its territory is inversely related in size
11 276 · 11 Blood Supply and Vascular Disorders of the Central Nervous System

Fig. 11.6 Blood supply of

the cerebellum, lateral
view
Posterior cerebral aa.

Oculomotor n.
Superior cerebellar a.

Basilar a.
Branches to the pons
(circumferential branches)
Anterior inferior
cerebellar a.
Posterior inferior
cerebellar a.
Vertebral aa.

Posterior cerebral a.
Superior cerebellar a.
Basilar a.
Anterior inferior
Basilar a. cerebellar a.

Superior
ce rebe llar a.
Anterior inferior
cerebellar a.
Posterior inferior
ce rebellar a.
Posterior inferior
Anterior spinal a. and para- cerebellar a.
median branches of the
vert ebral a. Vertebral a.

Fig. 11.7 Territories of the cerebellar and brainstem Fig. 11.8 Blood supply of the cerebellum and territories
arteries in midline sagittal section of the cerebellar arteries, inferior view

to th e ipsilateral PICA territory: in som e in dividu -

als, part of th e cerebellar h em isph ere th at is u su -
ally sup plied by th e PICA is actually su pplied by th e
AICA (as discu ssed on p. 275). Th e AICA also gives
off th e labyrinthine artery to t h e in n er ear.
Superior cerebellar artery (SCA). Th e su perior
cerebellar artery (Figs. 11.1, 11.2, an d 11.6–11.8)
arises from t h e basilar artery below its tip an d sup-
plies th e rostral portion of the cerebellar hem isphere
an d th e upper portion of the verm is. As it curves
arou n d t h e m idbrain , it gives off branches to the
tegm entum .
Th e basilar tip (en d of t h e basilar artery) is th e site
w h ere th e artery divides in to th e tw o p osterior
cerebral arteries (Fig. 11.2).
Posterior Cerebra l Artery
Th e posterior cerebral artery (PCA) h as con n ec-
tion s to both th e an terior an d p osterior circu lation .
Most of th e blood flow in g w ith in it is usually
derived from th e basilar t ip, bu t th ere is also a
sm aller con tribu tion from th e in tern al carot id
artery by w ay of th e posterior com m u n icat in g
artery (Fig. 11.1). At an earlier stage in on togen etic
develop m en t, th e posterior cerebral artery is a
bran ch of t h e in tern al carotid artery (as discu ssed
above, p. 273). Th e p osterior com m u n icatin g artery
join s th e posterior cerebral artery som e 10 m m dis-
tal to th e basilar tip. Th e segm en t of th e posterior
cerebral artery proxim al to th is poin t is called th e
precom m u n icat in g segm en t, or, in Fisch er’s ter-
m in ology, th e P1 segm en t, w h ile th e segm en t dis-
 Arteries of the Brain · 277
11
tal to th is poin t is th e postcom m u n icatin g or P2 Choroid Fim bria of the Lateral posterior Artery of
segm en t. Both t h e posterior cerebral artery an d th e plexus of hippocam pus choroidal a. Am m on’s horn
the inferior
posterior com m u n icatin g artery give off perforat- horn
Dentate
ing branches to the m idbrain and thalam us gyrus
(Fig. 11.3). Posterior
Th e posterior cerebral artery origin ates at th e cerebral a.

basilar bifu rcation an d th en cu rves arou n d th e m id- Long

branch (of
brain an d en ters th e am bien t cistern , w h ere it h as a Uchim ura)

close spatial relation to th e ten torial edge (Fig. 11.9). Collateral

With in th e am bien t cistern , th e posterior cerebral sulcus
Tentorium
artery divides in to its m ajor cort ical bran ch es, in -
clu din g th e calcarine an d occipitotem poral arteries Tem poral branch of
an d th e tem poral branches (Fig. 11.5). posterior cerebral a.

Fig. 11.9 Anatomical relation of the posterior cerebral

Th e anterior and posterior thalamoperforating ar- artery to the tentorial edge; blood supply of Am m on’s
teries (Fig. 11.10). Th e an terior th alam operforat in g horn
artery is a bran ch of th e posterior com m un icatin g
artery th at m ain ly su pplies th e rostral portion of
the thalam us. Th e p osterior th alam operforatin g
artery arises from t h e posterior cerebral artery
proxim al to t h e in sertion of th e posterior com -
m un icatin g artery an d su pplies th e basal and m e-
dial portions of the thalam us, as w ell as th e pulvi-
Anterior thalam o-
nar. Th e posterior th alam operforatin g arteries of perforating a.

th e tw o sides m ay sh are a com m on tru n k, called Middle cerebral a.

th e artery of Percheron; th is is often seen in asso- Anterior choroidal a. Posterior

cerebral a.
ciation w ith u n ilateral hypoplasia of th e P1 seg-
m en t an d fetal origin of th e posterior cerebral
artery (cf. p . 273). An altern ative n om en clature is Internal carotid a. Thalamogeniculate a.
Posterior com m uni- Lateral posterior
som etim es u sed for th e an terior an d posterior cating a. choroidal a.
th alam operforatin g arteries, in w h ich th e form er is Posterior thalamo- Basilar a.
perforating a.
called th e t h alam ot uberal artery, an d th e latter is
called th e t h alam operforat in g artery. Fig. 11.10 Arterial blood supply of the thalamus

Th e thalamogeniculate artery arises from th e pos-

terior cerebral artery distal to th e origin of th e pos-
terior com m un icatin g artery (Fig. 11.10). It su pplies
th e lateral portion of the thalam us.
Th e medial and lateral posterior choroidal arteries
also arise distal to th e origin of th e p osterior com -
m un icatin g artery (Figs. 11.9, 11.10). Th ey supp ly
th e geniculate bodies, m edial an d posterom edial
thalam ic nuclei, an d pulvinar. Th e m edial posterior
ch oroidal artery gives off branches to the m idbrain
an d supp lies th e ch oroid plexu s of t h e th ird ven -
tricle. Th e lateral posterior ch oroidal artery sup-
plies th e ch oroid plexus of th e lateral ven tricle an d
h as an an astom otic con n ection w ith th e an terior
ch oroidal artery.
Cortical branches of the posterior cerebral artery.
Th e territories of th e p osterior cerebral artery an d
m iddle cerebral artery vary w idely in exten t. In
som e cases, th e posterior cerebral artery territory
is delim ited by th e sylvian fissu re; in oth ers, th e
m iddle cerebral artery supp lies th e en tire convex-
ity of th e brain all th e w ay back to th e occipital
pole. Th e visual cortex of the calcarine sulcus is al-
w ays sup plied by th e posterior cerebral artery. Th e
optic radiat ion , h ow ever, is often su pplied by th e
m iddle cerebral artery, so th at h om onym ous h em i-
an opsia does n ot alw ays im ply an in farct in th e
territory of th e posterior cerebral artery. Th e poste-
rior cerebral artery supp lies n ot on ly th e occipital
lobe bu t also th e m edial tem poral lobe th rou gh its
tem poral bran ch es.
11 278 · 11 Blood Supply and Vascular Disorders of the Central Nervous System
Collateral Circulation in the Brain
Externa l-to-Interna l Colla tera liza tion
Wh en th e in tern al carotid artery is sten otic, blood
is diverted from bran ch es of th e extern al carotid
artery in to th e in tern al carot id artery distal to th e
sten osis, en ablin g con tin u ed perfu sion of th e
brain . Th e facial or su perficial tem poral artery, for
exam ple, can form an an astom otic con n ection
w ith th e ophthalmic artery by w ay of t h e an gular
artery; retrograde flow in th e oph t h alm ic artery
th en takes th e blood back in to th e carotid siph on
(Fig. 11.11). Collaterals to th e oph th alm ic artery
can also be fed by t h e bu ccal artery. Fu rth er exter-
n al-to-in tern al an astom otic con n ection s exist be-
tw een th e ascen din g ph aryn geal artery an d
m en in geal bran ch es of th e ICA. Th ese arteries, u su -
ally too sm all to be seen by an giography, are
kn ow n collectively as th e inferolateral trunk.
Leptomeningeal
branches and
anastomoses
Ophthalmic a.
Angular a.
Circle of
Willis
Superficial
temporal a.
Occipital a. Facial a.
Internal carotid a.
External carotid a.
Vert ebral a.
Comm on carotid a.
Fig. 11.11 Anastomoses of the arteries of the brain. The
following collateral pathways are shown: Collaterals from
the external to the internal carotid circulation: 1, exter-
nal carotid artery—facial artery—angular artery—internal
carotid artery; 2, external carotid artery—superficial tem -
poral artery—angular artery—internal carotid artery. 3, Col-
laterals from the external to the vertebral circulation:
external carotid artery—occipital artery—vertebral artery.
4, Circle of Willis. 5, Leptomeningeal collaterals between
the anterior, m iddle, and posterior cerebral arteries. After
Poeck K and Hacke W: Neurologie, 11th ed., Springer,
Berlin/Heidelberg, 2001.
Externa l-Ca rotid-to-Vertebra l
Colla tera liza tion
Th e bran ch es of th e extern al carotid artery an d
vertebral artery t h at sup ply th e cervical an d n uch al
m u scles are an astom otically con n ected at m ultiple
poin t s. Th e m ost im portan t bran ch of th e extern al
carotid artery in th is respect is th e occipital artery.
Collaterals can form in eith er direction (Fig. 11.11):
proxim al occlu sion of th e vertebral artery can be
com pen sated by blood from n uch al bran ch es of th e
occip ital artery, w h ile occlu sion of th e com m on
carotid artery or proxim al occlusion of th e in tern al
carotid artery can be com pen sated by blood en ter-
in g th e an terior circu lation from th e m uscu lar
bran ch es of th e vertebral artery by w ay of t h e
occip ital artery. As an oth er exam ple, if a proxim al
occlu sion of th e com m on carotid artery h as cu t off
both th e in tern al an d th e extern al cerebral arteries
from th e circu lation , th en blood from th e vertebral
artery can flow in t h e extern al carotid artery in ret-
rograde fash ion dow n to th e carot id bifurcation ,
an d th en u p again in th e in tern al carotid artery, re-
storin g perfu sion in th e ICA territory.
Arteria l Circle of Willis
Th e cerebral arteries are con n ected to each oth er
th rough a w reath like arran gem en t of blood vessels
at th e base of th e brain kn ow n as th e circle of Willis
(after Th om as Willis, an En glish an atom ist of th e
seven teen th cen tu ry). Th is in tercon n ection en ables
con tin u ed perfusion of brain tissu e even if on e of
th e great vessels is sten otic or occlu ded. Th e circle
itself con sists of segments of the great vessels an d
th e so-called communicating arteries lin kin g th em
to on e an oth er. Travelin g aroun d on e side of th e
circle from an terior to posterior, w e fin d th e anterior
com m unicating artery, th e proxim al (A1) segm ent of
the anterior cerebral artery, th e distal segm ent of the
internal carotid artery, th e posterior com m unicating
artery, th e proxim al (P1) segm ent of the posterior
cerebral artery, an d th e basilar tip (Fig. 11.12).
Decreased blood flow in a great vessel du e to slow ly
progressive sten osis below th e circle of Willis can
usu ally be com p en sated by in creased collateral
flow aroun d th e circle, so th at h em odyn am ic in farc-
tion w ill n ot occu r (see p . 285 ff.). Th ere are,
h ow ever, frequen t an atom ical varian ts of th e circle
of Willis in w h ich on e or m ore of its con stitu en t
arterial segm en ts m ay be hypoplastic or absen t. Th e
un lu cky com bin at ion of a sten otic great vessel w ith
 Veins of the Brain · 279
11
Fig. 11.12 Circle of Willis
Anterior com m uni-
cating a.
Anterior cerebral a.
Olfactory tract Superior chiasmatic a.
Ophthalm ic a. Perforated substance
Internal carotid a. Medial and lateral
striate branches
Anterior cerebral a.
Recurrent a.
Middle cerebral a. (of Heubner)

Superior
Infundibulum hypophyseal a.
Tuber cinereum Supraoptic and
paraventricular a.
Posterior com m uni-
cating a. Anterior choroidal a.
Arteries to the
Mam illary body tuber cinereum
Oculomotor n. Mam illary aa.
Posterior thalam o-
perforating a.
Posterior cerebral a.
Posterior perforating
branches
Superior cerebellar a.
Basilar a.

an an atom ical varian t of th e circle of Willis pre- Veins of the Brain

ven tin g adequ ate collateral flow can resu lt in
h em odyn am ic in farction (p. 287 an d Fig. 11.21).
Ca llosa l Anastomoses
Th e an terior an d posterior cerebral circulat ion s are
an astom ot ically con n ected t h rou gh t h e callosal ar-
teries (Fig. 11.1). Th u s, w h en th e an terior cerebral
artery is occlu ded, blood from t h e posterior cere-
bral artery m ay con tin u e to su pply th e cen tral re-
gion .
Leptomeningea l Anastomoses
Fu rth erm ore, th e bran ch es of th e an terior, poste-
rior, an d m iddle cerebral arteries are an astom oti-
cally lin ked to each oth er th rough th e arteries of
th e pia m ater an d arach n oid (Fig. 11.11). Th ere are
also leptom en in geal an astom oses lin kin g th e
bran ch es of t h e th ree m ain cerebellar arteries.
Superficial and Deep Veins of the
Brain
Th e vein s of th e brain , u n like th ose of th e rest of
th e body, do n ot run togeth er w ith its arteries. Th e
territories of th e cerebral arteries do n ot coin cide
w ith th e drain age areas of th e cerebral vein s.
Ven ou s blood from th e brain paren chym a crosses
th e su barach n oid an d su bdu ral sp aces in sh ort cor-
tical veins w h ose an atom y is relatively invariable:
th ese in clu de th e superior anastom otic vein (of
Trolard), th e dorsal superior cerebral vein, th e su-
perficial m iddle cerebral vein, an d th e inferior anas-
tom otic vein (of Labbé) on th e lateral surface of t h e
tem poral lobe (Fig. 11.13).
Ven ou s blood from deep region s of th e brain , in -
clu din g th e basal gan glia an d th alam u s, drain s in to
th e paired internal cerebral veins an d th e paired
basal veins of Rosenthal. Th e in tern al cerebral
vein s are created by th e con flu en ce of th e vein of
th e septu m pellucidu m (septal vein ) w ith th e
th alam ostriate vein . Th ese fou r vein s, com in g from
th e tw o sides, join beh in d th e splen ium to form th e
11 280 · 11 Blood Supply and Vascular Disorders of the Central Nervous System

Medial superior
cerebral vv.
Thalamostriate v.

Superior anastomotic v.
Dorsal
(of Trolard)
superior Superior
cerebral vv. sagittal sinus
Superior
sagittal sinus Inferior
sagittal sinus
Internal
Superficial occipital v.
m iddle Great cerebral
cerebral v. v. (of Galen)

Straight sinus
Transverse
sinus (truncated)
Inferior Inferior Occipital sinus Anterior cerebral v.
anastomotic v. cerebral v. (variant)
(of Labbé) Vein of
the septum pellucidum
Internal cerebral v.
Basal v. (of Rosenthal)

Fig. 11.13 Veins of the brain, lateral view Fig. 11.14 Veins of the brain, medial view

great vein of Galen. From h ere, ven ou s blood drain s

in to th e straigh t sin u s (sin us rectus) an d th en in to
th e con fluen ce of th e sin u ses (con flu en s sin uu m ,
Thalam ostriate v. torcu lar Heroph ili), w h ich is th e jun ction of th e
Internal cerebral v.
straigh t sin u s, th e superior sagittal sin u s, an d th e
tran sverse sin uses of th e tw o sides (Figs. 11.14–16).
Basal v.
(of Rosenthal) Dural Sinuses
Th e superficial an d deep vein s of th e brain drain
in to th e cranial venous sinuses form ed by double
Fig. 11.15 Veins of the interior of the brain and their foldin g of t h e in n er du ral m em bran e (Fig. 11.17).
territories in coronal section Most of th e ven ou s drain age from th e cerebral con -
vexities travels from fron t to back in th e superior
sagittal sinus, w h ich ru n s in th e m idlin e alon g th e
Anterior attach m en t of t h e falx cerebri. At t h e p oin t in th e
cerebral v. back of th e h ead w h ere th e falx cerebri m erges
Deep w ith th e ten toriu m , th e su perior sagittal sin u s is
m iddle
cerebral v.
join ed by th e straight sinus, w h ich run s in th e m id-
lin e alon g th e attach m en t of th e ten torium an d
Striate vv.
carries blood from deep region s of th e brain .
Ven ou s blood from th e su perior sagittal sin us an d
straigh t sin us is th en distribu ted to th e tw o trans-
Basal v.
verse sinuses in th e torcu lar Heroph ili (“w in epress
(of Rosenthal)
of Heroph ilu s,” after Heroph ilus of Alexan dria);
from each tran sverse sin u s, blood drain s in to th e
sigmoid sinus, w h ich th en con tin u es below th e
Internal ju gular foram en as th e in tern al ju gular vein . Th e
cerebral vv.
sin u ses are often asym m etric, an d t h ere are a n u m -
Great cerebral v. ber of an atom ical varian ts of th e ven ou s drain age
(of Galen) pattern in th e region of t h e torcu lar.

Fig. 11.16 Veins of the base of the skull


Sphenoparietal
sinus
Inferior sagittal
sinus
Superior sagittal
sinus
Transverse
sinus
Straight sinus
Internal
jugular vv.
Blood from th e brain drain s n ot on ly in to th e in -
tern al ju gular system , but also, by w ay of th e ptery-
goid p lexus, in to t h e ven ou s system of th e
viscerocran iu m . Th e cavernous sinus, form ed by a
double fold of du ra m ater at th e base of th e sku ll,
also drain s som e of th e ven ou s blood from basal re-
gion s of th e brain . It m ain ly receives blood from
th e tem poral lobe an d from th e orbit (by w ay of t h e
superior an d inferior ophthalmic veins). It drain s
in to a variety of ven ou s ch an n els. On e of th ese is
th e sigm oid sin u s, to w h ich it is con n ected by th e
superior an d inferior petrosal sinuses. Som e of its
blood also en ters th e pterygoid plexu s.
Path ologically elevated ven ou s p ressu re in th e
cavern ous sin u s, caused, for exam ple, by th e in tra-
cavern ou s ru ptu re of an an eu rysm of th e in tern al
carotid artery, causes reversal of flow in th ese
vein s, result in g in ch em osis an d exoph t h alm os.
Blood Supply of the Spinal Cord · 281
11
Fig. 11.17 Dural venous
sinuses
Falx cerebri
Cavernous sinus
Inferior petrosal sinus
Superior petrosal sinus
Tentorium
Sigm oid sinus
Blood Supply of the Spinal Cord
Arterial Anastomotic Netw ork
Th e spin al cord receives blood from an an astom otic
n etw ork of arteries on its su rface. Th ere are th ree
n am ed lon gitu din al arteries, but th ese are m u ltiply
in tercon n ected as th ey travel dow n th e spin al cord,
so t h at th e vascu lar pattern resem bles a ch ain of
an astom oses rath er t h an t h ree distin ct, in dep en d-
en t vessels.
Anterior spinal artery. Th e unp aired (sin gle) an te-
rior spin al artery ru n s dow n th e ven t ral su rface of
th e spin al cord at th e an terior edge of th e an terior
m edian fissu re. It receives segm en tal con tribu tion s
from a n um ber of arteries (see p. 282) an d su pplies
th e ven tral part of th e spin al gray m atter th rough
perforatin g vessels kn ow n as th e sulco-com m issural
arteries. Th ese arteries bran ch off segm en tally from
th e an terior spin al artery an d ru n tran sversely
th rough th e m edian fissure, from w h ich th ey en ter
th e paren chym a. Each sulco-com m issural artery
supp lies on e h alf of t h e spin al cord. Im port an t
11 282 · 11 Blood Supply and Vascular Disorders of the Central Nervous System
Posterolateral
spinal a.
Lateral
spinothalam ic
tract
Anterior
spinothalam ic
tract
Sulco-
com m issural a.
Anterior spinal a.
st ru ctures supp lied by th e an terior spin al artery in -
clu de th e anterior horns, th e lateral spinothalam ic
tract, an d part of the pyram idal tract (Fig. 11.18).
Posterolateral spinal arteries. Th e posterolateral
spin al arteries are th e m ajor lon gitu din al vessels
on th e dorsal side of t h e spin al cord; t h ey ru n
dow n th e cord bet w een th e posterior roots an d th e
lateral colu m n s on eith er side. Like th e an terior
spin al artery, th ey arise from a con flu en ce of
segm en tal arteries; t h is con flu en ce can be in -
com plete in p laces. Th e posterolateral spin al arter-
ies sup ply th e posterior colum ns, th e posterior
roots, an d th e dorsal horns (Fig. 11.18). Th e lon gi-
tu din al axes are con n ected by radicu lar an asto-
m oses. Th ese su pply th e an terior an d lateral
colu m n s th rough perforatin g bran ch es.
Th e arteries of th e spin al cord are in tercon -
n ected by m any an astom oses. Th u s, proxim al ste-
n osis or occlusion of on e of th ese arteries is u su ally
asym ptom atic. In th e periph ery, h ow ever, th e ar-
teries of th e spin al cord are fun ction al en d arteries;
in tram edullary em bolic occlu sion of a sulco-com -
m issural artery th erefore cau ses infarction of the
spinal cord.
Fig. 11.18 Arterial net-
w ork of the spinal cord
Posterolateral
spinal a.
Anterior
spinal a.
Vascular
corona
Lateral
corticospinal
tract
Postero-
lateral spinal a.
Arteries Contributing to the Arteria l Net work
of the Spina l Cord
Th e em bryon ic spin al cord receives its blood
supp ly from segm en tal arteries, in accordan ce
w ith th e m etam eric segm en tation of th e spin e.
Over th e cou rse of developm en t, m any of th ese ar-
teries regress, leavin g on ly a few m ajor on es to
supp ly th e cord. Th ere is n o w ay to kn ow w h ich of
th e origin al segm en tal arteries h as persisted in th e
m ature in dividual, except by an giograp hy. Yet th e
blood su pply of th e spin al cord does receive rela-
tively con stan t con tribu tion s from a n u m ber of
segm en tal levels (Fig. 11.19).
In th e up per cervical region , th e an terior spin al
artery receives m ost of it s blood from th e vertebral
artery. In prin ciple, both vertebral arteries m ay
su pply blood to th e an terior sp in al artery, but th e
vertebral artery of on e side is u su ally dom in an t.
Furth er dow n th e cord, th e an terior an d posterior
lon gitu din al vessels receive m ost of th eir blood
eith er from th e vertebral artery or from cervical
bran ch es of t h e subclavian artery (or both ). Spin al
cord arteries preferen tially arise from th e costocer-
vical or thyrocervical trunk. From T3 dow nw ard, th e
an terior spin al artery is fed by aortic bran ch es: th e
thoracic and lum bar segm ental arteries, in addit ion
 Cerebral Ischem ia · 283
11
to th e bran ch es th at th ey give off to th e m u scu la-
tu re, con n ective tissu e, an d bon es, also con tribute
a few bran ch es to th e an terior spin al artery or th e
posterolateral spin al artery. Th ese spin al bran ch es
are t h e segm en tal spin al cord arteries t h at did n ot
regress durin g em bryon ic developm en t. Each on e Vertebral a.
divides in to an an terior an d a posterior bran ch ,
w h ich en ter th e spin al can al w ith th e an terior an d Anterior radicular
a. of C4 – C5
posterior root , respect ively. Becau se t h e spin al
Anterior radicular
cord elon gates to a lesser exten t th an th e vertebral a. of C6 – C8
colu m n du rin g developm en t, each radicular artery Costocervical
en ters th e spin al cord som e dist an ce above it s level trunk
of origin . Th ere is usually on e part icularly large Thyrocervical
segm en tal artery su pplyin g th e low er spin al cord, trunk

w h ich is called th e great radicular artery or, m ore Com m on carotid a.

com m on ly, th e artery of Adam kiew icz. Th e Brachiocephalic
trunk
developm en tal “ascen t ” of th e spin al cord m akes
th is artery join th e an terior spin al artery at an Aorta
acute an gle (h airp in con figu ration ).
Anterior
spinal a.
Venous Drainage Posterior intercostal
a. of T4 – T6
Th e ven ou s blood of th e sp in al cord drain s in to
epim edu llary vein s th at form a ven ou s n etw ork in Great radicular a.
(of Adam kiewicz)
th e su barach n oid space, called th e in tern al spin al
ven ou s p lexus or t h e epimedullary venous net-
Posterior intercostal
w ork. Th ese vessels com m un icate via radicular a. of T9 – L1
vein s w it h th e epidural ven ou s plexu s (extern al
ven ou s p lexus, an terior an d p osterior extern al
vertebral ven ous plexus). Th e ven ou s blood th en
drain s from th e epidural venous plexus in to th e
large vein s of th e body. Th e ven ou s drain age of th e Fig. 11.19 Contributions of the segmental arteries to
sp in al cord is sh ow n in detail in Figu re 11.20. the arterial netw ork of the spinal cord. After Thron A in
Th e fin ite ability of th e radicu lar vein s to drain Poeck K and Hacke W: Neurologie, 11th ed., Springer,
blood from th e ep im edullary vein s m ay be Berlin/Heidelberg, 2001.
exceeded in th e presen ce of arterioven ou s m alfor-
m ation s, even w h en th e sh u n t volu m e is relatively
low. Th e resu lt is a rapid in crease of ven ous pres-
brain , w ith secon dary im p airm en t of t h e delivery
sure. Even sm all pressure in creases can dam age
of oxygen an d n u trien ts.
spin al cord t issu e (see th e section on im paired
ven ous drain age, p. 312).
Arterial Hypoperfusion
Genera l Pa thophysiology of Cerebra l Ischemia
Th e cen tral n ervou s system h as a very high
Cerebral Ischemia demand for energy th at can on ly be m et by t h e
con tin uou s, un in terru pted delivery of m etabolic
Isch em ic lesion s of th e brain paren chym a are substrates. Un der n orm al con dit ion s, t h is en ergy is
cau sed by persisten t disru ption of th e brain ’s blood derived exclusively from t h e aerobic m etabolism of
sup ply, u su ally eith er by blockage of the supplying glucose. Th e brain h as n o w ay of storin g en ergy to
(arterial) vessels or, m ore rarely, by an impediment tide itself over poten tial in terruption s of su bstrate
to venous outflow leadin g to stasis of blood in th e delivery. If its n euron s are n ot given en ou gh glu-
11 284 · 11 Blood Supply and Vascular Disorders of the Central Nervous System
Arach- Dura Posterior external
noid mater vertebral venous plexuses
Posterior spinal v.
Posterior central v.
Posterolateral spinal vv.
Sulcocom m issural v.
Sulcal v.
Vertebral vv.
Anterior Basiver- Anterior external spinal
spinal v. tebral v. venous plexuses
cose an d oxygen , th ey can cease fu n ction in g w ith in
secon ds.
Very differen t am ou n ts of en ergy are n eeded to
keep brain tissu e alive (structu rally in tact) an d to
keep it fu n ction in g. Th e m in im al blood flow re-
quirem en t for maintenance of structure is abou t
5–8 m l per 10 0 g per m in u te (in th e first h our of
isch em ia). In con trast, th e m in im al blood flow re-
quirem en t for continued function is 20 m l per
10 0 g p er m in u te. It follow s th at t h ere m ay be a
fu n ction al deficit in th e absen ce of deat h of tissue
(in farction ). If th e en dan gered blood su pply is
rap idly restored, as by spon t an eou s or th erapeutic
th rom bolysis, th e brain tissue rem ain s u n dam aged
an d recovers its fu n ction as before, i.e., th e n eu ro-
logical deficit regresses com pletely. Th is is th e
sequen ce of even ts in a transient ischemic attack
(TIA), w h ich is clin ically defin ed as a tran sien t n eu -
rological deficit of n o m ore t h an 24 h ou rs’ dura-
tion . Eigh ty percen t of all TIAs last less th an 30
m in u tes. Th eir clin ical m an ifestation s depen d on
th e particu lar vascu lar territory of t h e brain th at is
Fig. 11.20 Venous
drainage of the spinal
cord
Periosteum
Anterior and posterior
radicular vv.
Anterior internal spinal
venous plexuses
Intervertebral v.
affected. TIAs in th e territory of th e m iddle cerebral
artery are com m on ; patien ts report t ran sien t con -
tralateral paresth esiae an d sen sory deficits, as w ell
as tran sien t con tralateral w eakn ess. Such attacks
are som et im es h ard to distin gu ish from focal
epileptic seizu res. Isch em ia in th e vertebrobasilar
territory, on th e oth er h an d, causes tran sien t brain -
stem sym ptom s an d sign s, in clu din g vertigo.
Neu rological deficits due to isch em ia can som e-
tim es regress even th ough th ey h ave lasted for
m ore th an 24 h ou rs; in su ch cases, on e speaks, n ot
of a TIA, bu t of a PRIND (prolonged reversible
ischemic neurological deficit).
If hypoperfu sion p ersists lon ger th an th e brain
tissu e can tolerate, cell death en sues. Ischemic
stroke is n ot reversible. Cell death w ith collapse of
th e blood–brain barrier results in an in flu x of w ater
in to th e in farcted brain tissu e (accom panyin g cere-
bral edema). Th e in farct th u s begin s to sw ell
w ith in h ours of th e isch em ic even t, is m axim ally
sw ollen a few days later, an d th en gradu ally con -
tracts again .
 Cerebral Ischem ia · 285
11
In patien ts w ith large in farcts w ith exten sive ac- tion is better at th e p erip h ery of an in farct th an at
com p anyin g edem a, clinical signs of life -threaten- its cen ter. Th e isch em ic brain tissu e at th e periph -
ing intracranial hypertension such as headache, ery th at is at risk of dyin g (in farction ) bu t, because
vomiting, and disturbances of consciousness must of collateral circulat ion , h as n ot yet been irreversi-
be noted and treated appropriately (see below ). Th e bly dam aged is called th e penumbra (h alf-sh adow )
critical in farct volu m e n eeded for th is situation to of th e in farct. Rescu in g th is area is th e goal of
arise varies depen din g on th e patien t’s age an d brain th rom bolytic th erapy w ith recom bin an t tissu e
volum e. Youn ger patien t s w ith n orm al-sized brain s plasm in ogen activator (rtPA), w h ich can be given
are at risk after exten sive in farction in th e territory eith er system ically or in t ra-arterially (cf. Case Pre-
of th e m iddle cerebral artery alon e. In con trast, older sen t ation s 4 an d 5, pp. 291, 293 ff.).
patien ts w ith brain atrophy m ay n ot be in dan ger
un less th e in farct involves th e territories of tw o or
Ca uses of Cerebra l Ischemia: Types of
m ore cerebral vessels. Often , in su ch situation s, th e
Infa rction
patien t’s life can be saved on ly by tim ely m edical
treatm en t to low er t h e in tracran ial pressu re, or by Em bolic Infarction
surgical rem oval of a large piece of t h e sku ll
Eigh ty p ercen t of isch em ic st rokes are caused by
(h em icran iectom y) in order to decom press th e
em boli. Blood clots, or pieces of debris th at h ave
sw ollen brain .
broken aw ay from an at h erom atou s p laqu e in th e
In th e afterm ath of in farction , th e dead brain
w all of on e of t h e extracran ial great vessels, are
tissue liqu efies an d is resorbed. Wh at rem ain s is a
carried by th e bloodstream in to th e brain , w h ere
cystic cavity filled w ith cerebrospinal fluid, p erh aps
th ey becom e lodged in th e lu m en of a fu n ction al
con tain in g a few blood vessels an d stran ds of con -
en d artery. Proxim al em bolic occlusion of th e m ain
n ective tissu e, alon g w ith reactive glial ch an ges
tru n k of a cerebral artery cau ses exten sive in farc-
(astrogliosis) in th e surroun din g paren chym a. No
tion in its en tire territory (territorial infarction).
scar is form ed in t h e p roper sen se of th e term (pro-
Most em boli arise eith er from atheromatous le-
liferation of collagen ou s tissue).
sions of the carotid bifurcation or from th e heart.
Rarely, em boli arisin g in th e p eriph eral ven ous
The importance of collateral circulation. Th e tem -
circu lation are carried by th e bloodstream in to th e
poral cou rse an d exten t of cerebral paren chym al
brain (so-called paradoxical em boli). A precon dition
edem a depen d n ot on ly on th e paten cy of th e
for th is occu rren ce is a paten t foram en ovale,
blood vessel(s) th at n orm ally sup ply th e brain re-
w h ich fu rn ish es th e n ecessary con n ection be-
gion at risk, bu t also on th e availability of collateral
tw een th e ven ou s an d arterial circulation s at th e
circu lation th rou gh oth er p ath w ays. In gen eral, th e
level of th e atria. In th e n orm al case, th e foram en
arteries of th e brain are fu n ction al en d arteries:
ovale is closed an d ven ou s th rom bi are filtered out
collateral path w ays n orm ally can n ot provide
of th e circu lation in t h e lu n gs, so th at th ey can n ot
en ou gh blood to su stain brain tissue distal to a su d-
pass th rou gh to th e arterial side.
denly occlu ded artery. If an artery becom es n arrow
Em bolic th rom bi are som etim es sp on tan eou sly
very slow ly an d p rogressively, h ow ever, th e capac-
dissolved by th e fibrin olytic activity of th e blood. If
ity of th e collateral circu lation can in crease. Col-
th is h appen s rapidly, th e p atien t’s n eu rological
laterals can often be “train ed” by ch ron ic, m ild
deficit m ay regress, w ith fu ll recovery an d n o last-
tissue hyp oxia to th e exten t t h at th ey can m eet th e
in g dam age. If th e th rom bu s is n ot dissolved for
en erget ic n eeds of t issu e even if t h e m ain arterial
h ou rs or days, h ow ever, cell death en su es an d th e
supp ly is blocked for relatively lon g p eriods of
n eu rological deficit is u su ally irreversible.
tim e. Th e in farct is th en m u ch sm aller, an d far
few er n eu ron s are lost , th an on e w ou ld oth erw ise
Hem odynam ic Infarction
see if th e sam e artery w ere su dden ly occluded
from a state of n orm al paten cy. Hem odyn am ic in farction is caused by a critical
Collateral blood su pply m ay arrive from th e drop in perfusion pressure in a distal arterial seg-
basal an astom otic rin g of vessels (circle of Willis) m en t as th e resu lt of a m ore p roxim al sten osis.
or from su perficial leptom en in geal an astom oses of Su ch even ts u su ally occu r in th e territories of lon g,
th e cerebral arteries. As a ru le, collateral circu la- perforatin g arteries deep w ith in th e cerebral w h ite
11 286 · 11 Blood Supply and Vascular Disorders of the Central Nervous System
m atter. Th e resu ltin g in farcts are seen to lie like
ch ain s in th e w h ite m at ter of th e cen tru m sem i-
ovale.
Hem odyn am ic in farction is m uch rarer th an em -
bolic in farction . Th is fact m ay, at first, seem in com -
patible w ith th e observat ion t h at t h e risk of stroke
in creases in proportion to th e degree of carotid ste-
n osis; in fact, h ow ever, on ly very few patien ts w ith
slow ly progressive carot id sten osis ever develop
h em odyn am ic in farcts. Th is is becau se th e area of
brain at risk often receives an adequ ate collateral
blood su pply from th e con tralateral in tern al carotid
artery an d th e vertebral arteries, an d, in addition ,
an astom ot ic ch an n els open u p to convey blood
from th e extern al carotid artery to in t racran ial
bran ch es of th e in tern al carotid artery (cf. p. 271).
Th e real reason th at p atien ts w ith tigh ter sten oses
are at greater risk of st roke is th at, in su ch patien ts,
an em bolus is m ore likely to form or break aw ay
from t h e ath erom atous plaque in th e carotid w all.
Hem odyn am ic in farcts are u su ally foun d in th e
hemispheric w hite matter (see Fig. 11.21). Th ey are
align ed in ch ain s ru n n in g from an terior to p oste-
rior. Cortical isch em ia, in con t rast , is alm ost alw ays
of em bolic origin . In com pleten ess of th e circle of
Willis due to hypoplasia or absen ce of som e of its
com pon en t arterial segm en ts h as been sh ow n to
be a p recon dition for t h e occu rren ce of h em ody-
n am ic stroke. If th e circle of Willis is in tact, a sin gle
great vessel of th e n eck can su ffice to su pply blood
to th e en tire brain !
Hem odyn am ic in farction differs from em bolic
in farction in a n um ber of ch aracteristic w ays th at
facilitate its diagn osis. It often cau ses a fluctuating
neurological deficit, correspon din g to fluctu ation s
of blood flow in th e poststen otic arterial segm en t.
Becau se th e overall perfusion drops slow ly in su ch
situ ation s, th ere m ay be a protracted period of
tim e in w h ich th e brain tissue at risk lacks th e
blood it n eeds to fu n ction properly bu t is st ill re-
ceivin g en ough to sustain its stru ctu ral m etabo-
lism . In em bolic in farction , on th e oth er h an d, th e
region al blood flow im m ediately sin ks below th e
level n eeded to m ain tain tissu e stru cture—at least
at th e cen ter of t h e in farct . Th is explain s w hy n eu-
rological deficits due to h em odyn am ic isch em ia
are often reversible for a lon ger period of t im e th an
th ose du e to em bolic stroke.
Lacunar Infarction
Lacun ar in farcts are cau sed by microangiopathic
changes of smaller arteries w ith progressive n ar-
row in g of th e lu m en an d su bsequ en t occlu sion .
Th e m ost im portan t risk factor is arterial hyperten-
sion, w h ich leads to hyalin osis of th e vascu lar w all
of sm aller arteries. Th e perforatin g, lon g, an d th in
len ticulostriate arteries are m ost com m on ly in -
volved; th u s, lacu n ar in farct ion com m on ly occu rs
in th e internal capsule, t h e basal ganglia, th e
hem ispheric w hite m atter, an d th e pons. Th e lesions
are typically spherical or tubular, appearin g rou n d
on CT or MRI; th ey are u su ally less th an 10 m m in
diam eter. Lacu n ar in farction also occurs in th e
territory of th e p erforatin g brain stem arteries. Be-
cau se lacu n ar in farction u su ally occu rs in th e set-
tin g of arterial hyperten sion , it is often accom -
pan ied by m icroan giopath ic abn orm alities of th e
deep cerebral w h ite m atter (“m icroangiopathic
leukoencephalopathy” or leukoaraiosis). Acute
lacu n ar in farcts can be distin gu ish ed from older
on es on ly by diffusion -w eigh ted MRI, or by com -
parison w ith previou sly obtain ed radiological stu-
dies.
The Diagnostic Eva lua tion of Cerebra l
Ischemia
Th e goals of diagn ostic evaluation are to determ in e
the site and extent of the ischemic lesion an d, m ost
im portan tly, its cause. On ly a precise etiological di-
agn osis w ill lead to th e app ropriate treat m en t th at ,
in favorable cases, can h alt th e progression of an
in farct an d preven t fu tu re recu rren ces.
Th e diagn ostic tools used in th is evalu ation are a
precise case h istory an d a clin ical n eu rological an d
gen eral p hysical exam in ation , alon g w it h specifi-
cally ch osen , com plem en tary laboratory tests an d
im agin g stu dies. CT an d MRI are used to dem on -
strate th e presen ce of isch em ia an d differen tiate it
from h em orrh age (see p p. 288, 289). Fu rth erm ore,
th e site an d visu al form of an in farct m ay p rovide
in itial clues regardin g its type (em bolic/territorial,
h em odyn am ic, lacu n ar, cf. pp. 285, 286) an d, th ere-
fore, its cause: for exam ple, a territorial in farct in
th e m iddle cerebral artery territory is probably of
em bolic origin , an d th e em bolus, in turn , probably
cam e from th e carotid bifu rcation or th e h eart. Th e
search for an etiology also in clu des cardiovascu lar
studies: ECG an d echocardiography provide in for-
m ation about p ossible u n derlyin g h eart disease

Case Presentation 1: Hemodyna mic Infa rction
This retired 72-year-old m an had suffered from arterial hy-
pertension and diabetes m ellitus for m any years, but felt
generally well. His last routine m edical check-up had re-
vealed a high serum cholesterol concentration. One after-
noon, while taking a walk with his fam ily, he noticed that his
left arm felt heavy and that he could no longer walk
steadily. His daughter took him to the hospital, where the
adm itting physician found a left hem iparesis, m ore severe
in the arm than in the leg, with sinking of both left lim bs in
postural testing. He walked unsteadily because of the left
leg weakness, but had no sensory abnorm ality.
a b
d e
Fig. 11.21 Hemodynamic infarction due to high-grade
stenosis of the right internal carotid artery
c MR angiography of the arteries of the base of the brain. In
the flow-sensitive im age, the right internal carotid artery is
less well visualized than its counterpart on the left side. This
finding suggests that there m ay be a hem odynam ically sig-
nificant stenosis proxim al to the area of im paired flow.
d Contrast-enhanced MR angiography. e Color duplex
sonography reveals high-grade stenosis at the origin of the
Cerebral Ischem ia · 287
11
A diffusion-weighted MRI scan of the head revealed m ulti-
ple, neighboring zones of acute ischem ia in the deep white
m atter of the right cerebral hem isphere, appearing to form
a chain (Fig. 11.21a, b). These lesions were interpreted as
arterial end-zone infarcts due to hem odynam ic insuffi-
ciency. MR angiography (Fig. 11.21c, d) and Doppler ultra-
sonography (Fig. 11.21e) revealed a hem odynam ically sig-
nificant 90–95 % stenosis of the right internal carotid artery.
As soon as the diagnostic evaluation was com plete, the
patient underwent throm bendarterectomy, without com -
plication. He went on to recover fully from his hem iparesis
and was discharged hom e one week after adm ission.
c
internal carotid artery, with ulceration. Blood is flowing
from left to right, from the com m on carotid artery into the
internal carotid artery. The color indicates the speed of
flow. A plaque is evident as a dark structure behind the
lum en, which contains flowing blood. The red-colored area
in the craterlike pit (plaque) shows that there is flowing
blood here, too: this finding im plies ulceration (arrow).
(Im age kindly supplied by Dr. H. Krapf, Tübingen.)
11 288 · 11 Blood Supply and Vascular Disorders of the Central Nervous System
Case Presentation 2: Lacuna r Infa rction
This 58-year-old lawyer had had arterial hypertension for
many years. This had initially been well controlled; in recent
months, however, there had been m ultiple, prolonged, and
dangerous elevations of blood pressure, despite m edica-
tion. One night, he awoke with a feeling of weakness in the
right leg, which lasted only a few m inutes before returning
to norm al. He felt fully well the next day and went to work
as usual. A short tim e later, while talking and drinking
coffee with a client, he suddenly noticed that the coffee
was dribbling out of the right corner of his m outh, and he
had difficulty articulating words properly. At the sam e tim e,
his right arm felt very weak. He no longer had the strength
to get up and walk. His secretary called an am bulance, and
he was taken to hospital.
a b
Fig. 11.22 Lacunar infarct in the left internal capsule. a
Diffusion-weighted im age. The infarct in the posterior lim b
of the internal capsule and the posterior portion of the
thalam us is m arkedly hyperintense, im plying acute infarc-
tion. This im age was obtained 24 hours after the onset of
predisposin g to cerebral isch em ia (e.g., in su fficien t
cardiac p um p in g activity du e to arrhyth m ia or any
of th e m yriad cau ses of con gest ive h eart failure; in -
tracardiac th rom bi as a sou rce of em bolism ). Ab-
n orm alities of th e cerebral blood vessels th em -
selves can be detected w it h extracranial and trans-
cranial ultrasonography an d w ith angiography—for
exam p le, sten osis or ath erosclerotic plaqu e as a
source of arterioarterial em bolism . MR an giogra-
phy, in com bin at ion w it h u ltrason ography, often
suffices to establish th e diagn osis of vascular
path ology, but conven tion al an giography w ith digi-
tal subt raction (DSA) is still occasion ally n ecessary.
We w ill n ow briefly discu ss each of th e m ajor di-
agn ostic m eth ods in dividu ally.
The adm itting neurologist found a m ainly brachiofacial
right hem iparesis, without any accom panying sensory defi-
cit. MRI revealed the cause, a sm all infarct in the left inter-
nal capsule. The diffusion-weighted im age revealed an
acute ischem ic process (Fig. 11.22a), and the better spatial
resolution of the T2-weighted im age enabled its precise an-
atom ical localization (Fig. 11.22b).
Diagnostic studies of the heart revealed no abnorm ality.
The patient rem ained in the hospital for two weeks, during
which tim e his antihypertensive m edication was readjusted
for better blood pressure control. He was given an inhibitor
of platelet aggregation to prevent recurrent infarction. His
hem iparesis resolved to a m arked, but incom plete, extent,
and he was transferred from the hospital to an inpatient re-
habilitation unit.
sym ptom s. b The T2-weighted FLAIR im age reveals the
sam e hyperintense infarct in the internal capsule and
thalam us. T2 hyperintensity persists long after the acute
event; thus, a T2-weighted im age alone is insufficient for
estim ation of the age of the lesion.
Ancillary Diagnostic Studies in Cerebral
Ischem ia
Computerized tomography (CT) reveals isch em ic
areas n o soon er t h an tw o h ou rs after t h e on set of
hypoperfu sion . It does, h ow ever, sh ow in tracran ial
h em orrh age im m ediately an d reliably. Any patien t
w ith th e sudden or su bacute on set of a n eu rologi-
cal deficit sh ou ld th erefore receive a CT scan as
soon as possible, so th at a h em orrh age can be di-
agn osed or ruled ou t. A fu rth er advan tage of CT,
com pared to MRI, is its rapid availability. Its in abil-
ity to dem on strate th e in itial ph ase of acute
isch em ia is a m ajor disadvan tage: CT scan s are
gen erally n orm al precisely at th e m om en t w h en

cau sal treatm en t of cerebral isch em ia is still
possible. Furth erm ore, for tech n ical reason s (arti-
fact ), in farcts in t h e posterior fossa an d p urely cor-
tical isch em ia are often n ot revealed by CT u n t il
late in th eir cou rse, or m ay n ever be seen at all. If
th e in itial CT scan reveals n o lesion , it is rea-
son able to repeat th e stu dy ca. 24 h ou rs later, as an
in itially invisible in farct m ay be dem on strable th e
secon d tim e. Altern at ively, an MRI scan can be ob-
tain ed im m ediately after th e in itial, n egative CT
scan .
Recen tly, CT tech n iques h ave been develop ed
th at en able th e detection of vascu lar occlu sion in
th e acu te ph ase (CT an giography), or an in terru p-
tion of blood supp ly to an area of th e brain th at
oth erw ise ap pears n orm al (perfu sion CT). Th e
clin ical usefuln ess of th ese m eth ods is cu rren tly
bein g assessed.
Th ere is n o eviden ce to su ggest th at th e ad-
m in istration of con trast m ediu m in creases th e
size of in farct s, desp ite earlier specu lation to th at
effect. Non eth eless, in traven ou s con trast m ediu m
is on ly rarely n eeded in th e su bacute ph ase. In -
farcts begin to take u p con trast m ediu m st ron gly
on th e fou rth to sixt h day after th e acu te isch em ic
even t because of disru ption of t h e blood–brain
barrier. Th is p h en om en on , w h en com bin ed w ith
an im precise h istory, m ay lead to th e m isdiagn o-
sis of an in farct as a n eoplasm (e.g., lym p h om a).
Magnetic resonance imaging (MRI) reveals
isch em ia w ith in a few m in u tes of on set. Brain cells
dep rived of en ergy sw ell w ith w ater becau se th eir
en ergy-depen den t m em bran e pum ps cease to
fu n ction (cytotoxic edem a). Edem a, in tu rn , slow s
th e w ater m olecu les in th e blood vessels of th e in -
farct zon e, an d th is slow in g can be dem on strated
im m ediately after th e on set of isch em ia, an d very
rap idly, w ith diffu sion -w eigh ted MR sequ en ces.
Com bin ed w ith conven tion al sequ en ces for an a-
tom ical im agin g, diffusion -w eigh ted MRI detects
isch em ia h igh ly reliably anyw h ere in th e brain .
MRI also reveals cerebral in farcts th at are n ot seen
by CT in patien ts w it h tran sien t or on ly m ild n eu-
rological deficits (e.g., pu rely cortical in farcts in th e
so-called n on eloqu en t areas of th e brain , su ch as
th e fron tal association cortex or righ t in sula).
Brain stem in farcts, too, are readily seen . Furth er-
m ore, th e blood vessels su pplyin g th e brain are
w ell visu alized both extracran ially an d in -
tracran ially. MR an giography is risk-free, w h ich
Cerebral Ischem ia · 289
11
can n ot be said of conven tion al an giography w ith
in tra-arterial con trast m edium ; its qu ality,
h ow ever, still falls sh ort of th e stan dard set by DSA.
Tw o disadvan tages of MRI are its lim ited availabil-
ity as an em ergen cy stu dy an d th e relatively lon g
tim e n eeded to perform it, w h ich m akes it suscep-
tible to m ovem en t artifacts.
Of all n euroim agin g m eth ods, digital subtraction
angiography (DSA) (i.e., visu alization of th e blood
vessels of th e brain w ith in tra-arterially in jected
radiograph ic con trast m edium ) st ill provides th e
best m orph ological view of path ological ch an ges
in th e extracran ial an d in tracran ial vessels. Each
stu dy, h ow ever, carries its ow n sm all risk of stroke
or oth er com p lication s, an d its in dicat ion s are
th erefore bein g progressively lim ited to a sm all
n um ber of specific clin ical situ ation s. Con tem -
porary u ltrasou n d an d MRI tech n iqu es are avail-
able as risk-free altern atives. Because an giograp hy
does n ot visu alize brain tissu e, it can on ly reveal
in farcts in directly.
Ultrasonography is routin ely u sed in th e diagn ostic
evaluation of cerebral isch em ia. Modern color-
coded m eth ods en able rapid, risk-free, an d reliable
assessm en t of th e great vessels of th e n eck, w ith
qu an tificat ion of any sten oses th at m igh t be p re-
sen t (Fig. 11.21). Som e of th e in tracran ial vessels
can even be stu died by Doppler ultrason ography
th rough th e bony skull (i.e., tran scran ially), bu t th is
tech n iqu e is of lim ited reliability.
Radionuclide studies. In addition to th e tech n iqu es
discu ssed above for th e m orph ological stu dy of th e
brain an d t h e cerebral vasculature, m odern n u clear
m edicin e p rovides oth er tech n iques for th e stu dy
of fun ction al param eters su ch as region al cerebral
blood flow (rCBF). Th e t w o m ost im port an t t ypes of
fu n ction al stu dy are positron emission tomogra-
phy (PET) an d single -photon emission computer-
ized tomography (SPECT). Very recen tly, soph isti-
cated MRI an d CT tech n iqu es for th e m easu rem en t
of rCBF h ave also been in trodu ced. As a com m en t
on all of th ese types of studies, it sh ou ld be n oted
th at, becau se m ost strokes are due to em boli rath er
th an preexistin g deficien cies of region al p erfu sion ,
m easu rin g blood flow is gen erally u seless as a
m ean s of predictin g stroke. Th us, th e assessm en t
of rCBF by any of th ese tech n iques is on ly in dicated
in certain specific situ ation s.
11 290 · 11 Blood Supply and Vascular Disorders of the Central Nervous System

Case Presentation 3: The Use of Ima ging Studies for Definitive Diagnosis in Neurology
This case illustrates how clinical problem s in neurology can
be solved by precise correlation of the findings of clinical
history-taking, physical exam ination, and ancillary studies.
The history and physical exam ination often enable fairly
precise localization of the lesion, but further laboratory
tests and neuroim aging are usually needed to pinpoint its
etiology.
This previously healthy 59-year-old schoolteacher suddenly
becam e weak on the entire right side of his body, m ost
severely in the leg, and was well again a short tim e later.
During the episode, he also had transient sensory abnor-
malities in both legs. An MRI scan of the brain with diffu-
sion-weighted (Fig. 11.23a) and T2-weighted sequences
(not shown) revealed a sm all, acute infarct in the left
parietal lobe. MR angiography (Fig. 11.23b, c) and intra-
arterial digital subtraction angiography (Fig. 11.23d, e) re-
vealed a high-grade, calcific stenosis of the left internal
carotid artery. The infarct had apparently been caused by
transient hem odynam ic insufficiency on the basis of this
stenotic lesion. The infarct sufficed to explain the patient’s
transient right hem iparesis, but not the transient sensory
abnorm ality in his left leg, which could only be attributed to
hypoperfusion in the territory of the right anterior cerebral
artery. Because this vessel is ordinarily not a branch of the
left internal cerebral artery, a possible second cause of cere-
bral ischem ia had to be sought.
The left carotid lesion described above had no counterpart in
the right internal carotid artery, which was norm al. The MR
angiogram , however, showed both anterior cerebral arteries
receiving blood from the left internal carotid artery; a nor-
m al anatom ical variant was present, in which the initial, or
“precom m unicating,” segm ent of the left anterior cerebral
artery (the left A1 segm ent) was hypoplastic. The left carotid
stenosis thus sufficed to explain all of the patient’s sym p-
tom s, including weakness in the left leg, due to hypoperfu-
sion in the territory of the left anterior cerebral artery. In this
case, definitive diagnosis would have been im possible
without im aging studies of the cerebral vasculature.

a b
Fig. 11.23 Infarct in the territory of the left anterior
cerebral artery and transient ischemia in the right ante-
rior circulation due to high-grade stenosis of the left in-
ternal carotid artery. a Diffusion-weighted MRI. Abnor-
m ally bright signal is seen in the parasagittal portion of
the left postcentral gyrus, indicating acute ischem ia in the
territory of the left anterior cerebral artery. b MR angio-
graphy of the arteries of the base of the brain. Both ante-
rior cerebral arteries are supplied by the left internal
carotid artery. c Contrast-enhanced MR angiography of
the arteries of the neck. High-grade stenosis at the origin
of the left internal carotid artery is the probable cause of
the em bolic infarction in the left anterior circulation, clini-
cally m anifest as right hem iparesis m ainly affecting the
leg. The patient had also reported a transient sensory dis-
turbance in the left leg, which was m ost likely due to a
transient im pairm ent of flow in the right anterior cerebral
artery. Because both anterior cerebral arteries are supplied
c by the left internal carotid artery in this patient, the bi-
hem ispheric sym ptom s can be traced back to a single
com m on cause (left ICA stenosis). Fig. 11.23 d, e

d e
Fig. 11.23 d, e Infarct in the territory of the left anterior
cerebral artery and transient ischemia in the right ante-
rior circulation due to high-grade stenosis of the left in-
ternal carotid artery. d This intra-arterial digital subtrac-
tion angiogram dem onstrates the high-grade stenosis of
the left ICA very well (arrow). e This angiographic im age,
obtained after injection of contrast m edium into one of the
vertebral arteries, reveals a further sign of carotid stenosis:
Case Presentation 4: Thrombolysis in the Middle Cerebra l Artery
This 69-year-old m an was adm itted to the ophthalm ology
service of a teaching hospital for an elective retinal pro-
cedure. While undergoing preoperative evaluation, he sud-
denly developed left hem iplegia. A CT scan of the head,
ordered as an em ergency, was norm al and was followed
within 15 m inutes by an MRI scan, including visualization of
the blood vessels and diffusion-weighted sequences. The
cause of the acute left hem iplegia was found to be a distal
occlusion of the m ain trunk of the right m iddle cerebral
artery (Fig. 11.24a). The diffusion-weighted im age showed
no evidence of irreversible infarction (Fig. 11.24b).
The patient was transferred to the neurology service. Intra-
arterial throm bolysis was considered to be indicated, be-
Cerebral Ischem ia · 291
11
there is intracranial reversal of flow in the posterior com -
m unicating artery, which is supplied with blood in retro-
grade fashion from the basilar artery. The pericallosal artery
(arrow) obtains blood from the posterior com m unicating
artery and can thus be seen after vertebral injection. Nor-
m al flow in the posterior com m unicating artery is from the
anterior to the posterior circulation (internal carotid to
posterior cerebral artery).
cause less than three hours had elapsed from the onset of
the neurological deficit, and because it did not appear that
m ajor, irreversible parenchym al injury had already oc-
curred. He was taken to the angiography suite. First, the
vascular occlusion was dem onstrated angiographically
(Fig. 11.24c, d). Then, a m icrocatheter was introduced into
the m iddle cerebral artery just proxim al to the throm bus,
and 1 m illion units of urokinase were infused through it
(Fig. 11.24e). This resulted in the com plete dissolution of
the throm bus (Fig. 11.24f, g). The patient’s hem iplegia re-
solved com pletely, though a cortical infarct in the insular re-
gion rem ained visible by MRI (Fig. 11.24h). He was dis-
charged eight days after the acute event and received
further care as an outpatient.
11 292 · 11 Blood Supply and Vascular Disorders of the Central Nervous System
a b
c d
e f
Fig. 11.24 Thrombolysis in the right middle cerebral
artery after acute thrombotic occlusion of its main
stem. a MR angiography of the arteries of the base of the
brain. “Cut-off” of the right m iddle cerebral artery (MCA)
indicates occlusion. b Diffusion-weighted MRI. Only a m ild
abnorm ality of diffusion is visible as an area of hyperinten-
sity in the right insular cortex. There is thus no definitive
evidence of irreversible ischem ic injury (i.e., infarction).
Intra-arterial digital subtraction angiography in A-P (c) and
lateral (d) projections after injection of contrast m edium
into the right com m on carotid artery The m ain stem of the
m iddle cerebral artery is occluded distal to the origin of a
large tem poral branch. The anterior and posterior cerebral
arteries (ACA, PCA) can be seen m ore easily than usual on
the lateral projection because the norm ally overshadowing
branches of the MCA are absent. e A m icrocatheter has
been introduced by way of the internal carotid artery into
the m iddle cerebral artery; its tip lies just proxim al to the
throm bus (arrow). Urokinase was infused through this
catheter. f A follow-up angiogram obtained ca. 90 m inutes
after intra-arterial throm bolysis dem onstrates restoration
of flow in the m iddle cerebral artery.
Fig. 11.24 g, h

g h
Fig. 11.24 g Follow-up MR angiography also dem onstrates
recanalization of the m iddle cerebral artery (com pare to b).
h T2-weighted FLAIR im age. Despite rapid recanalization of
the right m iddle cerebral artery, infarction has occurred in
Case Presentation 5: Thrombolysis in a Case of Basila r Artery Thrombosis
This 27-year-old student was riding a bicycle when she no-
ticed a “fuzzy feeling.” Because she could no longer ride
straight, she got off her bicycle and sat down by the side of
the road. A short tim e later, she becam e nauseated and
vom ited several tim es. The driver of a passing car stopped
and got out to help. She could not respond adequately to
his questions, but m erely m um bled unintelligibly and lost
consciousness shortly afterward. The driver notified the
em ergency m edical service and the patient was taken to
the hospital.
a b
Fig. 11.25 Thrombolysis in basilar artery thrombosis. a
The initial MR angiogram reveals lack of flow in the distal
portion of the basilar artery (the course of the occluded
arterial segm ent is sketched in dotted lines). The basilar tip
receives blood from the anterior circulation through the
Cerebral Ischem ia · 293
11
part of the insular cortex. The underlying white m atter does
not appear to be involved to any significant extent. The
prom pt treatm ent of this patient with throm bolysis prob-
ably prevented m uch m ore extensive infarction.
On adm ission, she was unconscious and withdrew her lim bs
from noxious stim uli on the right side only; therefore, a left
hem iparesis was suspected. Her pupils were equal in size.
The physician on duty in the em ergency room ordered a CT
scan to rule out an intracranial hem orrhage. The CT scan
was norm al, and was therefore im m ediately followed by an
MRI scan including visualization of the cerebral vessels
(Fig. 11.25a) and a diffusion-weighted im age (Fig. 11.25b).
The cause of the neurological deficits was found to be
circle of Willis. b The diffusion-weighted im age of the brain
is norm al. Despite occlusion of the basilar artery, no infarc-
tion has occurred. The relatively intense signal in the pons is
norm al and is due to the m iddle cerebellar peduncles. The
bright areas in the tem poral lobes are due to artefact.
Fig. 11.25 c–j
11 294 · 11 Blood Supply and Vascular Disorders of the Central Nervous System
throm bosis of the basilar artery (Fig. 11.25a). No irreversi-
ble parenchym al injury was found to have occurred up to
this point (Fig. 11.25b). Conventional transfem oral catheter
angiography confirm ed distal occlusion of the basilar artery
(Fig. 11.25c, d); the tip of the basilar artery and the two
posterior cerebral arteries were still patent and were sup-
plied by the carotid artery by way of the posterior com -
municating artery (Fig. 11.25e, f). A m icrocatheter was in-
troduced to the level of the throm bus (Fig. 11.25g) and
c d
e f
Fig. 11.25 c–j c and d Digital subtraction angiography
after injection of contrast m edium into the left vertebral
artery; A-P (c) and lateral (d) projections. The basilar artery
is occluded distally (arrow a). Resistance to forward flow in
the basilar artery causes reflux of the injected contrast m e-
dium into the opposite (right) vertebral artery (arrow b).
Because the anterior and posterior inferior cerebellar arter-
ies rem ain open, a vascular flush is seen in the inferior por-
tion of the cerebellum . The superior cerebellar arteries,
however, lie distal to the obstruction, and there is therefore
no flush in the superior portion of the cerebellum . In d an
artefact caused by an ECG cable lying in the path of the
x-ray beam is seen (arrow c). e and f Digital subtraction an-
giography after injection of contrast m edium into the left
internal carotid artery. A large posterior com m unicating
100 m g of rtPA were infused, resulting in disappearance of
m ost of the throm bus (Fig. 11.25h).
The patient’s deficits resolved fully within two days, though
a follow-up MRI scan revealed sm all infarcts in the pons and
cerebellum (Fig. 11.25i, j). An exhaustive diagnostic evalua-
tion failed to reveal the cause of the basilar artery throm bo-
sis. The patient was asym ptom atic on her discharge from
the hospital 15 days after adm ission.
artery (a) supplies the left posterior cerebral artery (b) with
blood from the anterior circulation. The basilar tip (c), too,
fills with contrast m edium derived in retrograde fashion
from the initial segm ent of the posterior cerebral artery
(the P1 segm ent). Vessels filling with contrast from the
basilar artery include the left superior cerebellar artery (d),
the right posterior cerebral artery (e), and the doubled right
superior cerebellar artery (f). The apparently weak filling of
the right posterior cerebral artery is caused by “washout” of
contrast m edium by contrast-free blood that enters this
vessel from the anterior circulation via the right posterior
com m unicating artery, as was independently confirm ed by
injection of the right internal carotid artery (study not
shown).
Fig. 11.25 g–j

g h
i j
Fig. 11.25 g–j g Superselective m icrocatheterization of
the basilar artery. The tip of the m icrocatheter lies just prox-
im al to the throm bus (arrow). 100 m g of rtPA (recom binant
tissue plasm inogen activator) were injected through it.
h Follow-up study 90 m inutes after rtPA injection: the
basilar artery is fully recanalized (cf. d).
Particular Cerebrovascular
Syndromes
Th e dyn am ics of clin ical isch em ia, i.e., th e m an n er
in w h ich th e clin ical picture u n folds over tim e, de-
pen ds m ain ly on th e type of in farct (em bolic,
h em odyn am ic, or lacu n ar; see above), bu t th e par-
ticu lar n eurological deficits th at are presen t are a
fu n ction of th e site of th e lesion . In t h e follow in g
section s, w e w ill discuss th e m ost im portan t cere-
brovascular syn drom es caused by th e occlu sion of
in dividu al arteries su pplyin g th e brain .
Cerebral Ischem ia · 295
11
i and j Follow-up MRI two days later. The patient was
asym ptom atic at this tim e. i The T2-weighted im age re-
veals a sm all left pontine lesion (arrow) but no m ore exten-
sive infarct. j The diffusion-weighted im age additionally re-
veals a sm all lesion in the left cerebellar hem isphere
(arrow).
Vascula r Syndromes of the Cerebra l
Hemispheres
Ischem ic Syndrom es in the Anterior Circulation
Cerebral isch em ia m ost com m on ly arises in th e
territory of th e in tern al carotid artery. It is usually
cau sed eith er by cardiogen ic em boli or by arterio-
arterial em boli arisin g in ath erosclerotic plaqu es at
th e bifurcation of th e com m on carotid artery.
Oth er, rarer causes in clu de prim ary diseases of th e
vascu lar w all of t h e ICA (such as fibrom u scular
dysplasia) an d trau m atic or spon tan eou s dissec-
tion of th e ICA, leadin g to occlu sion . Dissection ,
usually spon tan eou s, is a com m on cau se of carotid
occlusion in you n ger pat ien ts.
11 296 · 11 Blood Supply and Vascular Disorders of the Central Nervous System
Isch em ic lesion s can develop in th e territory of
any of th e bran ch es of th e ICA, or in all of th ese
territories com bin ed. Th e n eu rological deficits re-
sult in g from isch em ia in each vascular territory
w ill be briefly described.
Ophthalmic artery. Sm all em boli can pass th rough
th e oph th alm ic artery an d lodge in th e cen tral ret i-
n al artery, cau sin g retin al isch em ia an d th us m on -
ocular blin dn ess. Th is is usually tran sien t (am auro-
sis fugax), becau se th e em bolus u su ally u n dergoes
spon tan eou s lysis. Perm an en t blin dn ess is excep-
tion al. Proxim al obstruction of th e oph th alm ic
artery does n ot cause tran sien t m on ocu lar blin d-
n ess, because th e cen tral retin al artery also obtain s
blood th rough collaterals from th e extern al carotid
artery.
Posterior communicating artery. Th e n ext t w o
bran ch es of th e in tern al carot id artery are th e pos-
terior com m u n icatin g artery an d th e an terior
ch oroidal artery. Em boli en terin g th e posterior
com m u n icatin g artery cau se isch em ia eith er in th e
territory of th e posterior cerebral artery (see
p. 298) or in th e th alam u s. Th e clin ical m an ifesta-
tion s are th u s contralateral hom onym ous hem i-
anopsia an d/or a thalam ic deficit (cf. p. 245).
Anterior choroidal artery. Th e territory of th e an te-
rior ch oroidal artery in clu des th e m edial portion of
th e tem p oral lobe w ith th e h ipp ocam pal form a-
tion , th e gen u of th e in tern al capsule, an d p arts of
th e optic tract an d radiation . Th e m an ifestation s of
ischem ia in th is territory are contralateral hem i-
paresis and hem ihypesthesia as w ell as contralateral
hom onym ous hem ianopsia. It is often difficu lt to
distin gu ish an in farct in th e territory of th e an te-
rior ch oroidal artery from a len ticulostriate in farct
on clin ical grou n ds alon e. Isch em ia of th e m edial
portion of th e tem poral lobe is a su re sign th at th e
an terior ch oroidal artery is involved; th ou gh th is is
n ot readily seen in a CT scan , MRI can dem on strate
it w it h h igh sen sitivity.
Bifurcation (“T”) of the internal carotid artery. Em -
bolic occlu sion of t h e in tern al carotid artery at its
bifurcat ion , cu ttin g off blood flow from t h e in ter-
n al carotid artery in to th e m iddle cerebral artery
an d th e an terior cerebral artery, is a life-th reaten -
in g situation . Wh en th is h appen s, th e circle of Wil-
lis provides n o collateral path w ay for blood to flow
in to th e m iddle cerebral artery. Th e u su al resu lt is
extensive infarction in the territory of the m iddle
cerebral artery, w ith th e correspon din g n eu rologi-
cal deficits (see below ). Th e an terior cerebral
artery, on th e oth er h an d, can often be filled w it h
blood from th e con tralateral an terior cerebral
artery by w ay of th e an terior com m u n icatin g
artery. If it can n ot be filled in th is w ay becau se th e
an terior com m u n icat in g artery is hypoplast ic, or
because em bolic m aterial h as occlu ded it distal to
th e in sertion of th e an terior com m un icatin g artery,
th ere is addition al infarction in the territory of the
anterior cerebral artery (see p. 297). Fu rth erm ore,
t h e in farct in th e territory of th e m iddle cerebral
artery is larger, becau se t h is territory can n ot be
su pplied by collateral circulat ion in to t h rou gh t h e
su perficial leptom en in geal an astom oses.
In addition to th e exten sive an d severe n eu ro-
logical deficits (see below ), th e in farcted territories
sw ell rapidly (cytotoxic edem a), cau sin g a rap id
rise in intracranial pressure. Th erefore, perm an en t
occlu sion of th e in tern al carotid artery at it s bifu r-
cation is u su ally fatal. It sh ou ld be rem em bered,
h ow ever, th at em bolic stroke is a dyn am ic even t.
Th e em bolu s u n dergoes spon tan eous lysis by
en dogen ou s p lasm in , even as it con tin ues to form
because of th e absen ce of blood flow. Th e n et resu lt
of th ese tw o com petin g processes m ay be in eith er
direction : if th rom bolysis p revails, th e artery is
spon tan eou sly recan alized, perh aps w it h distal
p ropagation of sm aller fragm en ts of clot; if clot for-
m ation prevails, th e artery is p erm an en tly oc-
cluded.
Middle cerebral artery. Em boli in th e territory of
t h e m iddle cerebral artery are th e m ost com m on
cau se of cerebral isch em ia. Th e clin ical m an ifesta-
t ion s depen d on th e site of arterial occlusion .
Main stem occlusion. Th e m ain stem (tru n k) of t h e
m iddle cerebral artery gives off th e sm all len -
ticu lostriate arteries at a righ t an gle; th ese arteries
supp ly th e basal gan glia an d in tern al capsu le.
With in th e sylvian fissu re, th e m iddle cerebral
artery divides in to its m ain bran ch es, w h ich su pply
large p ortion s of th e fron tal, p arietal, an d tem poral
lobes (cf. Fig. 11.4).
Occlusion of t h e m ain stem of th e m iddle cere-
bral artery leads to loss of n eu ron s in th e basal gan -
glia, an d, a sh ort tim e later, to n ecrosis in th e in ter-
n al capsu le as w ell. Th e basal gan glia, w h ich lack a

collateral circu lation , tolerate isch em ia poorly. Re-
gion al differen ces in isch em ic toleran ce depen d
n ot on ly on circulatory factors, h ow ever, but also
on t h e in trin sic properties of n euron s in differen t
parts of th e brain .
Because th e m iddle cerebral artery su pp lies an
exten sive area of th e cerebral h em isph ere, occlu-
sion of its m ain stem causes a large assort m en t of
n eu rological deficits: contralateral, m ainly bra-
chiofacial hem iparesis and hem ihypesthesia, oc-
casion ally contralateral hom onym ous hem ianopsia,
an d neuropsychological deficits in clu din g m otor/
sen sory aph asia, acalcu lia, agraph ia, an d m otor
ap raxia if th e lesion is in th e dom in an t h em i-
sph ere, or con stru ctive apraxia an d, possibly, an o-
sogn osia if it is in th e n on dom in an t h em isph ere. In
th e acu te ph ase of in farction , t h ere m ay also be
turning of the head to the opposite side, as w ell as
fixed gaze deviation to the opposite side (déviation
conjuguée).
Large in farcts in th e territory of th e m iddle cere-
bral artery an d th e exten sive accom panyin g cere-
bral edem a gen erally cau se intracranial hyperten-
sion, w h ich , if un treated, can lead to deat h .
Occlusion of peripheral branches of th e m iddle cere-
bral artery cau ses in farction in th e respective terri-
tories. Th e n eurological m an ifestation s vary ac-
cordin gly; t h ey are m ost pron oun ced w h en th e in -
farct involves th e cen tral region (contralateral focal
m otor and/or sensory deficits). Isch em ia in th e peri-
in su lar region on th e left (dom in an t) side, particu-
larly in th e in ferior fron tal gyrus or th e an gu lar
gyrus, cau ses m otor or sensory aphasia (p. 248 ff.).
Th e n eu ropsych ological deficits cau sed by lesion s
in correspon din g areas on th e righ t side (construc-
tive apraxia, anosognosia) are less obviou s an d m ay
on ly becom e eviden t on close exam in ation . Be-
cause th e exact border betw een th e territories of
th e m iddle cerebral artery an d t h e posterior cere-
bral artery is variable, th e form er som etim es sup-
plies part of th e optic radiation; if th is is th e case,
occlu sion of a bran ch of t h e m iddle cerebral artery
can cause contralateral hom onym ous hem ianopsia.
Prefron t al an d rostral tem poral in farcts are clin i-
cally silen t.
Anterior cerebral artery. In farcts in th e territory of
th e an terior cerebral artery are relatively rare (10–
20 %of all brain in farcts). Th ey m ay be un ilateral or
bilateral, depen din g on variation s in vascular an at-
Cerebral Ischem ia · 297
11
om y. Bilateral in farcts often occur w h en both an te-
rior cerebral arteries are sup plied by a sin gle in ter-
n al carotid artery. Em boli from an ath erosclerotic
plaque in th e carotid bifu rcation can th en en ter
both an terior cerebral arteries w ith in a sh ort period
of tim e (cf. Case Presen t ation 3, p. 290). Less com -
m on ly, th ere m ay be on ly on e (azygou s) an terior
cerebral artery, as a n orm al an atom ical varian t.
Fu rth er cau ses of in farction in th e territory of th e
an terior cerebral artery in clu de an eurysm s of th e
an terior com m u n icatin g artery an d sten osis of in -
flam m atory/in fect iou s origin , w h ich often occu rs in
th e p ericallosal segm en t of th e an terior cerebral
artery.
Un ilateral in farcts in th e territory of th e an terior
cerebral artery are often clin ically silen t. In farction
rarely occu rs in th e far rostral p ortion of th is arte-
rial territory, becau se of th e m any an astom otic
con n ection s betw een th e vessels of th e tw o h em i-
sph eres. Fu rth er tow ard t h e back of t h e h ead,
h ow ever, th e territories of th e tw o an terior cere-
bral arteries are separated by th e falx cerebri, so
th at n eith er side can obtain collateral circu lation
from th e oth er. Possible m an ifestat ion s of an in -
farct in th is (cen tral) area are hem iparesis m ainly
affecting the leg, isolated leg paresis, an d parapare-
sis (in bilateral in farction ). Th ese deficits are usu-
ally on ly tran sien t, h ow ever, becau se of restitu tion
of blood flow th rou gh collateral circu lation from
th e p osterior cerebral artery. Un ilateral dam age of
th e m edial aspect of th e fron tal lobe u su ally does
n ot p rodu ce any severe deficit, bu t bilateral dam -
age produces a very severe disturbance of drive: th e
patien t n o lon ger participates in any of th e n orm al
activities of life, becom es totally apath etic, an d
spen ds m ost of th e day in bed. Th is problem is
often accom pan ied by fu rt h er m ental abnorm ali-
ties, neuropsychological deficits (apraxia), bladder
dysfunction (in con tin en ce), and pathological,
“prim itive” reflexes (grasp, suck, an d palm om en tal
reflexes).
Ischem ic Syndrom es in the Posterior Circulation
Isch em ia in th e posterior circu lation , as in th e
an terior circulat ion , is usually of embolic origin .
Most of th e respon sible em boli arise from ath ero-
m atou s p laqu es in th e w all of th e vertebral artery.
In con trast to th e com m on carotid artery, in w h ich
ath erom a ten ds to form at t h e carotid bifu rcation ,
th e vertebral artery con tain s n o preferred sites of
11 298 · 11 Blood Supply and Vascular Disorders of the Central Nervous System
ath erom a form ation . Ath erom atou s plaques can be
fou n d anyw h ere alon g it s len gth .
Th is fact m akes it difficult to localize the source
of emboli precisely. Furth erm ore, ath erom atou s
plaqu es in th e righ t or left vertebral artery m ay give
rise to em boli th at t ravel distally in to th e basilar
artery or in to th e posterior cerebral artery on either
side. An in dication of t h e side of origin of em boli is
presen t, h ow ever, w h en th e posterior in ferior cere-
bellar artery is involved, becau se th is vessel is a
direct bran ch of th e term in al segm en t of th e verte-
bral artery. Th e radiograph ic dem on stration of
acu te occlu sion of on e vertebral artery is also h elp-
fu l in th is respect. Sten osis of th e vertebral artery,
like sten osis of th e in tern al carotid artery, u su ally
causes stroke n ot by dim in ish ed perfusion but
rath er by act in g as a source of em boli. It is u n clear to
w h at exten t cardiogen ic em boli m igh t be re-
spon sible for isch em ia in t h e posterior circu lation .
Th e vertebral an d basilar arteries su pply t h e
brain stem , am on g oth er parts of th e brain . Becau se
th e brain stem con trols m any essen tial fu n ction s,
in clu din g respiration an d cardiovascular fu n ction ,
brainstem infarction often h as m uch m ore serious
con sequ en ces th an in farction in th e territory of th e
in tern al carot id artery. Occlusion of th e basilar
artery in cludin g th e basilar tip is un iform ly fat al.
Fu rth erm ore, because th ere is on ly lim ited room in
th e p osterior fossa for sw ollen brain tissu e to ex-
pan d, even a relatively sm all cerebellar in farct can
cause life-th reaten in g in tracran ial hyp erten sion .
Com p ression of th e aquedu ct or fou rth ven tricle by
in farcted tissue can cau se occlu sive hydrocep h alu s,
raisin g th e in tracran ial pressu re even h igh er.
Em ergen cy extern al ven tricu lar drain age w ith or
w ith ou t subsequ en t n eurosu rgical decom pression
of th e posterior fossa is a life-savin g procedure in
such cases.
Basilar artery. Th e tw o vertebral arteries un ite in
fron t of t h e brain stem to form t h e basilar artery.
Th is vessel gives off m any sm all bran ch es to th e
brain stem , th e an terior in ferior cerebellar artery
(AICA), an d th e su perior cerebellar artery (SCA,
p. 276) before dividin g, at th e level of th e m idbrain ,
in to th e tw o p osterior cerebral arteries (basilar
tip). Th e vascu lar syn drom es cau sed by occlu sion
of th e perforat in g or circum feren t ial bran ch es of
th e basilar artery w ere described in Ch apter 4
(p . 147 ff.); th ose cau sed by occlu sion of th e cere-
bellar arteries are described on p . 299.
Posterior cerebral artery. Th e arteries in t h e n eigh -
borh ood of t h e basilar tip are of particular clin ical
sign ifican ce, becau se their p erforatin g bran ch es
supp ly th e im portan t stru ctures of th e m idbrain
an d th alam u s. Midbrain in farction du e to basilar
tip occlusion is alw ays fatal.
Em bolic occlu sion of th e basilar artery or of th e
proxim al (P1) segm en t of th e posterior cerebral
artery does n ot alw ays produ ce an isch em ic lesion
in th e p eriph eral territory of th e p osterior cerebral
artery, because collateral circu lation from th e in -
tern al carotid artery by w ay of th e posterior com -
m u n icatin g artery can often provide an adequ ate
flow of blood distal to the occlu sion . Th u s, basilar
artery occlu sion (em bolic or th rom botic) is by n o
m ean s excluded by n orm al fin din gs in h ead CT an d
Doppler u ltrason ography.
Am on g th e n u m erou s perforatin g arteries in th is
area, a few of th e larger on es w ill be sin gled ou t for
discu ssion :
¼ Medial and lateral posterior choroidal arteries.
Isch em ia in th ese territories is u su ally accom -
pan ied by isch em ia in th e territory of th e poste-
rior cerebral artery; th us, relatively little is
kn ow n abou t th e n eu rological deficits caused
by isolated occlusion s of th ese tw o sm all arter-
ies. Deficits th at h ave been described in isolated
occlusion of th e lateral posterior ch oroidal
artery in clu de h om onym ous qu adran tan opsia
du e to in farction of th e lateral gen icu late body,
h em isen sory deficits, an d n eu ropsych ological
abn orm alities (t ran scort ical aph asia, am n esia).
Isolated occlusion of th e m edial posterior
ch oroidal artery, w h ich is even rarer, h as been
reported to p rodu ce m idbrain dam age, w ith re-
sult in g ocu lom otor dysfu n ction .
¼ Cortical branches of the posterior cerebral artery.
Occlu sion of on e or m ore cortical bran ch es of
th e posterior cerebral artery can p rodu ce a w ide
variety of n eu rological deficits, n ot just because
th ese vessels take a h igh ly variable course but
also because th e territory of th e posterior cere-
bral artery varies in exten t . Its border w ith t h e
territory of th e m iddle cerebral artery ru n s
differen tly in differen t in dividuals, an d th e sizes
of t h ese t w o territories are recip rocally related.
In a case of focal cortical in farction , it is im por-
tan t to determ in e in w h ich vascu lar territory
th e lesion lies, because th is w ill, in tu rn , im ply
th e probable sou rce of em boli. If th e lesion is in
th e territory of th e m iddle cerebral artery, th e

em bolu s probably arose from t h e ipsilateral
com m on carotid bifurcation ; if it is in th e terri-
tory of th e posterior cerebral artery, th e em -
bolu s probably arose from t h e ipsilateral or con -
tralateral vertebral artery.
¼ Calcarine artery. Th is is clin ically th e m ost im -
portan t bran ch of th e p osterior cerebral artery
becau se it sup plies th e visu al cortex. A un i-
lateral in farct produ ces contralateral hom ony-
m ous hem ianopsia; bilateral lesion s can pro-
du ce cortical blindness. Often , h ow ever, an in -
farct in th e territory of th e calcarin e artery pro-
du ces n o m ore th an a part ial visu al field defect
(a quadrantanopsia or a blin d patch called a sco-
tom a), becau se the visu al cortex is also sup plied
by leptom en in geal collaterals from th e m iddle
cerebral artery.
Tha la mic Vascula r Syndromes
Anterior thalamoperforating artery (th alam o-
tu beral artery). Th is artery origin ates from th e
posterior com m u n icat in g artery an d m ain ly su p-
plies t h e rostral port ion of th e th alam us. In farction
in its territory causes a rest or intention trem or an d
choreoathetotic m otor restlessness w ith thalam ic
hand (an abn orm ally con tracted postu re of th e
h an d). Sen sory dist urban ces an d pain are typically
absen t .
Posterior thalamoperforating artery (th alam o-
perforat in g artery). Th e th alam op erforatin g arter-
ies of th e tw o sides som etim es arise from a com -
m on tru n k (th e artery of Percheron, cf. p. 277). Oc-
clu sion of th is artery causes bilateral in farction of
th e in tralam in ar n uclei of th e th alam us, resultin g
in a severe im pairm ent of consciousness.
Thalamogeniculate artery. Th e lateral portion of
th e th alam u s is m ain ly su pplied by th e th alam o-
gen icu late artery, w h ich arises from t h e P2 seg-
m en t of th e p osterior cerebral artery, i.e., distal to
th e posterior com m u n icat in g artery. In farcts in th e
territory of th e p osterior cerebral artery often in -
volve isch em ia in th e distribut ion of th e th alam o-
gen icu late artery. Th e correspon din g deficits w ere
first described by Dejerin e an d Rou ssy: tran sien t
contralateral hem iparesis, persisten t contralateral
hem ianesthesia for touch and proprioception (w ith
lesser im p airm en t of pain an d tem p eratu re sen sa-
tion ), spontaneous pain, m ild hem iataxia an d
Cerebral Ischem ia · 299
11
astereognosis, an d contralateral choreoathetotic
m otor restlessness.
Th e con tralateral h em iparesis u su ally resolves
rapidly. It is attribu ted to com pression of th e in ter-
n al capsu le by th e n eigh borin g, edem atous
th alam ic tissu e. Th e in tern al cap sule itself is n ot
isch em ic, as it is n ot su pplied by th e th alam ogen -
icu late artery.
Cerebella r Vascula r Syndromes
Th e cerebellar arteries h ave n u m erou s collaterals;
th us, th e occlu sion of a sin gle vessel often cau ses
n o m ore th an a sm all in farct, w h ich m ay be clin i-
cally silen t. More exten sive isch em ia, w h ich is less
com m on ly seen , produ ces cerebellar n eu rological
deficit s, particu larly in th e acu te p h ase. Th e ac-
com panyin g brain edem a m ay cau se rapidly pro-
gressive com p ression of th e fou rth ven tricle, re-
sult in g in occlusive hydrocep h alu s an d im pen din g
brain stem h ern iation .
Posterior inferior cerebellar artery (PICA). Proxi-
m al occlusion of th e PICA causes isch em ia of th e
dorsolateral portion of th e m edulla, usually pro-
du cin g a partial or com plete W allenberg syndrom e
(p. 147 ff.). Th e PICA also su pplies part of th e cere-
bellu m , bu t to a h igh ly variable exten t (p . 275);
th us, th ere m ay be accom panyin g cerebellar defi-
cits of variable severity, su ch as hem iataxia, dys-
m etria, lateropulsion, or dysdiadochokinesia. Th e
cerebellar deficits are alw ays fou n d on th e side of
th e in farct. Th ey are also often accom pan ied by
n au sea an d vom itin g; if th e latter are m isin ter-
preted as bein g of gastroin test in al rath er th an
n eu rological origin , th e diagn osis m ay be delayed
or m issed, w ith poten tially catastroph ic resu lts
(see Case Presen tation 7, p. 301). Occasion ally, if th e
PICA is occlu ded very n ear its origin , cerebellar
sign s m ay be en tirely absen t; conversely, brain stem
sign s m ay be absen t in distal occlu sion s.
Th e in itial CT scan m ay n ot reveal a cerebellar
stroke becau se it h as been obtain ed very early in
th e cou rse of in farction , or becau se th ere is too
m u ch artefact in th e posterior fossa for th e cerebel-
lu m to be seen clearly. As a result, even large cere-
bellar in farct s m ay escap e diagn osis un til th e in -
creasin g cytotoxic edem a of th e dam aged tissue
cau ses sym ptom atic brainstem com pression. Th is is
m an ifest as im pairm ent of consciousness, vom iting,
an d cardiorespiratory disturbances, u p to an d in -
11 300 · 11 Blood Supply and Vascular Disorders of the Central Nervous System
Case Presentation 6: Tha la mic Infa rction
Out of the blue, this 45-year-old office worker suddenly be-
cam e nauseated, vom ited, felt very dizzy, and saw double.
Thinking he had caught an acute stom ach virus, he went
hom e to bed. When he got up a few hours later to call a
friend, he found he was still very dizzy and had double vi-
sion. While talking on the phone, he could only produce
words with the greatest difficulty; his friend expressed sur-
prise at his atypically m onosyllabic responses. He was now
worried enough to take him self directly to the em ergency
room of a nearby hospital.
The adm itting house officer found skew deviation of the
eyes and an unsteady gait, but no weakness. There was also
a b
Fig. 11.26 Thalamic infarct. Diffusion-weighted (a) and
T2-weighted (b) im ages. An acute infarct is seen in the terri-
tory of the left posterior thalam operforating artery. Acute
clu din g respiratory arrest. Th u s, w h en ever a cere-
bellar or brain stem stroke is su spected an d t h e in i-
tial CT scan is n orm al, follow -u p im ages sh ou ld be
obt ain ed a few h ou rs later, eith er by CT or, prefera-
bly, by diffu sion -w eigh ted MRI.
Anterior inferior cerebellar artery (AICA). Occlu -
sion s of th is artery, like PICA occlu sion s, produ ce a
w ide variety of clin ical m an ifestation s, because its
cou rse an d th e exten t of its territory vary w idely
across in dividu als. Ipsilateral hem iataxia an d nys-
tagm us m ay occu r, an d th ere m ay also be deficits of
cranial nerves VII and VIII. Occlu sion of t h e labyrin -
th in e artery, a bran ch of th e AICA, can cause sudden
deafness.
a conduction-type aphasia (cf. Table 9.1, p. 249). Suspect-
ing a process involving the basilar artery, the physician
ordered an MRI scan, which revealed a left thalam ic infarct.
A m ore rostrally lying lesion that additionally affects the
subthalam ic nucleus and the pallidothalam ic fibers inner-
vating the ventrolateral nuclei can cause (usually transient)
hem iballism or, m ore com m only, chorea (cf. Case Presenta-
tion 3 in Chapter 8, p. 223). In such cases, the further clini-
cal course is often m arked by the developm ent of a so-
called “thalam ic hand,” with involuntary flexion of the wrist
and hyperextension of the finger joints. The thum b is either
abducted or pressed against the palm .
edem a and a m arked diffusion abnorm ality are present. Bi-
lateral infarcts in this area can severely im pair conscious-
ness (cf. Case Presentation 3 in Chapter 7, p. 211).
Superior cerebellar artery (SCA). Occlu sion of th e
sup erior cerebellar artery cau ses severe ataxia be-
cau se of in farction of th e su perior cerebellar
pedu n cle, as w ell as astasia an d abasia. Tissu e
dam age in th e pon tin e tegm en tu m cau ses a
sensory deficit in th e ipsilateral h alf of th e face an d
th e con tralateral h alf of th e body, involvin g all qu a-
lities of sen sation (syn drom e of th e oral p on tin e
tegm en tum , Fig. 4.66, p. 153).
Au topsy stu dies h ave sh ow n th at , in m any per-
son s, an elon gated loop of th e sup erior cerebellar
artery com es in to con tact w it h th e trigem in al
n erve ju st distal to th e exit of th e n erve from th e
pon s. It is of n o clin ical sign ifican ce as an in ciden tal
fin din g, but its occurren ce in m any patien ts w ith

Case Presentation 7: Cerebella r Infa rction
This 63-year-old m aster carpenter threw a big party for all
of his em ployees to celebrate the 30th anniversary of his
business. As usual at such events, the alcohol flowed plenti-
fully.
Late that night, he awoke with severe dizziness, a headache,
and nausea. When he tried to stand up, he fell to the
ground at once and had a great deal of trouble pulling him -
self back into bed. About half an hour later, he began to
vom it repeatedly, at brief intervals. His wife called the phy-
sician on night duty, despite the patient’s repeated as-
surances that he had sim ply had too m uch to drink. The
physician arrived a few m inutes later, took the history, and
perform ed a rapid general m edical and neurological exam i-
nation. The basic neurological tests were all norm al: the
patient’s m uscular strength, sensation, and reflexes were
intact and sym m etrical throughout. He was, however,
com pletely unable to sit up from a lying position, rem ain
upright in a seated position, or stand up and walk. The
physician attributed these findings to hypovolem ia because
of vom iting induced by an acute gastrointestinal infection.
He gave the patient m etoclopram ide and advised him to
drink plenty of fluids and to call his prim ary care physician
the first thing in the m orning.
The patient continued to vom it through the night and be-
cam e increasingly confused as m orning approached. At 4
a.m ., his wife could no longer wake him up, even with a
loud shout, and she called the em ergency m edical service.
On arrival in the hospital, the patient was first adm itted to
a b
Fig. 11.27 Cerebellar infarct, as seen by MRI. a The axial
T2-weighted im age reveals a hyperintense (bright) infarct
in the basal portion of the right cerebellar hem isphere, in-
volving the inferior portion of the verm is. b Another axial
im age at the level of the lateral ventricles reveals m arked di-
Cerebral Ischem ia · 301
11
the m edical service, where various tests, including an ECG,
were perform ed but yielded no clear diagnosis. A neurolo-
gist was consulted. The patient could barely cooperate with
the exam ination and seem ed not to know what he was
being asked to do, but the neurologist was able to get him
to follow a m oving flashlight with his eyes, and was thus
able to detect a gaze-evoked nystagm us. He ordered an
em ergency MRI scan of the head, which revealed a large in-
farct of the right cerebellar hem isphere, accom panied by
edem a that was already exerting a considerable m ass ef-
fect. Intensive treatm ent was given to com bat brain edem a,
but the patient’s state of consciousness failed to im prove.
He was therefore transferred to the neurosurgical service
for operative decom pression of the posterior fossa and in-
sertion of a ventricular shunt. After surgery, his condition
rapidly stabilized.
Cerebellar infarcts are often easy to m isdiagnose initially
because they often produce only m ild lim b ataxia along
with the m uch m ore severe truncal ataxia. In such cases,
the usual cerebellar tests involving lim b posture and inten-
tional m ovem ent m ay yield no pathological findings.
Vom iting m ay be ascribed to a gastrointestinal problem
and the necessary im aging studies m ay not be perform ed
until the increasing intracranial pressure finally causes the
patient’s state of consciousness to deteriorate. A CT scan
obtained early in the course of the acute illness m ay be nor-
m al, but a diffusion-weighted MRI scan will reveal the cause
of the problem (Fig. 11.27).
latation of the inner CSF spaces. Increased pressure in the
posterior fossa is im peding outflow of CSF, leading to hy-
drocephalus. At present, cerebellar infarcts can be dem on-
strated in an early phase with diffusion-weighted MRI (not
shown here).
11 302 · 11 Blood Supply and Vascular Disorders of the Central Nervous System
trigem inal neuralgia su ggests th at it m ay be in -
volved in t h e path ophysiology of th is con dition ,
w h ich is ch aracterized by paroxysm al, extrem ely
in ten se, ligh tn in glike (“lan cin atin g”) p ain on on e
side of th e face. Trigem in al n euralgia u sually re-
spon ds w ell to m edical th erapy (e.g., w ith car-
bam azepin e). In in t ractable cases, h ow ever, a n eu-
rosurgical operation can be perform ed in w h ich
th e n erve an d th e vascu lar loop are separated by a
pledget of syn th etic m aterial (“m icrovascular
decom pression ,” “th e Jan n etta procedu re”). For
m ore on t h e diagn osis an d treatm en t of trigem in al
n eu ralgia, see Ch apter 4, pp. 107, 108.
Bra instem Vascula r Syndromes
Th e m any differen t vascular syn drom es affect in g
th e brain stem can on ly be un derstood on th e basis
of a th orou gh kn ow ledge of its topograph ical an at-
om y. For th is reason , t h ey are discu ssed in th e
ch apter on th e brain stem (Ch apter 4, p. 147 ff.),
rat h er th an h ere.
Impaired Venous Drainage from the
Brain
Cerebral isch em ia, as w e h ave seen , is u su ally cau sed
by an im pairm en t of th e arterial blood sup ply of th e
brain . It can also be cau sed by an im pairm en t of th e
ou tflow of ven ou s blood, th ou gh t h is sit uat ion is
m uch less com m on . If a cerebral vein is blocked, th e
blood volu m e an d ven ou s pressu re rise in t h e region
of th e brain th at it n orm ally drain s. Th e arterio-
ven ous pressure differen ce across th e cerebral
capillaries falls (th e in flow of blood is “ch oked off”),
leadin g to diminished perfusion an d t h u s to
dim in ish ed supp ly of oxygen an d n u trien ts. Sim ul-
tan eou sly, th e tran scap illary p ressu re gradien t in -
creases, leadin g to in creased m ovem en t of w ater
from t h e capillaries in to th e su rrou n din g tissue
(vasogenic edema). Th e n eu ron s in th e affected
brain tissu e lose th e ability to fun ct ion n orm ally,
an d, if th e p roblem persists, th ey die. Venous infarc-
tion is usually accom pan ied by th e ru ptu re of sm all
vessels (probably vein s) in th e in farcted zon e, pro-
du cin g intraparenchym al hem orrhage (so-called
ven ou s h em orrh age, w h ich h as a ch aracteristic
“salt-an d-pepper” app earan ce in a CT scan ).
Acute Venous Outflow Obstruction
Acute Throm boses of the Cerebral Veins and
Venous Sinuses
Causes. Th e m ost com m on cau se of acu te obst ru c-
tion of ven ou s ou tflow from th e brain is th rom bo-
sis of th e du ral ven ou s sin uses an d th e paren chy-
m al vein s th at drain in to th em (ven ous sin u s
th rom bosis). Factors predisposin g to th is occu r-
ren ce in clu de coagu lopath ies su ch as p rotein S an d
C deficien cy, factor V deficien cy, an d cardiolip in
an t ibodies, as w ell as oral con traceptive u se, ciga-
rette sm okin g, steroid m edicat ion , dehydrat ion ,
au toim m un e diseases su ch as Beh çet disease an d
Croh n disease, an d th e puerperiu m .
Manifestations. Th e clin ical m an ifestation s of
ven ous sin u s th rom bosis are h igh ly varied an d de-
pen d on th e site an d exten t of ven ou s occlusion as
w ell as on th e degree to w h ich collateral drain age
is available. In on e patien t a relatively circu m -
scribed occlu sion m ay cau se a m ajor in tra-
paren chym al h em orrh age, w h ile in an oth er an ex-
ten sive occlu sion m ay rem ain n early asym pto-
m atic. Prospective assessm en t is u sually n ot
possible in in dividu al cases.
Th e gen eral clin ical m an ifestation s of ven ous
sin u s th rom bosis are headache an d epileptic
seizures. If th e p atien t also develops focal neuro-
logical deficits th at progress over th e course of a
few h ours, rath er th an su dden ly, th en ven ous sin u s
th rom bosis is th e likely diagn osis. Th e diagn osis is
fu rt h er su pported by eviden ce of intracranial hy-
pertension, e.g., p apilledem a.
In cases of ven ou s sin u s th rom bosis, m arked
clin ical deterioration can occur in a very sh ort
tim e, perh aps over th e cou rse of an h ou r. Su ch oc-
cu rren ces are u su ally du e to involvem en t of th e in -
tern al cerebral vein s or to exten sive in trap aren chy-
m al ven ou s h em orrh ages.
Diagnostic evaluation. Th e diagn osis or exclu sion
of ven ous sin u s th rom bosis is often difficu lt even
w h en m odern im agin g m eth ods are u sed—CT, MRI,
an d digital su btraction an giography (DSA).
CT. Classic, acu te cases can be diagn osed by CT, p ar-
ticularly w h en CT ven ography w ith con trast m e-
diu m is perform ed. Problem s are caused by con -
gen ital varian ts of th e vascular an atom y, by less ex-
ten sive occlusion s, an d by th rom boses of th e

Case Presentation 8: Superior Sagitta l Sinus Thrombosis
This 37-year-old secretary had a generalized epileptic
seizure at work. After a postictal twilight phase lasting
about 20 m inutes, she regained full alertness and com -
plained of a severe holocephalic headache. On adm ission to
the hospital, she was awake, but abnorm ally slow. She con-
tinued to com plain of severe headache. An MRI scan was
obtained at once: the T2-weighted im age revealed a left
frontal parenchym al lesion (Fig. 11.28a), while MR venogra-
phy (Fig. 11.28b, c) revealed throm botic occlusion of the
Cerebral Ischem ia · 303
11
rostral portion of the superior sagittal sinus. The sinus
throm bosis was treated with full heparinization followed by
oral warfarin adm inistration, and anticonvulsants were
given to prevent further seizures. The headache im proved
rapidly with analgesics, and the patient was asym ptom atic
a few days later. Further diagnostic testing revealed no un-
derlying hypercoagulable state. The only identifiable risk
factor for venous sinus throm bosis was the use of oral con-
traceptives.

a b

Fig. 11.28 Venous sinus thrombosis. a The T2-

weighted FLAIR im age reveals a hyperintense le-
sion in the left frontal lobe: this is an infarct due
to venous obstruction. b MR venography reveals
brisk flow in the posterior portion of the superior
sagittal sinus (bright) and in the large tributary
veins that join it. The rostral portion of the sinus,
however, is devoid of signal, indicating lack of
flow. There is also poor flow in the tributary veins
that enter this portion of the sinus. c The sam e
findings are evident in lateral projection: there is
flow in the posterior portion of the superior sagit-
tal sinus, as well as in the straight sinus (arrow)
and the internal cerebral veins, but not in the ros-
tral portion of the superior sagittal sinus.
c

straigh t sin us an d in tern al cerebral vein s. Older
ven ou s sin us th rom boses, too, are difficu lt to
assess w ith CT.
MRI. MRI is cu rren tly th e m ost im port an t diagn os-
tic tech n iqu e for evaluation of th e ven ous ou tflow
of t he brain . It reveals th e vein s in m ult iple plan es,
an d it is perform ed w ith flow -sen sit ive sequen ces
to dem on strate in traven ou s flow. Its resolution is
h igh en ough th at th e in tern al cerebral vein s are
w ell seen .
MRI also en ables visu alization of th e brain
p aren chym a. Th e site an d ap pearan ce of a
p aren chym al lesion m ay provide clu es to th e loca-
11 304 · 11 Blood Supply and Vascular Disorders of the Central Nervous System
tion of ven ou s obstruction : occlusion of th e in ter-
n al cerebral vein s, for exam ple, produ ces ch arac-
teristic th alam ic lesion s, w h ile tran sverse sin u s
th rom bosis produ ces ch aracteristic lesion s in th e
tem poral lobe. Th e diagn ostic pow er of MRI is re-
du ced, h ow ever, by an atom ical varian ts of th e
cerebral blood vessels (as in CT), an d also by cer-
tain flow -related effects t h at are in com pletely u n -
derstood at presen t. MRI th u s can n ot detect every
case of ven ou s sin u s th rom bosis, an d it occasion -
ally yields false-positive fin din gs as w ell. Fu rt h er-
m ore, MRI scan n in g of un cooperative or un con -
scious pat ien ts is som etim es very difficu lt, an d th e
resu ltin g scan s m ay be of m argin al diagn ost ic
valu e. In extrem e cases, patien t s m u st be scan n ed
un der gen eral an esth esia.
Intra-arterial DSA. In t ra-arterial an giography or
DSA w as on ce th e on ly m eth od of diagn osin g
ven ous sin us th rom bosis w it h certain ty. Un for-
tu n ately, th e u sefu ln ess of th is m eth od is lim ited in
precisely th e sam e situation s w h ere th e oth er
m et h ods fail to provide con clu sive fin din gs. DSA is
n o lon ger u sed to diagn ose ven ous sin u s th rom bo-
sis, except in rare cases, becau se it carries a m u ch
h igh er risk of com plication s th an MRI.
Clinical course, treatment, and prognosis. Th e
spon t an eous cou rse of ven ous sin u s th rom bosis is
n ot clear. It w as on ce th ou gh t th at m ost cases w ere
fatal, probably becau se m ost less exten sive th rom -
boses w en t u n detected an d on ly th e cases th at
tu rn ed ou t u n favorably w ere, in th e en d, correctly
diagn osed. Occlusion of th e straigh t sin u s an d/or
in tern al cerebral vein s is particu larly om in ou s; th is
type of ven ous obstru ct ion is st ill h igh ly leth al, be-
cause it often leads to n ecrosis in th e dien cep h alon
to an exten t th at is in com patible w ith life. It can
also cau se cerebellar h em orrh age w it h m ass effect .
Th e straigh t sin us an d th e in tern al cerebral vein s
som etim es u n dergo th rom bosis in isolation , but
m ore often do so as a later stage in th e progression
of exten sive t h rom bosis of th e rem ain in g ven ous
sin u ses.
Th e progn osis of ven ou s sin us th rom bosis h as
im proved m arkedly sin ce th e in troduction of ther-
apeutic anticoagulation w ith heparin. Heparin is
given even in th e face of a paren chym al h em or-
rh age du e to ven ous sin us th rom bosis. In su ch
cases, th e correct in terpretation of th e h em orrh age
as a sequela of t h rom bosis is essen t ial, becau se it
w ould oth erw ise absolutely con train dicate an ti-
coagu lation . Fibrin olytic tech n iqu es h ave n ot been
sh ow n to be of valu e in t h e treat m en t of ven ous
sin u s th rom bosis. Su rgical resection of ven ous
h em orrh ages is also n ot in dicated.
Th erapeutic an ticoagu lation is th ou gh t to h alt
th e p rogression of ven ou s sin us th rom bosis, to
prom ote th e open in g of collateral ven ou s path -
w ays, an d to p rom ote m icrocircu lation . In tra-
ven ous h eparin is given in th e acute ph ase, th en
converted to oral an ticoagu lation for a furth er six
m on th s. Follow -u p exam in ation s are perform ed to
detect recurren ces early, particularly w h en kn ow n
risk factors are p resen t. Patien ts fou n d to h ave
suffered ven ous sin u s t h rom bosis becau se of an
un derlyin g hyp ercoagulable disorder m u st be
th erapeu tically an ticoagulated for life.
Chronic Venous Outflow Obstruction
Th e m an ifestation s of ch ron ic ven ou s ou tflow ob-
struction differ m arkedly from th ose of acu te
th rom bosis.
Th e causes of ch ron ic ven ous ou tflow obstru ction
are m any, in clu din g m edication side effects an d bi-
lateral sten osis of th e ven ou s ou tflow ch an n els. In
on e pu blish ed case, a patien t w ith a con gen itally
hypoplastic t ran sverse sin us on on e side developed
obstru ction of th e tran sverse sin u s on th e opposite
side because of a slow ly grow in g m en in giom a of
th e sin u s w all.
Manifestations. Th e ch aracteristic m an ifestation s
of ch ron ic ven ou s ou tflow obstruction are head-
ache an d papilledem a, possibly accom p an ied by
im paired visual acuity. Focal n eurological deficits
or epileptic seizu res are usu ally n ot a com pon en t
of th e clin ical pictu re.
Diagnostic evaluation. No paren chym al lesion s are
seen in th e brain (in con trast to acu te ven ou s ou t-
flow obstru ction ). MRI som etim es reveals dilata-
tion of th e optic n erve sh eath s as a resu lt of in -
tracran ial hyp erten sion an d pressu re-related
ch an ges of th e sella tu rcica, but it gen erally does
n ot sh ow th e cau se of th e im pairm en t of ven ou s
outflow. In su ch cases, intra-arterial digital sub-
traction angiography is in dispen sable for th e de-
m on stration of circu m scribed sten oses an d for th e
assessm en t of ven ou s flow dyn am ics. Th e diagn o-

sis can be con firm ed by lu m bar pu n ctu re w ith
measurement of the cerebrospinal fluid pressure.
Treatment. If etiological treatm en t is n ot possible,
ch ron ic elevation of th e cerebrospin al fluid pres-
sure can be treated by a permanent CSF deviation
procedure (lum boperiton eal or ven tricu loperi-
ton eal sh un t).
Differential diagnosis. Ch ron ic in tracran ial hyper-
ten sion is seen w ith in creased frequ en cy in youn g,
overw eigh t w om en in th e absen ce of an obstru c-
tion to ven ous ou tflow. Th e cau se of th is con dition
is un kn ow n . Its poorly descriptive tradition al n am e
is pseudotum or cerebri.
Intracranial Hemorrhage
Spon tan eou s, i.e., n on trau m atic, bleedin g in th e
brain paren chym a (intracerebral hemorrhage) or
th e m en in geal com partm en ts arou n d it (sub-
arachnoid, subdural, and epidural hemorrhage) ac-
cou n ts for 15–20 % of clin ical strokes, in th e w ider
sen se of th e term . Alt h ou gh h eadach e an d im pair-
m en t of con sciou sn ess occu r in in tracran ial
h em orrh age m ore com m on ly th an in cerebral in -
farction , clin ical criteria alon e can n ot reliably dis-
tin gu ish h em orrh agic from isch em ic stroke. Th e
diagn ostic procedu re of ch oice is CT.
An u n derstan din g of su barach n oid, su bdu ral,
an d ep idu ral h em orrh age requires kn ow ledge of
th e an atom y of th e m en in ges, as described on
p. 260 ff.
Intracerebral Hemorrhage
(Nontraumatic)
Hypertensive Hemorrhage
Etiology. Th e m ost com m on cau se of in tracerebral
h em orrh age is arterial hypertension. Path ologically
elevated blood pressu re dam ages th e w alls of
sm aller arteries, creat in g microaneurysms (Ch arcot
an eu rysm s) th at can ruptu re spon tan eously. Sites of
predilection for hyperten sive in tracerebral h em or-
rh age are th e basal ganglia (Fig. 11.29), th e
thalam us, th e cerebellar nuclei, an d th e pons. Th e
deep cerebral w h ite m atter, on th e oth er h an d, is
on ly rarely involved.
Intracranial Hem orrhage · 305
11
Fig. 11.29 Large left basal ganglionic hemorrhage with
m idline shift and intraventricular hem orrhage
Manifestations. Th e m an ifestat ion s of in tracere-
bral h em orrh age depen d on it s location . Basal gan -
glion ic h em orrh age w ith destruction of th e in ter-
n al capsu le u su ally produ ces severe contralateral
hem iparesis, w h ile pon tin e h em orrh age produ ces
brainstem signs.
Th e m ain dan ger in in tracerebral h em orrh age is
intracranial hypertension due to th e m ass effect of
th e h em atom a. Un like an in farct, w h ich raises th e
in tracran ial p ressu re slow ly as th e associated cyto-
toxic edem a w orsen s, an in tracerebral h em orrh age
raises it very rapidly. Intraventricular rupture of an
in tracerebral h em orrh age can cau se hydro-
ceph alu s, eith er by obstructin g th e ven tricu lar ou t-
flow w ith blood clot or by im pairin g CSF resorption
from th e arach n oid gran u lation s; if presen t, hydro-
ceph alu s raises th e in tracran ial pressu re still
fu rth er. Th ere is h ardly any free sp ace in th e poste-
rior fossa, so in traparen chym al h em orrh ages
below t h e ten toriu m rap idly elevate th e local in -
tracran ial pressure, possibly resu ltin g in h ern iation
of t h e posterior fossa con ten ts, eit h er u pw ard
th rou gh th e ten torial n otch , or dow nw ard in to th e
foram en m agn um . Th u s, an in traparen chym al
h em orrh age in th e brain stem or cerebellu m carries
a m u ch w orse progn osis t h an an equal-sized
h em orrh age in a cerebral h em isph ere.
11 306 · 11 Blood Supply and Vascular Disorders of the Central Nervous System
Fig. 11.30 Cerebellar hemorrhage. CT scan of a hyper-
tensive patient who suddenly com plained of an intense
headache and then becam e less responsive. A large, hyper-
dense (bright) hem orrhage is seen in the region of the deep
cerebellar nuclei. The brainstem is ventrally displaced and
pushed against the clivus, and the prepontine cistern is
m arkedly narrowed.
Prognosis and treatment. Th e brain tissu e in an
area of h em orrh age (as opposed to an in farct) is
gen erally n ot totally destroyed; livin g brain tissu e
can often be fou n d am id th e extravasated blood.
Th is explain s w hy th e patien t’s n eu rological defi-
cits usu ally resolve m ore rapidly, as th e h em atom a
is resorbed, th an th ey w ou ld if p rodu ced by an
isch em ic stroke.
Th e goal of treatm en t is, th erefore, to preserve
w h atever brain tissu e rem ain s viable in th e area of
h em orrh age. Persistent intracranial hypertension
must be treated to preven t secon dary dam age, n ot
on ly of th e brain t issu e in side an d aroun d th e h e-
m atom a bu t also of distan t tissu e. Th e in tracran ial
pressu re can be low ered by pharmacotherapy an d/
or by neurosurgical removal of the hematoma.
Su rgery sh ould be perform ed on ly w h en in dicated
accordin g to strict criteria, takin g th e patien t’s age
in to accou n t , as w ell as th e locat ion an d size of th e
h em atom a. Large-scale st udies h ave sh ow n a th er-
apeut ic ben efit on ly from th e rem oval of large h e-
m atom as ( 20 cm 3 ). Th e operative rem oval of
sm aller h em atom as m ay actu ally be detrim en tal,
as it m ay destroy m ore viable brain tissu e th an it
saves; an d th e operat ive rem oval of h em atom as
deep w ith in th e brain alw ays involves th e destruc-
tion of som e n orm al brain tissu e alon g th e n eu ro-
su rgeon ’s path to th e h em atom a. For t h ese reason s,
th e n eu rosu rgical treatm en t of sm aller in tra-
paren chym al h em atom as is lim ited to th e treat-
m en t of hydroceph alu s (if presen t) w ith extern al
ven t ricu lar drain age, w h ich can be p erform ed w it h
m in im al in ju ry to n orm al brain tissue. Patien ts
w ith very large h em atom as ( 60 cm 3 ) w ill n ot
ben efit from rem oval of th e h em atom a becau se too
m uch brain tissu e h as already been destroyed.
Nonhypertensive Intracerebra l Hemorrhage
In tracerebral h em orrh age m ay be du e to m any
cau ses besides arterial hyperten sion . Th e m ore im -
portan t on es are arteriovenous m alform ations,
tum ors, aneurysm s, vascular diseases in clu din g
vascu litis an d am yloid an giop athy, cavernom as,
an d venous outflow obstruction (as discu ssed
above). An in tracerebral h em orrh age is likely to
h ave been caused by som eth in g oth er th an arterial
hyp erten sion w h en it is n ot located at on e of t h e
sites of predilection for hyp erten sive h em orrh age,
or w h en t h e patien t does n ot suffer from m arked
arterial hyp erten sion . In su ch cases (at least), a fol-
low -up MRI scan sh ould be perform ed on ce th e h e-
m atom a is resorbed to detect th e u n derlyin g cau se
of h em orrh age. Digital su btraction an giography is
som etim es in dicated as w ell.
Cerebella r Hemorrha ge
Th e cerebellar n u clei lie w ith in th e distribu tion of
th e sup erior cerebellar artery. On e particu lar
bran ch of th is artery, w h ich supp lies th e den tate
n ucleus, is particularly su sceptible to ru ptu re. In
hyp erten sive in dividu als, h em orrh age from th is
vessel is m ore com m on t h an isch em ia in its terri-
tory (Fig. 11.30).
Hem orrh age in th is region often cau ses an acu te
m ass effect in th e posterior fossa, w ith all of its at-
ten dan t con sequen ces (h ern iation of th e brain stem
an d cerebellum u pw ard th rough th e ten torial
n otch an d dow nw ard in to th e foram en m agn u m ).
Th e clin ical m an ifestation s are severe occipital
headache, nausea and vom iting, an d vertigo, gen er-
ally accom pan ied by unsteady gait, dysarthria, an d
head turning an d gaze deviation to the side opposite

the lesion. Large h em orrh ages rap idly produ ce som -
n olen ce, stu por, or com a. In th e late ph ase, p atien ts
m an ifest exten sor spasm s, h em odyn am ic in stabil-
ity, an d, fin ally, respiratory arrest, u n less t h e poste-
rior fossa can be operatively decom pressed.
Sm aller h em orrh ages, p articu larly in th e cere-
bellar h em isph eres, produ ce focal m an ifestat ion s
in clu din g lim b ataxia, a tendency to fall to the side of
the lesion, an d deviation of gait to the side of the le-
sion. Th ese m an ifestation s resolve in com pletely
w h en th e deep cerebellar n uclei are dam aged.
Fu rth er causes of cerebellar h em orrh age in clu de
th e ru ptu re of an arterioven ous m alform at ion or
an eurysm , an d bleedin g in to a tu m or (usually a
m etastasis).
Subarachnoid Hemorrhage
Aneurysms
Th e m ost com m on cau se of spon tan eou s sub-
arach n oid h em orrh age is t h e ru ptu re of an
an eu rysm of on e of th e arteries of t h e base of th e
brain . Th ere are differen t types of an eurysm s.
Saccular (“berry”) aneurysms are foun d at points
of bifurcation of th e in tracran ial arteries. Th ey
form on th e basis of a prior lesion of t h e vessel
w all, w h ich is eith er a (usu ally con gen it al) stru c
tu ral defect, or an in jury du e to hyperten sion . Th e
common sites of saccu lar an eu rysm s are t h e ante-
rior com m unicating artery (40 %), t h e bifurcation of
the m iddle cerebral artery in th e sylvian fissu re
(20 %), th e lateral w all of the internal carotid artery
(at th e origin of th e op h th alm ic or posterior com -
m un icatin g artery, 30 %), an d th e basilar tip (10 %)
(Fig. 11.31). An eu rysm s at oth er sites, such as th e
origin of th e PICA, th e P2 segm en t of t h e posterior
cerebral artery, or t h e pericallosal segm en t of th e
an terior cerebral artery, are rare. An eurysm s can
produ ce n eu rological deficits by pressin g on
neigh borin g structu res even before th ey ru ptu re.
For exam ple, an an eu rysm of th e posterior com -
m u n icatin g artery can com p ress th e ocu lom otor
nerve, cau sin g a th ird n erve palsy (th e patien t
com plain s of diplopia).
Fusiform aneurysms. An elon gated (“spin dle-
sh ap ed”) en largem en t of a vessel is called a
fu siform an eu rysm . Such an eurysm s preferen tially
involve th e intracranial segm ent of the internal
carotid artery, the m ain trunk of the m iddle cerebral
Intracranial Hem orrhage · 307
11
40–45 %
15–20 %
15–30 % 10 %
3–5 %
1–2 %
Fig. 11.31 Common sites of intracranial aneurysms
artery, an d th e basilar artery. Th ey are u su ally
caused by ath erosclerosis an d/or hyperten sion ,
an d t h ey are on ly rarely a source of h em orrh age.
Large fu siform an eu rysm s of th e basilar artery can
com p ress th e brain stem . Slow flow in side a
fu siform an eu rysm can p rom ote in tra-an eu rysm al
clot form ation , p articu larly at th e sides, w ith su b-
sequen t em bolic stroke or cut-off of perforatin g
vessels by t h e direct exten sion of t h rom bu s. Th ese
an eu rysm s u su ally can n ot be treated n eu rosu rgi-
cally, becau se th ey are elon gated en largem en ts of
n orm al vessels, rath er th an path ological structu res
(like saccu lar an eu rysm s) m akin g n o con tribu tion
to th e cerebral blood sup ply.
Mycotic aneurysms. An eu rysm al dilatation s of in -
tracran ial blood vessels are som etim es th e resu lt of
sepsis w ith bacterially in duced dam age to th e
vascu lar w all. Un like saccu lar an d fu siform
an eu rysm s, th ese m ycotic an eu rysm s are preferen -
tially fou n d on sm all arteries of t h e brain . Th e treat-
m en t con sists of treatm en t of th e u n derlyin g in fec-
tion . Mycotic an eu rysm s som etim es regress spon -
tan eou sly; th ey very rarely cau se subarach n oid
h em orrh age.
11 308 · 11 Blood Supply and Vascular Disorders of the Central Nervous System
Case Presentation 9: Multiple Unruptured Aneurysms
This previously healthy 43-year-old m echanic was briefly
unconscious after an autom obile accident (front-end colli-
sion) and was taken to hospital for observation. ACT scan of
the head was perform ed to rule out intracranial injury. The
noncontrast im ages revealed no hem orrhage or other ab-
norm ality, but the contrast-enhanced im ages revealed a
possible aneurysm of the right m iddle cerebral artery as an
incidental finding. This was followed up by cerebral angio-
graphy, which confirm ed the presence of an aneurysm at
the bifurcation of the right m iddle cerebral artery, as well as
a b
Fig. 11.32 Basilar tip aneurysm. Intra-arterial digital sub-
traction angiography before (a) and after (b) the aneurysm
was filled with coils. The basilar tip aneurysm is well seen on
Acute Nontra uma tic Suba rachnoid
Hemorrha ge
Non traum atic su barach n oid h em orrh age (SAH) is
usually cau sed by th e spontaneous rupture of a
saccular aneurysm, w ith escape of blood in to th e
subarach n oid space.
Manifestations. Th e leadin g sym ptom of a su b-
arach n oid h em orrh age is a sudden, very intense
headache (“th e w orst h eadach e of m y life”).
Men in geal irritation by su barach n oid blood cau ses
nuchal rigidity (differen t ial diagn osis: m en in gitis).
Consciousness may be impaired im m ediately or
w ith in th e first few h ou rs. Cranial nerve palsies an d
focal neurological signs m ay be presen t, depen din g
further aneurysm s of the left internal carotid artery and the
tip of the basilar artery (Fig. 11.32a). The MCA and ICA
aneurysm s were clipped in an open neurosurgical opera-
tion. The basilar tip aneurysm , however, was not am enable
to surgical treatm ent with an acceptably low risk. Instead, it
was treated with an interventional neuroradiological pro-
cedure: a m icrocatheter was inserted into it under angio-
graphic control, and its lum en was filled with m etal coils
(Fig. 11.32b).
the angiogram ; it is narrower at its base (neck). Coiling ex-
cludes the aneurysm from the circulation. (Im ages courtesy
of PD Dr. Skalej and Dr. Siekm ann, Tübingen.)
on th e site an d exten t of th e h em orrh age. Th e grad-
in g sch em e prop osed by Hu n t an d Hess in 196 8 is
still u sefu l in clin ical practice, as it gives a rough in -
dication of th e patien t’s progn osis (Table 11.1).
Diagnostic evaluation. CT sen sitively detects acute
su barach n oid h em orrh age (Fig. 11.33); yet, th e
lon ger th e in terval betw een th e acute even t an d th e
CT scan , th e m ore likely it is th at th e scan w ill be
n egative. If SAH is suspected despite a n egative CT
scan , a lum bar pu n cture m ust be perform ed. Th is
w ill en able th e direct dem on stration of blood or
sideroph ages in th e cerebrosp in al flu id.
On ce SAH h as been diagn osed, th e sou rce of
bleedin g m u st be iden tified. Th is can on ly be don e
 Intracranial Hem orrhage · 309
11
reliably by intra-arterial digital subtraction angio-
graphy, w h ich sh ou ld, h ow ever, be perform ed on ly
if th e patien t is a can didate for a su rgical procedure
to clip th e an eu rysm or to close it w ith th e m eth ods
of in terven tion al n euroradiology (see below ). DSA
reliably dem on strates th e presen ce of an an eurysm
an d illu strates its sp atial relat ion sh ip to th e n eigh -
borin g vessels. All fou r great vessels sup plyin g th e
brain are st udied w ith con trast m edium , because
abou t 20 % of patien t s w ith an eu rysm s h ave m ore
th an on e an eu rysm .

Treatment. An eu rysm s can be t reated w it h a n eu-

rosurgical operation in w h ich th e n eck of th e
an eu rysm is closed w it h a m etal clip. Th e
an eu rysm is t h ereby p erm an en tly exclu ded from
th e circu lation , so th at it can n ot bleed again . Th is
form of treatm en t is defin itive, bu t th e disadvan -
tage is t h at it requ ires operative open in g of t h e
sku ll (cran iotom y) an d n eu rosu rgical m an ipu la-
tion s arou n d th e base of th e brain th at m ay cause
fu rth er com p lication s. Su rgery sh ou ld be per-
form ed in th e first 72 h ou rs after subarach n oid
h em orrh age, i.e., before th e period of greatest risk
for th e developm en t of vasospasm (see below ).
Early surgery h as been sh ow n to im p rove th e prog-
n osis of patien ts w h o presen t w ith SAH in Hun t
an d Hess grades 1, 2, or 3. It is th e m ost im portan t
form of treatm en t for th e preven tion of rebleedin g.
An altern ative, less invasive form of treatm en t is
th e filling of the aneurysm w ith m etal coils (“coilin g,”
a procedu re belon gin g to th e field of in terven tion al
n eu roradiology). Th e coils are delivered from th e tip
of a specialized an giograp h ic cat h eter, w h ich is in -
serted tran sfem orally an d advan ced to th e level of
th e an eu rysm . Coilin g obviates th e n eed for cran i-
otom y, but it m ay n ot be an equ ally reliable m eth od
of perm an en tly obliteratin g th e an eu rysm .
Clinical course, prognosis, and complications.
Su barach n oid h em orrh age u su ally stop s spon -
tan eou sly, probably becau se it is tam pon aded by th e
risin g in tracran ial pressure. On ly patien ts in w h om
th e an eu rysm h as stopped bleedin g su rvive to be
tran sported to h ospital; th e preh ospitalization
m ortality of an eu rysm al SAH is approxim ately 35 %.
After th e acute even t, th e patien t faces th e risk of
th ree poten tially fatal com p lication s:
¼ Hydroceph alu s
¼ Vasospasm
¼ Rebleedin g
Fig. 11.33 Acute subarachnoid hemorrhage. The basal
cisterns are filled with hyperdense (bright) blood. The tem -
poral horns of the lateral ventricles are dilated because of
an obstruction of CSF outflow (hydrocephalus). Because
there is no blood in the ventricles, the internal CSF spaces
are dark, while the external CSF spaces are bright.
Table 11.1 Grading of Subarachnoid He morrhage
According to Hunt and Hess
Grade Clinical features
1 Asym ptom atic or m ild headache and m eningeal
irritation
2 Moderate or severe headache (worst headache
of life), m eningism , cranial nerve deficits (abdu-
cens palsy is com m on)
3 Drowsiness, confusion, m ild focal neurological
signs
4 Stupor, severe neurological deficits (e.g., hem i-
paresis), autonom ic m anifestations
5 Com a, decerebration
Hydrocephalus (im paired CSF circulation an d/or re-
sorption ), if it develops, ap pears very rapidly after
th e in itial SAH. Th e resu ltin g in tracran ial hyp er-
ten sion often im pairs th e patien t’s con sciou sn ess
an d m ay also cau se focal n eu rological deficits. Hy-
droceph alu s can be effectively treated by extern al
ven tricu lar drain age. Lu m bar drain age is less com -
m on ly u sed.
11 310 · 11 Blood Supply and Vascular Disorders of the Central Nervous System
Case Presenta tion 10: Acute Suba rachnoid Hemorrhage due to Aneurysma l Rupture
This previously healthy 46-year-old m an suddenly ex-
perienced the worst headache of his life, com bined with
profound anxiety and a sense of im pending doom . He also
com plained of double vision, particularly on looking to the
right. The physician who adm itted him to hospital ex-
am ined him neurologically and found a stiff neck and a
right partial third cranial nerve palsy, but no other neuro-
logical deficits. The presum ptive diagnosis of acute sub-
arachnoid hem orrhage was confirm ed by CT scan and lum -
bar puncture. The patient was stable enough to be con-
sidered a candidate for surgery, and cerebral angiography
was therefore perform ed at once, revealing an aneurysm of
the internal carotid artery arising at the origin of the poste-
a b
Fig. 11.34 Acute nontraumatic subarachnoid hemor-
rhage due to rupture of an aneurysm of the internal
carotid artery at the origin of the posterior communi-
cating artery. a Conventional angiography, lateral view.
The internal carotid artery aneurysm is seen at the origin of
the posterior com m unicating artery. b The aneurysm has
Vasospasm occu rs a few days later, presum ably
th rough th e effect of vasoactive su bstan ces con -
tain ed in th e extravasated subarach n oid blood. Th e
risk of vasospasm can be redu ced by th e rem oval of
as m uch subarach n oid blood as possible durin g
surgery, and by t h erap eu tically in duced hyperten -
sion . Th ese m easures u su ally su ffice to p reven t th e
develop m en t of vasospastic in farcts, a m uch -
feared com p lication . Vasospasm is a serious im -
pedim en t to th e effective diagn osis an d treatm en t
of an eu rysm al su barach n oid h em orrh age.
rior com m unicating artery (Fig. 11.34a). This aneurysm
proved to be am enable to treatm ent by interventional neu-
roradiological m ethods: im m ediately after the lesion was
identified by angiography, a m icrocatheter was introduced
into it under angiographic guidance, and its lum en was
filled with platinum coils (Fig. 11.34b, c).
Because coiling does not im m ediately reduce the volum e of
the aneurysm , im m ediate im provem ent of the cranial
nerve palsy was not expected. In the further course,
however, the aneurysm m ay shrink, leading to sym pto-
m atic im provem ent. This took six weeks in the present
case.
c
been excluded from the circulation by coiling. The m etal
coils strongly absorb x-rays and therefore appear dark in the
nonsubtracted im ages. c The coils are barely seen in the
subtracted im age, but the dom e of the aneurysm is clearly
no longer filled with blood. (Im ages courtesy of MD Dr.
Skalej and Dr. Siekm ann, Tübingen).
Rebleeding, if it occu rs, is m ore often leth al (50 %)
th an th e in itial su barach n oid h em orrh age. Th e risk
of rebleedin g is 20 % in th e first 14 days after th e
in itial SAH, an d 50 % in th e first six m on th s, if th e
an eurysm h as n ot been obliterated. Un like th e in i-
tial SAH, rebleeds often produce large in tra-
paren chym al h em atom as, because th e su b-
arach n oid space aroun d th e an eurysm is partly
sealed by adh esion s result in g from th e in it ial
bleed. In such cases, t h e clin ical m an ifest ation s
an d cou rse of th e an eurysm al rebleed are as de-
scribed above for spon t an eou s in tracerebral
h em orrh age.

Subdural and Epidural Hematoma
Subdura l Hema toma
In subdu ral h em atom a, th e collection of blood lies
in th e n orm ally on ly virtu al space betw een th e
du ra m ater an d th e arach n oid. Th e cause is u su ally
trau m a.
Acute Subdural Hem atom a
Acu te subdu ral h em atom a (Fig. 11.35) is foun d in
severe h ead t rau m a. It carries a poor progn osis, n ot
becau se of th e su bdural blood it self bu t becau se it
is very often associated w ith an u n derlyin g
paren chym al in ju ry. It s m ortalit y m ay be as h igh as
50 %. Its clin ical m an ifestation s are determ in ed by
th e site an d exten t of th e associated paren chym al
in ju ry.
Treatment is directed both at th e h em atom a itself
an d at th e associated p aren chym al in ju ry. If open
n eu rosu rgical rem oval of th e h em atom a is n eces-
sary, con tu sed brain tissu e m ust often be resected
as w ell. At su rgery, a durap lasty m ay be per-
form ed, an d th e bon e plate m ay be left ou t, rath er
th an put back in its origin al position , in order to
provide room for t h e sw ollen brain an d preven t
poten tially leth al in tracran ial hyperten sion —a
sim ilar procedu re to decom pressive cran iectom y
for m assive isch em ic stroke. Th e curren t tren d in
n eu rosu rgery is to perform su ch decom pression s
m ore frequ en tly, both for stroke an d for h ead
trau m a.
Chronic Subdural Hem atom a
Th e etiology of ch ron ic su bdural h em atom a re-
m ain s in com pletely u n derstood. Th ere is often an
an teceden t h istory of on e or m ore m in or traum atic
episodes. Th e flu id collection lies betw een t h e
in n er du ral m em bran e an d th e arach n oid an d is
probably derived from an in itial h em orrh age of th e
bridgin g vein s. In th e ch ron ic ph ase, gran u lation
tissue is foun d in th e w all of th e h em atom a. Th is
tissu e is th ou gh t to be th e source of repeated, sec-
on dary bleedin g in to th e flu id collection , so th at it
slow ly expan ds, rat h er t h an bein g resorbed.
Th e manifestations of ch ron ic su bdural h em atom a
are produced by pressure on th e u n derlyin g brain
tissu e an d depen d on th e site of th e h em atom a. A
ch ron ic su bdu ral h em atom a overlyin g t h e cen tral
Intracranial Hem orrhage · 311
11
Fig. 11.35 Acute subdural hematoma. The space-oc-
cupying lesion is concave in shape and poorly dem arcated
from the underlying brain tissue. There is a pronounced
m ass effect with m idline shift.
region m ay be clin ically in distin gu ish able from an
in farct.
Th e treatment con sists of operative removal or
percutaneous drainage. Th ere is a relatively h igh
recu rren ce rate. Th e presen ce of a subdu ral h em a-
tom a con train dicates th erapeu tic an ticoagu lation ,
w h ich m ay cau se addition al bleedin g in to th e h e-
m atom a cavity, producin g a m ass effect.
Epidural Hem atom a
In epidural h em atom a, th e blood collection lies be-
tw een th e du ra m ater an d th e periosteu m
(Fig. 11.36). It is classically p rodu ced by trau m atic
laceration of a m en in geal artery. Becau se th e du ra
m ater is tigh tly attach ed to th e in n er su rface of th e
sku ll, a great deal of p ressu re is requ ired to create a
flu id collect ion at th is site. Th e cause is alm ost al-
w ays a sku ll fractu re w ith a tear in th e m iddle
m en in geal artery, th e largest of th e m en in geal ves-
sels. Su ch fractu res often occu r w it h ou t produ cin g
any seriou s in jury to t h e brain ; t h u s, m any pat ien ts
w ith epidu ral h em atom a rem ain aw ake im m edi-
ately after t h e trau m atic even t an d do n ot lose con -
sciousn ess u n t il som e tim e later (after th e so-called
“lu cid in terval”). Th ey m ay th en die from th e
rapidly risin g in t racran ial p ressu re u n less t h e h e-
m atom a is rap idly diagn osed an d operatively re-
m oved. Prom pt treatm en t affords a good p rogn osis.
11 312 · 11 Blood Supply and Vascular Disorders of the Central Nervous System
Fig. 11.36 Acute epidural hematoma, left. The hem a-
tom a is convex. The central hypodensity is due to blood
that has not yet clotted. There is a pronounced m ass effect
with m idline shift.
Vascular Syndromes of the
Spinal Cord
Arterial Hypoperfusion
Spin al cord in farcts are m uch rarer th an cerebral
in farcts because of th e exten sive an astom otic n et-
w ork lin kin g th e arteries of th e spin al cord. Large
em boli can n ot lodge in th e sm all arteries of th e
cord, an d th e very sm all particles th at can do so
cau se n o clin ically sign ifican t dam age. Even aortic
an eu rysm s or occlu sion s rarely cau se dam age to
th e spin al cord.
Th e sym ptom s of spin al cord in farction depen d
on t h e vascu lar territory involved.
Infarction in the territory of the anterior spinal
artery. Th e clin ical m an ifestation s dep en d on th e
segm en tal level of th e lesion . An in farct in th e
u pper cervical sp in al cord produces th e follow in g
deficit s: dam age to th e an terior h orn s an d an terior
roots cau ses flaccid paresis of the arm s; dam age to
th e decu ssatin g fibers of th e lateral spin oth alam ic
tract cau ses analgesia and therm anesthesia in th e
u pper lim bs; an d dam age to th e corticospin al
tracts cau ses spastic paraparesis. Bladder and bow el
dysfunction are com m on . Because th e posterior
colu m n s lie ou tside th e territory of th e an terior
spin al artery, th ere m ay be n o deficit of epicritic
an d proprioceptive sen sation . Th e deficit s typically
appear sudden ly an d are accom pan ied by pain .
Infarction in the territory of the posterolateral spi-
nal artery produces deficits resu ltin g from dam age
to th e posterior colu m n s, posterior roots, an d p os-
terior h orn s. Th e corticospin al tracts m ay also be
dam aged. Th ere is th u s an im pairm ent of epicritic
sensation and proprioception below the level of the
lesion. At th e level of th e lesion , dam age to th e
posterior roots cau ses an addition al segm ental
sensory deficit. If th e corticospin al tracts are in -
volved as w ell, sp astic paraparesis result s.
Diagnostic evaluation. Th e diagn osis of spin al cord
in farction is usually difficu lt. Even w ith MRI, in -
farcts often can n ot be reliably distin guish ed from
oth er types of m yelopathy. An im portan t clu e to
th e presen ce of a spin al cord in farct, in addition to
th e typical h istory an d physical fin din gs, is th e
radiological dem onstration of ischem ic changes in a
vertebral body, because th e spin al cord an d th e
vertebral body are su pp lied by th e sam e radicular
artery. Th e blood–CNS barrier is n ot dem on strably
disrupted w ith in th e lesion u n til a few days after
th e acu te even t (th at is, th e lesion is n ot con trast-
en h an cin g u n til th is tim e). Th e fin al step of th e di-
agn ost ic evalu ation is a lu m bar pun cture to rule
ou t an in fectious process.
For tech n ical reason s, diffu sion -w eigh ted MRI,
w h ich reliably dem on strates acute isch em ia in th e
brain , is difficu lt to perform in th e spin al cord.
Impaired Venous Drainage
Th e m ost com m on cause of elevated ven ou s pres-
sure in th e sp in al vein s is a du ral arterioven ou s
fistu la.
Congestive Myelopathy
Etiology. Th e cau se of con gestive m yelopathy
(Foix–Alajouanine disease), a disorder th at m ain ly
affects elderly m en , w as first recogn ized in t h e
1980s: an arteriovenous fistula, usu ally located on
a sp in al n erve root. Arterial blood passes th rough
th e fistu la directly in to th e in tradu ral vein s. Th e
fist ula rem ain s clin ically silen t as lon g as th e
excess flow of blood in to th e vein s (th e shunt
volum e) does n ot exceed th eir drain age capacity. As
soon as it does, h ow ever, th e ven ous pressure rises,

Case Presenta tion 11: Spina l Dura l Arteriovenous Fistula
This 53-year-old wom an noticed increasing weakness of
both legs for several m onths. She had no pain, but com -
plained of a “woolly” feeling in the legs, and also had in-
creasing difficulty with urination and defecation. Peripheral
neuropathy was diagnosed at first, but, when her leg weak-
ness continued to progress, an MRI scan of the spinal cord
was ordered (Fig. 11.37). This was perform ed in an outlying
hospital and was initially interpreted as showing a tum or of
the spinal cord.
a b
Fig. 11.37 Spinal arteriovenous (AV) fistula. a Sagittal
T2-weighted im age. Intram edullary edem a is seen in the
lower portion of the spinal cord, including the conus m edul-
laris. Dilated epim edullary veins appear as dark, rounded
structures. b In this T1-weighted im age obtained after the
adm inistration of intravenous contrast, som e vessels ap-
pear bright, others dark. There is no contrast enhancem ent
within the spinal cord. c This axial T2-weighted im age of the
an d th e spin al cord, w h ich is very sen sitive to su ch
in creases, is dam aged.
Manifestations. Th e in itial m an ifest ation s are un-
steady gait an d spastic paraparesis, som etim es ac-
com pan ied by radicular pain. If th e disease pro-
gresses, autonom ic deficits ap pear, in cludin g blad-
der, bow el, an d sexu al dysfu n ction . Th e sensory
deficit at first m ain ly con cern s th e p rotopath ic
Vascular Syndrom es of the Spinal Cord · 313
11
The patient was transferred to the neurosurgical service.
The patient’s clinical history and MRI findings were con-
sidered to be m ore consistent with a spinal dural arteri-
ovenous fistula than with an intram edullary tum or. This sus-
picion was confirm ed by angiography, and the fistula was
surgically excised. The patient’s signs and sym ptom s re-
solved com pletely, except for residual bladder dysfunction.
c
spinal cord, obtained just above the level of the conus
medullaris, reveals intram edullary edem a sparing the ven-
tral portion of the cord. This is an im portant criterion for
the differential diagnosis of AV fistula versus arterial
ischem ia, in addition to the patient’s clinical m anifestations
and the dilated epim edullary veins that were seen in the
other MR im ages (above).
m odalities; later, epicritic sen sation an d proprio-
ception are also affected. Fu rth er progression w ith
n ecrosis of th e an terior h orn s converts th e spastic
p araparesis in to a flaccid paraparesis.
Diagnostic evaluation. MRI reveals dilated
ep im edullary vein s an d edem a of th e spin al cord.
Th e fistula itself can n ot be seen . It m ay also be very
difficu lt to dem on strate by angiography, becau se
11 314 · 11 Blood Supply and Vascular Disorders of the Central Nervous System
th e sh u n t volu m e m ay be very low, an d th e clin ical
m an ifestation s of con gestive m yelopathy m ay be
m ain ly due to im paired ven ous drain age.
Even today, arterioven ou s fist ulas cau sin g con -
gest ive m yelopathy are often n ot recogn ized
before t h e appearan ce of irreversible n eu rological
deficits. Th is is regret table, because su ch fist ulas
are a poten tially treatable cau se of progressive par-
aparesis.
Treatment. Th e treatm en t con sists of operative ob-
literation of th e fistu la after it h as been localized by
an giography.
Spinal Cord Hemorrhage and
Hematoma
Hematomyelia—a h em atom a w ith in th e sp in al
cord—is usually of traum atic origin , an d is on ly
rarely due to an an eu rysm or vascu lar m alform a-
tion . Becau se th e blood u su ally tracks lon gitudi-
n ally (i.e., up an d dow n ) in th e spin al gray m atter, a
clin ical syn drom e resem blin g th at of syrin gom yelia
results (cf. p. 47).
Spinal epidural hematoma u sually occu rs at
th oracic levels, p rodu cin g acu te radicu lar pain at
th e level of th e h em atom a, as w ell as a su bacute spi-
n al cord tran section syn drom e th at begin s w ith
p aresth esiae, sen sory deficits, an d w eakn ess in th e
feet an d toes, an d th en rapidly ascen ds to th e level
of th e h em atom a. Sym ptom atic spin al epidu ral h e-
m atom a is an acu te n eu rosu rgical em ergen cy: it
m u st be evacu ated im m ediately to p reven t irre-
versible paraplegia.

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318 · Further Reading
 319

Index
Page n um bers in italics refer to illu stration s or tables

A in tern al carotid artery 273 lesion s 101

m icroan eu rysm s 305 septal 82, 205
abasia 165, 166, 30 0 m ycotic 307 striate
abscess 264 p osterior com m un icatin g artery in ferior 85
acetylch olin e 7 (PCom m ) 273 sup erior 85
m u scarin ic receptor 7 saccu lar (berry) 307 su bcallosal 83, 230
n icotin ic receptor 7 treatm en t 309 vestibu lar 75, 76
acidoph il cells 185 an h idrosis 191 Wern icke’s 248
acopia 254 an isocoria 102 areflexia 4 4
acou stic m eatu s, in tern al 82, 111 an n u lu s fibrosu s 58 Argyll Robertson p up il 101
acou stic n eu rom a 120, 125–126, 167, an osm ia 84 arterioven ous fistu la 312–314
168 an osogn osia 255, 297 case presen tation 313, 313
acrom egaly 186 an sa arterioven ous m alform ation s 306
ACTH-secretin g aden om a 186–188 cervicalis 63 artery(ies)
action poten tial 5 len ticularis 178 Adam kiew icz’s 53, 283, 283
Adam kiew icz’s artery 53, 283, 283 an terograde tran sport 3, 4 basilar 75, 145, 146, 271, 272, 272,
aden ohypophysis 183 an ticoagulation 304 275, 276, 279
aden om a an tidiu retic h orm on e (ADH) 184, 185 arteriosclerosis 155
ACTH-secretin g 186–188 syn drom e of in ap propriate ADH occlu sion 147, 148, 149, 152, 298
grow th -h orm on e-secretin g 186 secretion (SADH) 184–185 th rom bolysis case presen tation
adren al glan d aorta 271, 283 293–294, 293, 294, 295
in n ervation 194 ap ertu re tip 276
m edulla 191 lateral 75, 158, 159 an eu rysm 308
adren ergic system 188 m edian 75, 158 calcarin e 277, 299
agn osia 255 ap h asia 249–253, 297 carotid
som atosen sory 255 Broca 249–253 com m on 270–271, 271, 283
visu al object 255 case presen tation 250–251, 250– extern al 271–272
agram m atism 249 251 in tern al (ICA) 89, 91, 270, 271–
agraph esth esia 29 selective 253 272, 271, 272, 273, 279
agraph ia 249 sen sory 118 an eurysm 273
Alexan der’s law 124 types of 249 bifu rcation , occlusion 296
alexia 249, 253, 255 Wern icke 253 dissection 192
allesth esia 255 case presen tation 252–253, 252 sten osis 287, 290
allocortex 203, 231 ap optosis 9 cerebellar
α m otor n euron s 43 apraxia 254 in ferior
Alzh eim er disease 208 con stru ction 254, 297 an terior (AICA) 108, 145, 271,
am au rosis fu gax 86, 296 m otor 254 272, 275–276, 276, 30 0
am en orrh ea, secon dary 186 ideation al 254 occlu sion 147, 299–30 0
am n esia 207 ideom otor 254 posterior (PICA) 108, 145, 146,
an terograde 208–209 aquedu ct 171 271, 272, 272, 275, 276, 299–
p osttrau m atic 208–209 cerebral 137, 217 30 0
retrograde 208–209 arach n oid 261, 262, 284 su perior (SCA) 91, 108, 145, 146,
am n estic syn drom e 208–209 gran ulation s 266 271, 272, 276, 276, 279
AMPA receptor 7 arch icerebellu m 122–123, 159 occlusion 149, 30 0–301
am p ullae 115, 120 arch icortex 202, 203, 226–227, 231 cerebral
am ygdala 82, 180, 202, 205–206, 215, area(s) an terior (ACA) 91, 145, 271, 272,
215 association 247–248, 247 274–275, 274, 275, 279
am yotrop h ic lateral sclerosis 4 8, 48 m u ltim odal 247–248 in farct 290, 290, 291, 296, 297
an arth ria 24 9 u n im odal 247 m iddle (MCA) 145, 271, 272, 274,
an astom oses 278–279, 278 au ditory 117–118 274, 275, 279
callosal 279 Broca’s 24 8 in farct 256, 296
leptom en in geal 279 in farct 250–251 occlu sion 296–297
an eu rysm 306, 307, 307 calcarin e 86 th rom bolysis case presen tation
an terior com m u n icatin g artery en torh in al 202, 204, 205 291, 292, 293
(ACom m ) 274 olfactory 216 posterior 91, 108, 145, 146, 271,
basilar tip 308 p ostrem a 76, 143 272, 274, 275, 276–277, 276, 277,
case presen tation s 308, 308, 310, 310 p repiriform 83 279
fu siform 307 p retectal 100 fetal origin 273
 320 · Index

artery(ies) an terior 277, 299 body

cerebral in farction 299 am ygdaloid 83
p osterior p osterior 274, 277, 279, 299 gen iculate
in farct 298–299 thyroid, su perior 271 lateral 76, 76, 84–85, 85, 86, 87,
occlu sion 152, 153 vertebral 108, 145, 146, 270, 271, 96, 100, 118, 172, 173–174, 173,
ch iasm atic, sup erior 279 272–273, 272, 275, 276, 282, 283 175, 204
ch oroidal occlu sion 147, 150 m edial 76, 76, 117, 118, 172, 173–
an terior 145, 272, 273–274, 274, art h rosis, un covertebral 58 174, 173, 175
279 asom atogn osia 255 Lew y 219–220
isch em ia 296 astasia 165, 166, 30 0 m am illary 76, 171, 175, 178, 179,
posterior 145, 146 th alam ic 177 202, 216, 279
lateral 274, 277, 298 astereogn osis 29, 32, 255 pedu n cle 180
m edial 277, 298 astrocytes 8 restiform 162
occlu sion 153, 298 astrocytom a 167 trapezoid 117, 118, 137, 139, 140–141
circle of Willis 278–279, 279 cystic 167 bon e
com m u n icatin g 278 p ilocytic 167 petrou s 89
an terior 274, 278, 279 ataxia 30 0 sph en oid 89
posterior 91, 145, 271, 272, 273, Friedreich 49 borreliosis 264
278, 279 gait 166 Bow m an ’s glan d 81
em boli 296 lim b 307 brach ia con jun ctiva 75
facial 271 stan ce 166 brach ialgia paresth etic n octu rn a 67
Heu bn er’s 275, 279 tru n cal 165 brach iofacial w eakn ess 41–42
hypophyseal ath etosis 219 brach iu m pon tis 75
in ferior 182 atrop hy, m u ltip le system 220 brain stem
su perior 183, 279 atten tion disturban ces 176 an atom y 74–76, 76, 134–145, 134–137
hypoth alam ic 183 au diom etry 119 blood su pply 145
in tercostal, posterior 283 au ditory perception 113 fiber con n ection s 138, 139
labyrin th in e 145, 272, 276 axon al tran sport 3 disorders 145–155
occlu sion 30 0 axon s 2–3 in farct 95, 95, 97, 97, 146, 298
lin gu al 271 m yelin ation 3–4 su bclavian steal syn drom e 147
m am illary 279 vascu lar syn drom es 302
m axillary 271 Broca aph asia 249–253
m en in geal B case presen tation 250–251, 250–251
an terior 260 Broca’s area 248–249
m iddle 260–261 Babin ski sign 41, 48, 49 in farct 250–251
p osterior 260 Balin t syn drom e 255 Brodm an n ’s cytoarch itectu ral m ap
occipital 278 ballism 219, 223 233
occipitotem poral 277 ban d of Baillarger Brow n –Séqu ard syn drom e 49–50, 49,
of Perch eron 277, 299 extern al 231, 232 56
oph th alm ic 91, 271, 273, 278, 279 in tern al 231, 232 bu lb
em boli 296 baroceptors 12 en d, of Krau se 12–13, 13
p araven tricu lar 279 barrels, cortical 235 olfactory 81–82, 82, 83
p erforatin g, occlusion 155 basket cells 7, 160, 232 bu n dle
radicular basoph il cells 185 m acu lar 87
an terior 283 bedw ettin g 198 m edial forebrain 83, 84, 179, 180,
great (of Adam kiew icz) 53, 283, beh avior con trol 255–257 180, 181, 190
283 Bell palsy 111, 112
recu rren t, of Heubn er 275, 279 Ben edikt syn drom e 152–153, 155
segm en tal ben ign paroxysm al position al vertigo C
lu m bar 282 (BPPV) 124–125
th oracic 282 Betz cells 37 cacosm ia 84
sp in al Bielsch ow sky test 93, 94 CAG trin ucleotide repeat, in Hu n tin g-
an terior 145, 146, 272, 272, 275, Bin g–Horton syn drom e 108 ton disease 221, 222
281–282, 282, 283 bladder Cajal–Retzius cells 227, 228, 231
syn drom e 55, 55 dysfu n ction 195–198 callosotom y 253
p osterolateral 282, 282 n eurogen ic 196–197 can al
in farction 312 n on n eu rogen ic 197–198 carotid 82
su bclavian 64, 271, 282 fu n ction 195 hypoglossal 82, 133, 134
occlu sion 147 in n ervation 193–195, 193, 194 optic 82
su lco-com m issural 281–282, 282 obstru ction sem icircu lar 115, 120
su praoptic 182, 279 in fravesical 197 can alolith iasis 125
tem poral, su perficial 271 n eck 196 capsu le
th alam ogen icu late 277 blin k reflex 102, 110 extern al 236
isch em ia 299 blood p ressu re regu lation 14 4, 184 in tern al 28, 29, 38, 171, 216, 227,
th alam operforatin g blood–CSF barrier 263 236
 Index · 321

gen u 37 sh un t 268, 305 syn drom es 46–47, 46, 49, 49

lesion s 42–43, 42, 288 volum e 264 com m a of Sch u ltz 31, 41
cardiorespiratory fun ction 145 cerebrum com m issu re
carotid-cavern ou s fistula 273 an atom y 228–230, 228, 229, 230 an terior 82, 171, 183, 202, 216, 236,
carp al tu n n el syn drom e 67, 68 con n ection s 232, 233 237, 238, 253
cau da equ in a 45, 54 develop m en t 226–227, 226, 228 h aben u lar 177
syndrom e 53, 54, 61, 62 evolu tion 226–227, 227 of th e forn ices 202
cavern om a 306 fu n ction al localization 238–248, 238 p osterior 171
cells h istological organ ization 231–235, com p lex region al pain syn drom e 67
acidoph il 185 231, 234 com p ression
air, eth m oid 89 isch em ia 283–289, 295–297 brach ial plexus 63
basket 7, 160, 232 diagn osis 286–289 p eriph eral n erves 67
basoph il 185 w h ite m atter 235–237 sp in al cord 52, 52
Betz 37 ch an delier cells 232 com p uterized tom ograp hy (CT) 288–
Cajal–Retziu s 227, 228, 231 ch arley-h orse 61 289, 302–303
ch an delier 232 Ch arlin n eu ralgia 108 con es 84
ch rom oph obe 185 ch em oceptors 12 con gestive m yopathy 312–314
Deiters 115, 116 ch iasm , optic 84, 86, 87, 89, 103, 171, con sciou sn ess 14 4, 176, 299, 308
double bou quet 232 179, 182, 183, 216 con tin en ce 195
gran ule 160, 160, 161, 231, 232 lesion s 86 con us m edullaris 45, 54
h air 115, 116, 118, 120–121 ch olin ergic system 188 con us syn drom e 53, 54
m itral 82 ch orda tym pan i 109, 111, 112, 113, 114 convergen ce of in form ation tran sfer 6
olfactory 81 ch orea 219, 221 cordotom y 31
bipolar 82 ch rom oph obe cells 185 corn eal reflex 105
Pillar 116 cin gulu m 203, 237, 238 ligh t test 92
Purkin je 160, 160, 161 circle of Willis 278–279, 279 corn u Am m on is 203–205
pyram idal 203–205, 231–233 circulation coron a radiata 28, 236
Ren sh aw 4 4 an terior 270 corp ora cavern osa 199
Schw an n 3 cerebrospin al fluid 263, 263 corp us callosu m 171, 175, 180, 216,
tu fted 82 bottlen ecks 264 217, 227, 237, 238
cen ter distu rban ces 264–267 agen esis 253
ciliospin al 102 collateral 278–279, 278 lesion s 209
gaze, lesion s 98 arterial circle of Willis 278–279, su rgical tran section 249
p on tin e m icturition 195 279 corp us striatu m 217, 218
cen tral sp astic paresis 41 extern al-carotid-to-vertebral col- corp uscles
cerebellum 158–168, 217 lateralization 278 Golgi–Mazzon i 14, 14
blood su pply 276 extern al-to-in tern al collateraliza- Meissn er 12, 13
con n ection s 161, 162–164 tion 278 Ru ffin i 13, 13
floccu lon odu lar lobe 122–123, 159, im portan ce of 285 Vater–Pacin i 12, 13–14, 13
159 posterior 270 cortex
fu nction 164 cistern (s) 262 au ditory 245–246, 246
h em orrh age 167, 306–307, 306 am bien t 204 lesion s 246
in tern al structu re 159 cistern a m agn a 262 cerebellar 159–160, 160
cortex 159–160, 159 Clarke’s colu m n 26 afferen t inpu t 160
n uclei 160 classical con dition in g 207 cerebral
isch em ia 167 clau stru m 29, 37, 215, 216 agran ular 233
in farction case presen tation 301, claw h an d 67 association areas 247–248, 247
301 clivu s 89 Brodm an n ’s cytoarch itectu ral
surface an atom y 158–159, 158, clon u s 41 m ap 233
159 cluster h eadach e 108 developm en t 226–227, 226, 227
syndrom es 164–166 coch lea 114, 115, 116 fron tal lobe 247–24 8
vascu lar 299 colliculu s(i) fun ction al localization 238–246,
tu m ors 167–16 8 brach iu m 137 238, 241, 242, 243, 244, 245
cerebrocerebellum 159 facial 76, 109 gran u lar 233
fu nction s 166 in ferior 76, 76, 96, 117, 118, 139, h igh er fun ction s 24 8–257
lesion s 166–167 141 h istological organ ization 231
cerebrospin al fluid (CSF) 263–266 su perior 76, 76, 96, 97, 137, 141 lam in ar arch itectu re 231–235,
circu lation 263–266, 263 colon in n ervation 194 232, 234
bottlen ecks 266 colu m n (s) lesion s 41–42, 42, 242–246, 248–
disturban ces 264–267 Clarke’s 26 257
fin din gs in diseases 264 cortical 242–24 4 prim ary cortical fields 239–247
p ressu re 264, 305 prim ary au ditory cortex 245–246 gustatory 246
see also hydroceph alu s; in tra- prim ary visu al cortex 245 h ipp ocam pal 203
cran ial hyp erten sion p osterior 25, 26, 28–30, 33 lim bic 202, 202
resorption 266 lesion s 29–30, 34 m otor 36, 36, 37, 240–242
 322 · Index

cortex Duch en n e–Erb palsy 63 excitation 6, 7

n eocerebellar 163 du ct excitatory postsyn aptic poten tial
orbitofron tal 206 coch lear 114–115, 115, 116 (EPSP) 5
prefron tal 248, 255 en dolym ph atic 115 exercise-dep en den t w eakn ess 72
lesion s 255–257 p erilym ph atic 115 exotropia 92
prem otor 248 du m bbell tu m ors 56, 57 exteroceptors 12
som atosen sory, p rim ary 240–244 du ra m ater 260–261, 261, 284 extin ction ph en om en on 255
lesion s 24 4 blood su pply 260–261 eye in n ervation
striate 85, 24 4 in n ervation 262 p arasym path etic 102, 103, 194
vestibu lar 246–247 orbital 262 sym path etic 102, 103, 104, 194
visu al 85, 24 4–245, 244, 245 spin al 261 eye m ovem en ts 89–102
lesion s 245 arterioven ou s fistu la 312–314, 313 accom m odation 99–101
cran iosacral system 188 dysarth ria 149, 249, 306 an atom ical substrate 10 0–101,
crista am pu llaris 120, 120 scan n in g 167 100
crocodile tears 111 dysarth roph on ia 167 con ju gate 90, 94–99, 118
cru ra cerebri 38, 75, 76, 171 dysdiadoch okin esia 166, 299 an atom ical basis 96
cu bital tun n el syn drom e 6 8, 68 dysequilibriu m 123–124, 165 reflex gaze m ovem en ts 98–99
cu lm en 158, 159, 161 dysgrap h ia 249 convergen ce 99–101
cun eu s 230 dyslexia 249 an atom ical substrate 10 0–101, 100
Cu sh in g syn drom e 186–188 dysm etria 166, 299 optokin etic nystagm u s 98–99
dysph agia 149 pu pillary con striction 10 0
dyssyn ergia 166 sm ooth pu rsu it m ovem en ts 98
D dyston ia 219, 223 volun tary 98
focal 223
decu ssation gen eralized 223
lem n iscal 135 F
pyram idal 38, 39, 75, 76, 135, 139
su perior cerebellar pedu n cles 137 E falx cerebelli 260
tegm en tal 137 falx cerebri 260, 281
Deiters cells 115, 116 ear 115 fascia den tata 203, 204
Dejerin e syn drom e 147, 150, 151 in n er 114–117 fascicu lus
case p resen tation 151 m iddle 114 arcu ate 235, 236, 237
dem en tia 208 edem a cu n eatus (of Bu rdach ) 26, 28, 28, 31
den drites 2 cerebral 284 fron totem p oral 236, 237
den dritic spin es 6 vasogen ic 302 gracilis (of Goll) 26, 28, 28, 31
derm atom es 17, 17, 18, 200 Edin ger–Westph al n u cleus 77, 78, 90, len ticular 178
sen sory deficits 17, 18 101, 103, 142 lon gitu din al
developm en t 8–9 electroen cep h alograp hy 238 dorsal (of Sch ü tz) 83, 137, 181,
cerebru m 226–227, 226, 228 em boli 285, 295–299 181, 190
déviation con juguée 98 p aradoxical 285 in ferior 237, 237
diabetes in sipidu s 184 see also isch em ia; th rom boses m edial (MLF) 95–96, 96, 118, 121,
diagon al ban d of Broca 83 em bolism 147 122, 123, 135, 137, 138, 139, 142,
diap h ragm 69 em in en ce, collateral 204 164–165
diap h ragm a sellae 260 en cep h alitis 209, 264 lesion s 97, 150, 152
dien ceph alon 8, 170–172, 171 case presen tation 209, 209–210 su perior 236–237, 237
digital su btraction an giograp hy (DSA) en d bu lbs of Krau se 12–13, 13 m am illotegm en tal 182
289, 290, 290, 291, 304, 309 en dolym ph 115 occip ital, vertical 237, 237
dip lopia 92, 92 en don eu riu m 14 occipitofron tal
discon n ection syn drom es 253–254 en op h th alm os 102, 191 in ferior 236, 237
olfactory system 253 en teroceptors 12 su perior 237
visu al system 253–254 en u resis 198 of Meyn ert 181
disin h ibition 6, 6 epicon u s 54 olfactory 79
disk(s) syn drom e 53, 54 optic 79
in tervertebral epidu ral h em atom a 311, 312 propriu s 20, 20
degen eration 58–62, 59 sp in al 314 sem ilu n ar 41
h ern iation 57, 58, 59–61 epin euriu m 14 subth alam ic 178
m assive prolapse 61, 62, 62 epiphysis 76, 171, 177, 178 th alam ic 178
protru sion 57, 60 epith alam us 171, 172, 177–178 u n cin ate (of Ru ssell) 122, 160, 236,
optic 87 epith eliu m 237, 237
lesion s 86 olfactory 81, 83 see also tract(s)
tactile, of Merkel 13, 13 p igm en t 103 fecal in con tin en ce 198
divergen ce of in form ation tran sfer 6 equ ilibriu m distu rban ces 123–124, fecal reten tion 198
dizzin ess 123–124 165 fen estra
dop am in e 7 esotropia 92 coch leae 114, 115
dou ble bou qu et cells 232 eth m oid air cells 89 vestibu li 114, 115
 Index · 323

fiber(s) 14, 77, 78 forceps gap ju n ction 6

an n u lospiral 41 m ajor 237, 238 gastroin testin al m otility 14 4
association 233, 236–238, 236, 237 m in or 237, 238 gaze 92, 93, 95–97, 96
cerebral arcu ate 236, 237, 237 forn ix 171, 175, 180, 181, 203, 205, 216 diagn ostic direction s of 91, 92
clim bin g 160, 160, 161 crux 171 h orizon tal 95
com m issural 233, 237, 238 fossa disturban ces 95–96
corticon uclear 137, 156 in terpedun cular 75 lesion s of gaze cen ters 98
corticop on tin e 75 p osterior 158 reflex gaze m ovem en ts 98–99
corticosp in al 137, 156 rh om boid 74–75 vertical 96–97
cran ial n erve 77–78 fovea 84 vertical gaze palsy 176
Golgi 41 Foville syn drom e 147 see also eye m ovem en ts
gu statory 111–112, 113, 130, 173 free n erve en din gs 13, 13 gen italia, m ale
in tracortical 237 Friedreich ataxia 49 dysfu n ction 198–199
m ossy 160, 160, 161 fu n ction al m agn etic reson an ce im ag- in n ervation 193, 194, 198, 199
m yelin ated 235 in g (fMRI) 239, 243 gen u
parallel 159, 160 fu n ction al n eu ral n etw orks 239 facial n erve
pon tin e 75 fu n icular m yelosis 34, 34, 47–4 8, 48 extern al 109
projection 235 fu n icu lu s, p osterior 28, 28, 31 in tern al 109
radial glial 227 Gerstm an n syn drom e 255
radicu lar 90, 91 glan d(s)
subcortical 237 G adren al 194
trigem in al 104–107, 105, 106 Bow m an ’s 81
lesion s 107 G-p rotein -cou pled receptors 5, 7 lacrim al 112, 114, 189, 194
m otor 107 gag reflex 145 n asal 112, 114
pain 106–107 galactorrh ea 186 p in eal 178
som atosen sory 104–105, 105, 106 γ m otor n eu ron s 22–24, 22, 43 salivary 189
tem peratu re 106–107 static an d dyn am ic 24 parotid 114, 189, 194
vestibulocerebellar 121 gam m a-am in obu tyric acid (GABA) 7 sublin gu al 112, 114, 194
visceral receptors 7 subm an dibu lar 112, 114, 194
afferen t 186 gan glion (a) sw eat 104, 189
efferen t 186 basal 39, 214 glial cells 7–8
see also n erve(s); n eu ron (s) con n ection s 217–219, 218 globu s pallidu s 40, 171, 172, 174, 175,
fim bria h ipp ocam pi 204, 205 fun ction 219 178, 178, 214, 215, 215, 216, 217, 218
fissure h em orrh age 177, 305, 305 glu tam ate 7
collateral 230 lesion s 219–223 an tagon ists 160
h ippocam pal 204 n uclei 215–217, 215, 216, 217 receptors 7
lon gitu din al, cerebral 228, 230 phylogen etic aspects 214–215 glycin e 7
in ferior 236 celiac 189, 191 receptors 7
su perior 236 cervical Golgi ten don organ s 13, 14
orbital, su perior 82, 89 m iddle 190 Golgi–Mazzon i corpu scle 14, 14
posterolateral 159 sup erior 63, 103, 104, 129, 190 Gordon reflex 41
sylvian 228, 229 cervicoth oracic (stellate) 190 Graden igo syn drom e 108
fistula ciliary 100, 101, 103, 105, 189, 192 gran u le cells 160, 160, 161, 231, 232
arterioven ou s 312–314 dorsal root 16 gran u lization 233
case presen tation 313, 313 syn drom e of 46, 46 gray m atter syn drom e 47, 47
carotid-cavern ou s 273 gen icu late 109, 111, 112, 113, 114 Gray type I syn apses 5
fixation reflex 98 glossoph aryn geal Gray type II syn ap ses 5
floccu lu s 122, 159, 159 in ferior (extracran ial) 126, 127, 130 grow th -h orm on e-secretin g aden om a
flow er-spray en din gs 22 su perior (in tracran ial) 126, 127, 130 186
Foix–Alajou an in e disease 312 m esen teric Gu illain –Barré syn drom e 264
foliu m (a) 158, 161 in ferior 189, 191, 193, 198 gyn ecom astia 186
food in take 145 su perior 189, 191 gyru s(i) 228–229
foram en (in a) otic 113, 114, 189, 192 am bien t 82, 83
in terven tricular, of Mon ro 170, 171, pterygopalatin e 105, 109, 112, 113, cin gu late 175, 202
262 114, 189, 192 den tate 203–205, 204, 230
in tervertebral 59, 60 sp iral 117, 117, 118 fron tal, m iddle 229
jugular 82, 131 su bm an dibular 112, 114, 189, 192 fu siform 230
laceru m 82 trigem in al (gasserian ) 79, 82, 89, 91, lin gu al 230
m agn u m 131 103–104, 105, 141 occipitotem poral
of Lu sch ka 75, 76, 158 vagal lateral 230
of Magen die 75, 76, 158 in ferior (n odose) 127, 128, 129, m edial 230
ovale 82, 114 130, 131 orbital 230
rotu n du m 82, 114 sup erior (jugu lar) 127, 128, 129, p arah ipp ocam pal 82, 204, 230
sten oses 57, 58, 59, 60, 61 131 p araterm in al 230
stylom astoid 111 vestibu lar (of Scarpa) 117, 121, 122 p ostcen tral 28, 29, 30
 324 · Index

gyru s(i) diagn osis 308–309 hyporeflexia 167

precen tral 36, 36, 37, 230 gradin g 308, 309 hyposm ia 84
rectu s 230 rebleedin g 310 hypoth alam ic–pitu itary axis 185, 186
sem ilu n ar 82, 83 see also h em atom a distu rban ces 185–186
tem poral h eparin 304 hypoth alam u s 170, 171, 172, 178–188,
in ferior 230 Herin g’s law 94–95 216
sup erior 231 h erpes sim plex en ceph alitis 209, 264 con n ection s 180–183, 180, 181, 190
tran sverse, of Hesch l 117, 118, 231 case presen tation 209, 209–210 fu n ction s 184–185
h erpes zoster 46 n u clei 179–180, 179
oticu s 112 hypoth erm ia 184
H Heu bn er’s artery 275, 279 hypoton ia 44, 167
h ipp ocam pu s 202, 203–205, 204, 216, hypotropia 92
h aben u la 177 227, 227
h air cells 115, 116, 118, 120–121 activation 205
h eadach e 302, 304, 308 con n ection s 205 I
clu ster 108 h om u n cu lus 28, 241
occipital 306 m otor 36–37 im poten ce 186, 198–199
h earin g 113–119 h orn in con tin en ce
diagn ostic evalu ation 119 Am m on ’s 203–205, 204 fecal 198
disorders 119–120, 126 an terior 135 u rin ary 196–197
h eart an terior h orn cells 43, 123 overflow 196
in n ervation 191, 194 in h ibition by Ren sh aw cells 4 4 stress 196–197
referred p ain 199 syn drom e 48, 48 u rge 196
regu lation 184 in ferior 204, 216 in cu s 115
h elicotrem a 115, 115, 116 p osterior 24–25, 30, 217 in dusiu m griseu m 202, 227, 227
h em an gioblastom a 167 lesion s 34 in farction
h em atom a syn drom e 47, 47 brain stem 95, 95, 97, 97, 146, 298
epidu ral 311, 312, 314 Horn er syn drom e 63, 102, 104, 149, Broca’s area 250–251
rem oval 306, 311 191–192 cerebellar, case presen tation 301,
sp in al cord 314 cau ses 192 301
su bdural 311, 311 h ou rglass tu m ors 57 cerebral artery 256, 290, 290, 291,
h em atom yelia 47, 314 Hu n tin gton disease 221 296–297, 298–299
h em ian esth esia 24 4, 299, 30 0 case p resen tation 222, 222 em bolic 285
h em ian opic ligh t reflex test 88 hydroceph alu s 266–268, 309 h em odyn am ic 285–286
h em ian opsia 245 active 266–267 case p resen tation 287, 287
bin asal 86 ch ildren 268 lacu n ar 286
bitem poral 86 com m un icatin g 266 case p resen tation 288, 288
h om onym ous 86, 88, 296, 297, 299 diagn osis 268 m idbrain 95, 95, 97, 97
h em iataxia 177, 299 epidem iology 268 pon tin e 154
h em iballism 178 ex vacu o 267 oral region 155
case presen tation 223, 223 hypersecretory 266 septal n u clei 209
h em icran iectom y 285 m alresorptive 266 spin al cord 55, 55, 282, 312
h em ihyp esth esia 24 4, 296, 297 case presen tation 267, 267 su bth alam ic n u cleus 223
h em ip aresis n on com m un icatin g 266 territorial 285, 290, 291
bilateral 43 n orm al pressure (NPH) 267 th alam ic 209
con tralateral 43, 24 4, 296, 297, 299, case presen tation 265, 265 case p resen tation 211, 211, 30 0,
305 occlusive 266 300
flaccid 43, 24 4 treatm en t 26 8, 309 Wern icke’s area 252
sp astic 43, 24 4 types of 266–267 see also isch em ia
h em ip legia hydrom yelia 47 in form ation flow 2
altern atin g 147, 148 hypercolum n s 245 in form ation processin g 2, 2
sp astic hyperkin esia 219 in fu n dibu lum 178, 279
con tralateral 42–43, 148 ch oreiform 221 in h ibition 6, 7
ip silateral 43 hyperosm ia 84 forw ard 6, 6
h em orrh age 305–311 hyperreflexia 41 recu rren t 6, 6
basal gan glia 177, 305, 305 detrusor m u scle 196 in h ibitory p ostsyn aptic poten tial
cerebellar 167, 306–307, 306 hyperten sion (IPSP) 5
in tracerebral 305–307 arterial 286, 305 in n ervation 68, 69–71
hyperten sive 305–306 in tracran ial 268, 285, 296, 297, 305 eye
in traven tricu lar ru ptu re 305 treatm en t 305, 306 p arasym path etic 102, 103
n on hyperten sive 306 hyperth erm ia 184 sym path etic 102, 103, 104
septal n uclei 209 hypertropia 92 som atosen sory 16–17
sp in al cord 314 hypokin esia 219, 220 in sula 29, 37, 216, 228, 231
su barach n oid (SAH) 267, 267, 307– hypom im ia 221 in tern eu ron (s) 20, 232
310, 309 hypophysis 171 GABAergic 205
 Index · 325

in tervertebral disks see disks ligam en t, sp iral 116 Merkel’s disks 13, 13
in testin e in n ervation 194 ligan d-gated ion ch an n els 5 m esen ceph alon 8
in tracran ial hyperten sion 266–267, ligan d-gated receptors 7 m esocortex 202
285, 296, 297, 305 lim bic system m etastases, drop 167
treatm en t 305, 306 an atom y 202–203 Meyer’s loop 87, 88
see also hydroceph alu s con n ection s 203 m icroan eu rysm s 305
in trafu sal m uscle fibers 13 fu n ction s 206–208 m icroan giopath ic leu koen -
isch em ia lim en in su lae 83 ceph alopathy 286
cerebellar 167 lin gu la 159, 161 m icroelectrode recordin g 238
cerebral 283–289, 295–297 lobe(s) m icroglial cells 8
diagn osis 286–289 flocculon odu lar 122–123, 159, 159 m icrovascu lar decom p ression 107
p eriph eral n erves 67 fron tal 228, 228, 229, 247, 248 m ictu rition 193, 195
p rolon ged reversible isch em ic n eu- occipital 97, 228, 228, 229 m idbrain 75–76, 136, 137, 141–143
rological defect (PRIND) 284 p arietal 228, 228, 229, 247–248 in farct 95, 95, 97, 97
sp in al cord 55, 55 tem poral 228, 228, 229 Millard–Gu bler syn drom e 147, 151
stroke 284 locu s ceruleu s 137, 143 m iosis 191
tran sien t isch em ic attack (TIA) 284, lun g in n ervation 191 m odiolu s 116
290 Lym e disease 264 m on key h an d 67
see also in farction lym p h om a 52, 52 m on oplegia 43
isocortex 204, 231 m otor en d p late 4 4
m otor system
M cen tral com pon en ts 36–43
J lesion s 41–43
m acules 87, 115, 121 perip h eral com p on en ts 43–4 4
jackson ian seizures 32–33, 42, 24 4 saccu lar 115, 120–121 m otor u n it 44
u tricular 115, 120–121 m ultiple sclerosis 86, 88, 88, 96
m agn etic reson an ce im agin g (MRI) CSF fin din gs 264
K 289, 290, 290, 291, 303–304 trigem in al n eu ralgia an d 108
fu n ction al (fMRI) 239, 243 m ultiple system atrophy 220
kain ate receptors 7 m agn etoen ceph alography 239 m uscle spin dles 13, 14, 20–21
kidn ey in n ervation 194 m alleu s 115 m uscle ton e 24
Klum pke palsy 63 m assa in term edia 171, 172, 180, 181 abn orm alities 41, 219, 221
Korsakoff syn drom e 208 m ech an oreceptors 12 m uscle(s)
Meckel’s cave 260 abdu ctor digiti qu in ti 70
m edu lla 38, 74–75, 134, 135, 136–140 abdu ctor p ollicis
L adren al 191 brevis 69
syn drom es 147, 149 lon gus 70
labyrin th 116, 120 m edu lloblastom a 167, 168 addu ctor
lacrim al glan d 112, 114, 189 m em bran e brevis 71
in n ervation 194 basilar 115, 116, 116 lon gu s 71
lam in a Reissn er’s 115, 116, 118 m agn u s 71
basilar 116, 117, 118 tectorial 116, 118 pollicis 70
ten sion regu lation 119 tym pan ic 115 an con eu s 70
m edullary m em ory 206 biceps brach ii 60, 69
extern al 171 dysfu n ction 208–209 biceps fem oris 71
in tern al 171 episodic 206–207 brach ialis 69
tectal 76, 171 exp licit (declarative) 207 brach ioradialis 60, 70
term in alis 171 fron tal-lobe-type fun ction s 207–208 ciliary 100
lan guage 248–249 im plicit (n on declarative) 207 con strictor p h aryn geu s 127
au tom atic 249 lon g-term (LTM) 206–208 coracobrach ialis 69
n on au tom atic 249 su btypes 206–207 deltoid 69
see also aph asia n eural su bstrates 206 detrusor 193, 195
lem n iscu s sem an tic 206–207 areflexia 196
lateral 118, 137, 138, 139 sh ort-term (STM) 206 detru sor-sph in cter dyssyn ergia 196
lesion s 151, 152, 153 Squ ire’s taxon om y of 207–208 hyp erreflexia 196
m edial 26, 27, 28, 29, 33, 106, 118, tests of 206 in stability 196
127, 129, 135, 137, 138, 139, 140, typ es of 206–208 digastric 108
142, 174, 217 Men del–Bekh terev reflex 41 dilator pu pillae 103, 104
lesion s 33, 150, 151, 152, 153, 155 Mén ière’s disease 119–120 exten sor carp i
sp in al 30, 33, 106 m en in ges 260, 261 radialis 70
trigem in al 33, 106, 142 m en in giom a 57 u ln aris 70
lateral 137 m en in gitis exten sor digiti qu in ti 70
lesion s 33 bacterial 264 exten sor digitoru m 70
leu koaraiosis 286 fu n gal 264 brevis 61, 71
Lew y bodies 219–220 tu bercu lou s 264 lon gus 71
viral 264

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m uscle(s) p elvic floor 195 N

exten sor h allu cis p eron eal 71
brevis 71 p eron eus n asal glan ds 112, 114
lon gu s 61, 71 brevis 61 n eglect 255
exten sor in dicis propriu s 70 lon gu s 61 case p resen tation 256, 256
exten sor pollicis piriform is 71 n eocerebellu m 159
brevis 70 plan tar, of th e foot 71 n eocortex 226–227, 227
lon gu s 70 pron ator teres 60, 69 n erve(s)
extraocu lar 89–92, 89, 91, 123 quadratus fem oris 71 abdu cen s (CN VI) 80, 81, 82, 89, 89,
pareses 92, 93 quadricep s fem oris 70 91, 91, 96, 151
flexor carpi rectu s p alsy 93, 94
radialis 69 in ferior 89, 90, 92 accessory (CN XI) 75, 80, 81, 82, 122,
u ln aris 70 lateral 89, 92 126, 131–132, 131
flexor digiti qu in ti brevis 70 paresis 93 lesion s 132
flexor digitoru m m edial 89, 90, 92, 100, 101 alveolar, in ferior 105
brevis 71 paresis 93 au ricu lar
lon gu s 71 sup erior 89, 90, 92 great 19, 63
profun dus 69, 70 rh om boids 69 posterior 109, 111
sup erficialis 69 sartoriu s 70 au ricu lotem p oral 105, 106
flexor h allu cis lon gus 71 scalen e 69 axillary 19, 64, 66, 69
flexor pollicis an terior 64 bu ccal 105
brevis 70 segm en t-in dicatin g 58, 60, 61 cardiac 191
lon gu s 69 sem im em bran osu s 71 cervical 19, 69
gastrocn em iu s 71 sem iten din osus 71 tran sverse 19, 63
gem elli 71 serratu s an terior 69 clu n eal 19
gen ioglossu s 133, 134 soleu s 71 coccygeal 15, 65
glu teu s stapediu s 114 coch lear 111, 117, 118
m axim u s 71 stern oclein om astoid 132 cran ial 77–78, 77–82
m ediu s 71 stern othyroid 133 n u clei 77, 78, 79
m in im us 71 styloglossus 134 see also specific nerves
gracilis 71 styloph aryn geu s 127 cutan eous
hyp oglossu s 134 su bscap ularis 69 an tebrach ial
hyp oth en ar 60 su pin ator 70 lateral 19
iliop soas 70 su prasp in atu s 69 m edial 19
in fraspin atus 69 syn drom es 72 posterior 19
in n ervation 68, 69–71 tarsal brach ial
in terossei in ferior 104 m edial 19
dorsal 70 su perior 104 posterior 19
palm ar 70 tem poralis 105, 107 fem oral
latissim u s dorsi 69 ten sion regulation 20–21, 22 lateral 19, 65
len gth regu lation 20–21, 22 ten sor fasciae latae 71 posterior 19, 65
dysfu n ction 41 ten sor tym p an i 114 facial (CN VII) 80, 81, 82, 109–111,
target values 22–24 teres 109, 111
levator m ajor 69 lesion s 110–111, 111
palpebrae 89 m in or 69 m otor com pon en t 109–111
su perioris 90 th en ar 60 palsy 43, 110–111, 110, 148
scapu lae 69 thyrohyoid 133 cen tral 110
lu m bricals 70 tibialis idiopath ic 111, 112
m asseter 105, 107 an terior 61, 71 fem oral 19, 65, 66, 70
m en tal 105 posterior 71 fibu lar 19
oblique trapeziu s 132 fron tal 105
in ferior 89, 90, 92 triceps brach ii 60, 70 gen itofem oral 19, 65
sup erior 89, 92 triceps su rae 61, 71 glossop h aryn geal (CN IX) 75, 80, 81,
paresis 93, 95 vastu s 82, 112, 126–127, 127, 129–131, 189
obtu rator lateralis 61 bran ch es 126
extern u s 71 m edialis 61 lesion s 126–127
in tern us 71 see also sph in cter syn drom e 126–127
om ohyoid 133 m u scu lar dystroph ies 72 glu teal
oppon en s digiti qu in ti 70 m yasth en ia 72 in ferior 65, 66, 71
oppon en s pollicis brevis 70 gravis 72 sup erior 65, 66, 71
orbitalis 104 m ydriasis 102 hyp ogastric 198
p alm aris lon gu s 69 m yelin sh eath 3–4, 4 hyp oglossal (CN XII) 63, 75, 80, 81,
p ectin eu s 71 m yelitis 82, 132–134, 133, 135
p ectoralis p arain fectiou s 51, 51 lesion s 134, 150
m ajor 69 tran sverse 50 palsy 43, 134, 148, 150
m in or 69 m yopathy 72

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iliohyp ogastric 19, 65 sp lan ch n ic n ervu s in term ediu s 78, 79, 80, 109,
ilioin gu in al 19, 65 greater 189, 191 111–112, 111, 189
in tercostal 19, 70 lesser 189, 191 n eural tu be 8
in tercostobrach ial 19 pelvic 189, 193, 193 n euralgia
laryn geal su bclaviu s 64 Ch arlin 108
recu rren t 128, 129 su boccipital 63 glossop h aryn geal 127
su perior 128 su bscapu lar 64 trigem in al 107–108, 108, 302
lin gual 105, 111, 113, 114 su praclavicular 19, 63 idiopath ic 107
lu m bar 19 su prascap ular 64, 69 n eurin om a 57
m an dibular 17, 19, 82, 104, 105, 106 su ral 19 n eu roblasts 8
m axillary 17, 19, 82, 104, 105, 106, th oracic 19 n eu roborreliosis 264
114 lon g 64, 69 n eurodevelopm en t 8–9
m edian 19, 64, 66, 69, 70 th oracodorsal 64, 69 n eu roglia 235
lesion s 67 tibial 65–66, 65, 66, 71 n eurohypophysis 171, 178, 179, 181, 182
palsy 67, 68 lesion s 66 n eu rom a, acou stic 120, 125–126, 167,
m u sculocu tan eous 64, 66, 69 trigem in al (CN V) 17, 19, 33, 75, 80, 168
m ylohyoid 105 81, 82, 91, 103–109, 137, 146 n eu ron al m igration disorders 227
n asociliary 105 lesion s 33–34, 107–108 n eu ron (s) 2–4, 3
obtu rator 19, 65, 66, 71 troch lear (CN IV) 76, 79, 81, 82, 89, association 20
occipital 89, 90–91, 91, 142 cellular proliferation 8
greater 19, 63 n uclear lesion 95, 95 com m issu ral 20
lesser 19, 63 p alsy 93, 94 EE 246
oculom otor (CN III) 75, 79, 81, 82, tym pan ic 126 EI 246
89, 90, 91, 96, 100, 103, 189, 279 u ln ar 19, 64, 66, 70 excitatory 6
palsy 93, 94, 148 lesion s 68 fu n icu lar 20, 30
olfactory (CN I) 79, 81–82, 81, 82, 83 p alsy 67, 68 GABAergic 7
oph th alm ic 17, 19, 82, 89, 104, 105, vagus (CN X) 75, 80, 81, 82, 112, 122, glu tam atergic 7
106 126, 127, 128–131, 129, 131, 189, 192 grow th of cellu lar processes 8
optic (CN II) 77, 79, 81, 82, 84, 85, bran ch es 128 in h ibitory 6
87, 91, 100, 103 lesion s 128–129 m otor 20, 37–38
lesion s 86, 101 vestibu lar 91, 111, 120, 122 α 43, 123
pectoral vestibu lococh lear (CN VIII) 80, 81, γ 22–24, 22, 43, 123
lateral 64, 69 82, 113–126 static an d dyn am ic 24
m edial 64, 69 zygom atic 114 postgan glion ic 188
pelvic 198 see also fiber(s); n eu ron (s) pregan glion ic 188
perip h eral 14, 14, 4 4, 66 n erve p lexu s see p lexu s program m ed cell death 9
lesion s 18, 67 n erve roots 16, 57 pyram idal 37
differen tial diagn osis 68 accessory 131–132 see also fiber(s); in tern eu ron (s);
som atosen sory in n ervation 16–17 cran ial 131, 131 n erve(s)
syn drom es 67–6 8, 67 lesion s 132 n eu ron al m igration 8
peron eal 66 spin al 131, 132 n eu ropathy, vestibu lar 125
com m on 19, 65–66, 65 coch lear 117 n eu ropeptides 7
deep 19, 71 dorsal root en try zon e (DREZ) 24 n eu rosecretion 185
lesion s 66 facial 109 n eu rosyph ilis 264
su perficial 19, 71 oculom otor 155, 156 n eurotran sm itters
p etrosal spin al 15–16, 15 excitatory 7
great 111, 113, 114 an terior 14, 15, 44 in h ibitory 7
lesser 106, 114 posterior 14–15, 15, 16 syn aptic tran sm ission 5
p h ren ic 63, 64, 69 syn drom es 57–62 NMDA receptor 7
p lan tar cervical 58–59, 59, 60 n ociceptors 12
lateral 19 lu m bar 59–62, 60, 61, 62 n ode of Ranvier 3
m edial 19 posterior 46, 46 n odu lu s 159, 159, 161
pterygoid trigem in al 106, 108, 154 n orep in eph rin e 7
lateral 106 u n m yelin ated p ortion s 108 n otch , preoccip ital 229
m edial 106 vestibu lar 117, 121 n u cleu s(i)
p uden dal 65, 71, 193, 198, 199 n ervou s system abdu cen s 78, 89, 91, 137
p ulm on ary 191 auton om ic 188–190 lesion s 152
radial 19, 64, 66, 70 parasym path etic 184, 188, 189, 192– accessory 77, 78, 90, 100, 131, 135
palsy 67 193, 194–195 am biguu s 77, 78, 127, 129–130, 129,
sacral 19 hypoth alam ic con trol 188–190 131, 135, 140
sap h en ous 19, 66 sym p ath etic 184, 188, 189, 190–192, lesion s 149
scapu lar, dorsal 64, 69 194–195 arcu ate 135
sciatic 65–66, 65, 66, 71 an atom y 190, 191 basal, of Mayn ert 178
lesion s 66 hypoth alam ic con trol 188–190 cau date 171, 214, 215, 215, 216, 217
sp in al 15–16, 57 lesion s 191–192 h ead 37, 38, 40, 175, 215, 216, 227
tail 38, 204, 215, 216

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 328 · Index

n eu ron (s) red 40, 91, 122, 137, 138, 139, 141– vestibu lar 75, 77, 79, 120, 121–123,
cen tral, su perior 143 142, 163, 163, 166, 217 121, 137, 140, 141, 161
cerebellar 160–162 syn drom e of 152–153, 155 in ferior (of Roller) 96, 121, 121,
coch lear 75, 77, 79, 135 reticu lar 137, 149
dorsal 117, 118 lateral 136 lateral (of Deiters) 40, 96, 121, 121,
lesion s 149 of th e th alam us 171, 172 137
ven tral 117, 118 reticu lar form ation 127 lesion s 149, 152
collicu lus au ton om ic 14 4–145 m edial (of Sch w albe) 96, 121, 121,
in ferior 217 salivatory 137
sup erior 137 in ferior 77, 78, 113, 114, 127, 130, su perior (of Bekh terev) 96, 121,
cun eate 26, 27, 33, 77, 106, 135, 136, 14 4 121, 137
138, 139 su perior 77, 78, 112, 113, 114, 14 4 n utrition al in take regulation 185
accessory 27, 135 septal 209 nystagm u s 124, 149, 165, 30 0
Darksh evich ’s 96–97, 96 lesion s 212, 212 com p lex 165
den tate 122, 137, 139, 142, 161, 162, Stillin g’s 26 gaze-evoked 165
163, 166, 174 su bth alam ic 171, 178, 178, 215, 216, optokin etic 98–99
Edin ger–Westp h al 77, 78, 90, 101, 217 periodic altern atin g 165
103, 142 in farct 223 reboun d 165
em boliform 122, 137, 142, 160–162, su prach iasm atic 178
161, 165, 175 su praoptic 182
facial 78, 109, 110, 111, 137 tegm en tal 40, 83 O
lesion s 151, 152 p edu n cu lop on tin e 143
obex 76
fastigial 40, 122, 137, 160, 161, 165 th alam ic 171, 172–176, 173, 174, 175
ocu lom otor disturban ces 165
globose 122, 137, 160–162, 161, 165 an terior 172, 173, 174, 175, 181, 203
olfactory system 81–84, 227
gracile 26, 27, 33, 77, 106, 135, 136, cen trom edian 172, 173, 175, 176,
discon n ection 253
138, 139 178, 217
oligoden drocytes 3, 4, 8
h aben ular 83, 171, 177–178, 205 dorsal 175
olive 75, 138, 150, 161, 163
hyp oglossal 75, 77, 78, 132–134, 133, in term ediate 175
accessory 138
135, 140 m edial 175, 206
in ferior 40, 76, 136, 139
lesion s 134 oral 175
lesion s 138
hyp oth alam ic 143, 179–180, 179 su perficial 175
op h th alm op legia
dorsom edial 179, 180, 180 in tralam in ar 173, 176
extern al 94
in fu n dibu lar 179, 180 lateral 172, 174, 175
in tern al 94
lateral (tu berom am illary) 180 dorsal 172, 173
in tern u clear (INO) 95–96, 97
m am illary 180 posterior 172, 173
Oppen h eim reflex 41
paraven tricu lar 179, 179, 181, 184 lesion s 176–177
optic radiation (of Gratriolet) 84–85,
posterior 179, 180 m edial 174, 175
85, 86, 100
preoptic 179, 179 dorsal 173
lesion s 88
sup raoptic 179, 179, 181, 184 n on specific 173, 176
optokin etic nystagm us 98–99
tu beral 179, 180 reticular 171, 172
organ
ven trom edial 179, 180, 180 sp ecific 173–174
of Corti 115, 116, 118
in term ediolateral 178, 191 ven tral 172, 174, 176
vestibu lar 160
in terpedun cular 83 an terior (VA) 172, 173, 174, 176
oscillop sia 124
in terstitial, of Cajal 96–97, 96, 122 in term ediate (VI) 173
osm oceptors 12
len tiform /len ticu lar 37, 38, 217 lateral (VL) 172, 173, 176
osteoch on drosis 58
m am illary body 171 oral 174
cervical 58–59
m esen cep h alic 77, 79, 106, 127 posterolateral (VPL) 28, 30, 172,
lum bar 59
ocu lom otor 77, 78, 89, 90, 90, 91, 173, 173, 176
oxytocin 182–183, 185
100, 137, 142 posterom edial (VPM) 112, 172,
of Darksh evich 122 173, 173, 176
of Perlia 90, 100, 101, 142 th oracic 26, 31 P
olivary 118, 136 tractus solitarius 77, 79, 112, 113, 114,
accessory 138, 139 127, 140 pain
in ferior 75, 135 lesion s 149 perception 240
sup erior 137 trigem in al 75, 103–107, 106, 127, ph an tom 242
p ara-abdu cen s 97 135, 137, 139, 140, 141 referred 199–20 0
p araven tricu lar 182 lesion s 149, 152, 153 visceral 199
p on tin e 40, 137, 154, 161, 163 m otor 77, 78, 106, 137, 141, 153 paleocerebellu m 27, 159
posterior com m issu re 96 prin cipal sen sory 77, 79, 106, 127, paleocortex 202, 226–227, 231
prestitial 96 137, 141, 153 palsy
pretectal 103, 141 troch lear 77, 78, 89, 90 abdu cen s n erve 93, 94
pu lposus 58 lesion 95, 95 accessory n erve 132
rap h e 217 vagal 75, 77, 78 brach ial plexu s
dorsalis 143 dorsal 129, 130, 135, 140, 143, 149, low er (Klu m p ke) 63
m agn u s 143 192 u pper (Du ch en n e–Erb) 63
pon tis 143 bulbar, p rogressive 4 8

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facial 43, 110–111, 110, 148 pedun cles p olyn eu ropath ies 68
cen tral 110 cerebellar 74–75, 159 p olyradicu litis 264
idiopath ic 111, 112 in ferior 76, 118, 135, 137, 138, 139, p olysen sory m ism atch 124
hyp oglossal 43, 134, 148, 150 149, 159, 162 p on s 38, 75, 76, 136, 137, 140–141
m edian 67, 67, 68 lesion s 149, 152, 153, 154 lesion s 42, 43, 98, 99
oculom otor 93, 94, 148 m iddle 75, 76, 137, 138, 139, 146, oral region in farct 155
peron eal 66 152, 154, 159, 163, 217 param edian in farct 154
radial 67 su perior 75, 76, 137, 138, 139, 146, p on tocerebellu m 159
sup ran u clear, progressive 220 153, 159, 163–164, 217 Pop e’s blessin g 67
tibial 66 cerebral 38, 75, 141, 142–143 p ositron em ission tom ography (PET)
toch lear 93, 94 lesion s 42, 43 239, 289
u ln ar 67, 68, 68 syn drom e of 153, 156 p osth erp etic n eu ralgia 46
vertical gaze palsy 176 m am illary body 180 p ostsyn aptic m em bran e 4–5
Pan coast tu m or 192 pen u m bra 285 p recociou s pu berty 178
p an creas in n ervation 194 perfu sion p ressu re 285 p replate 227, 228
p an hypop itu itarism 185–186 perikaryon 3 p resu bicu lu m 204
Papez circu it 203, 203 perin eu rium 14 p resyn aptic m em bran e 4–5
p apilledem a 86, 167, 262, 302 periosteu m 284 p rim in g effect 207
p aragram m atism 249 perip h eral n erves see n erve(s) p rogram m ed cell death 9
p aralysis peritrich ial n erve en din gs 12, 13 p rogressive sup ran u clear p alsy 220
flaccid 4 4–45 perseveration 257 p rolactin om a 186
spastic spin al 48–49, 48 ph otoreceptors 84 case presen tation 187, 187
p araparesis 297 pia m ater 261, 262–263 p rolon ged reversible isch em ic n eu ro-
flaccid 313 Pillar cells 116 logical defect (PRIND) 284
spastic 313 pin eal glan d 178 p roprioceptors 12
spin al cord com pression an d 52, 52 pin ealocytes 178 p rosen ceph alon 8, 226
p araplegia 43 pituitary glan d p rosopagn osia 255
p aresis an terior lobe (aden ohypophysis) 183 p seu do-depressive patien ts 257
eye m u scles 92, 93, 95 p osterior lobe (n eu rohyp ophysis) p seu do-psych op ath ic patien ts 257
flaccid 42, 67, 312 171, 178, 179, 181, 182 ptosis 94, 191
facial 111 plate p ulvin ar 76, 172, 173, 174, 174, 175
leg 297 cortical 227 p up illary con striction 10 0
spastic 41, 312 cribriform 82, 82 p up illary ligh t reflex 84, 101
stern oclein om astoid m u scle 132 qu adrigem in al 76, 76, 141 afferen t path w ay lesion s 101
trapezius m u scle 132 plegia 4 4 efferen t p ath w ay lesion s 101–102
up per lim b 42 plexus 14–15, 16 regulation 101–102
see also h em iparesis brach ial 63–64, 64, 69–70 Pu rkin je cells 160, 160, 161, 162
Parin aud syn drom e 97 lesion s 63–64 pu tam en 40, 174, 175, 178, 214, 215,
Parkin son disease 219–221 cau ses 63–64 215, 216, 217
akin etic-rigid 220–221 low er (Klu m pke p alsy) 63 pyram idal cells 203–205, 231–233
fam ilial 220, 220 u pper (Duch en n e–Erb palsy) pyram idalization 233
idiopath ic 219–220 63 pyram ids
case p resen tation 221 bu ccal 109 cerebellar 159, 161
m ixed-typ e 221 cardiac 191 m edu llary 38, 39, 40, 75, 76
trem or-dom in an t 221 carotid decu ssation 38, 39, 75, 76, 135,
Parkin son -plu s syn drom e 220 extern al 190 139
parkin son ism 219–221 in tern al 191 lesion s 42, 43
parosm ias 84 cervical 62, 63, 69
parotid glan d 114, 189 syn drom es 62
in n ervation 194 ch oroid 171, 204, 216 Q
path , perforan t 204, 205 hyp ogastric 189, 193, 199
path w ay in ferior 193 qu adran tan op sia 88, 245
au ditory 117, 118 su perior 193 qu adriparesis 43
cortico-striato-pallido-th alam o- lu m bosacral 65 qu adriplegia 43
cortical 218–219 lesion s 65–66
corticopon tocerebellar 140 lu m bar 65, 65, 70–71
dien ceph alobu lbar 129 sacral 65–66, 65, 71 R
gustatory 112, 113 ven ou s
olfactory 82–83, 83 an terior extern al spin al 284 radiation
reticu lar, descen din g 14 4 an terior in tern al spin al 284 au ditory 117, 118, 174
sym path etic, cen tral 135, 137, 142 epidural 283 callosal 238
lesion s 149, 152 posterior extern al vertebral 284 optic 173, 236, 245
visu al 84, 85 p oikiloth erm ia 184 th alam ocin gulate 203, 203
lesion s 86 p oliom yelitis 48 radicu lar lesion s 17, 18, 57–62
som atotopic organ ization 85–86 p olyn euritis 68 differen tial diagn osis 68
see also tract(s)

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radion u clide stu dies 289 Rom berg test 166 som a 3
ram u s com m u n ican s roots see n erve roots som atosen sory system
gray 190, 191 cen tral com pon en ts 24–31
w h ite 190, 191 cen tral processin g 32–34
Rath ke’s pou ch 179 S lesion s 32–34, 33
rebou n d p h en om en on 167 perip h eral com p on en ts 12–24
receptor organ s 12–14 saccadic p ursuit m ovem en ts 165 speech 249
skin 12–13, 13 saccu le 115, 120 sph in cter
recess salivary glan ds 112, 114, 189 an al 71
in fun dibu lar 171 salivation 112 extern al 198, 198
optic 171 regu lation 14 4 in tern al 198
rectu m saltatory con duction 3 pu pillae 100, 103
em ptyin g disorders 198 scala ureth ral
in n ervation 194, 198, 198 m edia 115 extern al 193, 195
Redlich –Oberstein er zon e 24 tym pan i 115, 115, 116 dysfu n ction 198
referred pain 199–20 0 vestibu li 115, 115, 116 in tern al 193, 195
reflex(es) scalen e syn drom e 63–64, 64 vesical 71
an kle-jerk 61 Sch w an n cells 3 spin al au tom atism s 50
an tagon ist m u scle relaxation 18–19, Sch w artz–Bartter syn drom e 184–185 spin al cord 45
21–22 sciatica 61–62 blood sup ply 281–283, 282, 283
biceps 23, 60 seizures arterial hypoperfu sion 312
blin k 102, 110 ep ileptic 302 im paired ven ous drain age 312–
corn eal 105 jackson ian 32–33, 42, 244 314
ligh t test 92 sella turcica 91 com p ression 52, 52
crossed exten sor 20 sen sorim otor area 32 cordotom y 32
fixation 98 sen sory con flict 124 h em orrh age 314
fligh t 19–20 sen sory deficits in farction 55, 55, 282, 312
gag 145 dissociated 31, 47 syn drom es 45–55
h em ian op ic ligh t reflex test 88 lesion s alon g som atosen sory path - an terior sp in al artery syn drom e
in trin sic 18, 23 w ays 32–34, 33 55, 55
m asseteric (jaw -jerk) 107 periph eral n erve lesion s 18, 19, 67 cau da equ in a syn drom e 53, 54,
m on osyn aptic 18, 24 radicular lesion s 17, 18 61, 62
p olysyn aptic 19–20, 20, 21 septum p ellu cidu m 171, 216 con u s syn drom e 53, 54
p roprioceptive 18 seroton in 7 epicon u s syn drom e 53, 54
p up illary ligh t reflex 84, 101 receptor 7 h em isection syn drom e 4 9–50, 49
regu lation 101–102 Sh errin gton ’s law 95 tran section syn drom es 50–53, 50
qu adriceps (kn ee-jerk) 21, 23, 61 sin gle-ph oton em ission com pu terized acute 50, 50
sn eeze 105 tom ography (SPECT) 289 cervical 53
stapediu s 110 sin u s(es) 280–281, 281 in com plete 51, 51
su ck 105–106 cavern ous 89, 281, 281 lu m bar 53
triceps 23, 60 fron tal 89 progressive 52
triceps su rae 23 occipital 280 th oracic 53
vestibu lo-ocular (VOR) 124, 165 petrosal vascu lar 56–57, 312–314
viscerocu tan eou s 20 0, 200 in ferior 281, 281 tu m ors 56–57
reflex sym p ath etic dystrophy 67 su perior 91, 281, 281 epidu ral lym ph om a 52, 52
Reissn er’s m em bran e 115, 116, 118 sagittal extradural 56, 56
release-in h ibitin g factors 183, 183 in ferior 280, 281 in tradu ral extram edullary 56–57,
releasin g factors 183, 183 su perior 261, 280, 280, 281, 303, 56
Ren sh aw cells 4 4 303 in tradu ral in tram edu llary 56, 56,
resp iration 14 4 sigm oid 280, 281 57
reticu lar form ation 31, 39, 40, 83, 122, sph en oid 89 ven ou s drain age 283, 284
127, 135, 137, 140, 143–145, 143, sph en oparietal 281 spin al sh ock 49, 50
149, 161, 163, 175 straigh t 280, 280, 281 spin ocerebellu m 159
param edian pon tin e (PPRF) 95 th rom boses 302–304 fu n ction s 165
retin a 84, 85, 87 case p resen tation 303, 303 lesion s 165–166
retin op athy 245 tran sverse 280, 280, 281 split-brain patien ts 253
retrobu lbar n euritis 86 skin spon dylarth rosis 58
retrograde tran sport 3, 4 receptors 12–13, 13 stapes 115
rh om ben ceph alon 8 segm en tal in n ervation 17 Steele–Rich ardson –Olszew ski syn -
rib 64 sen sory deficits 17–18 drom e 220
cervical 64 periph eral n erve lesion s 18, 19 Stein ert–Batten –Cursch m an n dystro-
rigidity 220 radicular lesion s 17, 18 phy 72
Rin n e test 119 sleep–w ake cycle 14 4 stereocilia 115, 116
rods 84 sn eeze reflex 105 stereogn osis 32
Rom berg sign 30, 46, 48, 49 social beh avior con trol 255–257 stereotaxy 238

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Stillin g’s n ucleu s 26 p osterolateral 76 Korsakoff 208

stratu m p recen tral 229 m edu llary
gan glion are 160 rh in al 230 dorsolateral (Wallen berg) 147,
gran ulosu m 160 tem poral 149, 150, 299
m oleculare 159–160 in ferior 229 case presen tation 150
zon ale 171 su perior 229 m edial (Dejerin e) 147, 150, 151
striae sw allow in g 14 4–145 case presen tation 151
lon gitu din al 83 sw eat glan d 104, 189 m u scle 72
lateral 202, 227 sym path ectom y 192 n erve root (radicu lar)
m edial 202, 227 syn apses 4–5 cervical root 58–59, 59, 60
m edullares 75, 76, 83, 118, 177, 181 asym m etrical 5 differen tial diagn osis 68
th alam i 84, 171 axo-axon al 6 lu m bar root 59–62, 60, 61, 62
olfactory axoden dritic 6 posterior root 46, 46
lateral 83 axosom atic 6 n eurom uscu lar ju n ction 72
m edial 82, 83 ch em ical 6 Parin au d 97
term in alis 180–181, 180, 205, 237 electrical 6 Parkin son -plus 220
striatu m 217 inp ut 6 p eriph eral n erves 67–6 8, 67
stroke 284 m otor tracts 41 p lexu s 62–67
see also in farction ; isch em ia stru ctu re 4–5, 5 brach ial 63–64, 64
su bacu te com bin ed degen eration sym m etrical 5 cau ses 63–64
(SCD) 34, 34, 47–48 syn aptic tran sm ission 5–6, 5 low er (Klu m pke palsy) 63
su barach n oid h em orrh age (SAH) 267, syn aptogen esis 8–9 up per (Du ch en n e–Erb palsy) 63
267, 307–310, 309 syn drom e(s) cervical 62, 63
diagn osis 308–309 am n estic 208–209 lu m bosacral 65–66
gradin g 308, 309 an terior h orn 4 8, 48 lu m bar 65, 65
rebleedin g 310 an terior spin al artery 55, 55 sacral 65–66, 65
su bclavian steal syn drom e 147 Balin t 255 p on tin e tegm en tum
su bdural h em atom a 311, 311 basal gan glia lesion s 219–223 caudal 148, 152
su bicu lu m 204, 205 basis pon tis oral 149, 153
su blin gu al glan d 112, 114 cau dal (Millard–Gu bler/Foville) p osterior colu m n 46–47, 46
in n ervation 194 147, 161 p osterior h orn 47, 47
su bm an dibular glan d 112, 114 m idportion 152, 154 red n ucleu s (Ben edikt) 152–153, 155
in n ervation 194 Bin g–Horton 108 scalen e 63–64, 64
su bstan ce Brow n –Séqu ard 49–50, 49, 56 sp in al cord 45–55
in n om in ate 178 carpal tu n n el 67, 68 cauda equin a syn drom e 53, 54,
perforated 279 cen tral spastic paresis 41 61, 62
an terior 83 cerebral pedu n cle (Weber) 153, 156 con u s syn drom e 53, 54
su bstan tia cerebrovascular 295–302 ep icon us syn drom e 53, 54
gelatin osa 26, 31, 135 com bin ed an terior h orn an d py- h em isection syn drom e 49–50, 49
n igra 2, 39, 40, 91, 137, 141, 142, 217, ram idal tract 48, 48 teth ered cord 197, 197
218 com bin ed involvem en t of p osterior tran section syn drom es 50–53, 50
lesion s 155, 156 colu m n s, spin ocerebellar tracts, acu te 50, 50
su bth alam u s 172, 178, 178 an d (possibly) pyram idal tracts cervical 53
su ck reflex 105–106 49, 49 in com plete 51, 51
Sudeck syn drom e 67 com bin ed posterior colu m n an d lu m bar 53
su lcu s(i) 228–229 corticosp in al tract 47–48, 48 progressive 52
an terolateral 76 com plex region al p ain 67 th oracic 53
calcarin e 85, 87, 230, 230 corticospin al tract 48–49, 48 vascular 56–57, 312–314
callosal 230 costoclavicular 63 th alam ic 176–177
cen tral 229, 230, 230 cu bital tun n el 68, 68 case presen tation 177
cin gu late 230, 230 discon n ection 253–254 vascu lar 295–302
collateral 230 olfactory system 253 syn kin esia, facial 111
fron tal visual system 253–254 syrin ges 47
in ferior 229 dorsal root gan glion 46, 46 syrin gobu lbia 47
sup erior 229 flaccid paralysis 4 4–45 syrin gom yelia 47
h ip pocam pal 230 fron tal brain 174 system
hyp oth alam ic 171 Gerstm an n 255 adren ergic 188
lateral 228, 229 glossoph aryn geal 126–127 ascen din g reticular activatin g
lu n ate 229 Graden igo 108 (ARAS) 143–14 4, 176
m edian , p osterior 76 gray m atter 47, 47 ch olin ergic 188
occipitotem poral 230 Guillain –Barré syn drom e 264 cran iosacral 188
olfactory 230 Horn er 63, 102, 104, 149, 191–192 descen din g reticu lar 190
orbital 230 causes 192 extrapyram idal 214
p arieto-occipital 229, 230, 230 hyperabdu ction 63 olfactory 81–84, 227
p ostcen tral 229 in ap propriate ADH secretion discon n ection 253
(SADH) 184–185

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system corticon uclear 38, 39, 127, 133, 133, sp in oreticu lar 31
pyram idal 214 138, 138, 139 spin otectal 25, 31, 31, 136, 137
th oracolu m bar 188 lesion s 148, 153 spin oth alam ic 138, 140, 142, 174
vagal 126–132 corticopon tin e 38, 137, 138, 156, 161, an terior 25, 26, 27, 30, 31, 136,
ven tricular 262, 262 163, 166 282
vestibu lar 120, 124 corticop on tocerebellar 39 lesion s 30, 33, 33
lesion s 124–126 corticospin al 29, 37, 38–39, 38, 40, lateral 25, 26, 27, 29, 30–31, 31,
visu al 84–88, 233 138, 138, 139, 163 106, 135, 136, 137, 139, 282
discon n ection 253 an terior 31, 38, 39, 40, 41, 138, lesion s 30–31, 33–34, 33, 149,
see also lim bic system ; n ervous 139 151, 152, 153
system lateral 31, 38, 39, 41, 138, 139, 282 sp in ovestibular 31
lesion s 148, 154 su praoptico-hypophyseal 181, 182
syn drom es of 47–4 9, 48 tectocerebellar 164
T cu n eocerebellar 165 tectospin al 31, 40, 41, 135, 137, 139–
den tatorubral 161, 163 140
tabes dorsalis 46–47 den tatoth alam ic 161, 163, 174, 174 lesion s 153
tapetum 217 den tatoth alam ocortical 166 tegm en tal
taste 111–112, 130 dorsolateral 31 cen tral 40, 135, 137, 138, 139, 161,
taste bu d 113 extrapyram idal 127 163
tectu m 75–76, 141 fastigiobulbar 160, 162 lesion s 138, 149, 152, 153
tegm en tu m fron top on tin e 37, 40, 138 tem p oropon tin e 37, 138
m idbrain 141–142 fron toth alam ic 37 th alam ocin gu late 203
pon tin e 140 h aben u loin terp edu n cu lar 83 th alam ocortical 28, 30, 161, 163
cau dal, syn drom e of 148, 152 Lissau er 31 trigem in al 77, 79, 127, 129, 137, 138,
oral, syn drom e of 149, 153 m am illotegm en tal 181, 190 139, 142
tela ch oroidea 76, 171 m am illoth alam ic 171, 174, 175, 181, trigem in oth alam ic
teleceptors 12 182, 203, 203, 216 dorsal 141
telen cep h alon 8, 226 m otor 40 ven tral 141
tem p eratu re regu lation 184 lateral 39–40 tu berohypop hyseal 181
ten din ous rin g 89 lesion s 42–43, 42 vestibu losp in al 31, 40, 41, 161, 164–
ten toriu m 260, 281 m edial 39–40 165
cerebelli 158 syn ap ses 41 lateral 121, 123
teth ered cord syn drom e 197, 197 occipitom esen ceph alic 40 m edial 122, 123
th alam ocortical reciprocity 235–236 occipitopon tin e 138 see also fascicu lus; p ath w ay
th alam u s 26, 28, 29, 33, 37, 38, 40, olfactory 82, 83, 279 tractus
161, 163, 170–177, 171, 215, 217, 218, olivocerebellar 138, 139, 161, 162, retroflexu s 181
235 163, 166 solitariu s 135, 137
blood su pply 277 olivospin al 31, 40, 41 tran sien t isch em ic attack (TIA) 284,
fu n ction s 176 optic 75, 76, 84, 85, 171, 216 290–291
in farction 209 lesion s 86–87, 88 trau m a
case presen tation 211, 211, 30 0, p arietopon tin e 138 brach ial plexu s lesion s 63
300 p arietotem p oropon tin e 40 perip h eral n erves 67
n uclei 171, 172–176, 173, 174, 175 p on tocerebellar 161, 163 trem or 220, 221
lesion s 176–177 pyram idal 37, 38–39, 38, 129, 135, in ten tion (action ) 166–167
syn drom es 176–177 137 trian gle
vascular 299 an terior 135 hypoglossal 75, 76
th erm oreceptors 12 lateral 135 of Guillain an d Mollaret 163
th oracolum bar system 188 lesion s 42, 43, 150, 151 vagal 75, 76
th rom bolysis case presen tation sign s 41 trigem in al n euralgia 107–108, 108,
basilar artery 293–294, 293, 294, syn drom es of 4 8, 48, 49, 49 302
295 reticulospin al 31, 40, 41, 122, 161, idiopath ic 107
m iddle cerebral artery 291, 292, 293 164–165 trigon e, olfactory 82
th rom boses 302–304 ru broreticu lar 142, 165 trun k
diagn osis 302–304 ru brospin al 31, 40, 41, 135, 137, 138, brach ioceph alic 271, 283
see also em boli 138, 139, 142, 161, 165 costocervical 282, 283
tic douloureux 107 sem ilu n ar 31 in ferolateral 278
ton otopy 245 spin o-olivary 25, 31, 31, 138, 161 trun k
ton sil, cerebellar 159 spin ocerebellar thyrocervical 282, 283
tract(s) an terior 25, 26–27, 26, 27, 31, 135, tu be, auditory 115
bu lboth alam ic 28 136, 137, 138, 139, 161, 164, 165 tu ber 158, 159, 161
cerebello-olivary 162 lesion s 149, 152 cin ereu m 171, 279
cerebelloreticu lar 162 lateral 25 tubercles 75
cerebelloru bral 138 posterior 25, 25, 26, 27, 31, 75, 135, cu n eate 74, 76
corticobu lbar 39 136, 137, 138, 139, 161, 162, 165 facial 75
corticom esen ceph alic 38, 39, 138 syn drom e of 49, 49 gracile 74, 76

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tuberculu m cin ereu m 75, 76 su perior rotatory 125

tum ors dorsal 279, 280 vestibu lar 124
cerebellar 167–16 8 m iddle 280 vestibular system 120, 124
Pan coast 192 th rom boses 302–304 lesion s 124–126
pitu itary 186–188 cortical 279 vestibulocerebellu m 159
case presen tation 187, 187 in tervertebral 284 fu n ction s 164–165
sp in al cord 56–57 jugular, in tern al 281 lesion s 165
du m bbell (h ou rglass) tu m ors 56, occipital, in tern al 280 vestibulu m 114
57 of th e septum pellu cidu m 280 Virch ow –Robin space 262
ep idu ral lym ph om a 52, 52 oph th alm ic visceral p ain 199
extradural 56, 56 in ferior 281 visceroceptors 12
in tradu ral, extram edullary 56–57, su perior 281 visu al system 84–88, 235
56 radicu lar discon n ection 253–254
in tram edu llary 56, 56, 57 an terior 284 vitam in B12 deficien cy 46, 47
p osterior 284 vom itin g 145
spin al
U an terior 284
p osterior 284 W
ultrason ograp hy 289 p osterolateral 284
un cus 83, 230 striate 280 Wallen berg syn drom e 147, 149, 150, 299
urin ary con tin en ce 195 su lcal 284 case p resen tation 150
see also in con tin en ce su lcocom m issu ral 284 w allerian degen eration 67
urin ary u rgen cy 196 th alam ostriate 216, 280 w ater balan ce 184–185
utricle 115, 120 vertebral 284 Weber syn drom e 153, 156
uvu la 159, 161 velu m , m edullary Weber test 119
an terior 137 Wern icke aph asia 253
su perior 76, 146, 159 case p resen tation 252–253, 252
V ven ous ou tflow obstru ction Wern icke’s area 248
acu te 302–304 in farct 252
vasodilation 191, 192 ch ron ic 304–305 w h ite m atter 235–237
vasopressin (ADH) 182, 183, 184, 185 ven tricle Wilson disease 219
vasosp asm 310 fou rth 76, 135, 262, 263 case p resen tation 224, 224
Vater–Pacin i corp uscles 12, 13–14, 13 floor 74–75, 76 w in dow
vein (s) 279–281, 280 roof 75, 135 oval 114, 115
an astom otic lateral 86, 215, 216, 227, 262, 263 rou n d 114, 115
in ferior (of Labbé) 279, 280 th ird 171, 262, 263 Wiscon sin Card Sortin g Test 257
sup erior (of Trolard) 279, 280 ven tricu lar system 262, 263 Word Flu en cy Test 257
basal (of Rosen th al) 279, 280 verm is 122, 158 w rist drop 67
basivertebral 284 in ferior 159
cen tral, posterior 284 lesion s 165
cerebral su perior 158 Z
an terior 280 vertigo 123–125
great (of Galen ) 217, 280, 280 p osition al 124–125 zon a in certa 171, 178, 178
in tern al 279, 280 ben ign paroxysm al (BPPV) 124– zon es of Head 199, 199, 20 0
m iddle 125
deep 280 cen tral 125
su perficial 279, 280 p roprioceptive 124

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tahir99-VRG & vip.persianss.ir