Axillary n. Lat. cut. Great auricular Med. cut. n.

(circumflex ) n. of forearm
rami
cut. rami of Ant. cut. n. of
Lower lat.cut. n.
of arm (from neck
radial n.) thor. n’s.
I T2 3 Supraclavicular
4 n’s.
II 5
Lat. cut. of 6
forearm III 7 Med. cut. n. of
(from
musculocut. n.) 8 arm
9 &
intercostobrachi
10 11
al n.
Ant.

12 Lat. cut. n. of thigh Dorsal n. of penis

Ilio
inguinal n.
Iliohypo Radial n. Median n.
gastric n.

Femoral branch
Genital
of genito Ulnar n.
branch of
femoral n.
genitofem. n.
(lumbo-inguinal n.)

Intermed. & med. Deep peroneal n. Lat.cut. n. of calf C5

cut. n’s. of thigh (from common (from common
(from femoral n.) peroneal n.) peroneal n.)
Scrotal branch of Lesser n. } occipital
Saphenous n. nerves Greater
(from femoral n.) perineal n. Obturator
Superficial peroneal Great auricular n.
n.
n. (from common
Ant. cut. n. of neck
peroneal n.)
T1
Med. & lat. Sural n. Axillary n. 4 n’s. Post.
plantar n’s. (from (from tibial n.) (circumflex) C6 cut.
posttibial n.) T2 3 Supraclavicular

Figure 9- permissio ries, 2nd arm (from 10 11 intercostobra

radial n.) rami of chial n.
1. The n from ed. thor. n’s.
cutaneous Haymaker Philadelp Lower
fields of W, Lat. cut. of Post. cut. n.
hia, L1
arm of forearm
peripheral Woodhall Saunders, Lat.
(from radial
5 cut.
nerves. B: 1953.) n.)
6 rami
(Reproduc Peripheral 7 Med. cut. n.
Lat. cut. n. of
8 of arm
ed by Nerve Inju forearm
Post cut. n. of 9 &
(from radial n.) S1 cut. n.
12
(from musculocut n.) Med.
Iliohypo gastric n. Post. rami of lumbar of Ulnar n.
sacral & coccygeal forearm
Inf. med. n’s. Radial n.

cluneal n. Lat. cut. n.of calf

Inf. lat.
(from common femoral n.)

cluneal n’s.
Saphenous n.
Inf. med. n. of thigh
(from femoral n.)

Superficial peroneal n.
(from common peroneal n.)

Obturator n. Sural n. (from tibial n.)

Post cut. n. of thigh
(from femoral n.)

Lat. plantar n.
Med. plantar

n. Lat.
plantar n.
Med. cut. n. of thigh Superficial
Median n. peroneal
n.
 Saphenous n. Calcanean branches

Calcanean branches of Figure 9-1. of tibial & sural n’s.

Sural n.
sural & tibial n’s.
(Continued)
C3 C6 T3 T4 T5 T6
T1 T3 T4 T5 T6 T7

T2
C4

T1
C4 T7
T2 T8
C5 T9
T2
T10
C3
T8
T9
T10 T11 T12
C5 C5
L1
C6
C6
C7 L3
C8
S1
S2

S4S5 L3

T11
T12
L1

L2

L
2
L3

L4 S3

S2
C8
L5 S1 L5
L4
L5 S1

F
i
g
u
r
e

9
-
2
.

D
i
s
t
r
i
b
u
t
i
o
n

o
f

t
h
e

s
e
n
s
o
r
y

s
p
i
n
a
l

r
o
o
t
s

o
n

t
h
e

s
u
r
f
a
c
e

o
f

t
h
e

b
o
d
y

(
d
e
r
m
a
t
o
m
e
s
)
.

(
R
e
p
r
o
d
u
c
e
d

b
y

p
e
r
m
i
s
s
i
o
n

f
r
o
m

S
i
n
c
 l
a
i
r
.
)

Adams and Victor’s

P
R
I
N
C
I
P
L
E
S
O
F
N
E
U
R
 O
L
O
G
N
Y
O
T
I
C
E

Medi
cine
is an
ever-
chan
ging
scien
ce.
As
new
resea
rch
and
clinic
al
expe
rienc
e
broa
den
our
kno
wled
ge,
chan
ges
in
treat
ment
and
drug
thera
py
are
requi
red.
The
auth
ors
and
the
publi
sher
of
this
work
have
chec
ked
with
sour
ces
belie
ved
to be
relia
ble
in
their
effort
s to
provi
de
infor
mati
on
that
is
com
plete
and
gene
rally
in
accor
d
with
the
stan
dard
s
acce
pted
at
the
time
of
publi
catio
n.
How
ever,
in
view
of
the
possi
bility
of
hum
an
error
or
chan
ges
in
medi
cal
scien
ces,
neith
er
the
auth
ors
nor
the
publi
sher
nor
any
other
party
who
has
been
invol
ved
in
the
prep
arati
on or
publi
ca
tion
of
this
work
warr
ants
that
the
infor
mati
on
conta
ined
herei
n is
in
ever
y
respe
ct
accur
ate
or
com
plete
, and
they
discl
aim
all
resp
onsib
ility
for
any
error
s or
omis
sions
or
for
the
resul
ts
obtai
ned
from
use
of
the
infor
mati
on
conta
ined
in
this
work
.
Read
ers
are
enco
urag
ed to
confi
rm
the
infor
mati
on
conta
ined
herei
n
with
other
sour
ces.
For
exam
ple
and
in
parti
cular
,
read
ers
are
advis
ed to
chec
k the
prod
uct
infor
mati
on
sheet
inclu
ded
in
the
pack
age
of
each
drug
they
plan
to
admi
niste
r to
be
certa
in
that
the
infor
mati
on
conta
ined
in
this
work
is
accur
ate
and
that
chan
ges
have
not
been
mad
e in
the
reco
mme
nded
dose
or in
the
contr
aindi
catio
ns
for
admi
nistr
ation
.
This
reco
mme
ndati
on is
of
parti
cular
impo
rtanc
 e in
conn
ectio
n
with
new
or
infre
quen
tly
used
drug
s.

Adams and Victor’s

PRINCIPLE
S OF
N
E
U
R
O
L
 O
G
Y
NINTH
EDITION

Allan H.
Ropper,
MD
Profe
ssor
of
Neuro
logy
Harvar
d
Medic
al
School
Executive Vice
Chair of
Neurology
Brigham and
Women’s
Hospital
Bosto
n,
Mass
achus
etts

Martin A.
Samuels, MD,
FAAN, MACP,
DSc (Hon)
C
ha
 ir
m
an
Departm
ent of
Neurolo
gy
Brigham and
Women’s
Hospital
Profe
ssor
of
Neuro
logy
Harvar
d
Medic
al
School
Bosto
n,
Mass
achus
etts

New York Chicago San Francisco Lisbon

London Madrid Mexico City
Milan New Delhi San Juan Seoul
Singapore Sydney Toronto

Copyright © 2009, 2005, 2001, 1997, 1993, 1989, 1985, 1981,

1977 by The McGraw-Hill Companies, Inc. All rights reserved.
Except as permitted under the United States Copyright Act of
1976, no part of this publication may be reproduced or
distributed in any form or by any means, or stored in a database
or retrieval system, without the prior written permission of the
publisher.

ISBN: 978-0-07-170281-2

MHID: 0-07-170281-4

The material in this eBook also appears in the print version of this
title: ISBN: 978-0-07-149992-7, MHID: 0-07-149992-X.
 All trademarks are trademarks of their respective owners. Rather
than put a trademark symbol after every occurrence of a
trademarked name, we use names in an editorial fashion only,
and to the benefi t of the trademark owner, with no intention of
infringement of the trademark. Where such designations appear
in this book, they have been printed with initial caps.

McGraw-Hill eBooks are available at special quantity discounts

to use as premiums and sales promotions, or for use in corporate
training programs. To contact a representative please e-mail us
at bulksales@mcgraw-hill.com.

TERMS OF USE

This is a copyrighted work and The McGraw-Hill Companies,

Inc. (“McGrawHill”) and its licensors reserve all rights in and to
the work. Use of this work is subject to these terms. Except as
permitted under the Copyright Act of 1976 and the right to store
and retrieve one copy of the work, you may not decompile,
disassemble, reverse engineer, reproduce, modify, create
derivative works based upon, transmit, distribute, disseminate,
sell, publish or sublicense the work or any part of it without
McGraw-Hill’s prior consent. You may use the work for your
own noncommercial and personal use; any other use of the work
is strictly prohibited. Your right to use the work may be
terminated if you fail to comply with these terms.

THE WORK IS PROVIDED “AS IS.” McGRAW-HILL AND

ITS LICENSORS MAKE NO GUARANTEES OR
WARRANTIES AS TO THE ACCURACY, ADEQUACY OR
COMPLETENESS OF OR RESULTS TO BE OBTAINED
FROM USING THE WORK, INCLUDING ANY
INFORMATION THAT CAN BE ACCESSED THROUGH
THE WORK VIA HYPERLINK OR OTHERWISE, AND
EXPRESSLY DISCLAIM ANY WARRANTY, EXPRESS OR
IMPLIED, INCLUDING BUT NOT LIMITED TO IMPLIED
WARRANTIES OF MERCHANTABILITY OR FITNESS FOR
A PARTICULAR PURPOSE. McGraw-Hill and its licensors do
not warrant or guarantee that the functions contained in the work
will meet your requirements or that its operation will be
uninterrupted or error free. Neither McGraw-Hill nor its licensors
shall be liable to you or anyone else for any inaccuracy, error or
omission, regardless of cause, in the work or for any damages
resulting therefrom. McGraw-Hill has no responsibility for the
content of any information accessed through the work. Under no
circumstances shall McGraw-Hill and/or its licensors be liable
for any indirect, incidental, special, punitive, consequential or
similar damages that result from the use of or inability to use the
work, even if any of them has been advised of the possibility of
such damages. This limitation of liability shall apply to any
claim or cause whatsoever whether such claim or cause arises in
contract, tort or otherwise.

International Disease, 3
Advisory Board, vii 2
Preface, ix Speci
al
PART 1: THE Tech
CLINICAL nique
METHOD s for
OF Neuro
NEUROLOG logic
Y, 1 Diagn
1 Approach to osis,
the Patient 13
with PART 2:
Neurologic CARDINAL
MANIFESTATI and
ONS OF Taste,
NEUROLOGIC 216 13
DISEASE, 39 Disturba
nces of
SECTION 1Disorders Vision,
of Motility, 41 225
14
3 Motor Paralysis, 43 Disord
4 Abnormalities ers of
of Movement Ocular
and Posture Move
Caused by ment
Disease of the and
Basal Ganglia, Pupilla
61 5 ry
Incoordination Functi
and Other on,
Disorders of 248
Cerebellar 15 Deafness,
Function, 78 Dizzines
6 Tremor, s, and
Myoclon Disorder
us, s of
Focal Equilibriu
Dystonia m, 276
s, and
Tics, 89 SECTION 4
7 Disorders of Stance Epilepsy
and Gait, 111 and
Disorders
SECTION 2
Pain of
and Other Conscious
Disorders of ness, 303
Somatic
Sensation, 16 Epilepsy and
Headache, Other Seizure
and Disorders, 304
17 Coma and
Backache, Related
123 Disorders of
Consciousness, 339
8 Pain, 124
18 Faintness and
9 Other Somatic
Syncope, 362
Sensation, 145
19 Sleep and Its
10 Headache and
Abnormalities, 374
Other Craniofacial
Pains, 162 11 Pain
in the Back, Neck, Content
s
and Extremities,
189

SECTION 3
Disorder
s of the SECTION 5
Special Derangements of
Senses, Intellect,
215 Behavior, and
Language Caused
12
Disorder
by Diffuse and
s of Focal Cerebral
Smell Disease, 397
 20 Delirium PART 3:
and Other GROWTH AND
Acute DEVELOPMENT
Confusion OF THE
al States, NERVOUS
398 SYSTEM AND
21 Dementia and the
Amnesic
THE
(Korsakoff) NEUROLOGY
Syndrome with OF AGING, 549
Comments on 28 Normal
the Neurology of Development
Intelligence and and Deviations
Memory, 410 in Development
22 Neurologic of the Nervous
Disorders Caused System, 551 29
by Lesions in The Neurology
Specific Parts of of Aging, 580
the Cerebrum, 430
23 Disorders of PART 4:
Speech and MAJOR
Language, 461 CATEGO
RIES OF
SECTION 6
Disorders NEUROL
OGIC
of Energy,
DISEASE,
Mood, and
589
Autonomic
and 30 Disturbances of
Endocrine Cerebrospinal Fluid
Functions, and Its Circulation,
481 Including
Hydrocephalus,
24 Fatigue, Pseudotumo
Asthenia, r Cerebri,
Anxiety, and and Low-
Depressive Pressure
Reactions, 482 Syndromes,
25 The 591
Limbic 31 Intracranial
Lobes Neoplasms
and the and
Neurolo Paraneoplastic
gy of Disorders, 612
Emotion, 32 Infections of the
493 Nervous System
26 Disorders of the (Bacterial, Fungal,
Autonomic Spirochetal,
Nervous System, Parasitic) and
Respiration, and Sarcoidosis, 667
Swallowing, 505 33 Viral Infections
27 The of the Nervous
Hypothalam System, Chronic
us and Meningitis, and
Neuroendoc Prion Diseases,
rine 711 34
Disorders, Cerebrovascular
536 Diseases, 746
35 Craniocerebral
Trauma, 846

v
vi Contents 36 Multiple
 Sclerosis and Aids in the
Allied Diagnosis of
Demyelinating Neuromuscular
Diseases, 874 Disease, 1231
37 Inherited 46 Diseases
Metabolic of the
Diseases of the Peripheral
Nervous Nerves, 1251
System, 904 47 Diseases
38 of the Cranial
Developme Nerves, 1326
ntal
Diseases of
the
Nervous 48 Principles of
System, Clinical Myology:
960 Diagnosis and
39 Classification of
Degenera Diseases of
tive Muscle and
Diseases Neuromuscular
of the Junction, 1341
Nervous 49 The Infectious and
System, Inflammatory
1011 Myopathies, 1353
40 The Acquired 50 The Muscular
Metabolic Dystrophies, 1366
Disorders of 51 The Metabolic
the and Toxic
Nervous Myopathies, 1384
System, 52 The
1081 Congenital
41 Diseases of the Neuromuscular
Nervous Disorders, 1398
System 53 Myasthenia
Caused by Gravis and Related
Nutritional Disorders of the
Deficiency, Neuromuscular
1108 Junction, 1405
42 Alcohol and 54 Ion Channel
Alcoholism, 1131 Disorders: The
43 Disorders of Periodic
the Nervous Paralyses and
System Hereditary
Caused by Nondystrophic
Drugs, Myotonias
Toxins, and (Channelopathies)
Other , 1422
Chemical 55 Disorders of
Agents, 1145 Muscle
Characterized by
PART 5: Cramp, Spasm,
DISEASES OF Pain, and Localized
SPINAL CORD, Masses, 1434
PERIPHERAL
NERVE, AND PART 6:
MUSCLE, 1179 PSYCHIATRIC
44 Diseases of the
DISORDERS, 1445
Spinal Cord, 1181 56 The
45 Anxiety
Electrophysiolo Neuroses,
gic and Hysteria,
Laboratory and
 Personality Schizophrenias and
Disorders, Paranoid States,
1447 1478
57 Depression and
Bipolar Disease, 1466 Index, 1495
58 The

International
Advisory Board

Lisa James
DeAngelis Lance
United States Australia

Roland Elio
Eastman South Lugaresi
Africa Italy

Werner Bihm
Hacke Singhal
Germany India

Jun Kimura Jaime

Japan Toro
Columbia
 vii
This page
intentiona
lly left
blank

Neurology is the broad asked his highly

field of clinical study of regarded young col
the ner vous system. As league Maurice Victor to
a profession, it is a round out the
highly enjoyable manuscript over the
endeavor that is a following year. Adams
constant source of and Victor attracted
professional and per considerable attention by
sonal enrichment. initiating a new style of
Through Principles of pedagogy that empha
Neurology we have the sized the basic principles
privilege of continuing a of neurology before
tradition established 35 introducing the disease
years ago by our entities.
esteemed teachers Dr. While the enormous
Raymond D. Adams and advances in imaging,
Dr. Maurice Victor. Our genetics, molecular
friend and colleague, Dr. biology, and
Robert Brown, ably pharmacology have
participated in the improved our capacity to
eighth edition, adding diagnose and treat
his expertise in the disorders of the nervous
neurosciences, much to system, they have not
our benefit and that of reduced the necessity to
the book. understand certain basic
Principles of principles of anatomy
Neurology originated and physiology, to
from the chapters on obtain the correct
neurological diseases in history, perform a
the first several editions capable neurological
of Harrison’s Principles of examination and to
Internal Medicine. The cohere them based on a
continued expansion of body of clini cal
these sections by Adams knowledge and
and Victor, despite experience. We continue
repeated com mitments the original structure of
to shortening them, led the book, re-affirming
an exasperated Tinsley that comprehensive
Harrison to exclaim to knowledge of clinical
Dr. Adams “…. we’ll neurology is required to
have to change the name meet the challenge of
of the book to Principles this sophisticated
of Internal Medicine and specialty. We have also
Details of Neurology.” maintained personal
Ray Adams wrote the authorship with the
entire first edi tion of the hope that a sin gle voice
book in longhand during will allow the reader to
his summer vacation of enjoy the experience of
1975 in Lausanne and learning the field from
two longtime manifestations in each
practitioners in a manner patient. A case in point is
similar to the way we the large number of
learned it from the previously inexplicable
original authors and de generative diseases
their colleagues. that have yielded to
In taking the scientific under standing
responsibility of revising on the levels of
this book, we pathology, genetics,
acknowledge that subcellular mechanisms,
pedagogy in medicine and neurochemistry. At
has changed enormously the same time, thera
to accommodate peutic advances often
technical advances, precede basic
particu larly those in understanding of dis
imaging. However, ease and the neurologist
certain principles seem has the duty to provide
immutable and they the best possible
derive from the treatment at the time,
traditional principles, even if science has not
virtues, and logic of pro vided a full
medicine that dominate explanation or
neurological thinking. mechanism. Examples
Clinical neurology, being abound; we have an
an applied science, incomplete
depends on a set of understanding of
heuristics that direct the epilepsy, Parkin son
clinician to the best disease and multiple
diagnosis and sclerosis but many
therapeutic plan. This reasonably ef fective
book pro vides an treatments have been
exposition of clinical devised. While the
material in an order that neurosciences are the
should allow the reader instruments of advance
to obtain a in under standing
comprehensive view of disease, the work of
the field and at the same clinical neurology is
time appreciate the full more pragmatic, yet it
breadth and depth of retains its own form of
each disease of the scholarship. Neu rology
nervous tissue. is not simply a trade in

Preface
relation to the sciences.
Dif ficulty in mastering
neurology derives from a
need to combine
considerable knowledge
At the same time we and personal experience
have written the with special skills of
chapters on major observation and
diseases in a manner that disciplined thinking.
allows the book to be Our goal is to present an
used as a reference in assemblage of clinical
depth. knowl edge, and we
hope wisdom, rather
Certainly, advances in
neuroscience inform than disembodied facts.
one’s per spective on the The book contains
nature of disease and information that should
produce a fuller ap be the property of the
preciation of the well-educated physician
 at all levels, in cluding epilepsy, movement
the medical student, disorders, sleep,
resident, practitioner neuromuscular disease,
and ac ademic physician. multiple sclerosis, pain
The neurologist stands at and headache,
the nexus of the study of otoneurology, neuro-
the nervous system and ophthalmology,
includes many as pects cognitive and behavioral
of general medicine, neurology, critical care
psychiatry, neurology, spinal
neurosurgery, pain disorders, neuro-
management, infectious diseases,
rehabilitation, cancer neurology, and
ophthalmology, pediatric neurology. Yet,
otolaryngol ogy, there is a need for all
anesthesiology, critical clinicians, including the
care and emergency subspecialist, to
medicine and Neurology maintain a
serves as Medicine’s comprehensive
spokesperson to soci ety understanding of the
on matters such as major categories of
mental capability, neurological dis eases.
learning and teaching, We respect and
aging and the brain, commend the
death, and disability. community practi tioner
There fore the breadth of who by necessity
Neurology has directed maintains a broad gauge
the liberal in clusion of view of the field and we
material in the book. write with them in mind.
Neurology, like We thank our many
internal medicine, has colleagues who
become increas ingly reviewed chapters and
subspecialized. Modern suggested alterations or
departments of additions. Several
neurology include readers
divisions of stroke,

ix
x Preface We thank Anne Sydor of
McGraw Hill for her
publishing expertise and
made invaluable for promoting the goals
contributions: Roland of the book.
Eastman, Anthony
This ninth edition
Amato, Edward introduces as an author a
Bromfield, James Lance, consummate neurologic
Marc Dinkin, Jun clinician and teacher, Dr.
Kimura, Jaime Toro, Elio Martin A. Samuels.
Lugaresi, and Werner Marty brings
Hacke. We are indebted intelligence, style and
to Susan Pioli for her accessibility to Neurol
superb editorial skills, ogy and particularly to
Desi Allevato of its interface with Internal
Silverchair for her Medicine. His
compositing efforts, and thoughtfulness and
Kim Davis of McGraw- clinical experience
Hill for her efficient extends to all aspects of
work as our clinical material, and his
developmental editor. exceptional teaching
skills have been used to mously talented
full extent in updating colleagues such as C.
the text. It has been a Miller Fisher and E.P.
pleasure for us to Richardson, among
challenge each other in many others of that time,
consid ering the needs of reflected an
our clinician colleagues unpretentious self-
during the pro cess of confidence, flexibility of
rewriting the text. mind, and mas tery that
We are, of course, derived enjoyment from
products of our exposure the brightness around
to influential if not him. He read widely in
charismatic teachers. neurology, medicine,
Raymond D. Adams was and literature (in several
the progenitor of several languages; he often
generations of influential reminded us by
neurolo gists. He providing articles that
inculcated a method for were beyond our
approaching personal reach) and was
complicated always ready to
neurological problems in incorporate the modern
a manageable way. advances in sci ence into
Observing his analysis of his thinking. His
a patient’s problem gave hundreds of residents
students the impres wished to model
themselves after him not
because of personal sua
sion or celebrity but
sion of remarkable ease because of a genuine
and fluidity reminiscent admiration for his
of watch ing a gifted intellect and intensely
artist or musician. Dr. cultivated clinical skills.
Adams knew the field so In tribute to Dr. Adams
well and thought so this ninth edition,
critically, based in large published soon after his
part on his experience death, serves as
with neuropathology, recognition of his lasting
that he allowed all of his accomplishments from
residents to believe that his grateful students.
they too, could and
should aspire to Allan H. Ropper, MD
excellence. His Martin A. Samuels, MD
encouragement and Boston, March 2009
cultivation of enor
 R
a
y
m
o
n
d

D
.

A
d
a
m
s

1
9
1
1
–
2
0
0
8

PART 1
THE
C
 LI
NI
C
A
L
M
E
T
H
O
D
O
F
N
E
U
R
O
L
O
G
Y
This page
intentiona
lly left
blank
 1
Approach
to
th
e
P
at
ie
nt
w
it
h
N
e
ur
ol
o
gi
c
D
is
e
a
s
e
Neurology is regarded method. Without a full
by many as one of the appreciation of this
most diffi cult and method, the student is
exacting medical virtually as helpless with
specialties. Students and a new clinical problem
resi dents who come to a as a botanist or chemist
neurology service for the who would undertake a
first time may be easily research problem
discouraged, and may without understanding
already be intimi dated the steps in the scientific
by the complexity of the method. Even the
nervous system through experienced neu rologist
their brief contact with faced with a complex
neuroanatomy, clinical problem depends
neurophysiology, on this basic approach.
neuropathology, The importance of the
neurogenetics, and cell clinical method stands
biology. The rit ual they out more clearly in the
then witness of putting study of neurologic
the patient through a disease than in certain
series of maneuvers other fields of medicine.
designed to evoke In most cases, the clinical
certain mysterious signs method consists of an
is hardly reassuring; in orderly series of steps, as
fact, the procedure often follows:
appears to conceal the
1. The symptoms and
intellectual processes by
signs are secured by
which neurologic
history and physical
diagnosis is made.
examination.
Moreover, the students
2. The symptoms and
have had little or no
physical signs
experience with the
considered relevant
many special tests used
to the problem at
in neurologic diagnosis
hand are interpreted
—such as lumbar punc
in terms of
ture, EMG
physiology and
(electromyography),
anatomy—that is,
electroencephalography,
one identifies the
CT, MRI, and other
disorder(s) of
imaging procedures—
function and the
nor do they know how
anatomic
to interpret the results of
structure(s) that are
such tests. Neurology
implicated.
textbooks only confirm
3. These analyses
their fears as they read
permit the physician
the detailed accounts of
to localize the
the many rare diseases
disease process, i.e.,
of the nervous system.
to name the part or
The authors believe
parts of the nervous
that many of the
system involved.
difficulties in com
This step is called
prehending neurology
anatomic,
can be overcome by
or topographic,
adhering to the basic
diagnosis. Often one
principles of clinical
recognizes a char
medicine. First and fore
acteristic clustering
most, it is necessary to
of symptoms and
learn and acquire facility
signs, constitut ing a
in the use of the clinical
syndrome of
 anatomic, practiced so as to
physiologic, or avoid the common
temporal type. The pitfall of retaining
formulation and an initially incorrect
aggregation of impression and
symptoms and signs selectively ignoring
in cohesive terms is data that would
particularly helpful bring it into ques
in ascertaining the tion. It is perhaps
locus and nature of not surprising that
the disease. This the method of
step is called successive
syndromic diagnosis estimations works
and is often con well in that evidence
ducted in parallel from neuroscience
with anatomic reveals that this is
diagnosis. the mechanism that
4. From the anatomic the nervous system
diagnosis and other uses to process
medical data— information.
particularly the 5. Finally, the physician
mode and speed of should assess the
onset, evolution, and degree of dis ability
course of the illness, and determine
the involvement of whether it is
nonneuro logic temporary or per
organ systems, the manent (functional
relevant past and diagnosis); this is
family histo ries, and important in
the laboratory managing the
findings—one patient’s illness and
deduces the judging the poten
pathologic diagnosis tial for restoration of
and, when the function.
mechanism and cau
All of these steps are
sation of the disease
undertaken in the service of
can be determined,
effective treatment, an
the etiologic diagnosis.
ever-increasing prospect
This may include the
in neurology. As is
rapidly increasing
emphasized repeatedly
num ber of
in later sections, there is
molecular and
always a premium in the
genetic etiologies if
diagnostic process on the
they have been
discovery of treatable
determined for a
diseases, but even when
particular process.
specific treatment is not
Expert diag
available, accurate
nosticians often
diagnosis may, in its
make successively
own right, func tion as a
more accurate esti
therapy, as uncertainty
mates of the likely
about the cause of a neu
diagnosis, utilizing
rologic illness may be
pieces of the history
more troubling to the
and findings on the
patient than the disease
examination to
itself.
either fur ther refine
Figure 1-1, a
or exclude specific
procedural diagram by
diseases. Flexibility
which the clinical
of thought must be
problem is solved in a
 series of sequential finite steps,

3
4 Part 1 THE CLINICAL METHOD OF
NEUROLOGY

Syndromic diagnosis

Mode of onset

Elicitation examinati physiolog localizatio hic data

of clinical on y and n of the
facts anatomy lesion Appropria
Interpreta te lab
By history and
tion of Syndromi course tests
symptom c
Pathologi
s and formulatio Other
By
signs in n medical c or
neurologi and etiologic
terms of and
c demograp diagnosis

Figure 1-1. Steps in the diagnosis of neurologic disease. The

clinician proceeds from left to right in order to make a
diagnosis.

summarizes the once apparent. In other

foregoing approach to
the diagnosis of
neurologic disease. This
systematic approach,
allowing the confident
localization and often
precise diagnosis of
disease, is one of the
intellectual attractions of
neurology.
Of course, the solution
to a clinical problem
need not always be
schematized in this way.
The clinical method
offers a much wider
choice in the order and
manner by which
information is collected
and interpreted. In fact,
in some cases, adherence
to a formal scheme is not
necessary at all. In
relation to the
aforementioned
syndromic diagno sis,
the clinical picture of
Parkinson disease, for
example, is usually so
characteristic that the
nature of the illness is at
cases it is not necessary
to carry the clinical
analysis beyond the
stage of the anatomic
diagno sis, which, in
itself, may virtually
indicate the cause of a
disease. For example,
when vertigo, cerebellar
ataxia, a unilateral
Horner syndrome,
paralysis of a vocal cord,
and analgesia of the face
of acute onset are
combined with loss of
pain and temperature
sensation in the opposite
arm, trunk, and leg, the
cause is an occlusion of
the vertebral artery,
because all the involved
structures lie in the
lateral medulla, within
the territory of this
artery. Thus, the ana
tomic diagnosis
determines and limits
the etiologic possi
bilities. If the signs point
to disease of the
peripheral nerves, it is
usually not necessary to an etiologic diagnosis
consider the causes of without knowing
disease of the spinal whether the disease
cord. Some signs involved the lungs,
themselves are almost stomach, or kidneys.
specific—e.g., Ascertaining the cause of
opsoclonus for a clinical syndrome
paraneoplastic cere (etiologic diagnosis)
bellar degeneration and requires knowledge of
Argyll Robertson pupils an entirely different
for neuro syphilitic or order. Here one must be
diabetic oculomotor conversant with the
neuropathy. clinical details, including
Nonetheless, one is the mode of onset,
cautious in calling any course, and natural
single sign history of a multiplicity
pathognomonic as of diseases. Many of
exceptions are found these facts are well
regularly. known and form the
The experienced substance of later
clinician acquires the chapters. When
habit of attempt ing to confronted with a con
categorize every case in stellation of clinical
terms of a characteristic features that do not lend
fea ture, or a syndrome. themselves to a simple or
One must always keep in sequential analysis, one
mind that syndromes are resorts to consider ing
not disease entities but the broad classical
rather abstractions set up division of diseases in all
by clinicians to facilitate branches of medicine, as
diagnosis. For example, summarized in Table 1-1.
the symptom complex of Irrespective of the
right–left confusion and intellectual process that
inability to write, one utilizes in solving a
calculate, and identify particular clinical
individual fingers consti problem, the
tutes the so-called fundamental steps in
Gerstmann syndrome, diagnosis always involve
recognition of which the accurate elicitation of
determines the anatomic symptoms and signs and
locus of the disease their correct
(region of the left interpretation in terms of
angular gyrus) and at disordered function of
the same time nar rows the nervous system.
the range of possible Most often when there is
etiologic factors. uncertainty or
In the initial analysis disagreement as to
of a neurologic disorder, diagnosis, it is found
anatomic localization later that the symptoms
takes precedence over or signs were incorrectly
etiologic diagnosis. To interpreted in the first
seek the cause of a place. Thus, if a
disease of the nervous complaint of dizziness is
system without first identified as vertigo
ascertaining the parts or instead of light-
structures that are headedness or if partial
affected would be continuous epilepsy is
analogous in internal mis taken for an
medicine to attempting extrapyramidal
 movement disorder such Genetic–congenital
as tremor or Traumatic
choreoathetosis, then the Degenerative
clinical method is Vascular
Toxic
Metabolic
Inherited
Table 1-1 Acquired
Neoplastic
THE MAJOR
CATEGORIES OF Inflammatory–immune
NEUROLOGIC DISEASE Psychogenic
Iatrogenic
Infectious
CHAPTER 1 Approach to the Patient with Neurologic
Disease 5

derailed from thelogic case.

beginning. Repeated Table 1-3
examinations may be APPROXIMATE
necessary to establish the ORDER OF
fundamental clinical INCIDENCE AND
PREVALENCE OF
findings beyond doubt. NEUROLOGIC
Hence the aphorism: A CONDITIONS IN A
second examina tion is the GENERAL PRACTICE
IN THE UNITED
most helpful diagnostic KINGDOM
test in a difficult neuro
INCIDENCE IN GENERAL PREVALENCE IN THE
PRACTICE COMMUNITY

PREVALENCE AND Carpal tunnel syndrome

Chronic tension
INCIDENCE headache Epilepsy
OF NEUROLOGIC Stroke
DISEASE Bell’s palsy
Alzheimer
disease Essential
To offer the physician the tremor Epilepsy
broadest perspective on Parkinson
the rela tive frequency of disease
neurologic diseases, our Essential tremor
Brain tumor
estimates of
Multiple
Stroke (all types) sclerosis
Migraine
their approximate several sources, (especially in
Scotland)
prevalence in the including the
Chronic fatigue
United States, NIH, are given in syndrome Parkinson
taken from Multiple sclerosis disease

Table 1-2. Donaghy and Table 1-3. More focused

colleagues have
provided a simi lar but
more extensive listing of
the incidence of various
neurologic diseases that
are likely to be seen by a
general physician
practicing in the United
Kingdom. They note
stroke as far and away
the most commonly
encountered condition;
those that follow in
frequency are listed in
surveys, such as the one
con ducted by Hirtz and
colleagues, give similar
rates of prev alence, with
migraine, epilepsy, and
multiple sclerosis being
the most common
neurologic disease in the
general population (121,
7.1, and 0.9 per 1,000
persons in a year);
stroke, traumatic brain
injury, and spinal injury
occurring in 183, 101,
and 4.5 per 100,000 per Unexplained motor
symptoms Migraine
year; and Alzheimer
Neurofibromatosis
disease, Parkinson Unexplained motor
disease, and symptoms Myasthenia
amyotrophic lateral scle gravis Trigeminal
rosis (ALS) among older neuralgia
individuals at rates of 67, Source: Adapted from
9.5, and 1.6 per 100,000 Donaghy and
yearly. Data such as colleagues: Brain’s
Diseases of the
these assist in guiding
Nervous System.
societal resources to the
cure of various
conditions, but they are somewhat less
helpful in leading the
physician to the correct
Table 1-2
diagnosis except insofar
RELATIVE
PREVALENCE OF THE
as they emphasize the
MAJOR NEUROLOGIC oft-stated dictum that
DISORDERS IN THE “common conditions
UNITED STATES
occur com monly” and
APPROXIMATE therefore should be
PREVALENCE
considered a priori to be
Degenerative diseases more likely diagnoses
Amyotrophic (see discussion, further
lateral sclerosis 5 ⋅
4 on under “Shortcomings
10 Huntington
of the Clinical Method”).
disease 5 ⋅ 10
4

Parkinson disease 5
⋅ 106 Alzheimer TAKING THE
disease 5 ⋅ 10
6
HISTORY
Macular
degeneration 5 ⋅
7 In neurology, more than
10 Autoimmune
neurologic diseases any other specialty, the
Multiple physician is dependent
sclerosis 4 ⋅ 10
5
upon the cooperation of
Stroke, all types 5 ⋅ the patient for a reli able
6
10 Central history, especially for a
nervous system description of those
trauma
symp toms that are
Head 2 ⋅ 10
6
unaccompanied by
Spinal cord 2.5 ⋅ 10
5
observable signs of
Metabolic
Diabetic
disease. If the symptoms
retinopathy 2 ⋅ 10
6 are in the sensory
Headache 3 ⋅ 10
7 sphere, only the patient
can tell what he* sees,
Epilepsy 3 ⋅
6
10
hears, or feels. The first
Back pain 5 ⋅
7
10
Peripheral step in the clinical
neuropathy encounter is to enlist the
Total 2.5 ⋅ 10
7 patient’s trust and
4 cooperation and make
Inherited 10
Diabetic neuropathy him realize the
2 ⋅ 10 Mental
6
importance of the history
retardation and examination
6
Severe 10 procedure.
7
Moderate 10 The practice of making
Schizophrenia 3 ⋅ notes at the bedside or in
6
10 Manic the office is particularly
depressive illness 3
recommended.
⋅ 106
Immediate recording of
Giant cell arteritis
 the history assures dizziness, imbalance,
maximal reliability. Of or vertigo. The
course, no matter how patient who is given
reliable the history to highly
appears to be, circumstantial and
verification of the rambling accounts
patient’s account by a can be kept on the
knowledgeable and subject of his ill ness
objective informant is by directive
always desirable. questions that draw
The following points out essential points.
about taking the 2. The setting in which
neurologic his tory the illness occurred,
deserve further its mode of onset
comment: and evolution, and
its course are of para
1. Special care must be
mount importance.
taken to avoid
One must attempt to
suggesting to the
learn pre cisely how
patient the
each symptom
symptoms that one
began and
seeks. Errors and
progressed. Often
inconsistencies in
the nature of the
the recorded history
disease process can
are as often the fault
be decided from
of the physician as
these data alone. If
of the patient. The
such information
patient should be
cannot be supplied
discouraged from
by the patient or his
framing his
family, it may be
symptom(s) in terms
necessary to judge
of a diagnosis that
the course of the
he may have heard;
illness by what the
rather,
patient was able to
do at different times
*Throughout this text we
(e.g., how far he
follow the traditional
could walk, when he
English prac tice of using
could no longer
the pronoun he, his, or
negotiate stairs or
him in the generic sense
carry on his usual
whenever it is not
work) or by changes
intended to designate the
in the clinical
sex of a specific
findings between
individual.
successive
6 Part 1 THE CLINICAL examinations.
METHOD OF NEUROLOGY
3. As neurologic
diseases often
he should be urged impair mental
to give as accurate a function, it is
description of the necessary in every
symptom as possible patient who might
—being asked, for have cere bral
example, to choose a disease, for the
single word that best physician to decide
describes his pain whether the patient
and to describe is competent to give
precisely what he a history of the
means by a particu illness. If the
lar term, such as patient’s powers of
 attention, memory, only to dis cover later
and coher ence of that these flaws in
thinking are memory were the
inadequate, the essential features of the
history must be illness. Asking the
obtained from a patient to give his own
spouse, relative, interpretation of the
friend, or employer. possible meaning of
Also, illnesses that symptoms may
are characterized by sometimes expose
seizures or other unnatural concern,
forms of episodic anxiety, suspicious ness,
confusion abolish or or even delusional
impair the patient’s thinking. Young
memory of events physicians and students
occurring during also have a natural
these episodes. In tendency to “normalize”
general, one tends to the patient, often
be careless in collaborating with a
estimating the hopeful family in the
mental capacities of misperception that no
patients. Attempts real problem exists. This
are sometimes made attempt at sympathy
to take histories does not serve the
from patients who patient and may delay
are cognitively the diagnosis of a
impaired or so potentially treatable
confused that they disease.
have no idea why
they are in a doctor’s
office or a hospital.
One then generally
proceeds from an
THE NEUROLOGIC examination of the
EXAMINATION cranial nerves, neck, and
trunk to the testing of
The neurologic motor, reflex, and
examination begins with sensory functions of the
observations of the upper and lower limbs.
patient while the history This is followed by an
is being obtained. The assessment of the
manner in which the function of sphinc ters
patient tells the story of and the autonomic
his illness may betray nervous system and
confusion or incoherence testing for meningeal
in thinking, impairment irritation by examining
of mem ory or judgment, the suppleness of the
or difficulty in neck and spine. Gait and
comprehending or station (standing
express ing ideas. The position) should be
physician should learn to observed before or after
obtain this type of the rest of the
information without examination.
embarrassment to the When an abnormal
patient. A com mon error finding is detected,
is to pass lightly over whether cogni tive,
inconsistencies in history motor, or sensory, it
and inaccuracies about becomes necessary to
dates and symptoms, analyze the problem in a
more elaborate fashion.
Details of these more seeking treatment for a
extensive examinations simple compression
are to be found in palsy of an ulnar nerve is
appropriate chapters of pointless and
the book (motor: Chaps. uneconomical. The
3, 4, and 5; sensory: examination must also
Chaps. 8 and 9; and be modified according to
cognitive and language the condition of the
disorders: Chaps. 22 and patient. Obviously,
23). many parts of the
The neurologic examination cannot be
examination is ideally carried out in a coma
performed and recorded tose patient; also, infants
in a relatively uniform and small children, as
manner in order to avoid well as patients with
omissions and facilitate psychiatric disease, must
the subsequent analysis be examined in special
of case records. Some ways.
variation in the precise Certain portions of the
order of examina tion general physical
from physician to examination that may be
physician is particularly informative
understandable, but each in the patient with
examiner should neurologic disease
establish an accustomed should be included. For
pattern. Even when it is example, examination of
impractical to perform the heart rate and blood
the examination in the pressure, as well as
customary way, as in carotid and cardiac
patients who are unable auscultation, are
to coop erate because of essential in a patient
age or cognitive with stroke. Likewise,
deficiency, it is good the skin can reveal a
practice to record the num ber of conditions
findings in an orderly that pertain to
fashion. If cer tain congenital, metabolic,
portions are not and infectious causes of
performed (e.g., neurologic disease.
olfactory testing in a
completely
uncooperative patient), EXAMINING
this omission should be PATIENTS
stated so that those WHO
reading the description PRESENT
at a later time are not left WITH
wondering whether an NEUROLOG
abnormality was not IC
previously detected. SYMPTOMS
The thoroughness of
the neurologic Numerous guides to the
examination of neces sity examination of the
must be governed by the nervous system are
type of clinical problem available (see the
presented by the patient. references at the end of
To spend a half hour or this chapter). For a full
more testing cerebral, account of these
cerebellar, cranial nerve, methods, the reader is
and sensorimo tor referred to several of the
function in a patient many monographs on
the subject, including
 those of Bickerstaff and (DeJong’s Neurological
Spill ane, Campbell Examination), and
CHAPTER 1 Approach to the Patient with Neurologic
Disease 7

of the staff members of examination has two

the Mayo Clinic, each of
which approaches the
subject from a somewhat
different point of view.
An inordinately large
number of tests of neuro
logic function have been
devised, and it is not
proposed to review all of
them here. Some are
described in subse quent
chapters dealing with
disorders of mentation,
cranial nerves, and
motor, sensory, and
autonomic func tions.
Many tests are of
doubtful value or are
repeti tions of simpler
tests and thus should not
be taught to students of
neurology. Merely to
perform all of them on
one patient would
require several hours
and, in most instances,
would not make the
examiner any the wiser.
The danger with all
clinical tests is to regard
them as indisputable
indicators of disease
rather than as ways of
uncovering disordered
functioning of the
nervous system. The
following approaches
are relatively simple and
provide the most useful
information.
Testing of Higher
Cortical Functions
These functions are
tested in detail if the
patient’s history or
behavior during the
general examination has
pro vided a reason to
suspect some defect.
Broadly speaking, the
mental status
main compo nents,
although the separation
is somewhat artificial:
the psychiatric aspects,
which incorporate affect,
mood, and normality of
thought processes and
content, and the neu
rologic aspects, which
include the level of
consciousness,
awareness (attention),
language, memory, and
visuospa tial abilities.
Questions are first
directed toward
determining the patient’s
orientation in time and
place and insight into his
current medical
problem. Attention,
speed of response,
ability to give relevant
answers to simple
questions, and the
capacity for sustained
and coherent mental
effort all lend themselves
to straightforward
observation. There are
many useful bedside
tests of attention,
concentration, memory,
and clarity of thinking
include the repetition of
a series of digits in
forward and reverse
order and serial
subtraction of 3s or 7s
from 100, and recall of
three items of
information or a short
story after an interval of
3 min. More detailed
examination procedures
appear in Chaps. 20
through 23. The patient’s
account of his recent
illness, dates of
hospitalization, and his
day-to-day recollection
of recent incidents are
excellent tests of
memory; the narra tion fossa, the sense of smell
of the illness and the should be tested in each
patient’s choice of words nostril; then it should be
(vocab ulary) provide determined whether
information about his odors can be
language ability and discriminated. Visual
coherence of thinking. fields should be outlined
If there is any by confrontation testing,
suggestion of a speech or in some cases by testing
language disor der, the each eye separately. If
nature of the patient’s any abnormality is
spontaneous speech suspected, it should be
should be noted. In checked on a perimeter
addition, the accuracy of and scotomas sought on
reading, writing, and the tan gent screen or,
spelling, executing more accurately, by
spoken commands, computerized perime
repeating words and try. Pupil size and
phrases spoken by the reactivity to light, direct,
examiner, naming consensual, and during
objects and parts of convergence, the
objects, and solving position of the eyelids,
simple arithmeti cal and the range of ocular
problems should be movements should next
assessed. be observed. Details of
The ability to carry out these test procedures
commanded tasks and their interpretation
(praxis) has great are given in Chaps. 12,
salience in the 13, and 14.
evaluation of several Sensation over the face
aspects of cor tical is tested with a pin and
function. Bisecting a line, wisp of cotton. Also, the
drawing a clock or the presence or absence of
floor plan of one’s home the corneal reflexes,
or a map of one’s direct and consensually,
country, and copying may be determined.
figures are useful tests of Facial movements
visuospatial percep tion should be observed as
and are indicated in the patient speaks and
cases of suspected smiles, for a slight
cerebral dis weakness may be more
ease. The testing of evident in these
language, cognition, and circumstances than on
other aspects of higher movements to
cerebral function are command.
considered in Chaps. 21, The auditory meati
22, and 23. and tympanic
membranes should be
inspected with an
Testing of Cranial
otoscope. A high-
Nerves
frequency (512 Hz)
The function of the tuning fork held next to
cranial nerves must the ear and on the
generally be inves mastoid dis closes
tigated more fully in hearing loss and
patients who have distinguishes middle-ear
neurologic symp toms (conduc tive) from
than in those who do neural deafness.
not. If one suspects a Audiograms and other
lesion in the anterior
special tests of auditory reflexes. The
and vestibular function maintenance of the
are needed if there is any supinated arms against
suspicion of disease of gravity is a useful test;
the eighth nerve or the the weak arm, tiring
cochlear and first, soon begins to sag,
labyrinthine end organs or, in the case of a
(see Chap. 15). The vocal corticospinal
cords must be inspected 8 Part 1 THE CLINICAL
with special instruments METHOD OF NEUROLOGY
in cases of suspected
medullary or vagus
lesion, to resume the
nerve disease, especially
more natural pronated
when there is
position (“pronator
hoarseness. Voluntary
drift”). The strength of
pharyngeal elevation
the legs can be similarly
and elicited reflexes are
tested with the patient
meaningful if there is a
prone and the legs
difference on the two
flexed at hips and knees
sides; bilateral absence of
and observing
the gag reflex is seldom
downward drift of the
significant. Inspection of
weak ened leg. In the
the tongue, both
supine position at rest,
protruded and at rest, is
weakness due to an
helpful; atrophy and
upper motor neuron
fascicula tions may be
lesion causes external
seen and weakness
rotation of the hip.
detected. Slight
It is essential to have
deviation of the
the limbs exposed and to
protruded tongue as a
inspect them for atrophy
solitary finding can
and fasciculations.
usually be disregarded,
Abnormalities of
but a major deviation
movement and posture
represents underac tion
as well as tremors may
of the hypoglossal nerve
be exposed by observing
and muscle on that side.
the limbs at rest and in
The pronunciation of
motion (see Chaps. 4, 5,
words should be noted.
and 6). This is
The jaw jerk and the
accomplished by
snout, buccal, and
watching the patient
sucking reflexes should
maintain the arms
be sought, particularly if
outstretched in the
there is a question of
prone and supine
dysphagia, dysarthria, or
positions; perform
dysphonia.
simple tasks, such as
alternately touch ing his
Testing of Motor nose and the examiner’s
Function finger; make rapid alter
nating movements that
In the assessment of
motor function, it should necessitate sudden
be kept in mind that acceleration and
observations of the deceleration and
speed and strength of changes in direction,
move ments and of such as tapping one
muscle bulk, tone, and hand on the other while
coordination are most alternating pronation
informative and are and supination of the
considered in the context forearm; rapidly touch
of the state of tendon the thumb to each
fingertip; and
accomplish simple tasks
such as but toning
clothes, opening a safety
pin, or handling
common tools. Estimates
of the strength of leg
muscles with the patient
in bed are often
unreliable; there may
seem to be little or no
weakness even though
the patient cannot arise
from a chair or from a
kneeling position
without help. Running
the heel down the front
of the shin, alternately
touching the examiner’s
finger with the toe and
the oppo site knee with
the heel, and
rhythmically tapping the
heel on the shin are the
only tests of
coordination that need
be carried out in bed.
Testing of Reflexes
Testing of the biceps,
triceps, supinator-
brachioradialis, patellar,
Achilles, and cutaneous
abdominal and plantar
reflexes permits an
adequate sampling of
reflex activity of the
spinal cord. Elicitation of
tendon reflexes requires
that the involved
muscles be relaxed;
underactive or barely
elicitable reflexes can be
facilitated by voluntary
contrac tion of other
muscles (Jendrassik
maneuver).
The plantar response
poses some difficulty
because sev eral
different reflex
responses besides the
Babinski re sponse can
be evoked by
stimulating the sole of
the foot along its outer
border from heel to toes.
These are (1) the normal
quick, high-level
avoidance response that
causes the foot and leg
to withdraw; (2) the
pathologic slower, spinal
flexor nocifensive
(protective) reflex
(flexion of knee and hip
and dorsiflexion of toes
and foot, “triple flex
ion”). Dorsiflexion of the
large toe and fanning of
the other toes as part of
this reflex is the well-
known Babinski sign
(see Chap. 3); (3) plantar
grasp reflexes; and (4)
sup port reactions in
infants. Avoidance and
withdrawal re sponses
interfere with the
interpretation of the
Babinski sign and can
sometimes be overcome
by utilizing the sev eral
alternative stimuli (e.g.,
squeezing the calf or
Achilles tendon, flicking
the fourth toe,
downward scraping of
the shin, lifting the
straight leg, and others)
or by having the patient
scrape his own sole. An
absence of the
superficial cutaneous
reflexes of the
abdominal, cremasteric,
and other muscles are
useful ancillary tests for
detecting corti cospinal
lesions particularly
when unilateral.
Testing of Sensory
Function
Because this part of the
examination is attainable
only through the
subjective responses of
the patient, it requires
great patient
cooperation. For the
same reason, it is subject
to overinterpretation
and suggestibility.
Usually, sensory testing
is reserved for the end of
the examination and, if
the findings are to be
reliable, should not be
prolonged for more than
a few minutes. Each test
should be explained
briefly; too much
discussion of these tests
with a meticu lous,
introspective patient
might encourage the
reporting of meaningless
minor variations of
stimulus intensity.
It is not necessary to
examine all areas of the
skin surface. A quick
survey of the face, neck,
arms, trunk, and legs
with a pin takes only a
few seconds. Usually
one is seeking dif
ferences between the
two sides of the body (it
is better to ask whether
stimuli on opposite sides
of the body feel the same
than to ask if they feel
different), a level below
which sensation is lost,
or a zone of relative or
absolute analgesia (loss
of pain sensibility) or
anesthesia (loss of touch
sensi bility). Regions of
sensory deficit can then
be tested more carefully
and mapped out.
Moving the stimulus
from an area of
diminished sensation
into a normal area is
recom mended because
it enhances the
perception of a of the soles may bring
difference.
The sense of vibration
may be tested by
comparing the
thresholds at which the
patient and examiner
lose percep tion at
comparable bony
prominences. We
suggest record ing the
number of seconds for
which the examiner
appreciates vibration at
the malleolus, toe, or
finger after the patient
reports that the fork has
stopped buzzing. The
finding of a zone of
heightened sensation
(“hyperesthesia”) calls
attention to a
disturbance of
superficial sensation.
Variations in sensory
findings from one
examination to another
reflect differences in
technique of
examination as well as
inconsistencies in the
responses of the patient.
Sen sory testing is
considered in greater
detail in Chaps. 8 and 9.
Testing of Gait and
Stance
The examination is
completed by observing
the patient stand and
walk. An abnormality of
stance or gait may be the
most prominent or only
neurologic abnormality,
as in certain cases of
cerebellar or frontal lobe
disorder; and an
impairment of posture
and highly automatic
adaptive movements in
walking may provide
the most definite diag
nostic clues in the early
stages of diseases such
as Parkinson disease.
Having the patient walk
tandem or on the sides
out a lack of balance or
dystonic pos tures in the
hands and trunk.
Hopping or standing on
one foot may also betray
a lack of balance or
weakness, and standing
with feet together and
eyes closed will bring
out a disequilibrium that
is due to deep sensory
loss (Romberg test).
Disorders of gait are
discussed in Chap. 7.
 TESTING THE
PATIENT WITHOUT
NEUROLOGIC
SYMPTOMS
In this situation, brevity
is desirable but any test
that is undertaken orientation,
should be done carefully
and recorded accu rately
and legibly. As indicated function are readily
in Table 1-4, the assessed in the course of
patient’s
Table 1-4
CHAPTER 1 Approach to the movements, visual and
Patient with Neurologic
Disease 9 tive function,
almost all parts of the
nervous system,
BRIEF NEUROLOGIC
EXAMINATION IN
THE GENERAL
MEDICAL OR
SURGICAL PATIENT
(PERFORMED IN 5
MIN OR LESS)
1. Orientation, insight
into illness,
language assessed
during taking of
the history
2. Size of pupils,
reaction to light,
visual and auditory
acuity 3. Movement
of eyes, face, tongue
4. Examination of the
outstretched hands
for atrophy,
pronating or
downward drift,
tremor, power of
grip, and wrist
dorsiflexion
5. Biceps, supinator, and
triceps tendon reflexes
6. Inspection of the legs
during active
flexion and
extension of the
hips, knees, and feet
7. Patellar, Achilles, and
plantar (Babinski) reflexes
8. Vibration sensibility in the does not add more than
fingers and toes
9. Finger-to-nose
and heel-to-shin
testing of
coordination 10.
Gait
insight,
judgment, and the
integrity of lan guage
taking the history. With
respect to the cranial
nerves, the size of the
pupils and their reaction
to light, ocular
auditory acuity, and
movements of the face,
palate, and tongue
should be tested.
Observing the bare
outstretched arms for
atrophy, weakness
(“pronator drift”),
tremor, or abnormal
movements; checking
the strength of hand grip
and dorsiflexion at the
wrist; inquiring about
sensory dis turbances;
and eliciting the biceps,
and triceps reflexes are
usually sufficient for the
upper limbs. Inspection
of the legs while the feet,
toes, knees, and hips are
actively flexed and
extended; elicitation of
the patellar, Achilles,
and plantar reflexes;
testing of vibration and
position sense in the fin
gers and toes; and
assessment of
coordination by having
the patient alternately
touch his nose and the
examiner’s finger and
run his heel up and
down the front of the
oppo site leg, and
observation of walking
complete the essential
parts of the neurologic
examination.
This entire procedure
a few minutes to the
physical examination
but the routine per
formance of these few
simple tests provides
clues to the presence of
disease of which the
patient is not aware. For
example, the finding of
absent Achilles reflexes
and diminished
vibratory sense in the
feet and legs alerts the
physician to the
possibility of diabetic or
alcoholic-nutri tional
neuropathy even when
the patient has no symp
toms referable to these
disorders. Carotid
auscultation has been
adopted as a component
of the screening examina
tion by many
neurologists and
recording of the heart
rate and rhythm, blood
pressure, and heart
auscultation is included
in the examination in
stroke patients.
Accurate recording of
negative data may be
useful in relation to
some future illness that
requires examination.
THE COMATOSE
PATIENT
Although subject to
obvious limitations,
careful examina tion of
the stuporous or
comatose patient yields
consider able
information concerning
the function of the
nervous system. It is
remarkable that, with
the exception of cogni
including the cranial
nerves, can be evaluated
in the coma tose patient.
The demonstration of
signs of focal cerebral or
brainstem disease or of
meningeal irritation is
particularly useful in the
differential diagnosis of
diseases that cause
stupor and coma. The
adaptation of the
neurologic exami nation
to the comatose patient
is described in Chap. 17.
THE PSYCHIATRIC
PATIENT
One is compelled in the
examination of
psychiatric patients to
rely less on the
cooperation of the
patient and to be
unusually critical of
their statements and
opinions. The depressed
patient, for example,
may perceive impaired
memory or weakness
when actually there is
neither amne sia nor
diminution in muscular
power, or the sociopath
or hysteric may feign
paralysis. The opposite
is sometimes true:
Psychotic patients may
make accurate
observations of their
symptoms, only to have
them ignored because of
their mental state.
If the patient will
speak and cooperate
even to a slight degree,
much may be learned
about the functional
integrity of different
parts of the nervous
system. By the manner
in which the patient
expresses ideas and
responds to spoken or
written requests, it is
possible to determine
whether there are
hallucinations or
delusions, defective
memory, or other
recognizable symptoms
of brain disease merely
by watching and
listening to the patient.
Ocular movements and
visual fields can be
tested with fair accuracy The findings on general
by observ ing the medical examination
patient’s response to a very often disclose
moving stimulus or evidence of an
threat in the visual underlying systemic
fields. Cranial nerve, disease that has
motor, and reflex secondarily affected the
functions are tested in nervous system. In fact,
the usual manner, but it many of the most
must be remembered serious neurologic
that the neurologic problems are of this
examination is never 10 Part 1 THE CLINICAL
complete unless the METHOD OF NEUROLOGY
patient will speak and
cooperate in testing. On
type. Two common
occa sion, mute and
examples will suffice:
resistive patients judged
adenopathy or a lung
to be psychotic prove to
infiltrate implicate
have some widespread
neoplasia or sarcoidosis
cerebral disease such as
as the cause of multiple
hypoxic or
cranial nerve palsies,
hypoglycemic
and the presence of low-
encephalopathy, a brain
grade fever, anemia, a
tumor, a vascular lesion,
heart murmur, and
or extensive
spleno megaly in a
demyelinative lesions.
patient with
unexplained stroke
points to a diagnosis of
INFANTS AND
bacterial endocarditis
SMALL CHILDREN
with embolic occlu sion
of brain arteries.
The reader is referred to
Certainly no
the special methods of
examination of a patient
examina tion described
with stroke is complete
by Gesell and
without a search for
Amatruda, Andrè-
hypertension, carotid
Thomas and colleagues,
bruits, heart murmurs,
Paine and Oppe, and the
and irregu lar heart
staff members of the
rhythm.
Mayo Clinic, which are
listed in the references
and described in Chap. IMPORTANCE OF A
28. Many of these WORKING
volumes address the KNOWLED
developmental aspects GE OF
of the child’s nervous NEUROANA
system, and although TOMY,
some signs may be NEUROPHY
difficult to obtain SIOLOGY,
because of the age of the MOLECULA
patient, they still stand R
as the best explica tions GENETICS,
of the child’s neurologic AND
examination. NEUROPAT
HOLOGY
THE GENERAL
MEDICAL Once the technique of
EXAMINATION obtaining reliable clinical
data is mastered,
students and residents
may find themselves
handicapped in the
interpretation of the
findings by a lack of
knowledge of the basic
sciences of neurology.
For this reason, each of
the later chapters
dealing with the motor
system, sensation,
special senses,
consciousness, and lan
guage is introduced by a
review of the anatomic
and physiologic facts
that are necessary for an
understanding of the
associated clinical
disorders.
At a minimum,
physicians should know
the anatomy of the
corticospinal tract; motor
unit (anterior horn cell,
nerve, and muscle); basal
ganglionic and cerebellar
motor connec tions; main
sensory pathways;
cranial nerves; hypothala
mus and pituitary;
reticular formation of
brainstem and thalamus;
limbic system; areas of
cerebral cortex and their
major connections;
visual, auditory, and
autonomic sys tems; and
cerebrospinal fluid
pathways. A working
knowl edge of
neurophysiology should
include an
understanding of the
nerve impulse,
neuromuscular
transmission, and
contractile process of
muscle; spinal reflex
activity; central
neurotransmission;
processes of neuronal
excitation, inhibi tion,
and release; and cortical
activation and seizure
pro duction. The genetics
and molecular biology of
neurologic disease have
assumed increasing
importance in the past
few decades. The
practitioner should, at
minimum, be familiar
with the terminology of
mendelian and mitochon
drial genetics and the
main aberrations in the
genetic code that give
rise to neurologic
disease.
From a practical
diagnostic and
therapeutic point of
view, we believe the
neurologist is helped
most by a knowledge of
pathologic anatomy—
i.e., the neuropathologic
changes that are
produced by disease
processes such as
infarction, hem orrhage,
demyelination, physical
trauma, compression,
inflammation, neoplasm,
and infection, to name
the more common ones.
Experience with the
gross and microscopic
appearances of these
disease processes greatly
enhances one’s ability to
explain their clinical
effects. The ability to
visualize the
abnormalities of disease
on nerve and muscle,
brain and spinal cord,
muscle, meninges, and
blood vessels gives one a
strong sense of which
clinical features to expect
of a particular disease
and which features are
untenable or inconsistent
with a particular
diagnosis. An additional
advantage of being
exposed to
neuropathology is, of
course,
that the clinician is better
able to evaluate
pathologic changes and
reports of material
obtained by biopsy.
 LABORATORY risk of developing
DIAGNOSIS certain diseases.
The laboratory
From the foregoing methods that are
description of the clinical available for neuro logic
method, it is evident that diagnosis are discussed
the use of laboratory aids in the next chapter and
in the diagnosis of in Chap. 45, on clinical
diseases of the nervous electrophysiology. The
system is ideally relevant prin ciples of
preceded by rig orous genetic and laboratory
clinical examination. As screening methods for
in all of medicine, labora the prediction of disease
tory study can be are presented in the
planned intelligently discussion of the disease
only on the basis of to which they are
clinical information. To applicable.
reverse this process is
wasteful of medical
resources and prone to SHORTCOMINGS
the discovery of irrele OF THE CLINICAL
vant information. METHOD
In the prevention of
neurologic disease, If one adheres faithfully
however, the clinical to the clinical method,
method in itself is neurologic diagnosis is
inadequate; thus, of greatly simplified. In
necessity, one resorts to most cases one can reach
two other approaches, an anatomic diagnosis
namely, the use of but discovering the
genetic information and cause of the dis ease may
laboratory screening prove more elusive and
tests. Bio chemical usually entails the selec
screening tests are tive employment of the
applicable to an entire laboratory procedures
popu lation and permit described in the next
the identification of chapter. However, even
neurologic diseases in after the most assiduous
individuals, mainly application of the clinical
infants and children, method and laboratory
who have yet to show proce dures, there are
their first symptom; in numerous patients
some diseases, treatment whose diseases elude
can be instituted before diagnosis. In such
the nervous system has circumstances we have
suffered damage. often been aided by the
Similarly in adults, following rules of
screening for thumb:
atherosclerosis and its 1. As mentioned
underlying metabolic earlier, when the
causes is profitable in main sign has been
certain populations as a misinterpreted—if a
way of preventing tremor has been
stroke. Genetic infor taken for ataxia or
mation enables the fatigue for weakness
neurologist to arrive at —the clinical
the diagnosis of certain method is de railed
illnesses and to identify from the start. Focus
patients and relatives at the clinical analysis
 on the principal premature fixation
symptom and signs on some item in the
and avoid being dis his tory or
tracted by minor examination, closing
signs and uncertain the mind to
clinical data. alternative
2. Avoid early closure diagnostic
of diagnosis. Often considerations. The
this is the result of first diagnostic
formu-
CHAPTER 1 Approach to the Patient with Neurologic
Disease 11

lation should be relation to

regarded as only a neurologic disease
testable hypothe sis, because of the
subject to impossibil ity of
modification when weighing the
new items of importance of each
information are clinical datum.
secured. Should the Nonetheless,
disease be in a stage implicit in all
of transition, time diagnostic methods
will allow the full is an assessment of
picture to emerge the likely causes of a
and the diagnosis to sign or syndrome in
be clarified. the context of the
3. When several of the patient’s broad
main features of a demographic charac
disease in its typical teristics including
form are lacking, an their sex, age, race,
alternative diagnosis ethnicity, and the
should always be geographical
entertained. In circumstances. For
general, however, example, the neurolo
one is more likely to gist in the United
encounter rare States considers it
manifestations of unlikely a case of
common diseases chronic meningitis
than the typical would be caused by
manifestations of Behçet disease,
rare diseases (a whereas a colleague
paraphrasing of the in Turkey might find
Bayes theorem). this to be a very
4. It is preferable to likely diagnosis.
base diagnosis on Moreover, as
clinical experience mentioned earlier,
with the dominant neurologists place a
symptoms and signs premium on finding
and not on sta treatable ill nesses,
tistical analyses of even if the odds do
the frequency of not favor its
clinical phenomena. presence.
For the most part,
As pointed out by
the methods of
Chimowitz, students
probability-based
tend to err in failing to
decision analysis
recognize a disease they
have proved to be
have not seen, and
disappointing in
experienced clinicians
may fail to appreciate a There are, in addition,
rare variant of a common many diseases in which
disease. There is no neurologic function can
doubt that some clini be restored to a varying
cians are more adept degree by appropriate
than others at solving rehabilitation measures
difficult clini cal or by the judicious use of
problems. Their talent is therapeu tic agents that
not intuitive, as have not been fully
sometimes is presumed, validated. Claims for the
but is attributable to effectiveness of a
having paid close atten particular therapy based
tion to the details of their on statistical analysis of
experience with many large-scale clinical
diseases and having studies must be treated
catalogued them for cir cumspectly. Was the
future reference. The study well conceived as
unusual case is recorded reflected in a clearly
in memory and can be stated hypothesis and
resur rected when outcome criteria; was
another one like it is there adherence to the
encountered. plans for randomization
and admission of cases
into the study; were the
THERAPEUTICS IN statistical methods
NEUROLOGY appropri ate; and were
the controls truly
Among medical comparable? It has been
specialties, neurology our experience that the
has traditionally original claims must
occupied a somewhat always be accepted with
anomalous position, caution and it is prudent
being thought of by to wait until further
many as little more than studies confirm the
an intellectual exercise benefits that have been
con cerned with making claimed. While sup
diagnoses of untreatable portive of the recent
diseases. This view of emphasis on evidence-
our profession is not at based medicine, we are
all valid. There are a in agreement with
growing number of Caplan’s point that much
diseases, some medical of this “evidence” is not
and others sur gical, for applicable to difficult
which specific therapy is individual thera peutic
now available; through decisions. This is in part
advances in true because small albeit
neuroscience, their statistically significant
number is steadily effects may be of little
increas ing. Matters consequence when
pertaining to these applied to an individual
therapies and to the dos patient. It goes without
ages, timing, and say ing that data derived
manner of from trials must be used
administration of in the context of a
particular patient’s overall physical
drugs are considered in and mental condition
later chapters in relation and age. Furthermore,
to the description of for many neurologic
individual diseases. conditions there is, at the
moment, inadequate lives of the affected
evidence on which to individuals.
base treat ment. Here, Furthermore, more so
the patient requires a than in other fields, the
skilled physician to make promise of cure or
judgments based on amelioration by new
partial or insufficient techniques such as
data. Even as sci ence molecu lar biology,
moves forward, wise genetic therapy, and
clinicians must treat brain–computer inter
patients in the present by faces has excited vast
prudent use of properly interest, for which
catalogued personal reason aspects of the
experience coupled with current scientific insights
the best current data. are included in
Even when no appropriate sections.
effective treatment is 12 Part 1 THE CLINICAL
possible, neurologic METHOD OF NEUROLOGY
diagnosis is more than
an intellectual pastime.
The first step in the
scientific study of a
References
disease process is its
identi fication in the Andrè-Thomas, Chesni Y,
living patient. The Dargassies St-Anne S: The
clinical method of neu Neurological Examination of the
rology thus serves both Infant. London, National
the physician in the Spastics Society, 1960.
Campbell WW: DeJong’s The
practical matters of
Neurological Examination, 6th
diagnosis, prognosis, ed. Philadelphia, Lippincott
and treatment, and the Williams & Wilkins, 2005.
clinical scientist, in the Caplan LR: Evidence-based
search for the medicine: Concerns of a
mechanism and cause of clinical neurologist. J Neurol
disease. Neurosurg Psychiatry 71:569,
In closing this 2001. [PMID: 11606661]
introductory chapter, a Chimowitz MI, Logigian EL,
Caplan LP: The accuracy of
comment regard ing the
bedside neurological
extraordinary burden of
diagnoses. Ann Neurol 28:78,
diseases of the nervous 1990. [PMID: 2375637]
system throughout the DeMyer WE: Technique of the
world and in the United Neurologic Examination: A
States is appropriate. It is Programmed Text, 4th ed. New
not just that conditions York, McGraw-Hill, 1994.
such as brain and spinal Donaghy M, Compston A,
cord trauma, stroke, Rossor M, Warlow C:
epilepsy, mental retarda Clinical diagnosis, in
Brain’s Diseases of the
tion, mental diseases,
Nervous System, 11th ed.
and dementia are
Oxford, UK, Oxford
ubiquitous and account University Press, 2001, pp
for the majority of 11–60.
illness, second only in
some parts of the world
to infectious disease, but
that these are highly
disabling and often
chronic in nature, Gesell A, Amatruda CS, in
Knoblock H, Pasamanick
altering in a
B (eds): Gesell and
fundamental way the
Amatruda’s Developmental
 Diagnosis, 3rd ed. New The analysis and
York, Harper, 1974. interpretation of data
Hirtz D, Thurman DJ, elicited by a care ful
Gwinn-Hardy K, et al:
history and examination
How common are the
may prove to be
“common” neurologic
disorders? Neurology
adequate for diagnosis.
68:326, 2007. [PMID: Special laboratory
17261678] examinations then do no
Holmes G: Introduction to more than corroborate
Clinical Neurology, 3rd ed. the clinical impression.
Revised by Bryan How ever, it happens
Matthews. Baltimore, more often that the
Williams & Wilkins, 1968. nature of the disease is
Mayo Clinic Examinations in not discerned by “case
Neurology, 7th ed. St.
study” alone; the
Louis, Mosby-Year Book,
diagnostic possibilities
1998.
Paine RS, Oppe TE: may be reduced to two
Neurological Examination or three, but the cor rect
of Children. London, one is uncertain. Under
Spastics Society Medical these circumstances, one
Education and resorts to ancillary
Information Unit, 1966. examinations. The aim of
Spillane JA: Bickerstaff’s the neurolo gist is to
Neurological Examination arrive at a final diagnosis
in Clinical Practice, 6th ed.
by artful analysis of the
Oxford, Blackwell
clinical data aided by the
Scientific, 1996.
least number of
laboratory procedures.
Only a few decades
ago, the only laboratory
proce dures available to
the neurologist were
examination of a sample
of cerebrospinal fluid,
conventional radiology
of the skull and spinal
column, contrast
myelography, pneu
moencephalography,
and
electroencephalography.
Now, through
formidable advances in
scientific technology, the
physician’s
armamentarium has
been expanded to
include a multitude of
neuroimaging,
biochemical, and genetic
methods. Some of these
new methods are so
impressive that there is a
temptation to substitute
them for a careful,
detailed history and
physical examination.
Use of the lab oratory in
this way should be
avoided. Reflecting this
limitation, in a carefully Special
Techniqu
examined series of 86
consecu tively
hospitalized neurologic
patients, laboratory find
ings (including MRI)
es for
clarified the clinical
diagnosis in 40 patients
Neurologi
but failed to do so in the
remaining 46 (Chimo c
witz et al). Moreover, it
is quite common in Diagnosi
s
modern prac tice for
ancillary testing to reveal
abnormalities that are of
no significance to the
problem at hand.
Consequently, the
physician should always
judge the relevance and
signifi cance of
laboratory data only in
LUMBAR
the context of clinical
PUNCTURE
findings. Hence the
AND
neurologist must be
EXAMINATION
familiar with all
OF
laboratory procedures
CEREBROSPIN
relevant to neurologic
AL FLUID
disease, their reliability,
and their hazards.
The information yielded
What follows is a
by examination of the
description of laboratory
cerebrospi nal fluid
procedures that have
(CSF) is crucial in the
application to a diversity
diagnosis of certain
of neurologic diseases.
neuro logic diseases,
Procedures that are
particularly infectious
pertinent to a particular
and inflammatory
symptom complex or
conditions, subarachnoid
category of disease—e.g.,
hemorrhage, and
audiography to study
diseases that alter
deafness;
intracranial pressure.
electronystagmography
Certain combinations of
(ENG) in cases of
find ings, or formulas, in
vertigo;
the CSF generally denote
electromyography
particular classes of
(EMG) and nerve
disease; these are
conduction studies, as
summarized in Table 2-
well as nerve and muscle
1.
biopsy, where there is
neuromuscular disease— Indications for
are presented in the Lumbar Puncture
chapters devoted to
these disorders. 1. To obtain pressure
measurements and

2
procure a sam ple of
the CSF for cellular,
cytologic, chemical,
and bacteriologic
examination.
 2. To aid in therapy by actually been employed
the administration as a therapeutic measure.
of spinal anes thetics In patients with purulent
and occasionally, meningitis, there is also a
antibiotics or small risk of herniation,
antitumor agents, or but this is far out
by reduction of CSF weighed by the need for
pressure. a definitive diagnosis
3. To inject a and the in stitution of
radiopaque substance, appropriate treatment at
as in myelography, or a the earliest moment.
radioactive agent, as in With this last exception,
radionuclide LP should generally be
cisternography. preceded by CT or MRI
whenever an elevation of
Lumbar puncture (LP)
intracranial pres sure is
carries certain risks if the
suspected. If radiologic
CSF pressure is very
procedures do disclose a
high (evidenced mainly
mass lesion that is
by headache and
causing displacement of
papilledema), for it
brain tissue to ward the
increases the possibility
tentorial opening or the
of a fatal cere bellar or
foramen magnum (the
transtentorial herniation.
presence of a mass alone
The risk is considerable
is of less concern) and if
when papilledema is the
it is con sidered
result of an intracranial
absolutely essential to
mass, but it is much
have the information
lower in patients with
yielded by CSF
subarachnoid hemor
examination, the LP may
rhage, in hydrocephalus
be performed— with
with communication
certain precautions. A
between all the
fine-bore (no. 22 or 24)
ventricles, or with
needle should be used,
pseudotumor cerebri,
and if the pressure
conditions in which
proves to be very
repeated LPs have

13
14 Part 1 THE CLINICAL METHOD OF
NEUROLOGY

Table 2-1
CHARACTERISTIC CSF FORMULAS
CONDITION CELLS PROTEIN GLUCOSE OTHER
FEATURES
Bacterial infection blood glucose level 3
WBC 10–100/mm
3
WBC >50/mm , often Gram stain shows 50–200 mg% Normal
greatly increased organisms; pressure or slightly reduced
100–250 mg% 20–50 increased Special culture
mg%; usually lower techniques required;
than half of Viral, fungal, pressure normal or
spirochetal infection

Tuberculous infection WBC slightly increased

3
>25/mm 100–1,000 mg% <50, Special culture techniques and
often markedly reduced PCR may be needed to detect
organisms
3
RBC >500/mm ; slight
Subarachnoid Cerebral increase in WBC
hemorrhage hemorrhage, trauma
 3 distinguished from greatly
RBC 50–200/mm ;
higher if ventricular traumatic lumbar increased pressure
rupture of blood puncture 50–150 mg% Normal
60–150 mg% Normal by presence of Pressure may be
Must be xanthochromia elevated
of spun sample;

Multiple sclerosis Normal or Normal Increased IgG fraction

few WBC Normal or slightly and oligoclonal bands
increased
SF; elevation of certain protein
markers (e.g., β2-
microglobulin)
IgG, immunoglobulin G; PCR, polymerase chain reaction; RBC, red
blood cells; WBC, white blood cells.

high—over 400 mm H2O cisternal fluid or for

—one should obtain the myelography above the
smallest necessary lesion.
sample of fluid and then,
according to the sus Technique of Lumbar
pected disease and Puncture
patient’s condition,
Experience teaches the
administer manni tol
importance of
and observe a fall in
meticulous tech nique.
pressure on the
LP should be done under
manometer.
locally sterile condi
Dexamethasone or an
tions. Xylocaine is
equivalent corticosteroid
injected in and beneath
may also be given in an
the skin, which should
initial intravenous dose
render the procedure
of 10 mg, followed by
almost painless.
doses of 4 to 6 mg every
Warming of the
6 h in order to produce a
analgesic by rolling the
sus tained reduction in
vial between the palms
intracranial pressure.
seems to diminish the
Corticosteroids are
burning sensation that
particularly useful in
accompanies cutaneous
situations in which the
infiltration. The patient
increased intracranial
is posi tioned on his side,
pressure is caused by
preferably on the left
vasogenic cerebral
side for right handed
edema (e.g., tumor-
physicians, with hips
associated edema).
and knees flexed, and
Cisternal puncture and
the head as close to the
lateral cervical
knees as comfort
subarachnoid punc ture,
permits. The patient’s
although safe in the
hips should be vertical,
hands of an expert, are
the back aligned near
too haz ardous to entrust
the edge of the bed, and
to those without
a pillow placed under
experience and do not
the ear. The puncture is
circumvent the problem
easiest to perform at the
of increased intracranial
L3-L4 inter space, which
pressure. LP is preferred
corresponds to the axial
except in obvious
plane of the iliac crests,
instances of spinal block
or at the interspace
requiring a sample of
above or below. In
 infants and young
children, in whom the
spinal cord may extend
to the level of the L3-L4
interspace, lower levels
should be used.
Experienced
anesthesiologists have
suggested that the
smallest possible needle
be used and that the
bevel be oriented in the
longitudinal plane of the
dural fibers (see below
regarding atraumatic
needles). It is usually
possible to appreciate a
palpable “give” as the
needle transgresses the
dura, followed by a
subtle “pop” on
puncturing the
arachnoid membrane. At
this point, the trocar
should be removed
slowly from the needle
to avoid sucking a nerve
rootlet into the lumen
and causing radicular
pain. Sciatic pain during
the insertion of the
needle indicates that it is
placed too far laterally. If
the flow of CSF slows,
the patient’s head can be
CHAPTER 2 Special Techniques for Neurologic
result of a reduction of
CSF pressure and
tugging on cere bral and
dural vessels as the
patient assumes the erect
posture. Although
neither recumbency nor
oral fluid administration
after LP has been shown
to prevent head ache,
they are often
implemented
nonetheless. Strupp and
colleagues found that the
use of an atraumatic
needle almost halved the
incidence of headache.
Curiously, head aches
are twice as frequent
after diagnostic LP as
they are after spinal
elevated slowly.
Occasionally, one resorts
to gentle aspiration with
a small-bore syringe to
overcome the resistance
of proteinaceous and
viscous CSF. Failure to
enter the lum bar
subarachnoid space after
two or three trials
usually can be overcome
by performing the
puncture with the
patient in the sitting
position and then
helping him to lie on one
side for pressure
measurements and fluid
removal. The “dry tap”
is more often the result
of an improperly placed
needle than of
obliteration of the sub
arachnoid space by a
compressive lesion of the
cauda equina or by
adhesive arachnoiditis.
LP has few serious
complications. The most
common is headache,
estimated to occur in
one-third of patients, but
in severe form in far
fewer. The pain is
presumably the
Diagnosis 15
anesthesia. Patients who
are prone to frequent
headaches before LP
reportedly have higher
rates of head ache
afterwards, which
accords with our
experience. Severe
headache can be
associated with vomiting
and mild neck stiffness.
Unilateral or bilateral
sixth nerve or other
cranial nerve palsies
(VII, VIII) occur rarely
after lumbar puncture,
even at times without
headache. The syndrome
of low CSF pressure, its
treatment by “blood
patch,” and other
complications of lumbar pH, CO2, enzymes, and
puncture are considered substances elaborated by
further in Chap. 30. -
Bleeding into the tumors (e.g., β2
spinal meningeal or microglobulin); and (6)
epidural spaces can bac
occur in patients who are teria and fungi (by
taking anticoagulants culture), cryptococcal
(gen erally with an antigen, myco bacteria,
international normalized the DNA of herpesvirus,
ratio [INR] >1.7), have cytomegalovirus and
low platelet counts other organisms (by
3
(<50,000/mm ), or polymerase chain
impaired platelet reaction), and viral
function (alcoholism, isolation.
uremia). Treatment is by
reversal of the
Pressure and Dynamics
coagulopathy and, in With the patient in the
some cases, surgical lateral decubitus
evacuation of the clot. position, the CSF
Purulent meningitis and pressure is measured by
disc space infections a manometer attached to
rarely complicate LP as the needle in the
the result of imperfect subarachnoid space. In
sterile technique, and the the normal adult, the
introduction of opening pressure varies
particulate mat ter (e.g., from 100 to 180 mm
talc) can produce a H2O, or 8 to 14 mm Hg.
sterile meningitis. In children, the pressure
is in the range of 30 to 60
Examination mm H2O. A pressure
Procedures above 200 mm H2O with
Once the subarachnoid the patient relaxed and
space has been entered, legs straightened reflects
the pres sure and—in in creased intracranial
now uncommon special pressure. In an adult, a
cases—“dynamics,” pressure of 50 mm H2O
of
the CSF are determined or below indicates
(see below) and samples intracranial hypotension,
generally caused by
of fluid are obtained. The
gross appearance of the leakage of spinal fluid or
fluid is noted, after systemic dehydration.
which the CSF, in When measured with the
separate tubes, can be needle in the
exam ined for (1) lumbar sac and the
number and type of cells patient in a sitting
and presence of position, the fluid in the
microorganisms by manometer rises to the
direct observation; (2) level of the cisterna
protein and glu cose magna (pressure is
content; (3) tumor cells approximately double
(cytology); (4) content of that obtained in the
gamma globulin and recumbent position). It
other protein fractions, fails to reach the level of
presence of oligoclonal the ven tricles because
bands, and serologic the latter are in a closed
tests; (5) pigments, lac system under slight
tate, NH3 (ammonia), negative pressure,
whereas the fluid in the
manom eter is influenced
by atmospheric pressure.
Normally, with the
needle properly placed
in the subarachnoid
space, the fluid in the
manometer oscillates
through a few
millimeters in response
to the pulse and
respiration and rises
promptly with coughing,
straining, and with
jugular vein or
abdominal compression.
An apparent low
pressure can also be the
result of a needle
aperture that is not fully
within the subarachnoid
space; this is ev idenced
by the lack of expected
fluctuations in pressure
with these maneuvers.
The presence of a
spinal subarachnoid
block was in the past
confirmed by jugular
venous compression
(Quecken stedt test,
which tests for a rapid
rise in pressure within a
few seconds after release
of the pressure on the
vein). The maneuver
risks worsening of a
spinal block or of raised
intracranial pressure and
is of historical interest.
Gross Appearance
and Pigments
Normally, the CSF is
clear and colorless.
Minor degrees of color
change are best detected
by comparing test tubes
of CSF and water against
a white background (by
daylight rather than by
fluorescent illumination)
or by looking down into
the tubes from above.
(Examining the fluid col
umn in a hemorrhage, the RBCs
microhematocrit tube is
too narrow for this pur
pose.) The presence of
red blood cells imparts a
hazy or ground-glass
appearance; at least 200
red blood cells (RBCs)
per cubic millimeter
3
(mm ) must be present
to detect this change.
The presence of 1,000 to
6,000 RBCs per cubic
millimeter imparts a
hazy pink to red color,
depend ing on the
amount of blood;
centrifugation of the
fluid or allowing it to
stand causes
sedimentation of the
RBCs. Several hundred
or more white blood
cells (WBCs) in the fluid
(pleocytosis) may cause
a slight opaque haziness.
A traumatic tap, in
which blood from the
epidural venous plexus
has been introduced into
the spinal fluid, may
seriously confuse the
diagnosis if it is
incorrectly interpreted to
indicate a preexistent
subarachnoid hem
orrhage. To distinguish
between these two types
of “bloody taps,” two or
three serial samples of
fluid should be taken at
the time of the LP. With
a traumatic tap, there is
usually a decreasing
number of RBCs in the
second and third tubes.
Also with a traumatic
tap, the CSF pressure is
usually normal, and if a
large amount of blood is
mixed with the fluid, it
will clot or form fibrin
ous webs. These are not
seen with preexistent
hemor rhage because the
blood has been greatly
diluted with CSF and
defibrinated. In
subarachnoid
begin to hemolyze
within a few hours,
imparting a pink-red
discoloration
(erythrochromia) to the
 superna tant fluid; following subarach noid
allowed to stand for a hemorrhage are
day or more, the fluid oxyhemoglobin,
becomes yellow-brown bilirubin, and methe
(xanthochromia). Prompt moglobin. In pure form,
centrif ugation of bloody these pigments are
fluid from a traumatic colored red (orange to
tap will yield a colorless orange-yellow with
supernatant; only with dilution), canary yellow,
large amounts of blood and brown, respectively.
(RBC more than Oxyhemoglobin appears
3
100,000/mm ) will the within sev eral hours of
supernatant fluid hemorrhage, becomes
16 Part 1 THE CLINICAL maximal in approxi
METHOD OF NEUROLOGY mately 36 h, and
diminishes over a 7- to 9-
day period. Bilirubin
be faintly xanthochromic begins to appear in 2 to 3
due to contamination days and increases in
with serum bilirubin and amount as the
lipochromes. oxyhemoglobin
The fluid from a decreases.
traumatic tap should Methemoglobin appears
contain one or two when blood is loculated
WBCs per 1,000 RBCs or encysted and isolated
assuming that the from the flow of CSF.
hematocrit is normal, but Spectrophotometric
in reality this ratio varies techniques can be used
widely. With sub to distinguish the
arachnoid hemorrhage, various hemoglobin
the proportion of WBCs breakdown products and
rises as RBCs hemolyze, thus determine the
sometimes reaching a approximate time of
level of several hundred bleeding.
per cubic millimeter; but Not all xanthochromia
the vagaries of this of the CSF is caused by
reaction are such that it, hemoly sis of RBCs.
too, cannot be relied With severe jaundice,
upon to dis tinguish both conjugated and
traumatic from unconjugated bilirubin
preexistent bleeding. The diffuse into the CSF. The
same can be said for quantity of bilirubin in
crenation of RBCs, which the CSF ranges from
occurs in both types of one-tenth to one-hun
bleeding. dredth that in the serum.
Why red corpuscles Elevation of CSF protein
undergo rapid hemolysis from any cause results in
in the CSF is not clear. It a faint opacity and
is surely not because of xanthochromia, more or
osmotic differences, as less in proportion to the
the osmolarity of plasma albumin-bound fraction
and CSF is essentially of bilirubin. Only at
the same. Fishman protein levels greater
suggests that the low than 150 mg/ 100 mL
protein content of CSF does the coloration
disequilibrates the red become visible to the
cell membrane in some naked eye.
way. Hypercarotenemia and
The pigments that hemoglobinemia
discolor the CSF
(through hemoglobin cells, mononuclear cells,
breakdown products, arachnoid lining cells,
particularly oxyhemo macro phages, and
globin) also impart a tumor cells. Bacteria,
yellow tint to the CSF, as fungi, and fragments of
do blood clots in the echinococci and
subdural or epidural cysticerci can also be
space of the cranium or seen in cell stained or
spinal column. Gram-stained
Myoglobin does not preparations. An India
enter the CSF because a ink preparation is useful
low renal threshold for in distinguishing
this pigment permits between lympho cytes
rapid clear ing from the and cryptococci or
blood. Candida. Acid-fast bacilli
will be found in
Cellularity appropriately stained
During the first month of samples. The mono
life, the CSF may contain graphs of Dufresne and
a small number of of den Hartog-Jager and
mononuclear cells. the arti cle of Bigner are
Beyond this period, the older but still excellent
CSF is normally nearly references on CSF
acellular (i.e., fewer than cytology. Special cell
5 lymphocytes or other separation and
mononuclear cells per immunostain ing
cubic milli meter). An techniques permit the
elevation of WBCs in the recognition of
CSF always signifies a lymphoma cell markers,
reactive process to glial fibrillary acidic
bacteria or other protein, and other
infectious agents, blood, special cellular elements
chemical substances, an and antigens. These and
immunologic inflamma other special methods
tion, a neoplasm, or for the examination of
vasculitis. The WBCs can cells in the CSF are men
be counted in an tioned in the appropriate
ordinary counting chapters.
chamber, but their
identification requires Proteins
centrifugation of the In contrast to the high
fluid and a Wright stain protein content of blood
of the sediment or the (5,500 to 8,000 mg/dL),
use of a Millipore filter, that of the lumbar spinal
cell fixation, fluid is 45 to 50 mg/dL or
less in the adult. The
protein content of CSF
from the basal cisterns is
and staining. One can 10 to 25 mg/dL and that
then recognize and count from the ventricles is 5 to
differen tially 15 mg/dL. This gradient
neutrophilic and may reflect the fact that
eosinophilic leukocytes CSF proteins leak from
(the latter being the blood plasma
prominent in Hodgkin through capillary tight
disease, some parasitic junctions, which form
infections, and the blood–brain and
cholesterol emboli), blood–CSF barrier. The
lymphocytes, plasma spinal fluid is an
 ultrafiltrate of blood
made by the choroid
plexus in the lateral and
the fourth ventricles in a
manner that is analogous
to the for mation of urine
by the glomerulus. The
amount of protein in the
CSF would then be
proportional to the
length of time it is in
contact with the blood–
CSF barrier. Thus shortly
after it is formed in the
ventricles, the protein is
low. More caudally in
the basal cisterns, the
protein is higher and in
the lumbar subarachnoid
space it is highest of all.
In children, the protein
concentration is
somewhat lower at each
level (<20 mg/dL in the
lumbar subarach noid
space). Levels higher
than normal indicate a
patho logic process in or
near the ependyma or
meninges—in either the
brain, spinal cord, or
nerve roots—although
the cause of modest
elevations of the CSF
protein, in the range of
75 mg/dL, frequently
remains obscure.
As one would expect,
bleeding into the
CHAPTER 2 Special Techniques for Neurologic
lesser elevation of
protein—usually 50 to
100 mg/dL but
sometimes up to 200
mg/dL; in some instances
of viral meningitis the
protein content is
normal. Paraventricular
tumors, by reducing the
blood–CSF barrier, often
raise the total protein to
over 100 mg/dL. Protein
values as high as 500
mg/dL are found in
exceptional cases of the
Guillain Barré syndrome
and chronic
ventricles or
subarachnoid space
results in spillage not
only of RBCs but of
serum proteins. If the
serum protein
concentrations are
normal, the CSF protein
should increase by about
1 mg per 1,000 RBCs
provided that the same
tube of CSF is used in
determining the cell
count and protein
content. (The same holds
for a traumatic puncture
that allows seepage of
venous blood into the
CSF at the puncture site.)
How ever, in the case of
subarachnoid
hemorrhage, caused by
the irritating effect of
hemolyzed RBC upon
the lepto meninges, the
CSF protein may be
increased by many times
this ratio.
The protein content of
the CSF in bacterial
meningitis, in which
choroidal and meningeal
perfusion are increased,
often reaches 500 mg/dL
or more. Viral infections
induce a less intense and
mainly lymphocytic
reaction and a
Diagnosis 17
inflammatory
demyelinating
polyneuropathy. Values
of 1,000 mg/dL or more
usually indicate a block
to CSF flow; the fluid is
then deeply yel low and
clots readily because of
the presence of fibrino
gen; a combination
called Froin syndrome.
Partial CSF blocks by
ruptured discs or tumor
may elevate the protein
to 100 to 200 mg/dL. Low
CSF protein values are
some times found in
meningismus (a febrile 30.0 g/dL 70.0 g/dL
Uric acid 0.24 mg/dL
illness with signs of
5.5 mg/dL Urea 4.7
meningeal irritation but mmol/L 5.4 mmol/L
normal CSF), in Creatinine 1.1 mg/dL
hyperthyroidism, or in 1.8 mg/dL Phosphorus
conditions that produce 1.6 mg/dL 4.0 mg/dL
Total lipid 1.5 mg/dL
low CSF pressure (e.g., 750.0 mg/dL
after a recent LP as Total cholesterol 0.4
indicated in Chap. 30). mg/dL 180.0 mg/dL
The quantitative Cholesterol esters 0.3
mg/dL 126.0 mg/dL
partition of CSF proteins
Glucose 60 mg/dL 90.0
by electro phoretic and mg/dL Lactate 1.6 mEq/L
immunochemical 1.0 mEq/L Total protein
methods demonstrates 15–50 mg/dL 6.5–8.4
the presence of most of g/100 dL Prealbumin 1–
7% Trace
the serum proteins with
Albumin 49–73% 56%
a molecular weight of
less than 150,000 to Alpha1 globulin 3–7% 4%
200,000. The protein frac Alpha2 globulin 6–13% 10%
tions that have been gives the quantitative
identified values of the different
electrophoretically are fractions.
pre albumin and Immunoelectrophoretic
albumin as well as methods have also
alpha1, alpha2, beta1, demonstrated the
presence of
beta2, and gamma
glycoproteins,
globulin fraction, the last
ceruloplasmin,
of these being accounted
hemopexin, beta-
for mainly by
amyloid and tau
immunoglobulins (the
proteins. Large
major immunoglobulin
molecules—such as
[Ig] in normal CSF is
fibrinogen, IgM, and
IgG). Table 2-2
lipoproteins—are mostly
excluded from the CSF
unless generated there.
Table 2-2 There are other
notable differences
AVERAGE VALUES
OF CONSTITUENTS between the protein
OF NORMAL CSF fractions of CSF and
AND SERUM plasma. The CSF always
CEREB contains a prealbumin
ROSPI fraction and the plasma
NAL
FLUID SERUM does not. Although
derived from plasma,
Osmolarity 295
mOsm/L 295 this fraction, for an
mOsm/L Sodium 138.0 unknown reason,
mEq/L 138.0 mEq/L concentrates in the CSF,
Potassium 2.8 mEq/L and its level is greater in
4.1 mEq/L Calcium 2.1
ventricu lar than in
mEq/L 4.8 mEq/L
Magnesium 2.3 mEq/L lumbar CSF (perhaps
1.9 mEq/L Chloride because of its concentra
119 mEq/L 101.0 tion by choroidal cells).
mEq/L Bicarbonate Also, the CSF tau
23.0 mEq/L 23.0
mEq/L Carbon dioxide
fraction (also identified
tension 48 mm Hg 38 as beta2-transferrin) is
mm Hg (arterial) essentially detected only
pH 7.31–7.33 7.41
(arterial) Nonprotein
in the CSF and not in
nitrogen 19.0 mg/dL other fluids; its
27.0 mg/dL Ammonia concentration is higher
 in the ventricular than in
the spinal fluid. The con
centration of tau protein
and in particular the
ratio of tau to beta-
amyloid, has found use
in the diagnosis of
Alzhei mer disease, as
discussed in Chap. 39.
The gamma globulin
fraction in CSF is
approximately 70
percent of that in serum.
At present only a few
of these proteins are
known to be associated
with specific diseases of
the nervous system. The
most important is IgG,
which may exceed 12
percent of the total CSF
protein in diseases such
as multiple sclerosis, neu
rosyphilis, subacute
sclerosing
panencephalitis and
other chronic viral
meningoencephalitides.
The serum IgG is not
correspondingly
increased, which means
that this immune
globulin originates in (or
perhaps is preferentially
trans ported into) the
nervous system.
However, an elevation of
serum gamma globulin
—as occurs in cirrhosis,
sarcoidosis, myxedema,
and multiple myeloma—
will be accompanied by
a rise in the CSF
globulin. Therefore, in
patients with an elevated
CSF gamma globulin, it
is necessary to determine
the electrophoretic
pattern of the serum
proteins as well. Certain
qualitative changes in
Beta globulin (beta1 (0.6 to 0.7 of
plus tau) serum
9–19% 12%
concentrations).
Gamma globulin 3–12% 14%
Source: Reproduced by permission marked hyperglycemia,
from Fishman.
the blood glucose in this
the CSF immunoglobulin
pattern, particularly the
demonstration of several
discrete (oligoclonal)
electrophoretic “bands,”
each representing a
specific immune
globulin, and the ratio of
IgG to total pro tein, are
of special diagnostic
importance in multiple
sclero sis, as discussed in
Chap. 36.
The albumin fraction
of the CSF increases in a
wide variety of central
nervous system (CNS)
and craniospinal nerve
root diseases that
increase the permeability
of the blood–CSF barrier,
but no specific clinical
correlations can be
drawn. Certain enzymes
that originate in the
brain, especially the
brain-derived fraction of
creatine kinase (CK-BB)
but also enolase and
neopterin, are found in
the CSF after stroke,
global ischemic hypoxia,
or trauma, and have
been used as markers of
brain damage in
experimen tal work.
Other special markers
such as the 14-3-3
protein, which has some
diagnostic significance in
prion disease, may be
useful in specialized
circumstances.
Glucose
Normally the CSF
glucose concentration is
in the range of 45 to 80
mg/dL, i.e., about two-
thirds of that in the
blood
Higher levels
parallel
proportion; but with
the ratio of CSF to blood
glucose is
18 Part 1 THE CLINICAL
METHOD OF NEUROLOGY lowered the CSF glucose
by their active me
tabolism, but the fact
reduced (0.5 to 0.6). With
that the glucose remains
extremely low serum
at a subnor mal level for
glucose, the ratio
1 to 2 weeks after
becomes higher,
effective treatment of the
approximating 0.85. In
meningitis suggests that
general, CSF glucose
another mechanism is
values below 35 mg/dL
operative. Theoretically
are abnormal. After the
at least, an inhibition of
intravenous injection of
the entry of glucose into
glucose, 2 to 4 h are
the CSF, because of an
required to reach
impairment of the
equilibrium with the
membrane transfer
CSF; a similar delay
system, can be
follows the lowering of
implicated. As a rule,
blood glucose. For these
viral infec tions of the
reasons, samples of CSF
meninges and brain do
and blood for glucose
not lower the CSF glu
determinations should
cose, although low
ide ally be drawn
glucose values have been
simultaneously in the
reported in a small
fasting state or the serum
number of patients with
should be obtained a few
mumps
hours before the
meningoencephali tis,
puncture (this is often
and rarely in patients
not practical). Low
with herpes simplex and
values of CSF glucose
zoster infections.
(hypoglycorrhachia) in
the presence of Serologic and Virologic
pleocytosis usually Tests
indicate pyogenic,
tuberculous, or fungal It has become routine to
meningitis, although test the CSF for
similar reductions are cryptococcal sur face
observed in some antigen as a rapid
patients with method if this infection
widespread neoplastic is suspected. On
infiltration of the occasion, a false-positive
meninges and reaction is obtained in
occasionally with the presence of high
sarcoidosis and titers of rheumatoid
subarachnoid hem factor or antitrepone mal
orrhage (usually in the antibodies, but otherwise
first week). the test is diagnostically
The almost invariable more dependable than
rise of CSF lactate in the conventional India
purulent meningitis ink prepara tion. The
probably means that nontreponemal antibody
some of the glucose is un tests of the blood—
dergoing anaerobic Venereal Disease
glycolysis by Research Laboratories
polymorphonuclear leu (VDRL) slide floc
kocytes and by cells of culation test and rapid
the meninges and plasma reagin (RPR)
adjacent brain tissue. For agglutination test—can
a long time it was also be performed on the
assumed that in CSF. When positive,
meningitis the bacteria these tests are usually
diagnostic of its genomic material is
neurosyphilis, but false most prevalent; after this
positive reactions may time, serologic
occur with collagen techniques for viral
diseases, malaria, and infection are more
yaws, or with sensitive. Amplification
contamination of the CSF of DNA by PCR is
by seropositive blood. particularly useful in the
Tests that depend on the rapid detection of tuber
use of trepone mal cle bacilli in the CSF, the
antigens, including the conventional culture of
Treponema pallidum which takes several
immobiliza tion test and weeks at best. Tests for
the fluorescent the detection of prion
treponemal antibody proteins in the spinal
test, are more specific fluid are available and
and assist in the may aid in the diagnosis
interpretation of false- of the spongiform
posi tive reactions. The encephalopathies, but
value of CSF the results have been
examinations in the diag erratic (Chap. 33).
nosis and treatment of
neurosyphilis is Changes in Solutes
discussed in Chap. 32, and Other
but routine testing of Components
CSF for treponemal The average osmolality
antibodies is no longer of the CSF (295 mOsm/L)
practiced. Serologic tests is iden tical to that of
for the Lyme spirochete plasma. As the
are useful in osmolality of the plasma
circumstances of is increased by the
suspected infection of intravenous injection of
the central nervous hypertonic solu tions
system with this agent. such as mannitol or urea,
The utility of serum there is a delay of up to
serologic tests for viruses several hours in the rise
is limited by the time of osmolality of the CSF.
required to obtain It is dur ing this period
results, but they are that the hyperosmolality
useful of the blood dehydrates
the brain and decreases
the volume of CSF.
Table 2-2 lists the CSF
in determining
and serum levels of
retrospectively the
sodium, potassium,
source of meningitis or
calcium, and
encephalitis. More rapid
magnesium. Neurologic
tests that use the
disease does not alter the
polymerase chain
CSF concentrations of
reaction (PCR) in CSF,
these constituents in any
which amplifies viral
characteristic way. The
DNA fragments, are
low CSF concentration of
now widely available for
chloride that occurs in
diagnosis, partic ularly
bacterial meningitis is
for herpesviruses and
not specific but a
cytomegalovirus. These
reflection of
tests are most useful in
hypochloremia and, to a
the first week of
slight degree, of a greatly
infection, when the virus
elevated CSF protein.
is being reproduced and
 Acid–base balance in the
CSF is of interest in
relation to metabolic
acidosis and alkalosis
but pH is not routinely
measured. Normally, the
pH of the CSF is
approximately 7.31—i.e.,
somewhat lower than
that of arterial blood,
CO
which is 7.41. The P 2
in the CSF is in the range
of 45 to 49 mm Hg—i.e.,
higher than in arterial
blood (about 40 mm Hg).
The bicarbonate levels of
the two fluids are about
the same, 23 mEq/L. The
pH of the CSF is
precisely regulated, and
it tends to remain
relatively unchanged
even in the face of severe
systemic acidosis and
alkalosis. Acid–base
changes in the lumbar
CSF do not necessarily
reflect the presence of
similar changes in the
brain, nor are the CSF
data as accurate an index
of the systemic changes
as direct measurements
of arterial blood gases.
The ammonia content of
the CSF is one-third to
CHAPTER 2 Special Techniques for Neurologic
one-half that of the
arterial blood; it is
increased in hepatic
enceph alopathy, the
inherited
hyperammonemias, and
the Reye syndrome; the
concentration
corresponds roughly
with the severity of the
encephalopathy. The
uric acid content of CSF
is approximately 5
percent of that in serum
and varies with changes
in the serum level (high
in gout, ure mia, and
meningitis, and low in
Wilson disease). The
urea concentration in the
CSF is slightly lower
than that in the serum; in
uremia, it rises in
parallel with that in the
blood. An intravenous
injection of urea raises
the blood level
immediately and the
CSF level more slowly,
exerting an osmotic
dehydrating effect on the
central nervous tissues
and CSF. All 24 amino
acids have been isolated
from the CSF. The
concentration of amino
acids in the CSF is
Diagnosis 19

approximately one-third enzyme changes has

that in plasma. proved to be a specific
Elevations of glutamine indicator of neurologic
are found in hepatic disease with the possible
coma and the Reye syn exception of lactic
drome and of dehydrogenase, espe cially
phenylalanine, histidine, isoenzymes 4 and 5,
valine, leucine, which are derived from
isoleucine, tyrosine, and granu locytes and are
homocystine in the elevated in bacterial
correspond ing meningitis but not in
aminoacidurias. aseptic or viral
Many of the enzymes meningitis. Lactic
found in serum are dehydrogenase is also
known to rise in CSF elevated in cases of
under conditions of meningeal metastases, as
disease, usually in is carcino embryonic
relation to a rise in the antigen; the latter,
CSF protein. None of the however, is not elevated
in bacterial, viral, or
fungal meningitis. As to
lipids, the quan tities in
CSF are small and their
measurement is difficult.
The catabolites of the
catecholamines can be
measured in the CSF.
Homovanillic acid
(HVA), the major
catabolite of dopamine,
and 5-
hydroxyindoleacetic acid
(5-HIAA), the major
catabolite of serotonin,
are normally present in
the spinal fluid; both are
five or six times higher
in the ventric ular than
the lumbar CSF. The
levels of both catabolites
are reduced in patients
with idiopathic and
drug-induced
parkinsonism.
Finally, it may be said
that with continued
development of
microchemical
techniques for the
analysis of the CSF, we
can look forward to a
better understanding of
the met abolic
mechanisms of the brain,
particularly in the heredi
tary metabolic diseases.
Ultrarefined methods
such as gas liquid
chromatography will
probably reveal many
new catabolic products,
the measurement of
which will be of value in
diagnosis and therapy.
Thompson has reviewed
the biochemical analysis
of CSF and its use for
diagnostic purposes.
IMAGING
TECHNIQUES OF
THE SKULL, BRAIN,
AND SPINE
In the past, plain films of
the cranium constituted
a “rou tine” part of the
study of the neurologic
patient, but it is has
become evident that the
yield of useful
information from this
procedure is relatively
small. Even in patients
with head injury, where
radiography of the skull
would seem to be an
optimal method of
examination, a fracture is
found in only 1 of 16
cases, at a cost of
thousands of dol lars per
fracture and a small risk
from radiation exposure.
Nevertheless plain skull
films do demonstrate
fractures, changes in
contour of the skull,
bony erosions and hyper
ostoses, infection in
paranasal sinuses and
mastoids, and changes in
the basal foramina. Plain
films of the spine are
able to demonstrate
osteoarthritic bony
overgrowth, de structive
lesions of vertebrae, both
neoplastic and infec
tious, fracture
dislocations and other
spondylolistheses, and
Pott and Paget diseases.
Sequential refinements
of radiologic technique
have greatly increased
the yield of valuable
information in special
cases, but without
question the most
important advances in
neuroradiology have
come about with the
development of
CT and MRI. They
represent a quantum
improvement in our
ability to visualize
pathology in the living
person.
Computed
Tomography
In this procedure,
conventional x-radiation
is attenuated as it passes
successively through the
skull, CSF, cerebral gray
and white matter, and
blood vessels. The
intensity of the exiting
radiation relative to the
incident radiation is
measured, the data are
integrated, and images
are recon structed by
computer. This major
achievement in method
ology, attributed to
Hounsfield and others,
permitted the
astonishing technologic
advance from plain
radiographs of the skull
to reconstructed images
of the cranium and its
contents in any plane.
More than thirty
thousand 2- to 4- mm x-
ray beams are directed
successively at several
hori zontal levels of the
cranium. The differing
densities of bone, CSF,
blood, and gray and
white matter are distin
guishable in the
resulting picture. One
can see hemor rhage,
softened and edematous
brain, abscess, and
tumor tissue and also the
precise size and position
of the ventri cles and
midline structures. The
radiation exposure is not
significantly greater than
that from plain skull
films.
The latest generation
of CT scanners affords
pictures of brain, spine,
and orbit of great clarity.
As illustrated in Fig. 2-
1A-D, in transverse
section of the brain, one
actually sees displayed
the caudate and
lenticular nuclei and the
internal capsules and
thalami. The position
and width of all the main
sulci can be measured,
and the optic nerves and
medial and lateral rectus
muscles stand out clearly
in the posterior parts of
the orbit. The brainstem,
cerebellum, and spinal
cord are easily visible in
the scan at appropriate
levels. The scans are also
useful in imaging parts
of the body that
surround peripheral
nerves and plexuses,
thereby demonstrating
tumors, inflammatory
lesions, and hematomas
that involve these
nerves. In imaging of the
head, CT has a number
of advantages over MRI,
the most important being
safety when metal is
present in the body and
the clarity of blood from
the moment of bleeding.
Other advantages are its
lower cost, easy
availability, shorter
examination time, and
equivalent or superior
visualization of calcium,
fat, and bone,
particularly of the skull
base and vertebrae. Also,
if constant monitoring
and use of life support
equipment is required
during the imag ing
procedure, it is
accomplished more
readily in the CT than
the MRI machine. Recent
advances in CT
technology have greatly
increased the speed of
the scanning proce dure
and have made possible
the visualization, with
great clarity, of the
cerebral vasculature (CT
angiography; see further
on).
Contrast
Myelography
By injecting 5 to 25 mL
of a water-soluble
radiopaque dye through
an LP needle and then
tipping the patient down LP except for cases of
ward on a tilt table, the complete spinal block, in
entire spinal which high
subarachnoid space can concentrations of dye
be visualized (Fig. 2-1E near the block can cause
and F). The procedure is pain and regional
almost as harmless as the myoclonus. Herniated
20 Part 1 THE CLINICAL METHOD OF
NEUROLOGY

Figure 2-1. Normal axial CT scans of the brain, orbits,

and lumbar spine from a young healthy man. A. Image
through the cerebral hemispheres at the level of the
corona radiata. The dense bone of the calvarium is white.
Gray matter appears denser than white matter. The
triangular shape of the sagittal sinus in axial section is
seen posteriorly. B. Image at the level of the lenticular
nuclei. The caudate and lenticular nuclei are denser than
the adjacent internal capsule. CSF within the frontal and
occipital horns of the lateral ventricle as well as
surrounding the pineal body appears dark. Calcium is
seen in the left choroid plexus and, to a slight extent, in
the pineal. C. Image at the level of the posterior fossa.
Again, the CSF within the fourth ventricle and prepontine
cisterns appears dark. The basilar artery is seen as a
small, round, dense focus anterior to the pons. Typ ical
artifact generated by temporal bones creates streaking
across the inferior temporal lobes. The mastoid and
sphenoid sinuses are black as a result of their aeration. D.
Thin-section axial image through the midorbits. The
sclera appears as a dense band surrounding the globe.
 Medial and lateral rectus muscles have a fusiform shape.
Orbital fat appears dark because of its low attenuation
value. Air contained within the sphenoid sinus and
ethmoid air cells appears black. (continued)

lumbar and cervical lesion that completely

discs, cervical
spondylotic bars and
bony spurs encroaching
on the spinal cord or
roots, and spinal cord
tumors can be diagnosed
accurately. Iophendy late
(Pantopaque), a formerly
used fat-soluble dye, is
still approved by the
FDA but is now
employed only in special
circumstances
(visualizing the upper
level of a spinal canal
CHAPTER 2 Special Techniques for Neurologic
obstructs the flow of
water soluble dye). If
iophendylate is left in
the subarachnoid space,
par ticularly in the
presence of blood or
inflammatory exudate, it
may incite arachnoiditis
of the spinal cord and
brain.
The CT body scan also
provides excellent
images of the spinal
canal and intervertebral
foramina in three planes,
Diagnosis 21

Figure 2-1. (Continued) E. and F. Axial images of the

lumbar spine following myelography. Contrast contained
within the thecal sac appears white. The filling defects are
caused by nerve roots at the L3-L4 and L5-S1 levels. Bony
structures appear dense, and the facet joints are well
seen.

making the combination visualizing small areas

of water-soluble dye and within the spinal canal,
CT scan ning a useful such as the lateral
means of visualizing recesses and spinal
spinal and posterior nerve root sleeves. MRI
fossa lesions. Contrast pro vides even sharper
myelography is visualization of the
particularly useful in spinal canal and its
contents, as well as the the signals being
vertebrae and measured after the
intervertebral discs; application of each
consequently, it has pulse. The scanner stores
largely replaced contrast the signals as a matrix of
myelography because it data,
does not require LP. which is subjected to
computer analysis and
Magnetic Resonance from which an image is
Imaging constructed.
Nuclear magnetic
MRI also provides resonance can be
“slice” images of the detected from several
brain in any plane, but it endogenous isotopes,
has the great advantages but current technology
over CT of using uses mainly signals
nonionizing energy and derived from hydrogen
providing better 1
atoms ( H), because
resolution of dif ferent
hydro gen is the most
structures within the
abundant element in
brain and other organs.
tissue and yields the
For the visualization of
strongest magnetic
most neurologic
signal. The image is
diseases, MRI is the best
essentially a map of the
procedure.
hydrogen content of
An MRI examination
tissue, therefore
is accomplished by
reflecting largely the
placing the patient
water concentration, but
within a powerful
influenced also by the
magnetic field, causing
physical and chemical
certain endogenous
environment of the
isotopes (atoms) of the
hydrogen atoms. Differ
tissues and CSF to align
ent tissues have different
themselves in the
rates of proton
longitudinal orientation relaxation, yield ing
of the magnetic field. different signal
Application of a brief intensities and hence
(few milliseconds) tissue contrast. The
radiofrequency (RF) terms T1 and T2 refer to
pulse into the field the time constants for
changes the axis of proton relaxation; these
alignment of the atoms may be altered to
from the longitudinal to highlight certain features
the transverse plane. of tissue structure. In the
When the RF pulse is T1-weighted image, the
turned off, the atoms CSF appears dark and
return to their original the cortical border and
alignment. The RF cortical–white matter
energy that was junction are well
absorbed and then defined, as in CT
emitted results in a images, whereas T2-
magnetic signal that is weighted images show
detected by the CSF as white. T2-
electromagnetic receiver weighted images
coils. To create highlight alterations in
contrasting tissue white matter such as
images from these infarc tion,
signals, the RF pulse demyelination, and
must be repeated many edema (Table 2-3).
times (a pulse sequence), Gradient-echo (GRE)
sequences, a type of
susceptibility technique,
is espe cially sensitive to
blood and its breakdown
products, which appear
as dark regions in the
image.
So-called FLAIR
(fluid-attenuated
inversion recovery)
imaging is a technique
that gives a high signal
for paren chymal lesions
and a low signal for CSF.
It is sensitive to calcium
and iron within brain
tissue, shows early
22 Part 1 THE CLINICAL METHOD OF
NEUROLOGY
stages of infarction, and
accentuates
inflammatory
demyelinating lesions.
The images generated by
the latest MRI machines
are truly remarkable
(Fig. 2-2A to C). Because
of the high degree of
contrast between white
and gray matter, one can
identify all discrete
nuclear structures and
lesions within them.
Deep lesions in the
temporal lobe and
structures in

Table 2-3
CT AND MRI IMAGING CHARACTERISTICS OF
VARIOUS TISSUES
TISSUE CT GRAY SCALE MRI T1 SIGNAL MRI T2 SIGNAL

Brain Gray Gray Gray Air Black Black Black CSF

Black Black White Fat Black White Black
Calcium White Black Black Bone Very white
Black Black Extravasated blood White White
Black Inflammation Contrast enhancing Gray,
gadolinium enhancing White Edema Dark gray
Gray White Tumor Gray or white and contrast
enhancing Gray or white and gadolinium
enhancing White
Figure 2-2. Normal MRI of the brain and the cervical and
lumbar spine. A. T2-weighted (SE 2500/90) axial image at
the level of the lenticular nuclei. Note that gray matter
appears brighter than white matter. The CSF within the
lateral ventricles is very bright. The caudate nuclei,
putamen, and thalamus appear brighter than the internal
capsule, while the globus pallidus is darker. B. T2-
weighted (SE 2500/90) axial image at the level of the
midbrain. The red nucleus and substantia nigra are dark
due to normal iron accumulation. The CSF within the
lateral ventricles and subarach noid spaces appears bright,
as does the vitreous. Signal is absent (“flow void”) from
the rapidly flowing anterior, middle, and posterior
cerebral arteries. C. T1-weighted (SE 700/17) midline
sagittal image of the brain. Note that white matter appears
brighter than gray matter and the corpus callosum is well
defined. Subcutaneous fat and calvarial marrow appear
very bright. The pons, medulla, and cervicomedullary
junction are well delineated, and the region of the
pituitary gland is normally demonstrated. D. Gradient-
echo sagittal image of the cervical spine. Note the bright
signal intensity of the CSF, which provides a
“myelographic” effect. Intervertebral discs also
demonstrate high signal intensity. The spinal cord and
brain demonstrate intermediate signal intensity, and the
craniocervical junction is clearly defined. (continued)
CHAPTER 2 Special Techniques for Neurologic
Diagnosis 23
 Figure 2-2. (Continued) E. T2 axial
image
of the lumbar spine at the L3-L4
level.
The CSF within the thecal sac is
bright.
The sensory ganglia can be seen in
the
lateral portions of the neural
foramina.
The inferior articulation of the facet
joint
is demonstrated. F. Gradient-echo
sagit
tal image of the lumbar spine, again
showing bright CSF signal intensity,
cre
ating a “myelographic” effect. The
conus
medullaris is well demonstrated and
in
dividual nerve roots of the cauda equina
can be seen streaming toward their lev
els of exit.

the posterior fossa and at to F) and of

the cervicomedullary syringomyelia and other
junction are seen much lesions (herniated discs,
better than with CT; the tumors, epidural or
structures can be subdu ral hemorrhages,
displayed in three planes areas of demyelination,
and are unmarred by and abscesses). It has
signals from adjacent replaced contrast
skeletal structures (bony myelography except in
artifact). Demyelin ative certain cir cumstances
lesions stand out with where very-high-
greater clarity and resolution images of
infarcts can be seen at an nerve roots and spinal
earlier stage than with cord are required.
CT. Each of the prod ucts The administration of
of disintegrated RBCs— gadolinium, a
methemoglobin, paramagnetic agent that
hemosiderin, and ferritin enhances the process of
—can be recognized, proton relaxation dur
enabling one to date the ing the T1 sequence of
age of hemorrhages and MRI, permits even
to follow their sharper defini tion and
resolution, as dis cussed highlights regions
in Chaps. 34 and 35. surrounding many types
Similarly, CSF, fat, of lesions where the
calcium, and iron have blood–brain barrier has
their own signal been disrupted in the
characteristics in brain, spinal cord, or
different imaging nerve roots.
sequences. The degree of
MRI imaging of the cooperation that is
spine provides clear required to perform MRI
images of the vertebral limits its use in young
bodies, intervertebral children and in the
discs, spinal cord, and cognitively impaired.
cauda equina (Fig. 2-2D
Some form of sedation is that have been tested for
required in these indi their ferromagnetic
viduals and most susceptibility and their
hospitals have services safety in the MRI
to safely accom plish machine can be found in
conscious sedation for the monograph by
this purpose. Studying a Shellock, which is
patient who requires a updated regularly. MRI
ventilator is difficult but entails some risk in these
manage able by using situations unless there is
either hand ventilation direct knowledge of the
or nonferromagnetic type of material that had
ventilators (Barnett et al). been used. There have
The main dangers in also been numerous
the use of MRI are instances over the years
torque, dislodge ment or in which physicians have
heating of metal clips on rushed into the MRI
blood vessels, of dental room to assist an acutely
devices and other ill patient, only to have
ferromagnetic objects, metal instruments drawn
and of small metal from their pockets and
fragments in the orbit, forcibly strike the patient
often acquired unnoticed or magnet.
by opera tors of machine Because of the
tools. For this reason it is development of cataracts
wise, in appropri ate in the fetuses of animals
patients, to obtain plain exposed to MRI, there
radiographs of the skull has been hesitation in
so as to detect metal in per forming MRI in
these regions. Corneal pregnant patients,
metal fragments can be especially in the first
removed by an trimester. However,
ophthalmic surgeon if an current data indicate that
MRI is consid ered to be imaging may be
obligatory. The presence performed provided that
of a cardiac pacemaker, the study is medically
defibrillator, or indicated. In a study of
implanted stimulator in 1,000 pregnant MRI
the brain or spinal cord technicians who entered
is an absolute the magnetic field
contraindication to the frequently (the magnet
use of MRI as the remains on between
magnetic field induces procedures), no adverse
unwanted currents in the effects on the fetus could
device and the wires be discerned (Kanal et
exiting from it. However, al).
most of the newer, Many types of MRI
weakly ferromagnetic artifacts are known,
prosthetic heart valves, most having to do with
intravascular access malfunction of the
ports, modern aneurysm electronics of the
clips, and ventricular magnetic
shunts and adjustable 24 Part 1 THE CLINICAL
valves do not represent METHOD OF NEUROLOGY
an untoward risk for
magnetic imaging. The
field or of the mechanics
same is true for modern
involved in the imaging
joint prostheses. An
proce dure (for details,
extensive list of devices
see the monograph of
Huk et al). Among the drawn to diffusion
most common and weighted imaging
problematic are CSF (DWI), a procedure that
flow artifacts in the takes only a minute to
thoracic spinal cord, accomplish and has been
giving the impression of invaluable in detect ing
an intradural mass; the earliest stages of
distortions of the ischemic stroke
appearance of struc tures (generally within 2 h or
at the base of the brain less of the onset); it is
from ferromagnetic also particularly useful
dental appliances; and in dis tinguishing
lines across the entire between cerebral
image induced by blood metastases and
flow and patient abscesses. Here, the
movement. restricted diffusion of
In recent years an water in the region of
additional risk of cerebral infarction
nephrogenic fibrosis has appears as a bright white
been identified related to signal. Com plementary
the administration of perfusion-weighted
gado linium. Most imaging (PWI) may be
instances occur in used to detect areas that
patients with preexisting are lacking in blood
renal failure, for which flow; in par allel with
reason it has become DWI, it may be able to
common to obtain BUN delineate regions of
and creatinine ischemia that are not yet
measurements before irrevocably infarcted and
adminis tering the agent. there fore subject to the
The problem had not restoration of blood flow
been appreciated by various techniques
previously in part (Chap. 34). The capacity
because of its rarity (the of MRI to quantitate the
frequency has not been volume of anatomic
well established) and structures also offers the
because of a delay in prospect of
toxic effects on the demonstrating neuronal
kidney, ranging from atrophies.
several days to two Every few years some
months. refinement in the
The technology of MRI interpretation of signal
is constantly evolving. characteristics and
The visu alization of morphologic changes
blood vessels in the appears, as do new ways
brain (magnetic of using this technology
resonance angiography; in the study of brain
see further on) as well as metabolism and blood
tumors, compres sive flow (“functional” MRI,
lesions, traumatic or fMRI). These
discontinuities of functional images taken
peripheral nerves (Filler in normal patients
et al), and during the performance
developmental defects of of cognitive and motor
the CNS are among the tasks and in those with
more refined and neurologic and
promising applications psychiatric disease are
of MRI. Particular exposing novel patterns
attention should be of cerebral activation and
alter ing some of the
traditional concepts of
cortical function and
localization. The main
technique currently in
use measures the
difference between oxy-
and deoxyhemo globin,
which reflects blood
delivery to a region. This
blood oxygen level-
dependent (BOLD) signal
can be extracted from
MRI data and used as a
surrogate for local
cerebral metabolic
activity.
Increasing use is being
made of diffusion tensor
imag ing (DTI), mainly
in delineating nerve fiber
tracts in the brain, but
other algorithms are
being developed for spe
cial study. The technique
depends on the
observation that water
and other molecules, in
their random movement
by diffusion, probe
tissues at resolutions
well beyond that of
usual imaging. The
movement of these
molecules in three
dimensions is impeded
by brain tissue and thus
is not uni form; DTI
measures the degree of
nonuniformity, or
anisotropy, which gives
a very detailed picture of
the local tissue structure
with extraordinary
resolution.
The increasing use of
MRI and the sensitivity
of current machines and
computer algorithms
have had the unin
tended effect of
revealing a large number
of unimportant findings
that create undue worry
and often trigger a neu
rologic consultation.
However, a surprising
number of incidental
brain lesions of
consequence are also
exposed. For example, a
large survey of
asymptomatic adults
who were being
followed in the
“Rotterdam Study” is in
accord with several prior
studies in which cerebral
aneu rysms were found
in approximately 2
percent, meningio mas in
1 percent, and a smaller
but not insignificant
number of vestibular
schwannomas and
pituitary tumors; the
meningiomas, but not
the aneurysms, increased
in fre quency with age.
One percent had the
Arnold-Chiari mal
formation, and a similar
number had arachnoid
cysts. In addition, seven
percent of adults older
than age 45 years had
occult strokes, mostly
lacunar. Because this
survey was performed
without gadolinium
infusion, it might be
expected that even more
small lesions could be
revealed (Vernooij et al).
The technique of
magnetic resonance
spectroscopy, actually a
derivative of nuclear
magnetic resonance
(NMR), is beginning to
find increasing use in the
analysis of certain
cerebral lesions. As
currently used, a region
of brain is chosen for
analysis and magnetic
resonance frequency
sequences are applied
that detect signals from
the relax ation of the
electrochemical bonds of
various constituents of
brain tissue. The main
ones are choline and N-
acetyl aspartate (NAA);
the choline is contained
 mainly in cell advent of CT and MRI,
membranes of myelin the use of angiogra phy
and NAA is a marker for has practically been
neurons. Also detectable limited to the diagnosis
are breakdown products of these vascular
of myelin, which appear disorders, and
to the right of NAA on refinements in the
the spectrogram. In this former two tech niques
way, a lesion caused by (magnetic resonance
infarction, tumor, or angiography [MRA] and
demyelina tion can be spiral and helical CT
distinguished. scanning, described
The use of CT further on) promise to
scanning and MRI in the eliminate even these
diagnosis of par ticular applications of
neurologic disorders is conventional x-ray
considered in the angiography. However,
appropri ate chapters. new endovascular
procedures for the
Angiography ablation of aneurysms,
arteriovenous
This technique has malformations, and
evolved over the past 50 vascular tumors still may
years to the point where require the incorporation
it is a safe and valuable of conventional
method for the diagno angiography.
sis of aneurysms, Following local
vascular malformations, anesthesia, a needle is
narrowed or occluded placed in the femo ral or
arteries and veins, brachial artery; a
arterial dissections, and cannula is then threaded
angi itis. Since the through the
CHAPTER 2 Special Techniques for Neurologic
Diagnosis 25

needle and along the the injected medium

aorta and the arterial may induce vascular
branches to be spasm and occlusion,
visualized. In this way, a and clots may form on
contrast medium can be the catheter tip and
injected to visualize the embolize the artery.
arch of the aorta, the Overall morbidity from
origins of the carotid and the procedure is
vertebral systems, and approximately 2.5
the extensions of these percent, mainly in the
systems through the form of worsening of a
neck and into the cranial preexistent vascular
cavity. Experienced lesion or from
arteriographers can complications at the site
visualize the cerebral of artery puncture.
and spinal cord arteries Occasionally, a frank
down to about 0.1 mm in brain or leg ischemic
lumen diameter (under lesion is produced,
optimal conditions) and probably the result of
small veins of particu late
comparable size. atheromatous material
Angiography is not that is dislodged by the
altogether without risk. catheter or less often, by
High concen trations of dissection caused by the
catheter. The patient
may be left hemiplegic,
quadriplegic, or blind;
for these reasons the
procedure should not be
undertaken unless it is
deemed necessary to
obtain a clear diagnosis
or in anticipation of
surgery that requires a
definition of the location
of the vessels. A cervical
myelopathy is a very
infre quent but
disastrous complication
of vertebral artery dye
injection; the problem is
heralded by pain in the
back of the neck
immediately after
injection. Progressive
cord ischemia from an
ill-defined vascular
pathology ensues over
the fol lowing hours.
This same complication
may occur at other levels
of the cord following
visceral angiography.
With current
refinements of radiologic
technique that use
digital computer
processing of radiologic
data to pro duce images
of the major cervical and
intracranial arteries, the
vessels can be visualized
with relatively small
amounts of dye that are
introduced through
smaller catheters than
those used previously.
Magnetic
Resonanc
e and
Computed
Tomograp
hic
Angiogra
phy
These are noninvasive
techniques for
visualizing the main
intracranial arteries.
They can reliably detect
intra cranial vascular
lesions and extracranial
carotid artery ste nosis
and are supplanting
conventional
angiography. They
approach, but have not
yet reached, the
radiographic resolution
of invasive angiography
for distal vessels and for
the fine detail of
occlusive lesions, but
they are very useful in
gauging the patency of
the large cervical and
basal vessels (Fig. 2-3A
to D). Visualization of
the cerebral veins is also
possible. Unlike MRA,
the CT technique
requires the injection of
intravenous dye but has
the great advantage of
showing blood vessels
and their anomalies in
relation to adjacent brain
and bone (Fig. 2-3E). The
use of these and other
methods for the
investigation of carotid
artery disease
(ultrasound Doppler
flow and imaging
techniques) is discussed
further below and in
Chap. 34, on cerebral
vascular disease.
Positron Emission
Tomography
This technique,
commonly known as
PET, measures the
regional cerebral
concentration of
systemically adminis
tered radioactive tracers.
Positron-emitting
11
isotopes (usu ally C,
18 13 15
F, N, and O) are
produced in a cyclotron
or linear accelerator and
incorporated into
biologically active
compounds in the body.
The concentration of the
tracers in various parts
of the brain is
determined
noninvasively, by This technique, which
detectors outside the has evolved from PET,
body, and tomographic uses isotopes that do not
images are constructed require a cyclotron for
by techniques similar to their production. Radioli
those used in CT and gands (usually
MRI. containing iodine) are
Local patterns of incorporated into bio
cerebral blood flow, logically active
oxygen uptake, and compounds, which, on
glucose utilization can decay, emit only a single
be measured by PET photon. This procedure
scanning, and the allows the study of
procedure has proved to regional cerebral blood
be of value in grading flow under conditions of
primary brain tumors, cerebral ischemia or
distinguishing tumor during intense tissue
tissue from radiation metabolism. The
necrosis, localizing restricted anatomic
epileptic foci, and, resolution provided by
especially, single-photon emission
differentiating types of computed tomography
dementing diseases. The (SPECT) has limited its
technique was recently clinical usefulness, but
applied to specially its wider availability
labeled ligands of patho makes it appealing for
logic chemical species clinical use. This has
such as beta-amyloid, proved particularly true
enabling imaging of the in helping to distinguish
deposition of these between Alzheimer
proteins in the brain as dementia and a number
an experimental method of focal cerebral (lobar)
for detecting and atrophies, and in the
following Alz heimer localization of epileptic
disease. No doubt this foci in patients who are
approach will become candidates for cortical
increasingly important resection. Once injected,
in the study of the isotope localizes
degenerative dis eases rapidly in the brain, with
and their response to regional absorption
treatment. The ability of proportional to blood
the technique to flow, and is then stable
quantitate for an hour or more. It is
neurotransmitters and thus possible, for
their recep tors also example, to inject the
promises to be of isotope at the time of the
importance in the study seizure onset, while the
of Par kinson disease patient is undergoing
and other degenerative video and
diseases. This electroencephalographic
technology requires monitoring, and to scan
costly facilities and has the patient later.
limited avail ability at
the moment.
Ultrasonography
In recent years this
Single-Photon
technique has been
Emission
refined to the point
Computed
where it has become a
Tomography
principal methodology
for clinical study of the
fetal and neonatal brain
and an important ancil
lary test for the cerebral
vessels in adults. The
instrument for this
application consists of a
26 Part 1 THE CLINICAL METHOD OF
NEUROLOGY
transducer capable of
convert ing electrical
energy to ultrasound
waves of a frequency
ranging from 5 to 20
kHz. These are
transmitted through the

Figure 2-3. A. Magnetic resonance angiogram (MRA) of the

intracranial vessels (antero
posterior projection). Visualized are the large carotid
arteries ascending on either side
of the smaller vertebral arteries, which join to form the
basilar artery in the midline.
This technique allows resolution of the middle and anterior
cerebral arteries beyond
their first branchings. B. Lateral views of the intracranial
MRA, showing the two large
carotid arteries superimposed on each other anteriorly,
giving rise to the middle and
anterior cerebral arteries, and the vertebral and basilar
 arteries posteriorly, which in
turn give rise to the posterior cerebral arteries. C. Normal
MRA of the cervical portions
of the common, internal, and external carotid arteries, and
the lone, smaller vertebral
artery. D. CT angiogram (CTA) performed by injection of
intravenous contrast, show
ing intracranial vessels. E. CT angiogram, lateral view of the
extracranial carotid circu
lation (densely opacified common [bottom white arrow],
internal and external carotid
arteries) and adjacent less opacified jugular vein. The distal
extracranial vertebral
artery can be seen looping around C-2 posteriorly (upper
black arrow).

intact skull into the and central nuclear

brain. Different tissues masses. Usually several
have a variable acoustic coronal and parasagittal
impedance and send views are obtained by
echoes back to the placing the transducer
transducer, which over open fontanelles or
displays them as waves the child’s thin
of variable height or as calvarium. Intracer ebral
points of light of varying and subdural
intensity. In this way, hemorrhages, mass
one can obtain images in lesions, and congen ital
the neonate of choroid defects can readily be
plexuses, ventricles, visualized.
CHAPTER 2 Special Techniques for Neurologic
Diagnosis 27

Similar instruments stenosis as reflected by

are used to insonate the
basal ves sels of the circle
of Willis (“transcranial
Doppler”), the cer vical
carotid and vertebral
arteries, and the
temporal arteries for the
study of cerebrovascular
disease. Their greatest
use is in detecting and
estimating the degree of
stenosis of the origin of
the internal carotid
artery. In addi tion to
providing a sound image
of the vascular
structures, the Doppler
frequency shift caused
by flowing red blood
cells creates a display of
velocities at each site in a
vessel. The two
techniques combined
have been called “carotid
duplex”; they allow an
accurate localization of
the locus of maximal
the highest rates of flow
and turbulence. The
display scale for the
Doppler shift is color
coded so as to make the
insonated image and
flow map easy to view
and interpret.
The transcranial
Doppler uses a 2-MHz
pulsed signal that is able
to transgress the
calvarial bone in adults
and then receives a
frequency-shifted signal
from the blood flowing
in the lumen of the basal
vessels. This allows the
detection of vascular
stenoses and the greatly
increased blood flow
veloc ity caused by
vasospasm from
subarachnoid
hemorrhage.
Ultrasound has several
advantages, notably that
it is noninvasive, in neurology cannot
harmless (hence can be suitably be assigned to
used repeatedly), any other single chapter.
convenient because of The
the portability of the electroencephalograph
instrument, and records spontaneous
inexpensive. More electrical activity
specific applications of generated in the cerebral
this tech nique are cortex. This activity
discussed in Chap. 38, reflects the electrical
on developmental dis currents that flow in the
eases of the nervous extracellular spaces of
system, and in Chap. 34, the brain that are the
on stroke. summated effects of
The related technique innumerable exci tatory
of echocardiography has and inhibitory synaptic
also assumed a central potentials upon cortical
role in the evaluation of neu rons. This
stroke, as indi cated in spontaneous activity of
Chap. 34. cortical neurons is much
influenced and
synchronized by
subcortical structures,
ELECTROENCEPHA
par ticularly the
LOGRAPHY
thalamus and high
brainstem reticular
The
forma tion. Afferent
electroencephalographic
impulses from these
examination, for many
deep structures are
years a standard
probably responsible for
laboratory procedure in
entraining cortical
the study and
neurons to pro duce
localization of all forms
characteristic rhythmic
of cerebral disease, has to
brain-wave patterns,
a large extent been sup
such as alpha rhythm
planted by CT and MRI
and sleep spindles (see
for the purposes of
further on).
localization. Nev
Electrodes, which are
ertheless, it continues to
silver or silver-silver
be an essential part of the
chloride discs 0.5 cm in
study of patients with
diameter, are attached to
seizures and those
the scalp by means of a
suspected of having
conductive paste. The
seizures, as well as in
electroencephalograph
brain death and for the
has 8 to 32 or more
study of sleep (polysom
amplifying units capable
nography). It is also used
of recording from many
in evaluating the cerebral
areas of the scalp at the
effects of many systemic
same time. The amplified
metabolic diseases and
brain rhythms are seen
in the operating room to
as waveforms of brain
monitor cerebral activity
activity in the fre quency
in anesthetized patients.
range of 0.5 to 30 Hz
For a few diseases, such
(cycles per second) on a
as subacute spongiform
stan dard display of 3
encephalopathy, it can be
cm/s. In the past, the
the defining laboratory
amplified signals were
test. The technique is
recorded by a bank of
described here in some
pens but more often
detail, as its general use
now, a dig ital format is
displayed on a computer
screen and stored in
digital format. The
resulting
electroencephalogram
(EEG), essentially a Hyper
voltage-versus-time graph,
is a number of simul
taneous parallel wavy
lines, or “channels” (Fig.
2-4A). Each channel
represents the difference
in electrical potential
between two electrodes
(a common or ground
electrode may be used as
one recording site, but
the channel still rep
resents a bipolar
recording). The channels
are arranged for viewing
into standard montages
that generally compare
the activity from one
region of the cerebral
cortex to that from the
corresponding region of
the opposite side. The
cur rently favored
configuration of
electrode pairs is the
“Inter national 10-20”
system, which uses 10
electrodes on each side
of the cranium and
emphasizes contiguous
regions of the brain for
ease of visual inspection
of the record.
Patients are usually
examined with their eyes
closed and while relaxed
in a comfortable chair or
bed. Conse quently, the
ordinary EEG represents
the electrocerebral
activity that is recorded
under restricted
circumstances, usually
during the waking or
sleeping state, from
several parts of the
cerebral convexities
during an almost infini
tesimal segment of the
person’s life.
In addition to the
resting record, a number
of so-called acti vating
procedures are usually
employed. First, the
patient is asked to
breathe deeply 20 times
a minute for 3 min.
ventilation,
through a mechanism
yet to be determined,
may activate
characteristic seizure
patterns or other
abnormalities. Second, a
powerful strobe light is
placed about 15 inches
from the patient’s eyes
and flashed at
frequencies of 1 to 20 per
second with the patient’s
eyes open and closed.
The occipital EEG leads
shows waves
corresponding to each
flash of light (photic
driving, Fig. 2-4B) or the
stroke may precipitate
abnormal discharges
(Fig. 2-4C).
The EEG is recorded
after the patient is
allowed to fall asleep
naturally or following
sedative drugs given in
chil dren. Sleep is
extremely helpful in
bringing out abnormal
ities, especially where
temporal lobe epilepsy
and certain other
syndromes are
suspected.
Through the medium
of lengthy EEG
recordings (as described
in Chap. 19), many
abnormalities associated
with sleep can be
demonstrated and EEG
activity synchronized
with videographically
recorded seizure activity.
Also useful clinically are
EEGs recorded by small
digital devices or
telemetry from freely
moving ambulatory
patients with suspected
seizure disorders.
Chapter 16 discusses
these techniques more above) and should not
fully. have been without food
Certain precautions for a long time, for both
are necessary if sedative drugs and
electroencephalog raphy relative hypoglycemia
is to be most useful. The might modify the normal
patient should not be EEG pat tern. The same
sedated (except as noted may be said of mental
concentration and
28 Part 1 THE CLINICAL METHOD OF
NEUROLOGY

C
50µV
1Sec
Figure 2-4. A. Normal alpha (9 to 10 per second) activity
is present posteriorly (bottom channel). The top channel
contains a large blink artifact. Note the striking reduction
of the alpha rhythm with eye opening (arrow). B. Photic
driving. During stroboscopic stimulation of a normal sub
ject, a visually evoked response is seen posteriorly after
each flash of light (signaled on the bottom channel). C.
Stroboscopic stimulation at 14 flashes per second (bottom
channel) has produced a photoparoxysmal response in
this epileptic patient, evidenced by the abnormal spike
and slow-wave activity toward the end of the period of
 stimulation. (continued)

extreme nervousness or or two in order to

drowsiness, all of which increase the chance of
tend to suppress the recording a sei zure
normal alpha rhythm discharge.
and increase muscle and The proper
other artifacts. When interpretation of EEGs
dealing with patients involves the recogni tion
who are suspected of of several characteristic
having epilepsy and are normal and abnormal
already being treated for pat terns and
it, most physicians prefer background rhythms (in
to record the EEG while accordance with the age
the patient continues to of the patient), the
receive anticonvulsant detection of asymmetries
drugs. Under special and peri odic changes in
circumstances, for rhythm, and,
example during importantly, the
inpatient monitoring, differentia tion of
these drugs are artifacts from genuine
withdrawn for a day abnormalities.
CHAPTER 2 Special Techniques for Neurologic
Diagnosis 29

50µV
1Sec

F
 Figure 2-4. (Continued) D. An EEG showing focal spike-
and-wave discharges over the right frontal region
(channels 1 to 3). There were convul sive movements of
the left side of the body. E. Absence seizures, showing
generalized 3-per-second spike-and-wave discharge. The
abnormal activity ends abruptly and normal background
activity appears. F. Large, slow, irregular delta waves are
seen in the right frontal region (chan nels 1 and 2). In this
case a glioblastoma was found in the right cerebral
hemisphere, but the EEG picture does not differ basically
from that pro duced by a stroke, abscess, or contusion.
(continued)

Types of Normal temporal regions,

Recordings somewhat more so in
persons older than 60
The normal record in years of age. Delta (1- to
adults shows somewhat 3-Hz) activity is not
asymmetri cal 8- to 12- present in the normal
per-second 50-mV waking adult.
sinusoidal alpha waves in During stroboscopic
both occipital and stimulation, an occipital
parietal regions. These response to each flash of
waves wax and wane light may normally be
spontaneously and are seen (photic or occip ital
attenuated or suppressed driving). The presence of
completely with eye such a response
opening or mental indicates that
activity (see Fig. 2-4A).
The frequency of the
alpha rhythm varies
mini mally for an
individual patient,
although the
individual’s rate may
slow during aging.
Waves faster than 12 Hz
and of lower amplitude
(10 to 20 mV), called beta
waves, are normally
recorded from the
frontal regions
symmetrically.
When the normal subject
falls asleep, the alpha
rhythm slows
symmetrically and
characteristic waveforms
(vertex sharp waves and
sleep spindles) appear
(see Fig. 19-1). If
benzodiazepines or other
sedating drugs have
been administered, an
increase in the fast
frequencies normally
occurs. A small amount
of theta (4- to 7-Hz)
activity may normally be
present over the
30 Part 1 THE
CLINICAL
METHOD OF
NEUROLOGY

50µV
1Sec

H 50µV
1Sec

1Sec
Figure 2-4. (Continued) G. Grossly disorganized
background activity interrupted by repetitive
“pseudoperiodic” discharges consisting of large, sharp
waves from all leads about once per second. This pattern
is characteristic of Creutzfeldt-Jakob disease. H.
Advanced hepatic coma. Slow (about 2 per second)
 waves have replaced the normal activity in all leads. This
record demonstrates the triphasic waves often seen in this
disor der. I. Deep coma following cardiac arrest, showing
electrocerebral silence. With the highest amplification,
electrocardiogram (ECG) and other artifacts may be seen,
so that the record is not truly “flat” or isoelectric.
However, no cerebral rhythms are visible. Note the ECG
(channel 5). (Illustrations courtesy of Dr. Susan Chester.)

the patient can at least occur with some regu

perceive light, and if larity during periods of
there is a claim to the withdrawal from alcohol
contrary, the patient is and other sedative
either hysterical or drugs.
malingering. The evoked Children and
visual responses (see adolescents are more
further on) are an even sensitive than adults to
more sensitive means of all the activating
detecting psy chogenic procedures mentioned. It
blindness than occipital is customary for children
driving on EEG. Spread to develop delta waves
of the occipital response (3 to 4 Hz) during the
to photic stimulation, middle and latter parts
with the production of of a period of
abnormal sharp or overbreathing
paroxysmal waves, pro (hyperventilation). This
vides evidence of EEG activity, referred to
abnormal excitability as “breakdown” of
(Fig. 2-4B and C). Seizure “buildup,” disappears
patterns may be soon after
produced during this hyperventilation has
type of EEG testing, stopped. The frequency
accompanied by gross of the dominant rhythms
myoclonic jerks of the in infants is normally
face, neck, and limbs about 3 Hz, and they are
(photomyogenic or very irregular. With
photomyoclonic maturation, there is a
response) or by gradual increase in
convulsions frequency and regularity
(photoparoxysmal or of these occipital
photo convulsive rhythms; an alpha
response). Such effects rhythm appears by
CHAPTER 2 Special Techniques for Neurologic
Diagnosis 31

age 6 years and the adult range of normal patterns

frequency is reached by at each age period (see
the age of 10 to 12 years; Hahn and Tharp).
normal alpha waves are Nevertheless,
the domi nant pattern asymmetrical records or
(see Chap. 28 for further records with seizure
discussion of mat patterns are clearly
uration of the brain as abnormal in children of
expressed in the EEG). any age. Also, normal
The interpretation of patterns in the fetus,
records of infants and from the seventh month
children require onward, have been
considerable experience established. Certain
because of the wide changes in these
patterns, as described by
Stockard Pope et al and
by deWeerd, are clearly
indicative of a recording speeds and
developmental disorder
or disease.
Types of Abnormal
Recordings
Localized regions of
greatly diminished or
absent brain waves may
be seen when there is a
particularly large area of
infarction, traumatic
necrosis, or tumor or
when an extensive clot
lies between the cerebral
cortex and the
electrodes. With such a
finding, the EEG
localization of the
abnormality is
reasonably precise—but,
of course, the nature of
the lesion is not
disclosed. However,
most such lesions are
not large enough,
relative to the recording
arrangement, to abolish
the brain waves, and the
EEG may then record
abnormal slow waves
arising from func tioning
brain at the borders of
the lesion.
Two types of
abnormal waves, already
mentioned, are of lower
frequency and higher
amplitude than normal.
Waves below 4 Hz with
amplitudes from 50 to
350 mV are called delta
waves (Fig. 2-4G and H);
those with a fre quency
of 4 to 7 Hz are called
theta waves. Fast (beta)
activ ity tends to be
prominent frontally and
usually reflects the
effects of sedative drugs
or, if focal, an
immediately underlying
skull defect (bone
normally filters the abun
dant fast activity of the
cortex). Spikes or sharp
waves are transient high-
voltage waveforms that
have a pointed peak at
duration of 20 to 70 ms
and 70 to 200 ms (Fig. 2-
4D). Spikes or sharp
waves that occur
interictally in people
with epilepsy or in
individuals with a
genetic disposition to
seizures are referred to
as epilepti form discharges.
These abnormal fast
and slow waves may be
com bined, and when a
series of them interrupt
relatively normal EEG
patterns in a paroxysmal
fashion, they are highly
suggestive of epilepsy.
The ones associated with
absence seizures are 3-per-
second spike-and-wave
com plexes that
characteristically appear
in all leads of the EEG
simultaneously and
disappear almost as
suddenly at the end of
the seizure (Fig. 2-4E).
This finding led to the
theoretic localization of
a pacemaker for primary
generalized seizure
discharges in the
thalamus or other deep
gray structures
(“centrencephalic
seizures”), but such a
center has not been
verified anatomically or
physiologically.
The most pathologic
finding of all is the
replacement of the
normal EEG pattern by
“electrocerebral silence,”
meaning that the
electrical activity of the
cortical mantle, recorded
from the scalp, is absent.
Artifacts of various
types should be seen as
the amplifier gains are
increased;
if not, there is a risk that
the leads are not
properly con nected to
the machine. Acute
intoxication with high
levels of drugs such as
barbiturates can
transiently produce this
sort of isoelectric EEG
(Fig. 2-4I). In the absence
of ner vous system
depressants or extreme
degrees of hypother mia,
a record that is “flat” (<2
μV except for artifacts)
over all parts of the head
is almost always a result
of profound cerebral
hypoxia or ischemia or
of trauma and raised
intracranial pressure.
Such a patient—without
EEG activ ity, brainstem
reflexes, and
spontaneous respiratory
or muscular activity of
any kind—is said to be
“brain dead.” The brain
of such a patient is
largely necrotic, and
there is no chance of
neurologic recovery.
Chapter 17 further dis
cusses brain death.
Neurologic
Conditions Causing
Abnormal
Electroencephalogr
ams
Epilepsy
All types of generalized
epileptic seizures (grand
mal and typical and
atypical absence; see
Chap. 16) are usually
associated with some
abnormality in the EEG
provided that it is being
recorded at the time of
the seizure. Also, the
EEG is usually abnormal
during more restricted
types of seizure activity.
Rare exceptions are
seizure states that
originate in deep
temporal, medial, or
orbital frontal foci, from
which the discharge fails
to reach the scalp in suffi
cient amplitude to be
seen against the normal
background activity of
the EEG. Most often, a
completely normal EEG
during a convulsion
indicates a
“pseudoseizure” (a psy
chogenic nonepileptic
seizure).
Some of the different
types of seizure patterns
are shown in Fig. 2-4C,
D, and E. The absence,
myoclonic, and grand
mal patterns correlate
closely with the clinical
seizure type and may be
present in milder form
in the interictal EEG.
A fact of importance is
that, between seizures, a
single EEG recording
will show a normal
pattern in as many as 30
percent of patients with
absence seizures and 50
per cent of those with
grand mal epilepsy (this
percentage is less with
repeated recordings).
Anticonvulsant therapy
also tends to diminish
the interictal EEG
abnormalities. The
records of another 30 to
40 percent of those with
epi lepsy, although
abnormal between
seizures, are nonspecif
ically so; consequently,
the diagnosis of epilepsy
can be made only by the
correct interpretation of
clinical data in relation
to the EEG abnormality.
Focal Brain Lesions
(Brain Tumor,
Abscess, Subdural
Hematoma, Stroke,
and Encephalitis)
In a very high
proportion of patients,
intracranial mass lesions
are associated with focal
or localized slow-wave
activity (usually delta, as
in Fig. 2-4F) or,
 occasionally, sei zure roughly 50 percent of
activity. Although the patients with infarction
EEG may be in the territory of the
diagnostically help ful in middle cerebral artery,
cases of brain tumor or the focal EEG slowing
abscess, particularly becomes normal.
when integrated with Perhaps half these
the other laboratory and patients will have had
clinical findings, reliance normal EEGs even in the
is now placed almost week or two following
exclusively on CT and the stroke. A persistent
MRI. abnormality is gen erally
However, EEG associated with a poor
remains of considerable prognosis for further
value in the diagnosis of recov ery. Large lesions
herpes simplex of the diencephalon or
encephalitis in which midbrain produce
periodic high-voltage bilaterally synchronous
sharp waves and slow- slow waves, but those of
wave complexes at the pons and medulla
intervals of 1 to 3 per (i.e., below the
second in the temporal mesencephalon) are
regions are usually associated with a
32 Part 1 THE CLINICAL normal or near-normal
METHOD OF NEUROLOGY EEG pat tern despite
catastrophic clinical
changes.
characteristic. The other
A brief episode of
infectious encephalitides
cerebral concussion in
are often associated with
animals is accompanied
sharp or spike activity,
by a transitory
particularly if there have
disturbance in the EEG,
been seizures. Figure 2-
but in humans this is
4G shows the highly
usually no longer
characteristic pattern of
evident by the time a
sharp waves that are
recording can be made.
almost peri odic in
Large cerebral
Creutzfeldt-Jakob
contusions produce focal
disease.
EEG slowing similar to
The EEG is now little
those described for
used in the differential
cerebral infarction. Sharp
diagnosis of stroke,
waves or spikes
except to distinguish a
sometimes emerge as the
transient ischemic attack
focal slow-wave
from a seizure. In the
abnormality resolves and
past, one practical value
may precede the
was in the ability to
occurrence of
differentiate an acute
posttraumatic epilepsy;
ischemic lesion in the dis
serial EEGs may be of
tribution of the middle
prognostic value in this
cerebral artery, which
regard. During syncope,
produces a broad area of
the EEG is slowed and of
slowing, from lacunar
reduced amplitude even
infarction deep in the
to the point of becoming
cerebrum or brainstem,
“flat.” Upon recovery, a
in which the surface EEG
number of patterns have
is usu ally normal
been described as
despite prominent
discussed further in
clinical abnormalities.
Chap. 18.
After 3 to 6 months, in
Diseases That Cause
Coma and
States of Impaired
Consciousness
The EEG is abnormal in
almost all conditions in
which there is
impairment of the level
of consciousness. There
is, for example, a fairly
close correspondence
between the severity of
acute anoxic damage
from cardiac arrest and
the degree of EEG
slowing. The mildest
forms are associ ated
with generalized theta
activity, intermediate
forms with widespread
delta waves and the loss
of normal back ground
activity, and the most
severe forms with “burst
suppression,” in which
brief isoelectric periods
are fol lowed by high-
voltage sharp and
irregular delta activity.
The latter pattern usually
progresses to the
electrocerebral silence of
brain death, a condition
discussed earlier.
The term alpha coma
refers to a unique EEG
pattern in which an
apparent alpha activity
in the 8- to 12-Hz range
is distributed widely
over the hemispheres
rather than in its normal
location posteriorly.
When analyzed
carefully, this apparent
alpha activity, unlike the
normal mono rhythmic
alpha, is found to vary
slightly in frequency
within in a narrow band.
This is usually a slowing is more typical
transitional pat tern after
global anoxia; less often,
alpha coma is seen with
large acute pontine
lesions. With severe
hypothyroidism,
the brain waves are
normal in configuration
but usually of decreased
frequency.
In altered states of
alertness, the more
profound the depression
of consciousness, in
general, the more abnor
mal and slower the EEG
rhythms. In states of
deep stupor or coma, the
slow (delta) waves are
bilateral and of high
amplitude and tend to be
more conspicuous over
the fron tal regions (Fig.
2-4H). This pertains in
such differing con
ditions as acute
meningitis or
encephalitis and
disorders that severely
derange blood gases,
glucose, electrolytes, and
water balance; uremia;
diabetic coma; and
impair ment of
consciousness
accompanying the large
cerebral lesions
discussed above. In
hepatic coma, the degree
of abnormality in the
EEG corresponds most
closely with the degree
of confusion, stupor, or
coma. Characteristic of
hepatic coma are
paroxysms of bilaterally
synchronous large, sharp
“triphasic waves” (Fig.
2-4H), although such
waveforms may also be
seen with less regularity
in encephalopathies
related to renal or
pulmonary failure and
with acute
hydrocephalus (frontal
of hydrocephalus).
An EEG may also be of
help in the diagnosis of
coma when the pertinent
history is unavailable
and in the dis closure of
status epilepticus in the
absence of obvious
 convulsions
(“nonconvulsive status
epilepticus,” or “spike
wave stupor”) and of
partial complex seizures
that induce a fugue state.
It may also point to an
otherwise unexpected
cause, such as hepatic
encephalopathy, intoxi
cation with barbiturates
or other sedative-
hypnotic drugs, the
effects of diffuse anoxia–
ischemia, catatonia, or
hysteria (in which the
EEG is normal).
Diffuse Degenerative
Diseases
Alzheimer disease and
other degenerative
diseases that cause
serious impairment of
cerebrocortical function
are accompanied by
relatively slight degrees
of diffuse slow wave
abnormality in the theta
(4- to 7-Hz) range; many
recordings are normal in
the early and midstages
of ill ness. More rapidly
progressive disorders—
such as sub acute
sclerosing
panencephalitis (SSPE),
Creutzfeldt-Jakob
disease, and to a lesser
extent the cerebral
lipidoses—often have, in
addition, very
characteristic and almost
CHAPTER 2 Special Techniques for Neurologic
as hypokinetic delirium
(Chap. 20). Interestingly,
the psychoses (bipolar
disorders or
schizophrenia), intoxica
tion with hallucinogenic
drugs such as lysergic
acid diethylamide (LSD),
and the majority of cases
of mental retardation are
associated either with no
modification of the
pathog nomonic EEG
changes consisting of
periodic bursts of high-
amplitude sharp waves,
usually bisynchronous
and symmetrical (Fig. 2-
4G). In a negative sense,
a normal EEG in a
patient who is
profoundly apathetic is a
point in favor of the
diagnosis of hysteria,
catatonia, or
schizophrenia (see
below).
Other Diseases of the
Cerebrum
Many disorders of the
brain cause little or no
alteration in the EEG.
Multiple sclerosis and
other demyelinating
diseases are examples,
although as many as 50
percent of advanced
cases will have an
abnormal record of
nonspe cific type (focal
or diffuse slowing).
Delirium tremens and
Wernicke-Korsakoff
disease, despite the
dramatic nature of the
clinical picture, cause
little or no change in the
EEG. Some degree of
slowing usually
accompanies confusional
states that some
clinicians have
designated
Diagnosis 33
normal record or with
only minor nonspecific
abnor malities unless
seizures are present.
Clinical Significance
of Minor
Electroencephalogra
m Abnormalities
The gross EEG
abnormalities discussed
above are by themselves latencies, and
clearly abnormal, and asymmetries in timing.
any formulation of the Norms have been
patient’s clinical state established, but it is
should attempt to advisable to confirm
account for them. Lesser these in each laboratory.
degrees of abnormality Typically 2.5 or 3
form a continuum standard deviations
between the above the mean latency
undoubtedly abnormal for any measurement is
and the completely taken as the definition of
normal and are of abnormality (Table 2-4).
correspondingly less The amplitudes of the
significance. Findings waves are less
such as 14- and 6-per- informative.
second positive spikes or
small sharp waves Visual Evoked
during sleep, scattered 5- Potentials
or 6-per-second slowing, For many years it had
minor voltage been known that a light
asymmetries, and stimulus flashing on the
persistence of retina often initiates a
“breakdown” for a few discernible wave form
minutes after over the occipital lobes.
hyperventilation are In the EEG, such
interpreted as normal responses to fast rates of
variants or borderline stimulation are referred
abnormalities. Whereas to as the occipital driving
borderline deviations in response (Fig. 2-4B and
an otherwise entirely C). It was appreciated 50
normal person have no years ago that a visual
clinical significance, the evoked response is
same min imal EEG produced by the sudden
findings associated with change of a viewed
particular clinical signs checkerboard pattern.
and symptoms become These responses,
important. The produced by rapidly
significance of a normal repeating the pat tern
or “negative” EEG in reversal, are easier to
certain patients detect and measure than
suspected of having a flash responses and
cerebral lesion was more consistent in
discussed above. waveform from one
As a general clinical individual to another.
principle, the results of This type of stimulus,
the EEG, like those of the applied first to one eye
EMG and and then to the other,
electrocardiogram, are can demonstrate conduc
mean
The interpretation of
evoked potentials
Table 2-4
(visual, audi tory, and
MAIN SENSORY
somatosensory) is based EVOKED POTENTIAL
on the prolongation of LATENCIES FROM
STIMULUS,
the latencies of the a
MILLISECONDS
waveforms after the
UPPER LIMIT
stimulus, the interwave
ingful only in illnesses under the clinical state
relation to the consideration and of the patient at
the time the POTENTIAL MEAN
record PSVER (70-min check (MEAN + 3 SD)
TYPE OF EVOKED
ings were made.
EVOKED
POTENTIALS
The stimulation of sense
organs or peripheral
nerves evokes an electrical
receptive areas cannot place a
and in a number recording
of subcortical electrode near the for most latencies
relay sta tions. nuclear relay
However, one stations, nor can Absolute latency
potentials of only a few
microvolts among the
much larger background
activity in the EEG. The
use of computerized
averaging methods,
introduced by Dawson in
1954, has provided a
means of overcoming
these problems. Initially,
emphasis was on the
study of late waves (over
75 ms after the stimulus)
because they are of high
amplitude and easy to
record. However, there is
more clinical utility in
record ing the much
smaller, so-called short-
latency waveforms,
which are received at
each nuclear relay within
the main sensory
systems. These
waveforms are
maximized by the
computer to a point
where their latency and
voltage can easily be
measured. One of the
most remarkable proper
ties of evoked potentials
is their resistance to
anesthesia, sedative
drugs, and—in
comparison with EEG
activity— even damage
size)
response in the
corresponding cortical
P100 absolute
latency 104 118
Intereye difference 2 8
BAER (60 dBSL, 10/s
monaural stimuli)
Interwave latency
I–III 2.1 2.6 III–V
1.9 2.4 I–V 4.0 4.7
one detect tiny
Interside difference
SEP—median nerve
(wrist stimulation)
0.1 0.4
of the cerebral
hemispheres. This
permits their use for
monitoring the integrity
of cerebral pathways in
situations that render the
EEG useless. The details
of these techniques are
reviewed in Chiappa’s
monograph.
Erb’s point 9.7
12.0 P/N 13
(cervicomedullary)
13.5 16.3 N 19/P 21
(cortical) 19.0 22.1
Interwave latency
Erb’s-P/N 13 3.8
5.2 P/N 13–N 19
5.5 6.8 Interside
difference
P/N 13–N 19 0.3 1.1
SEP—tibial nerve (ankle
stimulation; Fz-Cz recording;
165-cm height; absolute
latencies are shorter for
stimulation at the knee)
Absolute latency
Lumbar point
(cauda equina) 20
25 N/P 37 (cortex)
36 42.5 Interwave
latency
Lumbar–N/P 37
16.4 21.6 Interside
difference
Lumbar–N/P 37 0.7 1.9
a
Norms must be verified in each
laboratory; in most instances
they are sensitive to the
technique and stimulus used
and height of the patient in
the cases of limb
 stimulation. evoked response; SEP,
PSVER, pattern shift visual somatosensory evoked
evoked response; BAER, response.
brainstem auditory
34 Part 1 THE CLINICAL METHOD OF
NEUROLOGY

tion delays in the visual pathways of patients who

have
had disease of the optic nerve—in particular when
there
R

are no residual signs of reduced visual acuity,

visual field
abnormalities, alterations of the optic nerve head,
or
changes in pupillary reflexes. Furthermore, the
presence
L

o
of a normal visual evoked response belies
blindness from
a lesion in the anterior visual pathways and their
projec
tions to the occipital cortex.
This procedure, called pattern-shift visual evoked
responses
(PSVERs, or VERs) or pattern-reversal visual
evoked
potentials, has been widely adopted as one of the
most
R

delicate tests of lesions in the visual system. Figure

2-5
illustrates the normal PSVER and two types of
delayed
responses. Usually, abnormalities in the amplitude
and
L

duration of PSVER accompany the abnormally

prolonged
latencies, but they are difficult to quantify. The
expected
latency for the positive polarity, by convention a
down
ward deflection, PSVER is near 100 ms (thus the
term
R

P100); an absolute latency from the stimulus over

approxi
mately 118 ms or a difference in latencies of
greater than 9
 ms between the two eyes signifies involvement of
one
optic nerve (Table 2-4). Bilateral prolongation of
latencies,
L

demonstrated by separate stimulation of each eye,

can be
caused by lesions in both visual acuity has little
optic nerves, the optic effect on the latency but
chiasm, or the visual does correlate well with
pathways posterior to the amplitude of the
the chiasm. As indicated PSVER (a property that
above, PSVER is is exploited in
especially valuable in computerized testing for
proving the existence of visual acuity). The use of
active or residual disease testing in detecting
of an optic nerve. psychogenic blindness
Patients with previous has already been men
optic neuritis will have tioned. By presenting the
normal latencies. pattern-shift stimulus to
Furthermore, similar one hemifield, it is
prolonga tions of PSVER possible to isolate a
are found in about one- lesion to an optic tract or
third of multiple radiation, or one
sclerosis patients who occipital lobe, but with
have had no history or much less pre cision than
clinical evi dence of optic that provided by the
nerve involvement. This usual monocular test.
acquires signifi cance in
that the finding of Brainstem Auditory
abnormal PSVER in a Evoked Potentials
patient with a clinically
The effects of auditory
apparent demyelinating
stimuli can be studied in
lesion elsewhere in the
the same way as visual
CNS may usually be
ones by a procedure
taken as evidence of
called brainstem audi tory
multiple sclerosis.
evoked responses or
A compressive lesion
potentials (BAERs, or
of an optic nerve will
BAEPs). Between 1,000
have the same effect as a
and 2,000 clicks,
primarily demyelinating
delivered first to one ear
one. Many other diseases
and then to the other, are
of the optic nerves—
recorded through scalp
including toxic and nutri
elec
tional amblyopias,
ischemic optic Figure 2-5. Pattern-shift
neuropathy, and the visual evoked responses
(PSVERs). Latency measured
Leber type of hereditary
to first major positive peak
optic neuropathy—show (termed P100 because of its
abnor malities of the latency from the stimulus of
PSVER. Glaucoma and approximate 100 msec) and
other diseases involving marked by “o.” Upper two
structures anterior to the tracings: These, from the right
and left eyes, are nor mal.
retinal ganglion cells, if
Middle tracings: PSVER from
severe enough to affect
the right eye is normal but
the optic nerve, may also the latency of the response
pro duce increased from the left eye is prolonged
latencies. Impaired and its duration is increased.
 Lower tracings: PSVER from
both eyes show abnormally
prolonged latencies,
somewhat greater on the left
than on the right. Calibration:
50 ms, 2.5 mV.
trodes and maximized
by computer. A series of
seven waves appears at
the scalp within 10 ms
after each stim ulus. On
the basis of depth
recordings and the study
of lesions produced in
cats as well as pathologic
studies of the brainstem
in disease, it has been
suggested that each of
the first five waves is
generated by a specific
brain stem structure, as
indicated in Fig. 2-6, but
this is not entirely clear
in humans. The
generators of waves VI
and VII in particular are
uncertain. Clinical
interpretations of BAERs
are based mainly on
latency measurements of
waves I, III, and V. The
most important are the
interwave latencies stimulus
between I and III and III CHAPTER 2 Special
and V (see Table 2-4).
The presence of wave I Techniques for Neurologic
and its absolute latency
are of particular value in
testing the integrity of Diagnosis 35 LATENCY,
the auditory nerve.
A lesion that affects msec
one of the relay stations
or its immedi ate
connections manifests
itself by a delay in its
appearance and an
absence or reduction in
amplitude of subsequent
waves. These effects are
more pronounced on the
side of the stimulated ear
than contralaterally. This
is difficult to under
stand, as a majority of
the cochlear-superior
olivary-lateral lemniscal-
medial geniculate fibers
cross to the opposite
side. It is also surprising
that a severe lesion of
one relay station would
allow impulses, even
though delayed, to
continue their ascent and
be recordable in the
cerebral cortex.
BAEPs are a
particularly sensitive
means of detecting
lesions of the eighth
cranial nerve (acoustic
neuroma and

0.1 III IV VII

V

II
,

VI
E

D
I
U

TI

LP

12345 1
MA

0.4 0.3 0.2

V
6 7 8 9 10
0 Hair Organ ry (pons) Lateral Inferior VI Audito
2 cells of nerve III lemnis Medial ry
Corti II Superi cus collicul geniculradiati
I Cochle or V us ate(?) ons(?)
ar olivary (midbr
Audito nuclei IV VII
ain)

Cochlear nerve Cochlear nuclei Nucleus of lateral

lemniscus

Figure 2-6. Short-latency brainstem auditory evoked

responses (BAERs). Diagram of the proposed
electrophysiologic–anatomic correlations in human
subjects. Waves I through V are the ones measured in
clinical practice.

other tumors of the sensory systems. The

cerebellopontine angle)
and of the auditory
pathways of the
brainstem. Almost one-
half of patients with
definite multiple
sclerosis and a lesser
number with a possible
or probable diagnosis of
this dis ease will show
abnormalities of the
BAEPs (usually a the clavicle, over the C2
prolongation of
interwave latencies I to
III or III to V), even in
the absence of clinical
symptoms and signs of
brainstem disease. The
BAEPs are also useful in
assess ing hearing in
infants who have been
exposed to ototoxic
drugs, in young children
who cannot cooperate
with audiometry, and in
those with psychogenic
or feigned deafness.
Somatosensory Evoked
Potentials
Somatosensory evoked
potentials (SEPs) are used
in most clinical
neurophysiology
laboratories to confirm
lesions in the somatic
technique consists of
applying 5-per-second
painless transcutaneous
electrical stimuli to the
median, peroneal, and
tibial nerves and
recording the evoked
potentials (for the upper
limb) as they pass the
brachial plexus over the
Erb point above
vertebra, and over the
opposite parietal cortex,
and (for the lower limb)
sequentially over the
lumbar roots of the
cauda equina, the nuclei
over the cervical spine,
and the opposite parietal
cortex. The impulses
generated in large touch
fibers by 500 or more
stimuli and averaged by
computer can be traced
through the peripheral
nerves, spinal roots, and
posterior col umns to the
nuclei of Burdach and
Goll in the lower
medulla, through the
medial lemniscus to the
contralat eral thalamus,
and thence to the
sensory cortex of the
parietal lobe. Delay
between the stimulus
 site and the Erb point or delays of subsequent
the lumbar spine waves recorded from the
indicates peripheral parietal cortex (Fig. 2-7).
nerve disease; delay The normal waveforms
from the Erb point (or are designated by the
lumbar spine) to C2 symbols P (positive) and
implies an abnormality N (negative), with a
in the appropriate nerve number indicating the
roots or, more interval of time in
frequently, in the milliseconds from
posterior columns; the stimulus to record ing
presence of lesions in the (e.g., N11, N13, P13, P22,
medial lemniscus and etc.). As shorthand for
thalamoparietal pathway the
can be inferred from
36 Part 1 THE CLINICAL METHOD OF
NEUROLOGY

U
P
P
E
R

L
I
M
B

NORMAL ABNORMAL

EP-Cc

3SD
N19 N
19

FZ-Cc

N /P P
13 13 22

FZ-C2 FZ-EP
 50 msec 50 msec

EP
EP
Figure 2-7. Short-latency SEPs produced by stimulation
of the median nerve at the wrist. The set of responses
shown at left is from a normal subject; the set at right is
from a patient with multiple sclerosis who had no
sensory symptoms or signs. In the patient, note the
preservation of the brachial–plexus component (EP), the
absence of the cervical cord (N11) and lower-medullary
components (N/P13), and the latency of the
thalamocortical components (N19 and P22), prolonged
above the normal mean +3 SD for the interval from the
brachial plexus potential. Unilateral stimulation occurred
at a frequency of 5 per second. Each trace is the averaged
response to 1,024 stimuli; the superimposed trace
represents a repetition to demonstrate waveform
consistency. Recording electrode locations are as follows:
FZ, midfrontal; EP, the Erb point (the shoulder); C2, the
middle back of the neck over the C2 cervical vertebra;
and Cc, the scalp overlying the sensoriparietal cortex
contralateral to the stimulated limb. Relative negativity at
the second electrode caused an upward trace deflection.
Amplitude calibration marks denote 2 mV. (Reproduced
by permission from Chiappa and Ropper.)

polarity and corresponding cortical

approximate latency, the wave after tibial or
summated wave that is peroneal nerve
recorded at the stimulation is called
cervicomedullary N/P37.
junction is termed N/P13, For purposes of
and the cortical potential clinical interpretation,
from median nerve the generators of the SEP
stimulation seen in two waves are assumed to be
contiguous waves of linked in series, so that
oppo site polarity is an interwave
called N19–P22. The prolongation in latency
indicates a conduction clinical recovery is to be
defect between the expected.
generators of the two Evoked potential
peaks involved (Chiappa techniques have also
and Ropper). Normal been used in the
values are shown in experimental study of
Table 2-4. Recordings olfactory sensation (see
with pathologically Chap. 12).
verified lesions at these
levels are to be found in Magnetic
the monograph by Stimulation of the
Chiappa. This test has Motor System
been most helpful in
establishing the It is now possible, by
existence of lesions in using single-pulse high-
spinal roots, posterior amplitude magnetic
columns, and brainstem stimulation, to directly
in disorders such as the activate the motor cor tex
ruptured lumbar and (transcranial magnetic
cervical discs, multiple stimulation) and cervical
sclero sis, and lumbar spine segments, and to
and cervical spondylosis detect delays or lack of
when the clini cal data conduction in
are uncertain. The descending motor
central counterpart also pathways. This
pertains—namely, that technique, introduced by
obliteration of the Marsden and associates,
cortical waves (assuming painlessly stimulates
that all preceding waves only the largest motor
are unaltered) reflects neurons (presumably
profound damage to the Betz cells) and the
somatosensory path fastest-conducting axons.
ways in the hemisphere Cervical stimulation is
or to the cortex itself. As believed to activate the
corol anterior roots. The
laries, the bilateral difference in time
absence of cortical between the motor
somatosensory waves cortical and cervical
after cardiac arrest is a activation of hand or
powerful predictor of a forearm muscles reflects
poor clinical outcome; the conduction velocity
the persistent absence of of the cortical–cervical
a cortical potential after cord motor neurons. The
stroke usually indicates tech nique has been used
such profound damage to understand the
that only a limited organization,
CHAPTER 2 Special Techniques for Neurologic
Diagnosis 37

function, and recovery of electro physiologic

of the motor cortex and change, one expects that
the patho physiology of refinements of this
stroke, multiple technique will be useful
sclerosis, and in evaluating the status
amyotrophic lateral of the corticospinal
sclerosis. Although the motor system as well as
degree of functional other cortically based
deficit does not precisely functions.
correlate with the degree
Endogenous Event- Huntington chorea. The
Related Evoked amplitude is reduced in
Potentials schizophrenia and
depres sion. The
Among the very late
potential has been
brain electrical
interpreted by some as a
potentials (>100-ms
reflection of the subject’s
latency), which can be
orienting behavior or
extracted from
attention and by others,
background activ ity by
including Donchin, who
computer methods, are a
discovered the
group that cannot be
phenomenon, as related
classified as sensory or
to an updating of the
motor but rather as
brain’s representation of
psychophysi cal
the environment. The
responses to
P300 remains a curiosity
environmental stimuli.
for the clinical
These responses are of
neurologist because
very low voltage, often
abnormali ties are
fleeting and inconsistent,
detected only when
and of unknown
large groups are
anatomic origin. The
compared to normals,
most studied types occur
and the technique is
approximately 300 ms
hardly as standardized
(P300) after an atten tive
as the conventional
subject identifies an
evoked potentials. A
unexpected or novel
review of the sub ject
stimulus that has been
can be found in sections
inserted into a regular
by Altenmüller and
train of stimuli. Almost
Gerloff and by Polich in
any stimulus modality
the Niedermeyer and
can be used and the
Lopes DaSilva text on
potential occurs even
electroencephalography.
when a stimulus has
been omitted from a
regular pattern. The ELECTROMYOGRA
amplitude of the PHY AND
response depends on the NERVE
difficulty of the task and CONDUCTION
has an inverse STUDIES
relationship to the
frequency of the These are discussed in
unexpected or “odd” Chap. 45.
event; the latency
depends on the task
difficulty and other PSYCHOMETRY,
features of testing. There PERIMETRY,
is therefore no single AUDIOMETRY,
P300; instead, there are AND TESTS OF
numerous types, LABYRINTHINE
depending on the FUNCTION
experimental paradigm.
A prolongation of the These methods are used
latency is found with in quantitating and
aging and in dementia defining the nature of
as well as with the special psychologic
degenerative diseases or sensory deficits pro
such as Parkinson duced by disease of the
disease, progressive nervous system. They
supranuclear palsy, and are per
formed most often to structure, as detailed in
obtain confirmation of a Chap. 37.
disorder of function in
particular parts of the
nervous system or to BIOPSY OF
quantitate, by MUSCLE, NERVE,
subsequent SKIN,
examinations, the TEMPO
progression of the RAL
underlying illness. A ARTERY
description of these , BRAIN,
methods and their AND
clinical uses is found in OTHER
the chapters dealing TISSUE
with cerebral function
(Chap. 22),The application of light,
developmental disor phase, and electron
ders of the cerebrum microscopy to the study
(Chap. 28), dementia of these tissues may be
(Chap. 21), and highly informative. The
disorders of vision findings are discussed in
(Chap. 13) and of Chaps. 37 (skin and con
hearing and equilib rium junctivum in the
(Chap. 15). diagnosis of storage
diseases), 45 (mus cle),
and 46 (nerve).
GENETIC TESTING Temporal artery biopsy
is indicated when giant
Numerous genetic cell arteritis is suspected.
markers of Brain biopsy, aside from
heredofamilial disease its main use in the direct
have become available to sampling of a suspected
the clinician and greatly neoplasm, may be
advanced both diagnosis diagnostic in cases of
and categorization of granulomatous angiitis,
hitherto obscure causes some forms of
of disease. The main encephalitis, subacute
examples are analyses of spongiform
DNA extracted from encephalopathy (biopsy
blood or other cells for now performed
the identifica tion of infrequently because of
mutations (e.g., the risk of transmitting
muscular dystrophy, the infectious agent),
spinocerebel lar and a number of other
atrophies, and rare diseases. Biopsy of
genetically determined the pachy meninges or
polyneuropathies) and leptomeninges may
the quantification of disclose vasculitis, sar
abnormally long coidosis, other
repetitions of certain granulomatous
trinucleotide sequences, infiltrations, or an
most often used for the obscure infection, but its
diagnosis of Huntington sensitivity is low. This is
chorea. A special field of usually per formed in
mito chondrial genetics concert with a biopsy of
has allowed the the underlying brain.
detection of an entire Abdominal fat pad
category of diseases that biopsy is used in the
affect this subcellular diagnosis of
 amyloidosis. of pigments in the
An important advance cerebrospinal fluid. Brain
in recent years has been 78:59, 1955. [PMID:
14378450]
the use of CT- or MRI-
Bigner SH: Cerebrospinal
guided stereotactic
fluid (CSF) cytology:
biopsy, which is particu Current status and
larly valuable in tumor diagnostic applications. J
diagnosis and exposes Neuropathol Exp Neurol
the patient to less risk 51:235, 1992. [PMID:
than does a craniotomy 1583530]
and open biopsy. In Blume WT, Kaibaro, Masato:
choosing to perform a Atlas of Pediatric
biopsy in any of these Electroencephalography,
clinical situa tions, the 2nd ed. New York, Raven
Press, 1999.
paramount issue is the
Chiappa KH (ed): Evoked
likelihood of Potentials in Clinical
establishing a definitive Medicine, 3rd ed. Phila
diagnosis—one that delphia, Lippincott-
would permit successful Raven, 1997.
treatment or otherwise Chiappa KH, Ropper AH:
enhance the Evoked potentials in clinical
management of the medicine. N Engl J Med
disease. 306:1140, 1205, 1982. [PMID:
38 Part 1 THE CLINICAL 6280049 and 7040957]
METHOD OF NEUROLOGY Chimowitz MI, Logigian EL,
Caplan LR: The accuracy of
bedside neurological
diagnoses. Ann Neurol 28:78,
1990. [PMID: 2375637]
Ebersole JA, Pedley TA (eds):
References Current Practice of Clinical
Altenmüller EO, Münte TF, EEG, 3rd ed. Philadelphia,
Gerloff C: Neurocognitive Lippincott Williams &
function and the EEG, in Wilkins, 2003.
Niedermeyer E, Lopes Dawson GD: A summation
DaSilva F (eds): technique for the
Electroencepha lography: detection of small evoked
Basic Principles, Clinical potentials.
Applications, and Related Electroencephalogr Clin
Fields, 5th ed. Neurophysiol 6:65, 1954.
Philadelphia, Lippincott [PMID:13141922]
Williams & Wilkins, 2005, Den Hartog-Jager WA: Color
pp 661–682. Atlas of CSF Cytopathology.
American New York, Elsevier-North
Electroencephalographic Holland, 1980.
Society: Guidelines in DeWeerd AW: Atlas of EEG
electroen cephalography, in the First Months of Life.
evoked potentials, and New York, Elsevier, 1995.
polysomnography. J Clin Dufresne JJ: Cytopathologie de
Neurophysiol 11:1–147, CSF. Basel, Ciba Foundation,
1994. [PMID: 8195412] 1973. Filler AG, Kliot M,
Barnett GH, Ropper AH, Howe FA, et al: Application
Johnson KA: of magnetic reso nance in the
Physiological support evaluation of patients with
and monitoring of peripheral nerve pathol ogy.
critically ill patients J Neurosurg 85:299, 1996.
during magnetic [PMID: 8755760]
resonance imaging. J Fishman RA: Cerebrospinal
Neurosurg 68:246, 1988. Fluid in Diseases of the
[PMID: 3339441] Nervous System, 2nd ed.
Barrows LJ, Hunter FT, Philadelphia, Saunders,
Banker BQ: The nature 1992.
and clinical signifi cance
Goldenshohn ES, Wolf S,
Koszer S, Legatt A (eds):
EEG Interpretation, 2nd
ed. New York, Futura,
1999.
Greenberg JO (ed):
Neuroimaging: A Companion
to Adams and Victor’s
Principles of Neurology, 2nd
ed. New York, McGraw-Hill,
1999. Hahn JS, Tharp BR:
Neonatal and pediatric
electroencephalography,
in Aminoff MJ (ed):
Electrodiagnosis in Clinical
Neurology, 4th ed. New
York, Churchill
Livingstone, 1999, pp 81–
128.
Horowitz AL: MRI Physics for
Radiologists, 2nd ed. New
York, Springer, 1992.
Hughes JR: EEG in Clinical
Practice, 2nd ed. Woburn,
MA, Butterworth, 1994.
Huk WN, Gademann G,
Friedman G: MRI of
Central Nervous System
Diseases. Berlin, Springer-
Verlag, 1990.
Kanal E, Gillen J, Evans JA, et
al: Survey of reproductive
health among female MR
workers. Radiology 187:395,
1993. [PMID: 8475280]
Latchaw RE (ed): MRI and
CT Imaging of the Head, Neck,
and Spine, 2nd ed. St. Louis,
Mosby-Year Book, 1991.
Marsden CD, Merton PA,
Morton HB: Direct
electrical stimulation of
corticospinal pathways
through the intact scalp
and in human subjects.
Adv Neurol 39:387, 1983.
[PMID: 6318533]
Modic MT, Masaryk TJ, Ross
JS, et al: Magnetic
PART 2
CARDI
NAL
MAN
Resonance Imaging of the
Spine, 2nd ed. St. Louis,
Mosby-Year Book, 1994.
Polich J: P300 in clinical
applications, in
Niedermeyer E, Lopes
DaSilva F (eds):
Electroencephalography:
Basic Principles, Clinical
Applications, and Related
Fields, 4th ed. Baltimore,
Williams & Wilkins, 1999,
pp 1073–1091.
Scher MS, Painter MJ:
Electroencephalographic
diagnosis of neonatal
seizures, in Wasterlain
CG, Vert P (eds): Neonatal
Seizures. New York,
Raven Press, 1990.
Shellock FG: Reference
Manual for Magnetic
Safety. CRC, Boca Raton,
2002.
Stockard-Pope JE, Werner SS,
Bickford RG: Atlas of
Neonatal Electroen
cephalography, 2nd ed.
New York, Raven Press,
1992.
Strupp M, Schueler O,
Straube A, et al:
“Atraumatic” Sprotte
needle reduces the
incidence of post-lumbar
puncture headache.
Neurol ogy 57:2310, 2001.
[PMID: 11756618]
Thompson EJ: Cerebrospinal
fluid. J Neurol Neurosurg
Psychiatry 59:349, 1995.
[PMID: 7561910]
Vernooij MW, Ikran MA,
Tanghe HL, et al:
Incidental findings on
brain MRI in the general
population. N Engl J Med
357:1821, 2007. [PMID:
17978290]
 IFES
TATI
ONS
OF
NEU
ROL
OGI
C
DISE
ASE
This page
intentiona
lly left
blank S

Disorders
Of Motility N

CHAPTER 3 Motor Paralysis

CHAPTER 4 Abnormalities of Movement and
Posture Caused by
Disease of the Basal Ganglia
CHAPTER 5 Incoordination and Other
Disorders of Cerebellar Function
CHAPTER 6 Tremor, Myoclonus, Focal
Dystonias, and Tics
CHAPTER 7 Disorders of Stance and Gait

The control of
motor function, to
 which much of the
human nervous
system is largely
com mitted, is
accomplished
through the
integrated action of
a vast array of
segmental and
suprasegmental motor neurons. As originally
conceived by Hughlings Jackson in 1858,
purely on the basis of clinical observations, the motor
system is organized hierarchically in
three levels, each
higher level
controlling the one
below. It was
Jackson’s concept
that the spinal and
brainstem neurons
represent the
lowest, simplest,
and most closely
organized
motor centers; that the motor neurons of the posterior
frontal region represent a more com
plex and less closely organized second motor center;
and that the prefrontal parts of the
cerebrum are the third and highest motor center. This
scheme is still regarded as being
essentially correct,
although Jackson
failed to recognize
the importance of
the parietal lobe
and basal ganglia in
motor control.
Since Jackson’s time, physiologists
have repeatedly analyzed these three
levels of motor
organization and have found their relationships to be
remarkably complex. Motor and sen
sory systems, although separated for practical clinical
purposes, are not independent enti
ties but are closely integrated. Without sensory
feedback, motor control is ineffective. And
at the higher
cortical levels of
motor control,
motivation,
planning, and other
frontal lobe
activities that
subserve volitional
movement are
always preceded
and modulated by
activity in the
parietal sensory
cortex.
Motor activities include not only
those that alter the position of a limb
or other part of the
 body (isotonic contraction) but also those that
stabilize posture (isometric contraction).
Movements that are performed slowly are called ramp
movements. Very rapid movements
are called ballistic (they are too fast for sensory
control). Another way of classifying move
ments, stressed by Hughlings Jackson, is in terms of
their automaticity: reflex movements
are the most automatic, willed movements the least
automatic. Physiologic studies, cast in
their simplest terms, indicate that the following parts
of the nervous system are engaged
primarily in the control of movement and, in the
course of disease, yield a number of char
acteristic derangements.
1. The large motor neurons in the
anterior horns of the spinal cord and
the motor nuclei
of the brainstem. The axons of these nerve cells
comprise the anterior spinal roots, the spi
nal nerves, and the
cranial nerves, and
they innervate the
skeletal muscles.
These nerve cells
and their axons
constitute the
primary, or lower,
motor neurons,
complete lesions of
which result in a
loss of all
movement—
voluntary,
automatic, postural,
and reflex. The
lower motor
neurons are the
final common path
by which all neural
impulses are
transmitted to
muscle.
2. The motor neurons in the frontal
cortex adjacent to the rolandic
fissure connect with
the spinal motor
neurons by a
system of fibers
known, because of
the shape of its
fascicu lus in the
medulla, as the
pyramidal tract.
Because the motor
fibers that extend
from the
cerebral cortex to the spinal cord are not confined to
the pyramidal tract, they are more
accurately designated as the corticospinal tract, or,
alternatively, as the upper motor neu
rons, to distinguish them from the
lower motor neurons.
3. Several
brainstem nuclei
that project to the
spinal cord, notably
the pontine and
med ullary reticular
nuclei, vestibular
nuclei, and red
nuclei. These nuclei
and their
descending fibers
subserve the neural
mechanisms of
posture and
movement,
particularly when
move ment is highly
automatic and
repetitive. Certain
of these brainstem
nuclei are
influenced by the
motor or premotor
regions of the
cortex, e.g., via
corticoreticulospina
l relays.
4. Two
subcortical
systems, the basal
ganglia (striatum,
pallidum, and
related structures,
including the
substantia nigra
and subthalamic
nucleus) and the
cerebellum. Each
system plays an
important role in
the control of
muscle tone,
posture, and
coordination. These
are the subjects of
the following
chapters.
Definitions
When applied to motor
function, paralysis
means loss of voluntary
movement because of
interruption of one of the
motor pathways at any
point from the cerebrum
to the muscle fiber. A
lesser degree of paralysis
is spoken of as paresis.
The word plegia comes
from a Greek word mean
ing “to strike,” and the
word palsy from an old
French word that has the
same meaning as
paralysis. All these words
are used
interchangeably,
although generally one
uses paralysis or plegia for
severe or complete loss
of motor function and
paresis for partial loss.
THE LOWER
MOTOR NEURON
Anatomic and
Physiologic
Considerations
Each spinal and cranial
motor nerve cell,
through the extensive
arborization of the
terminal part of its
efferent fiber, comes into
contact with only a few
or up to 1,000 or more
muscle fibers; together,
the nerve cell, its axons,
and the muscle fibers
they subserve constitute
movements recruit many
more units of increasing
size.
Within a few days
after interruption of a
motor nerve, the
individual denervated
muscle fibers begin to
contract spontaneously.
This isolated activity of
individual muscle fibers
is called fibrillation.
Inability of the isolated
fiber to maintain a stable
membrane potential is
the likely expla nation.
Fibrillation is so fine that
it cannot be seen through
the intact skin, but it can
be recorded as a small,
repetitive, short-
duration potential in the
electromyogram (EMG)
(Chap. 45). When a
motor neuron becomes
diseased, as in
progressive spinal
muscular atrophy, it
may manifest increased
irritability, i.e., the axon
is unstable and capable
of ectopic impulse
generation, and all the
muscle fibers that it
controls may discharge
sporadically, in isolation
from other units. The
result of contraction of
one or sev eral such
motor units is a visible
twitch, or fasciculation,
that appears in the EMG
as a large spontaneous
muscle action potential.
Simultaneous or
sequential spontaneous

3
the motor unit. All
variations in the force,
range, rate, and type of
move ment are
determined by the
number and size of
motor units called into
action and the frequency Motor
Paralysis
and sequence of firing of
each motor unit. Feeble
movements involve rela
tively few small motor
units; powerful
contractions of multiple
motor units cause a
rippling of muscle, a
condition known as
myokymia. If the motor
neu ron is destroyed, all
the muscle fibers that it
innervates undergo
profound atrophy—
termed denervation
atrophy.
The motor nerve fibers
of each ventral root
intermingle with those of
neighboring roots to
form plexuses, and
although the muscles are
innervated roughly
according to segments of
the spinal cord, each
large muscle comes to be
supplied by two or more
roots. In contrast, a
single periph eral nerve
usually provides the
complete motor
innervation of a muscle
or group of muscles. For
this reason, paralysis
caused by disease of the
anterior horn cells or
anterior roots has a
different pattern than
paralysis following
interruption of a and extensor muscles
peripheral nerve. These
patterns follow the
distribution shown in
Table 46-1. For example,
section of the L5 motor
root causes paralysis of
the extensors of the foot
and a foot drop, whereas
a lesion of the peroneal
nerve does the same but
does not affect the
invertors of the foot that
are also innervated by L5
but via the tibial nerve.
All motor activity,
even the most
elementary reflex type,
requires the synchronous
activity of many
muscles. Anal ysis of a
relatively simple
movement, such as
clenching the fist,
conveys some idea of the
complexity of the under
lying neuromuscular
arrangements. In this act
the pri mary movement
is a contraction of the
flexor muscles of the
fingers, the flexor
digitorum sublimis and
profundus, the flexor
pollicis longus and
brevis, and the abductor
pol licis brevis. In the
terminology of Beevor,
these muscles act as
agonists, or prime movers.
For flexion to be smooth
and forceful, the
extensor muscles
(antagonists) must relax
at the same rate as the
flexors contract
(reciprocal innervation,
or Sherrington’s law).
The muscles that flex the
fingers also flex the
wrist; because it is
desired that only the
fingers flex, the extensors
of the wrist must be
brought into play to
prevent its flexion; they
are synergists. Lastly,
during this action of the
hand, appropriate flexor
stabilize the wrist,
elbow, and shoul der;
muscles that accomplish
this serve as fixators. The
coordination of agonists,
antagonists, synergists,
and fix ators is effected
mainly by segmental
spinal reflexes under the
guidance of
proprioceptive sensory
stimuli. In general, the
more delicate the
movement, the more
precise must be the
coordination between
agonist and antagonist
muscles.
All voluntary ballistic
(phasic) movements to a
target are effected by the
activation of ensembles
of motor neu rons, large
ones supplying large
 motor units and small
44 Part 2 CARDINAL MANIFESTATIONS OF
NEUROLOGIC DISEASE
ones, small motor units.
The smaller ones are
more effi ciently
activated by sensory
afferents from muscle
spin dles, more tonically
active, and more readily
recruited in reflex
activities, postural
maintenance, walking,
and run ning. The large
motor units participate
mainly in phasic
movements, which are
characterized by an
initial burst of activity in
the agonist muscles, then
a burst in the antago
nists, followed by a third
burst in the agonists. The
strength of the initial
agonist burst determines
the speed and distance of
the movement, but there
is always the same
triphasic pattern of
agonist, antagonist, and
agonist activity (Hallett
et al). The basal ganglia
and cerebellum set the
pattern and timing of the
muscle action in any pro
jected motor
performance. These
points are discussed fur
ther in Chaps. 4 and 5.
Unlike the phasic
movements just
described, certain basic
motor activities do not
involve reciprocal
innervation. In support
of the body in an upright
posture, when the legs
must act as rigid pillars,
and in shivering,
agonists and antagonists
contract simultaneously.
Locomotion requires that
the extensor pattern of
reflex standing be
inhibited and that the
coordinated pattern of
43
alternating stepping
move ments be
substituted; the latter is
accomplished by multi
segmental spinal and
brainstem reflexes, the
so-called locomotor
centers. Suprasegmental
control of the axial and
proximal limb
musculature (antigravity
postural mecha nisms) is
mediated primarily by
the reticulospinal and
ves tibulospinal tracts
and manipulatory
movements of the distal
extremity muscles, by
the rubrospinal and
corticospi nal tracts.
These aspects of motor
function are also elabo
rated further on.
Muscle stretch
(tendon) reflex activity
and muscle tone depend
on the status of the large
motor neurons of the
anterior horn (the alpha
motor neurons), the
muscle spin dles and
their afferent fibers, and
the small anterior horn
cells (gamma neurons),
whose axons terminate
on the small intrafusal
muscle fibers within the
spindles. Each anterior
horn cell has on its
surface membrane
approximately 10,000
receptive synaptic
terminals. Some of these
termi nals are excitatory,
others inhibitory; in
combination, they
determine the activity of
the neuron. Beta motor
neurons effect
cocontraction of both
spindle and nonspindle
fibers, but the
physiologic significance
of this innervation is not alpha and gamma
fully understood. Some neurons (influenced
of the gamma neurons greatly by descending
are toni cally active at fiber systems) determine
rest, keeping the the level of activity of the
intrafusal (nuclear chain) tendon reflexes and
muscle fibers taut and muscle tone (the
sensitive to active and responsiveness of muscle
passive changes in to stretch). Other
muscle length. mechanisms, of an
A tap on a tendon inhibitory nature,
stretches or perhaps involve the Golgi tendon
causes a vibration of the organs, for which the
spindle and activates its stimulus is tension
nuclear bag fibers. produced by active con
Afferent projections traction of muscle. These
from these fibers encapsulated receptors,
synapse directly with which lie in the
alpha motor neurons in tendinous and
the same and adjacent aponeurotic insertions of
spinal segments; these muscle, activate afferent
neurons, in turn, send fibers that end on
impulses to the skeletal internuncial cells, which,
muscle fibers, resulting in turn, project to alpha
in the familiar motor neurons, thus
monosynaptic muscle form ing a disynaptic
con traction or reflex arc. Golgi tendon
monophasic (myotatic) receptors are silent in
stretch reflex, commonly relaxed muscle and
referred to as the tendon during passive stretch;
reflex or “tendon jerk” they serve, together with
(Fig. 3-1), more correctly muscle spindles, to
called the muscle stretch monitor or cali brate the
or proprioceptive reflex. length and force of
All this occurs within 25 muscle contraction
ms of sudden stretch. under dif ferent
The alpha neurons of conditions. They also
antagonist muscles are play a role in naturally
simultaneously inhibited occurring limb
but through disynaptic movements, particularly
rather than in locomotion.
monosynaptic The alpha neurons of
connections. This is the medial parts of the
accomplished in part by anterior horn supply
inhibitory trunk or axial muscles,
interneurons (reciprocal and neurons of the
inhibition), which also lateral parts supply the
receive input from appendicular muscles.
descending pathways. The larg est neurons, in
Renshaw cells also Rexed layer IX (see Fig.
participate by providing 8-1B), innervate large
negative feedback muscles with large
through inhibitory syn motor units. Smaller
apses of alpha motor anterior horn cells
neurons (recurrent innervate small muscles
inhibition). and control more del
Thus the setting of the icate movements,
spindle fibers and the particularly those in the
state of excitability of the fingers and hand. Both
 groups of alpha neurons
receive projections from
neurons in the
intermediate Rexed
layers (V to VIII) and
from propriospinal
neurons in the fasciculi
proprii of adjacent spinal
segments (see Fig. 8-1B).
All the facilitatory and
inhibitory influences
supplied by cutaneous
and proprioceptive
afferent and descending
suprasegmental neurons
are coordinated at
segmental levels in such
activities as phasic and
tonic reflexes, flexor
withdrawal and crossed
extensor reflexes, pos
tural support, tonic neck
and lumbar reflexes, and
more complex synergies
such as rhythmic
stepping (e.g., the reflex
stepping of neonates).
For further details the
reader may consult
Burke and Lance and
also Davidoff (1992).
There is considerable
information concerning
the phar macology of
motor neurons. The
large neurons of the
anterior horns of the
spinal cord contain high
concentra tions of
choline acetyltransferase
and use acetylcholine as
their transmitter at the
neuromuscular junction.
The main
neurotransmitters of the
descending corticospinal
tract, in so far as can be
determined in humans,
are aspartate and
glutamate. Glycine is the
neurotransmitter
released by Renshaw
cells, which are
responsible for recurrent
inhibi tion, and by
interneurons that
mediate reciprocal inhibi
tion during reflex action.
Gamma-aminobutyric
acid (GABA) serves as
the inhibitory
neurotransmitter of inter
neurons in the posterior
horn. L-glutamate and L-
aspartate are released by
primary afferent
terminals and interneu
rons and act specifically
on excitatory amino acid
recep tors. There are also
descending cholinergic,
adrenergic, and
dopaminergic axons,
which play a less-well-
defined role in reflex
functions.

Dorsal root Descending Muscle B

ganglion fiber systems
CHAPTER 3
L3 S2
ᵧ Efferent fiber
L2 spindle
Motor
Paralysis 45 Motor
end
plates
Fiber

Golgi
Muscle spindle Afferent spindle
tendon organ
Golgi tendon fiber
organ A
Motor
end plates
 Figure 3-1. A. Patellar tendon reflex. Sensory fibers of the
femoral nerve (spinal segments L2 and L3) mediate this
myotatic reflex. The principal receptors are the muscle
spindles, which respond to brisk stretching of the muscle
effected by tapping the patellar tendon. Afferent fibers
from muscle spindles are shown entering only the L3
spinal segment, while afferent fibers from the Golgi
tendon organ are shown entering only the L2 spinal
segment. In this monosynaptic reflex, afferent fibers
entering spinal segments L2 and L3 and efferent fibers
issuing from the anterior horn cells of these and lower
levels complete the reflex arc. Motor fibers shown leaving
the S2 spinal segment and passing to the hamstring
muscles demonstrate the disynaptic pathway by which
inhibitory influences are exerted upon an antagonistic
muscle group during the reflex. B. The gamma loop is
illustrated. Gamma efferent fibers (γ) pass to the polar
portions of the muscle spindle. Contractions of the
intrafusal fibers in the polar parts of the spindle stretch
the nuclear bag region and thus cause an afferent impulse
to be conducted centrally. The afferent fibers from the
spindle synapse with many alpha motor neurons.
Because the alpha motor neurons innervate extrafusal
muscle fibers, excitation of the alpha motor neurons by
spindle afferents causes a cocontraction of the muscle. In
this way, both gamma and alpha fibers (α) can
simultaneously activate muscle contraction. Both alpha
and gamma motor neurons are influenced by descending
fiber systems from supraspinal levels. (Adapted by
permission from Carpenter MB, Sutin J: Human
Neuroanatomy, 8th ed. Baltimore, Williams & Wilkins,
1983.)

Paralysis Due to Damage restricted to

Lesions of
the Lower Motor
Neurons
If all, or practically all,
peripheral motor fibers
supplying a muscle are
interrupted, all
voluntary, postural, and
reflex movements of that
muscle are abolished.
The mus cle becomes lax
and soft and does not
resist passive stretching,
a condition known as
flaccidity. Muscle tone—
the slight resistance that
normal relaxed muscle
offers to passive
movement—is reduced
(hypotonia or atonia). The
denervated muscle
undergoes extreme
atrophy, being reduced
to 20 or 30 percent of its
original bulk within 3 to
4 months. The reaction of
the muscle to sudden
stretch, as by tapping its
tendon, is lost (areflexia).
only a portion of the
motor fibers supplying
the muscle results in
partial paralysis, or
paresis, and a
proportionate
diminution in the force
and speed of contraction.
The atro phy will be less
and the tendon reflex
reduced instead of lost.
The electrodiagnosis of
denervation depends
upon finding
fibrillations,
fasciculations, and other
abnormali ties on needle
electrode examination.
However, some of these
abnormalities do not
appear until several days
or a week or two after
nerve injury (see Chap.
45).
Lower motor neuron
paralysis is the direct
result of loss of function
or destruction of anterior
horn cells or their axons
in anterior roots and
nerves. The signs and
symp toms vary
according to the location
of the lesion. In any
individual case, the most
important clinical
question is whether
sensory changes coexist.
The combination of a
flaccid, areflexic
paralysis and sensory
changes usually
indicates involvement of
mixed motor and
sensory nerves or of both
anterior and posterior
roots. If sensory changes
are absent, the lesion
must be situated in the
anterior gray matter of
the spinal cord, in the
anterior roots, in a
purely motor branch of a
peripheral nerve, or in
motor axons alone (or in
the muscle itself). At
times it may be impossi
ble to distinguish
between nuclear (spinal)
and anterior root
(radicular) lesions.
Preserved and often
heightened tendon
reflexes and spasticity in
muscles weakened by
46 Part 2 CARDINAL MANIFESTATIONS OF
NEUROLOGIC DISEASE
lesions of the cortico
spinal systems attest to
the integrity of the spinal
seg ments below the
level of the lesion.
However, acute and
profound spinal cord
lesions and, to a lesser
extent, corti cospinal
lesions in the brainstem
and cerebrum may tem
porarily abolish spinal
myotatic reflexes
(“spinal shock”; see
Chap. 44). This is caused
by the interruption of
descending tonic
excitatory impulses,
which normally
maintain a sufficient
level of excitation in
spinal motor neurons to
permit the peripheral
activation of segmental
reflexes. The attenuation
of spinal shock by opiate
antago nists, such as
naloxone, suggests that
the phenomenon is at
least in part mediated by
the release of previously
stored endogenous
opiates from the distal
terminals of neurons in
the periaqueductal gray
matter. Once the

stored opiates are

used interchangeably,
released, the presynapticalthough they are not
inhibition of motor
alto gether synonymous.
neurons ceases,
The pyramidal tract,
heralding the end of strictly speak ing,
spinal shock and the designates only those
beginning of the period fibers that course
of spasticity. longitudinally in the
pyramid of the medulla
oblongata. Of all the
THE UPPER MOTOR fiber bundles in the
NEURON brain, the pyramidal
tract has been known for
Anatomic and the longest time, the first
Physiologic accurate description
Considerations having been given by
Türck in 1851. It
The terms pyramidal,
descends from the
corticospinal, and upper
cerebral cortex; traverses
motor neuron are often
the subcortical white
matter (corona radi ata),
internal capsule, cerebral
peduncle, basis pontis
(ven tral pons), and
pyramid of the upper
medulla; decussates in
the lower medulla; and
continues its caudal
course in the lateral
funiculus (column) of the
spinal cord—hence the
alternative name
corticospinal tract. This is
the only direct long-fiber
connection between the
cerebral cortex and the
spinal cord (Fig. 3-2).
The indirect pathways
through which the cortex
influences spinal motor
neurons are the
rubrospinal,
reticulospinal,
vestibulospinal, and
tectospinal; these tracts
do not run in the
pyramid. All of these
pathways, direct and
indirect, are embraced
by the term upper motor
neuron.
A major source of
confusion about the
pyramidal tract stems
from the traditional
view, formulated at the
turn of the 20th century,
that it originates entirely
from the large motor
cells of Betz in the fifth
layer of the precentral
con volution (the
primary motor cortex, or
area 4 of Brod mann)
(Figs. 3-3 and 22-1).
However, there are only
some 25,000 to 35,000
Betz cells, whereas the
medullary pyra mid
contains about 1 million
axons (Lassek). Thus the
pyramidal tract contains
many fibers that arise
from corti cal neurons
other than Betz cells,
particularly in Brod
mann areas 4 and 6 (the
frontal cortex
immediately rostral to
area 4, including the
medial portion of the
superior frontal gyrus,
i.e., the supplementary
motor area); in the
primary somatosensory
cortex (Brodmann areas
3, 1, and 2); and in the
superior parietal lobule
(areas 5 and 7). Data
concerning the origin of
the pyramidal tract in
humans are scanty, but
in the monkey, by
counting the pyramidal
axons that remained
after cortical excisions
and long sur vival
periods, Russell and
DeMyer found that 40
percent of the
descending axons arose
in the parietal lobe, 31
per cent in motor area 4,
and the remaining 29
percent in pre motor
area 6. Studies of
retrograde transport of
tracer substance in the
monkey have confirmed
these findings.
Fibers from the motor
and premotor cortices
(Brodmann areas 4 and
6, Fig. 22-1),
supplementary motor
cortex, and portions of
parietal cortex (areas 1,
3, 5, and 7) converge in
the corona radiata and
descend through the
posterior limb of the
internal capsule, basis
pedunculi, basis pontis,
and medulla. As the
corticospinal tracts
descend in the cere brum
and brainstem, they send
collaterals to the
striatum, thalamus, red
nucleus, cerebellum, and
reticular forma
tions. Accompanying the
corticospinal tracts in the
brain stem are the
corticobulbar tracts,
which are distributed to
motor nuclei of the
cranial nerves
ipsilaterally and con
tralaterally (Fig. 3-2). It
has been possible to
trace the direct
projection of axons of
cortical neurons to the
trigem inal, facial,
ambiguus, and
hypoglossal nuclei
(Iwatsubo et al). No
axons were seen to
terminate directly in the
ocu lomotor, trochlear,
abducens, or vagal
nuclei. Insofar as the
corticobulbar and
corticospinal fibers have
a similar origin and the
motor nuclei of the
brainstem are the
homologues of the motor
neurons of the spinal
cord, the term upper
motor neurons may
suitably be applied to
both these systems of
fibers.
The corticospinal
tracts decussate at the
lower end of the
medulla, although some
of their fibers may cross
above this level. The
proportion of crossed
and uncrossed fibers
varies to some extent
from one person to
another. Most textbooks
state that 75 to 80
percent of the fibers
cross and that the
remaining fibers descend
ipsilaterally, mostly in
the uncrossed ventral
corticospinal tract. In
exceptional cases, these
tracts cross completely;
equally rarely, they
remain uncrossed. These
variations are proba bly
of functional significance
in determining the
amount of neurologic
deficit that results from a
unilateral lesion such as
capsular infarction. A
few well-studied cases
are found, such as the
one described by
Terakawa and col
leagues, of acute stroke
of the cerebral
hemisphere causing
hemiplegia on the same
side. Also, Yakovlev
found 3 instances of
completely uncrossed
pyramids among 130
autopsies of mentally
retarded neonates but
considering the
maldevelopment of these
brains, the finding is not
sur prising (personal
communication).
Beyond their
decussation, the
corticospinal pathways
descend as well-defined
bundles in the anterior
and pos terolateral
columns of white matter
(funiculi) of the spinal
cord (Fig. 3-2). The
course of the
noncorticospinal motor
pathways
(vestibulospinal,
reticulospinal, and
descending
propriospinal) have been
traced in humans by
Nathan and his
colleagues. The lateral
vestibulospinal tract lies
at the periphery of the
cord, where it occupies
the most anterolat eral
portion of the anterior
funiculus. The medial
vestibu lospinal fibers
mingle with those of the
medial longitudinal
fasciculus. Reticulospinal
fibers are less compact;
they descend bilaterally,
and most of them come
to lie just ante rior to the
lateral corticospinal tract.
The descending pro
priospinal pathway
consists of a series of
short fibers (one or two
segments long) lying
next to the gray matter.
The somatotopic
organization of the
corticospinal system is of
 importance in clinical caudally, the descend
work, especially in ing motor fibers
relation to certain stroke converge and are
syndromes. As the collected in the poster ior
descending axons sub limb of the internal
serving limb and facial capsule, so that even a
movements emerge from small lesion there may
the corti cal motor strip, cause a “pure motor
they maintain the hemiplegia,” in which
anatomic specificity of the face, arm, hand, leg,
the overlying cortex; and foot are affected to
therefore a discrete more or less the same
cortical–subcorti cal degree (Lacunar
lesion will result in a syndromes). The axons
restricted weakness of subserv ing facial
the hand and arm or the movement are situated
foot and leg. More rostrally in the posterior
CHAPTER 3 Motor Paralysis 47

Trunk Lower limb

MOTOR
Paracentral gyrus CORTEX

Upper limb Eye field

Eye muscle ||||| Cerebral peduncle

innervation | |
||| ||||||||||||||
|
|
||| |
|

Genu of internal Face

capsule |

Posterior limb of
III N. nucleus internal capsule
|| || |||||| |||||||||||||
Dorsal thalamus

V N. motor nucleus MIDBRAIN

|

| | | | | | | |||
|

|
| |

VII N. nucleus Motor nerves ||

| | Pyramid
| ||| ||
for upper limb |
|

V N. Uncrossed
|

lateral
|

VII N. |

corticospinal
|

Crossed lateral
|

fibers
|

corticospinal
XII N. nucleus
tract
Upper limb
Nucleus |
|||||||
ambiguus PONS

Motor
decussation
|

MEDULLA
|

|
CERVICAL Ventral LUMBOSACRA Motor nerves
ENLARGEMEN corticospinal L for lower limb
T tract ENLARGEMEN
T

Figure 3-2. Corticospinal and corticobulbar tracts. The

various lines indicate the trajectories of these pathways,
from their origin in particular parts of the cerebral cortex
to their nuclei of termination.

limb of the capsule, in the basis pontis (base,

those for hand and arm
in the central portion,
and those for the foot
and leg caudally (see
Brodal).
This topographic
distribution is more or
less maintained in the
cerebral peduncle, where
the corticospinal fibers
occupy approximately
the middle of the
peduncle, the fibers
destined to innervate the
facial nuclei lying most
medially. More caudally,
48 Part 2 CARDINAL MANIFESTATIONS OF
NEUROLOGIC DISEASE
or ven tral part of the
pons), the descending
motor tracts separate
into bundles that are
interspersed with masses
of ponto cerebellar
neurons and their
cerebellipetal fibers. A
degree of somatotopic
organization can be
recognized here as well,
exemplified by selective
weakness of the face and
hand with dysarthria, or
of the leg, which may
occur with

6a studies that mids and is

6aß 4
corticobulbar certainly
fibers des tined reconstituted in
8αßδ
for the facial the lateral
nucleus descend columns of the
in the spinal cord (Fig.
ventromedial 8-3), but it should
pons to the level be emphasized
of the upper that the
medulla, where topographic
they decus sate separation of
8
and then ascend motor fibers at
6b again; but there is cervical, thoracic,
considerable vari lumbar, and
3,1,2 ability between sacral levels is not
5a individuals in this as discrete as usu
configuration. ally shown in
5b The descending schematic
7a pontine bundles, diagrams of the
now devoid of spinal cord.
their
corticopontine A
fibers, reunite to 17 22 7b 18
form the
19 The corticospinal
medullary pyra
found in the tracts and other
mid. The
report by Terao upper motor
brachial–crural
and colleagues. neurons
pattern may
They con clude terminate mainly
persist in the pyra
from imaging in relation to
nerve cells in the 18 19
interme diate
The Motor,
zone of spinal Premotor, and
gray matter Supplementar
(internuncial y Motor
neurons), Cortex and the
6aß 6a 4
Cerebral
Control of
Movement
The motor area of
the cerebral cortex
19 is defined
from which motor physiologi cally
impulses are then as the region of
transmitted to the electrically
anterior horn excitable cortex
cells. Only 10 to from which
20 percent of isolated
B corticospinal movements can
3,1,2 fibers be evoked by
(presumably the stimuli of
5a 17
thick, rapidly
5b
minimal intensity.
conducting axons
The muscle
derived from Betz
groups of the
cells) establish
contralateral face,
direct synaptic
arm, trunk, and
connec tions with
leg are
18 the large motor
represented in the
neurons of the
primary
anterior horns.
Figure 3-3. Lateral (A) and the pons less certain.
medial (B) surfaces of the However, a study con
human cerebral hemispheres,
ducted by Marx and
showing the areas of excitable
cortex, i.e., areas, numbered
colleagues using
according to the scheme of sophisticated MRI
Brodmann. (Reprinted with mapping techniques of
permission from House EL, patients with hemiplegia
Pansky B: A Functional from brainstem lesions
Approach to Neuroanatomy,
suggests that the usual
2nd ed. New York, McGraw-
Hill, 1967.) See also Fig. 22-1.
somatotopic
organization breaks
down in the base of the
pons, and there is,
pontine lacunar instead, a concentration
infarctions. Anatomic of fibers innervating
studies in nonhu man proximal muscles lying
primates indicate that more dorsally and those
arm–leg distribution of exciting distal parts of
fibers in the rostral pons the limbs, more
is much the same as in ventrally.
the cerebral peduncle; in Another point of
the caudal pons this uncertainty has been the
distinction is less-well existence and course of
defined. In humans, a fibers that descend
lack of systematic through the lower pons
anatomic study leaves and upper medulla and
the precise somatotopic then ascend again to
organization of innervate the facial
corticospi nal fibers in
motor nucleus on the that are similar to those
opposite side. Such a elicited from area 4.
connec tion must exist to These responses are
explain occasional probably effected by
instances of facial palsy transmission of impulses
from brainstem lesions from all of area 6a to
caudal to the midpons. A area 4 (as they cannot be
discussion of the various obtained after ablation of
hypothesized sites of this area 4). Stimulation of
path way, including a the rostral premotor area
recurrent tract (Pick (area 6aβ) elicits more
bundle), can be general movement
motor cortex (area 4 in patterns, predominantly
Fig. 3-3), those of the face of proximal limb
being in the most musculature. The latter
inferior part of the movements are effected
precentral gyrus on the via pathways other than
lateral surface of the those derived from area
cerebral hemisphere and 4 (hence,
those of the leg in the “extrapyramidal”). Very
paracentral lobule on the strong stimuli elicit
medial surface of the movements from a wide
cere bral hemisphere. area of premotor frontal
The parts of the body and parietal cortex, and
capable of the most the same move ments
delicate movements may be obtained from
have, in general, the several widely separated
largest cortical points. From this it may
representation, as be assumed, as Ash and
displayed in the motor Georgop oulus point out,
homunculus (“little that the premotor cortex
man,” a term first includes several
suggested by Wilder anatomically distinct
Penfield) shown in Fig. subregions with different
3-4. afferent and efferent
Area 6, the premotor connections. In general,
area, is also electrically it may be said that the
excitable but requires motor–premotor cortex
more intense stimuli is capable of
than area 4 to evoke synthesizing ago nist
move ments. Stimulation actions into an infinite
of its caudal aspect (area variety of finely graded,
6aα) pro duces responses highly

Motor B
t

CHAPTER 3 A
and

homunculus

Motor

H
i
p
Paralysis 49
k
re

Kne
ur si
dl

e r

H
Little
u
w ob
n

T
o

Ring Middle
h
lE

Ankl Toe
e s Lips
S

Brow
Index l Jaw
Eyelid and eyebal Face
b ngu
Thum Neck To e
Fingers
]

Swa ow n
t

–
z

l
ll i g
n no
]
o a co
i

Figure 3-4. The motor homunculus. evident. B in the

representation of The large area of smaller diagram
body parts in the cortex devoted to astication]
[M [
Salivati

motor cortex, motor control of the

V

commonly called the hand, lips, and face is[

represents the motor cortex; A is the sensory cortex.

Medial Lateral

differentiated patterns. representation of muscle

These are directed by
visual (area 7) and tactile
(area 5) sensory
information and
supported by
appropriate postural
mechanisms.
The supplementary
motor area is the most
anterior portion of area 6
on the medial surface of
the cerebral hemisphere
(6aβ in Fig. 3-3B).
Stimulation of this area
may induce relatively
gross ipsilateral or
contralateral
movements, bilateral
tonic contractions of the
limbs, contraversive
movements of the head
and eyes with tonic
contraction of the
contralateral arm, and
sometimes inhibition of
volun tary motor activity
and vocal arrest.
Precisely how the
motor cortex controls
movements is still a
controversial matter. The
traditional view, based
on the interpretations of
Hughlings Jackson and
of Sher rington, is that
the motor cortex is
organized not in terms of
individual muscles but
of movements, i.e., the
coordi nated contraction
of groups of muscles.
Jackson visualized a
widely overlapping
groups in the cerebral
cortex on the basis of his
observation that a
patient could recover the
use of a limb following
destruc tion of the limb
area as defined by
cortical stimulation. This
view was supported by
Sherrington’s
observations that
stimulation of the
cortical surface activated
not soli tary muscles but
a combination of
muscles, and always in a
reciprocal fashion—i.e.,
in a manner that
maintained the expected
relationship between
agonists and antagonists.
He also noted the
inconstancy of
stimulatory effects; the
stimulation of a given
cortical point that
initiated flexion of a part
on one occasion might
initiate extension on
another.
These interpretations
must be viewed with
circumspec tion, as must
all observations based on
the electrical stim ulation
of the surface of the
cortex. It has been shown
that to stimulate motor
cells from the surface,
the electric cur rent has
to penetrate the cortex to
layer V, where these
neurons are located,
inevitably activating a elementary functional
large number of other units of the cortex. This
cortical neurons. The notion received strong
elegant experiments of support from
Asanuma and of Evarts Mountcastle’s
and his colleagues, who observations that all the
stimu neurons in a column
lated the depths of the receive impulses of the
cortex with same sensory modality,
microelectrodes, dem from the same part of the
onstrated the existence body. It is still not
of discrete zones of entirely clear whether
efferent neurons that the columns contribute
control the contraction of to a movement as units
individual mus cles; or whether individual
moreover, the continued cells within many
stimulation of a given columns are selectively
effer ent zone often acti vated. Both
facilitated rather than Henneman and
inhibited the contraction Asanuma have
of the antagonists. These summarized the
investigators have also evidence for these
shown that cells in the disparate views.
efferent zone receive Evarts and his
afferent impulses from colleagues also have
the particular muscle to elucidated the role of
which the efferent cortical motor neurons in
neurons project. When sensory evoked or
the effects of many planned movement.
stimulations at various Using single-cell
depths were correlated recording techniques,
with the exact sites of they showed that
each penetration, cells pyramidal cells fire
that projected to a about 60 ms prior to the
particular pool of spi nal onset of a movement in a
motor neurons were sequence determined by
found to be arranged in the required pattern and
radially aligned columns force of the movement.
approximately 1 mm in But other, more complex
diameter. The columnar properties of the
arrangement of cells in pyramidal cells were
the sensorimotor cortex also noted. Some of them
had been appreciated for received a
many years; the wealth somatosensory input
of radial transcortically from the
interconnections parietal lobe (areas 3, 1,
between the cells in and 2), which could be
these columns led turned on or off or gated
Lorente de Nó to suggest according to whether the
that these “vertical movement was to be
chains” of cells were the controlled, i.e., guided,
50 Part 2 CARDINAL MANIFESTATIONS OF
NEUROLOGIC DISEASE

by sensory input. Many planned movement.

neurons of the Thus pyramidal (area 4)
supplementary and motor neurons were
premotor cortices were prepared for the
activated before a oncoming activation by
impulses from the Terminatio
parietal, prefrontal, n of the
premotor, and auditory Corticospi
and visual areas of the nal and
cortex. This preparatory Other
“set signal” could occur Descendin
in the absence of any
g Motor
Tracts
activity in the spinal
cord and muscles. The This has been studied in
source of the activation the monkey by
signal was found to be interrupting the
mainly in the descending motor
supplementary motor pathways in the medulla
cortex, which appears to and more ros tral parts
be under the direct of the brainstem and
influence of the tracing the distribution
“readiness stimuli” of the degenerating
(Bereitschaft potential) elements in the spinal
reaching it from the pre gray matter. On the basis
frontal areas (for of such experiments and
planned movements) other physiologic data,
and the posterior parietal Lawrence and Kuypers
cortex (for motor proposed that the
activities initiated by functional orga nization
sensory perceptions). of the descending
There are also fibers that cortical and subcortical
reach the motor area path ways is determined
from the limbic system, more by their patterns of
presumably subserving termination and the
moti vation and motor capacities of the
attention. Roland has internuncial neurons
used functional cerebral upon which they
blood flow terminate than by the
measurements to follow location of their cells of
these neural events. origin. Three groups of
Thus the prefrontal motor fibers were
cortex, supplementary distinguished according
motor cortex, premotor to their differential
cortex, and motor cortex terminal distribution: (1)
are all responsive to The corticospinal and
various afferent stimuli corticobulbar tracts,
and are involved in set which project to all
discharges prior to and levels of the spinal cord
in coordinated fashion and brainstem,
with a complex move terminating dif fusely
ment. And, as remarked throughout the nucleus
later on, the proprius of the dorsal
striatopallidum and horn and the
cerebellum, which intermediate zone. A
project to these cortical portion of these connect
areas, are also activated directly with the large
prior to or concurrently motor neurons that
with the discharge of innervate the muscles of
corticospinal neurons the fingers, face, and
(see Thach and tongue; this system pro
Montgomery for a vides the capacity for a
critical review of the high degree of
physiologic data). fractionation of
movements, as
exemplified by relation to limb
independent finger move movements. Lesions in
ments. As alluded to these systems are less
above, a large fraction of well understood than
the fibers in the those of the corticospinal
corticospinal originate system. They cause no
from the sensory cortex paralysis of muscles but
and appear to function result in the liberation of
in the modulation of unusual postures (e.g.,
movement by afferent hemiplegic dystonia),
neurons. (2) A heightened tonic neck
ventromedial pathway, and lab yrinthine
which arises in the reflexes, and decerebrate
tectum (tectospinal tract), rigidity. In a strict sense
vestibular nuclei (vestibu these are all
lospinal tract), and “extrapyramidal,” as
pontine and medullary discussed in the next two
reticular cells chapters.
(reticulospinal tract) and
terminates principally on Paralysis Caused
the internuncial cells of by Lesions of
the ventromedial part of
the Upper Motor
the spinal gray matter.
Neurons
This system is mainly
concerned with axial The corticospinal
movements—the pathway may be
maintenance of posture, interrupted by a lesion at
integrated movements of any point along its
body and limbs, and course—at the level of
total limb movements. the cerebral cortex,
(3) A lateral pathway, subcortical white matter,
which is derived mainly internal capsule, brain
from the magnocellular stem, or spinal cord.
part of the red nucleus Usually, when
and terminates in the hemiplegia is severe and
dorsal and lateral parts permanent as a
of the internuncial zone. consequence of disease,
This pathway adds to much more than the
the capacity for long, direct corticospinal
independent use of the pathway is involved. In
extremities, especially of the cerebral white matter
the hands. (corona radiata) and
Reference has already internal capsule, the
been made to the corticospinal fibers are
corticomesen cephalic, intermingled with cor
corticopontine, and ticostriate,
corticomedullary fiber corticothalamic,
sys tems that project corticorubral,
onto the reticulospinal, corticopontine, cortico-
vestibulospinal, olivary, and
rubrospinal, and corticoreticular fibers. It
tectospinal nuclei. These is noteworthy that
control stability of the thalamocortical fibers,
head (via labyrinthine which are a vital link in
reflexes) and of the neck an ascending fiber
and body in relation to system from the basal
the head (tonic neck ganglia and cerebel lum,
reflexes) as well as also pass through the
postures of the body in internal capsule and
cerebral white matter.
Thus lesions in these monkeys—as shown by
parts simultaneously Tower in 1940 and
affect both corticospinal subse-
and extrapyramidal
systems. Attribution of a
capsular hemiplegia
solely to a lesion of the quently by Lawrence
corticospinal orand Kuypers and by
pyramidal pathway isGilman and Marco—
therefore not entirelyinterruption of both
correct. The term upper pyramidal tracts results
motor neuron paralysis,in a hypotonic paralysis;
which recognizes theultimately, these animals
involvement of severalregain a wide range of
descending fiber systemsmovements, although
that influence and slowness of all move
modify the lower motor ments and loss of
neuron, is more individual finger
appropriate. movements remain as
In primates, lesionspermanent deficits. Also,
limited to area 4 ofthe cerebral peduncle
Brodmann, the motorhas been sectioned in
cortex, cause mainlypatients in an effort to
hypotonia and weaknessabolish involuntary
of the distal limb movements (Bucy et al);
muscles. Lesions of the in some of these patients,
premotor cortex (area 6) a slight degree of
result in weakness,weakness or only a
spasticity, and increasedBabinski sign was
stretch reflexes (Fulton). produced but no
Lesions of the spasticity developed.
supplementary motorThese observations
cortex lead to indicate that a pure
involuntary grasping. pyramidal tract lesion
Resection of cortical does not result in spas
areas 4 and 6 and ticity. Furthermore, to
subcortical white matterreiterate a previous
causes complete and comment, con trol over a
permanent paralysis and wide range of voluntary
spasticity (Laplane et al).movements depends at
These clinical effectsleast in part on
have not been as clearly nonpyramidal motor
defined in humans as inpathways. Animal
monkeys. experiments suggest that
the corticoreticulospinal
The one place where
corticospinal fibers are path ways are
entirely iso lated is the particularly important in
pyramidal tract in the this respect, because
medulla. In humans, their fibers are arranged
there are a few somatotopically and are
documented cases of a able to influence stretch
lesion more or less reflexes. Further studies
confined to this location. of human dis ease are
The result of such lesions necessary to settle
has been an initial flaccid problems related to
hemiplegia (with sparing volitional movement and
of the face), from which spasticity. The motor
there is considerable organization of the cat
recovery. Similarly in and even of the monkey
is so different from that
of humans, and the peculiarities of retained
range of volitional movement. There is
activity and motor skills decreased voluntary
is so much less in drive on spinal motor
animals, that direct neurons (fewer motor
comparisons are not units are recruitable and
justified. their firing rates are
The distribution of the slower), resulting in a
paralysis caused by slowness of movement.
upper motor neuron There is also an
lesions varies with the increased degree of
locale of the lesion, but cocontraction of
cer tain features are antagonistic muscles,
characteristic of all of reflected in a decreased
them. A group of rate of rapid alternating
muscles is always movements. These
involved, never abnormalities probably
individual muscles, and account for the greater
if any movement is sense of effort and the
possible, the proper manifest fatigability in
relationships between effecting voluntary
agonists, antagonists, movement of the
synergists, and fixators weakened muscles.
are preserved. On Another phenomenon is
careful inspection, the the activation of
paralysis never involves paralyzed mus cles as
all the muscles on one parts of certain
side of the body, even in automatisms
the severest forms of (synkinesias). The
hemiplegia. Movements paralyzed arm may
that are invariably move suddenly during
bilateral—such as those yawning and stretching.
of the eyes, jaw, phar Attempts by the patient
ynx, upper face, larynx, to move the hemiple gic
neck, thorax, diaphragm, limbs may result in a
and abdomen—are variety of associated
affected little or not at movements. Thus,
all. This comes about flexion of the arm may
because these muscles result in involuntary
are bilaterally prona tion and flexion of
innervated; i.e., the leg or in dorsiflexion
stimulation of either the and eversion of the foot.
right or left motor cortex Also, volitional
results in contraction of movements of the
these muscles on both paretic limb
sides of the body. Upper CHAPTER 3 Motor
motor neuron paralysis Paralysis 51
is rarely complete for
any long period of time;
may evoke imitative
in this respect it differs
(mirror) movements in
from the absolute
the normal one or vice
paralysis that results
versa. Mirror movements
from destruction of
are also a feature of
anterior horn cells or
Parkinson disease and of
interruption of their
lesions in the upper
axons.
cervical spi nal cord. In
Upper motor neuron
some patients, as they
lesions are characterized
recover from hemiple
further by certain
gia, a variety of
movement abnormalities comparable state of
emerge, such as tremor, shock may occur with
athetosis, and chorea on acute cerebral lesions but
the affected side. These is less sharply defined
are expressions of than is the spinal state.
damage to basal With some acute cerebral
ganglionic and tha lamic lesions, spastic ity and
structures and are paralysis develop
discussed in Chap. 4. together; in others,
If the upper motor especially with parietal
neurons are interrupted lesions, the limbs remain
above the level of the flaccid but reflexes are
facial nucleus in the retained.
pons, hand and arm mus
cles are affected most Spasticity,
severely and the leg Hyperreflexia, and the
muscles to a lesser Babinski Sign
extent; of the cranial
musculature, only A predilection for
muscles of the tongue involvement of certain
and lower part of the muscle groups, a specific
face are involved to any pattern of response of
significant degree. muscles to passive
Because Broadbent was stretch (where resistance
the first to call attention increases linearly in
to this distribution of relation to velocity of
facial paralysis, it is stretch), and a manifest
some times referred to as exaggeration of tendon
“Broadbent’s law.” The reflexes are the
precise course taken by identifying
fibers that innervate the characteristics of
facial nucleus is still spasticity. The anti
somewhat uncertain, as gravity muscles—the
described earlier (Pick flexors of the arms and
bundle); but it is clear the extensors of the legs
that some descend to the —are predominantly
upper medulla and then affected. The arm tends
ascend recurrently to the to assume a flexed and
pons. This accounts for pronated position and
the mild facial weakness the leg an extended and
that is seen with lesions adducted one, indicating
of the lower pons and that certain spinal
upper medulla. neurons are reflexly
At lower levels, such more active than others.
as the cervical cord, At rest, with the muscles
complete acute lesions of shortened to
the upper motor neurons midposition, they are
not only cause a flaccid to palpation and
paralysis of voluntary electromyographically
movement but also silent. If the arm is
abolish tempo rarily the extended or the leg
spinal reflexes subserved flexed very slowly, there
by segments below the may be little or no
lesion. This is the change in muscle tone.
condition referred to By contrast, if the
above as spinal shock, a muscles are briskly
state of acute flaccid stretched, the limb
paralysis that is replaced moves freely for a very
later by spasticity. A short distance (free
interval), beyond which
 there is an abrupt catch
and then a rapidly
increasing muscular
resis tance up to a point;
then, as passive
extension of the arm or
flexion of the leg
continues, the resistance
melts away. This
sequence constitutes the
classic “clasp-knife” phe
52 Part 2 CARDINAL MANIFESTATIONS OF
NEUROLOGIC DISEASE
tial feature of spasticity
is a velocity-dependent
increase in the resistance
of muscles to a passive
stretch stimulus.
Although a clasp-knife
relaxation following
peak resis tance is highly
characteristic of cerebral
hemiplegia, it is by no
means found
consistently. In some
cases, the arm flexors
and leg extensors are
spastic, while the
antagonist muscles show
an even resistance
throughout the range of
passive movement—i.e.,
rigidity as discussed in
Chap. 4. It is notable that
there is not a constant
relationship between
spasticity and weakness.
In some cases, severe
weakness may be
associated with only the
mildest signs of
spasticity, detectable as a
“catch” in the pronators
on pas sive supination of
the forearm and in the
flexors of the hand on
extension of the wrist.
Contrariwise, the most
extreme degrees of
spasticity, observed in
certain patients with
cervical spinal cord
disease, may so vastly
exceed paresis of
voluntary movement as
to indicate that these two
states depend on
separate mechanisms.
nomenon. With the limb
in the extended or flexed
posi tion, a new passive
movement may not
encounter the same
sequence; this entire
pattern of response
constitutes the
lengthening and
shortening reaction.
Thus the essen-
Indeed, the selective
blocking of small gamma
neurons is said to abol
ish spasticity as well as
hyperactive segmental
tendon reflexes but to
leave motor performance
unchanged. Until
recently, it was taught
that the heightened
stretch reflexes (tendon
jerks) of the spastic state
are “release” phenomena
—the result of
interruption of
descending inhibitory
pathways. This appears
to be only a partial
explanation. Animal
experiments have
demonstrated that this
aspect of the spastic state
is also mediated through
spindle afferents
(increased tonic activity
of gamma motor
neurons) and, centrally,
through reticu lospinal
and vestibulospinal
pathways that act on
alpha motor neurons.
The clasp-knife
phenomenon appears to
derive at least partly
from a lesion (or
presumably a change in
central control) of a
specific portion of the
reticulospinal system.
P. Brown, in a
discussion of the
pathophysiology of spas
ticity, emphasized the
importance of two
systems of fibers: (1) the
dorsal reticulospinal sign consists of extension
tract, which has of the large toe and
inhibitory effects on extension and fanning of
stretch reflexes; and (2) the other toes dur
the medial reticulospinal ing and immediately
and vestibulospinal after stroking the lateral
tracts, which together plantar sur face of the
facilitate exten sor tone. foot. The stimulus is
He postulates that in applied along the
cerebral and capsular dorsum of the foot from
lesions, cortical the lateral heel and
inhibition is weakened, sweeping upward and
resulting in spastic hemi across the ball of the
plegia. In spinal cord foot. The stimulus must
lesions that involve the be firm but not
corticospinal tract, the necessarily painful.
dorsal reticulospinal Several dozen surrogate
tract is usually involved responses (with
as well. If the latter tract numerous eponyms)
is spared, only paresis, have been described
loss of support reflexes, over the years, most
and possibly release of utilizing alternative sites
flexor reflexes (Babinski and types of stimula
phenomenon) occur. tion, but all have the
Pantano and colleagues same significance as the
suggested that primary classic Bab inski
involvement of the response.
lentiform nucleus and Clinical and
thalamus is the feature electrophysiologic
that determines the observations indicate
persistence of flaccidity that the extension
after stroke, but the movement of the toe is a
anatomic and component of a larger
physiologic evidence for synergistic flexion or
this view is insecure. shortening reflex of the
The most sensitive leg— i.e., toe extension
indication of an upper when viewed from a
motor neuron lesion is physiologic per spective
the sign described by is a flexor protective
Babinski in 1896. (nocifensive, or
Numerous monographs defensive, Fulton’s
and articles have been terms) response.
written about the sign: a These spinal flexion
quite comprehensive reflexes, of which the
one, by van Gijn, and a Babinski sign is a part,
classic but more arcane are common
one by Fulton and accompaniments to—but
Keller. A movement not essential components
resembling the Babinski of—spasticity. They, too,
sign is present in normal are exaggerated because
infants, but it disappears of disinhibition or
and its persistence or release of motor
emergence in late programs of spinal
infancy and childhood or origin. Important
later in life is an characteristics of these
invariable indi cator of a responses are their
lesion at some level of capacity to be induced
the corticospinal tract. In by weak superficial stim
its essential form, the uli (such as a series of
pinpricks) and their muscle spindles. The
tendency to persist after cuta neomuscular
the stimulation ceases. In abdominal and
their most complete cremasteric reflexes are
form, a nocifensive usu ally abolished in
flexor synergy occurs, these circumstances, and
involving flex ion of the a Babinski sign is
knee and hip and usually, but not
dorsiflexion of the foot invariably, present.
and big toe (triple flexion Spread, or irradiation of
response). With reflexes, is regularly
incomplete supraseg associated with
mental lesions, the spasticity, although the
response may be latter phenomenon may
fractionated; for be observed to a slight
example, the hip and degree in normal
knee may flex but the persons with brisk
foot may not dorsiflex, or tendon reflexes. Tapping
vice versa. In the more of the radial periosteum,
chronic stages of for example, may elicit a
hemiplegia, the upper reflex contraction not
limb is characteristically only of the
held stiffly in partial brachioradialis but also
flexion. of the biceps, triceps, or
The hyperreflexic state finger flexors. This
that characterizes spread of reflex activity
spasticity may take the is probably not the result
form of clonus, a series of of an irradiation of
rhythmic involuntary impulses in the spinal
muscular contractions cord, as is often taught,
occurring at a frequency but a result of the
of 5 to 7 Hz in response propagation of a
to an abruptly applied vibration wave from
and sustained stretch bone to muscle,
stimulus. It is usually stimulating the excitable
designated in terms of mus cle spindles in its
the part of the limb to path (Lance). The same
which the stimulus is mechanism is probably
applied (e.g., patella, operative in other
ankle). The frequency is manifestations of the
constant within 1 Hz and hyperre flexic state, such
is not appreciably as the Hoffmann sign
modified by altering and the crossed
peripheral or cen tral CHAPTER 3 Motor Paralysis
nervous system 53
activities. Clonus
depends for its elici
adductor reflex of the thigh
tation on an appropriate
muscles. Also, reflexes may
degree of muscle
relaxation, integrity of be
the spinal stretch reflex
mechanisms, sus tained
hyperexcitability of
Table 3-1
alpha and gamma motor
“inverted,” as in the case
neu rons of a lesion of the fifth or
(suprasegmental effects), sixth cervical segment;
and synchronization of here the biceps and
the contraction– brachioradialis reflexes
relaxation cycle of are abolished and only
the triceps and finger flex S BETWEEN
UPPER AND
ors, whose reflex arcs are LOWER
intact, respond to a tap MOTOR
over the NEURON
PARALYSIS
DIFFERENCE
LOWER MOTOR NEURON OR
distal radius. and brisk the result of disuse
contractions of Spasticity with
With bilateral
hyperactivity of the
cerebral lesions, the orbicularis tendon reflexes and
exaggerated oris muscles in extensor plantar
stretch reflexes response to reflex
can be elicited in tapping the (Babinski sign)
NUCLEAR-
cranial as well as philtrum or INFRANUCLEAR
limb and trunk corners of the PARALYSIS
muscles because mouth. In
Individual muscles
of interruption of advanced cases, may be affected
the corticobulbar weakness or Atrophy
path ways. These paralysis of vol pronounced; up to
70% of total bulk
are seen as easily UPPER MOTOR
NEURON OR Flaccidity and
triggered SUPRANUCLEAR hypotonia of
masseter contrac PARALYSIS affected muscles with
tions in response Muscles affected in loss of tendon
to a brisk reflexes
groups; never
Plantar reflex, if
downward tap on individual muscles
present, is of
the chin (jaw jerk) Atrophy slight and
untary movements of the phar
face, tongue, larynx, and Fasciculations absent normal
flexor type
ynx are added spasticity and the corticospinal
(bulbar spasticity mechanisms of Normal nerve
conduction studies;
or action of anti
no denervation
“pseudobulbar” spasticity drugs potentials in EMG
palsy; see also have been Fasciculations may
Chap. 25). reviewed by be present Abnormal
The many Davidoff. Because nerve conduction
studies; denervation
investigations of glutamic acid is
potentials
the biochemical the (fibrillations,
changes that neurotransmitter fasciculations,
underlie of the positive sharp
waves) in EMG

tracts, one would expect transmitters from the

its action on inhibitory presynaptic terminals of
interneu rons to be lost. primary afferent
As mentioned earlier, terminals. Actually, none
GABA and glycine are of these agents is entirely
the major inhibitory satisfactory in the
transmitters in the spinal treatment of spasticity
cord; GABA functions as when adminis tered
a presynaptic inhibitor, orally; the
suppressing sensory administration of
signals from muscle and baclofen intrathecally
cutaneous receptors. may have a more
Baclofen, a derivative of beneficial effect. Glycine
GABA, as well as is the transmitter
diazepam and released by inhibitory
progabide, are thought interneurons and is
to act by reducing the measurably reduced in
release of excitatory quantity, uptake, and
turnover in the spastic parietal lesions
ani mal. There is some (involving areas 5
evidence that the oral
and 7 in Fig. 3-3) are
administration of glycine
more detrimental in this
reduces experimentally
respect than anterior
induced spasticity, but
ones (areas 1, 3, and 5),
its value in patients is
but both regions are
uncertain. Interruption
affected in patients with
of descending
the most severe deficits.
noradrenergic,
dopaminergic, and
serotonergic fibers is APRAXIA
undoubtedly involved in AND OTHER
the genesis of spasticity, NONPARAL
although the exact mode YTIC
of action of these DISORDERS
neurotransmitters on the OF MOTOR
various components of FUNCTION
spinal reflex arcs
remains to be defined.
All that has been said
Table 3-1 summarizes about the cortical and
the main attributes of spinal control of the
upper motor neuron motor system gives one
lesions and contrasts only a limited idea of
them with those of the human motility. Viewed
lower motor neuron objectively, the conscious
discussed above. and sentient human
organism is continuously
Motor Disturbances active—fidgeting, adjust
Caused by ing posture and position,
Lesions of the sitting, standing,
Parietal Lobe walking, run ning,
speaking, manipulating
As indicated earlier in
this section, a significant tools, or performing the
portion of the pyramidal intricate sequences of
tract originates in movements involved in
neurons of the parietal athletic or musical skills.
cor tex. Also, the parietal Some of these activities
lobes are important are relatively simple,
sources of visual and automatic, and
tactile information stereotyped. Others have
necessary for the control been learned and
of move ment. Pause and mastered through
colleagues have intense conscious effort
described the motor dis and with long practice
turbances caused by have become habitual—
lesions of the parietal i.e., reduced to an auto
cortex. The patient is matic level—a process
unable to maintain stable not at all understood
postures of the out physiologi cally. Still
stretched hand when his others are complex and
eyes are closed and voluntary, parts of a
cannot exert a steady carefully formulated
contraction. Exploratory plan, and demand
movements and continuous atten tion
manipula tion of small and thought. What is
objects are impaired, and more remarkable, one
the speed of tapping is can be occupied in
diminished. Posterior several of these variably
 conscious and habit ual motor function.
activities How is all this
simultaneously, such as possible?
driving through heavy Neuropsychologists, on
traffic while dialing a the basis of studies of
cellular phone (not large numbers of
endorsed) and engaging patients with lesions of
in animated dif ferent parts of the
conversation. Moreover, cerebrum, believe that
when an obstacle the planning of complex
prevents a particular activities,
sequence of movements conceptualizing their
from accomplishing its final purpose, and
goal, a new sequence can continuously modifying
be under taken the individual
automatically for the components of a motor
same purpose. As stated sequence until the goal is
above, these activities, in achieved are initiated
the scheme of Hughlings and directed by the
Jackson, repre sent the frontal lobes. Lesions of
third and highest level of the frontal lobes
54 Part 2 CARDINAL MANIFESTATIONS OF
NEUROLOGIC DISEASE

have the effect of as described below.

reducing the impulse to The apraxias are
think, speak, and act described in greater
(i.e., abulia, or reduced detail in Chap. 23 but a
“cortical tone,” to use brief account is provided
Luria’s expression), and here because of their inti
a complex activity will mate involvement with
not be initiated or motor activity. Any
sustained long enough explanation of apraxia
to permit its completion. requires an appreciation
The term apraxia is of the interplay between
defined as a state in modular cortical areas
which an atten tive that create highly
patient loses the ability complex motor
to execute previously behaviors. Many of their
learned activities in the functions are imputed
absence of weakness, but are nonetheless
ataxia, sensory loss, or confirmed by clinical
extrapyramidal experience with damage
derangement that would of these cerebral regions.
be adequate to explain Anatomic and functional
the deficit. All of the imag ing data indicate
elements of the activity that planned or
may be demonstrated in commanded action is
circumstances other than normally developed not
in response to the in the frontal lobe, where
command to execute the the impulse to action
activity or ges ture. This arises, but in the parietal
was the meaning given lobe of the lan guage-
to apraxia by Liepmann, dominant hemisphere,
who introduced the term where visual, auditory,
in 1900. Apraxia has and somesthetic
been divided into three information is
types: ideational, integrated. Presumably
ideomotor, and kinetic, the for mation of
ensembles of skilled
movements, which Liep
mann called a “space-
time plan,” depends on
the integrity of the
dominant parietal lobe; if
this part of the brain is
damaged, the patterns
cannot be activated at all
or the movements are
awkward and
inappropriate.
The failure to conceive
or formulate an action,
either spontaneously or
to command was
referred to by Liep mann
as ideational apraxia.
Sensory areas 5 and 7 in
the dominant parietal
lobe, the supplementary
and premotor cortices of
both cerebral
hemispheres and their
integral connections are
involved as an ensemble
to accomplish these
actions. In ideomotor
apraxia, the patient may
know and remember the
planned action, but
because these areas or
their connections are
interrupted, he cannot
actually execute it with
either hand. Certain
tasks are said to differ
entiate ideomotor from
ideational apraxia, as
discussed further on, but
the distinction may be
quite subtle. None
theless, ideational
apraxia has been said to
be character ized by
difficulty in “what to
do,” whereas ideomotor
apraxia is a block in
“how to do” as a result
of an inability to
transmit the gesture to
executive motor centers.
A third disorder, limb-
kinetic apraxia (also called
kinetic limb apraxia), is an
ill-defined clumsiness
and maladroit ness that
is the result of an
inability to connect or
isolate individual
movements of the hand
and arm as described by
Kleist. In the originally
conceived form, a hand
dis plays awkwardness
that is disproportionate
to weakness or sensory
loss, yet gestures and
complex movements can
be accomplished, unlike
the case in ideomotor
apraxia. The term has
also been applied to
cases of paralysis that
obscure the apraxia on
one side but cause a
breakdown of fine
fractionated finger
movements on the
opposite side, but we
have infrequently
detected this
phenomenon in
clinical work and it
seems to us to be more in
the way of the
“sympathetic apraxia”
discussed below. The
nature of limb kinetic
apraxia and its
differentiation from a
mild corticospinal
disorder has been
elusive enough that
many neurologists do
not view it as a true
apraxia. In a right
handed person there is a
type of left-limb apraxia
from a lesion in the left
frontal lobe that includes
the Broca area, the left
motor cortex, and the
deep underlying white
mat ter. Clinically, there
is a nonfluent aphasia, a
right hemipa resis, and a
type of apraxia of the
nonparalyzed hand,
which has been termed
sympathetic apraxia. If the
lesion in the deep white
matter separates the
language areas from the
right motor cortex but
not from the left, the
patient can write with
the right hand but not
with the left, or he may
write correctly with the
right hand and
aphasically with the left.
Perhaps surprisingly,
there are but a few cases
of apraxia of any type
with proven prefrontal
lesions.
These high-order
abnormalities of learned
movement patterns have
several unique features.
Seldom are they evident
to the patient himself,
and therefore they are
not sources of complaint,
even if they disrupt daily
activities such as
dressing. Or, if the
patient appreciates them,
he has difficulty
describing the problem
except in narrow terms
of the activity that is
impaired, such as using
a phone or dressing. For
this reason they are also
often over looked by the
examining physician.
Their evocation requires
special types of testing
that may be difficult
because of the presence
of other neurologic
deficits. Obvi ously, if
the patient is confused or
aphasic, spoken or writ
ten requests to perform
an act will not be
understood and one
must find ways of
persuading him to
imitate the movements
of the examiner.
Moreover, the patient
must be able to
recognize and name the
articles that he attempts
to manipulate; i.e., there
must not be an agnosia.
In practical terms, the
lesion responsible for
ideomotor apraxia, which
affects both hands,
usually resides in the left
parietal region. Kertesz
and colleagues provided
evi dence that the lesions
responsible for aphasia
and apraxia are different,
although the two
conditions are frequently
associated because of
their origin in the left
hemisphere. The exact
location of the parietal
lesion, whether in the
supramarginal gyrus or
in the superior parietal
lobe (areas 5 and 7) and
whether subcortical or
cortical, has been vari
able. Although the
majority of ideational
and ideomotor apraxias
occur with lesions in the
left cerebral hemisphere,
the right hemisphere
retains some of these
capacities. A small
number of apractic
patients have right
hemisphere damage.
This also explains the
preservation of most
praxis skills in the left
hand following callosal
lesions.
Geschwind accepted
Liepmann’s proposition
that a lesion of a
subcortical tract
(presumably the arcuate
fascic ulus) disconnects
the parietal from the left
frontal cortex,
accounting for the
ideomotor apraxia of the
right limbs, and that the
apraxia in the left limb is
the consequence of a
functional disconnection
of the left and right
premotor association
cortices. These
conceptualizations,
while pos sibly valid, are
of more theoretic than
practical signifi cance
and depend heavily on
the disconnection model;
there is not an actual
disconnection of the two
frontal lobes as much as
there is a putative failure
of the left to active the
right frontal lobe
 because the former is not apraxia in many ways
acti- resembles an ideomotor
apraxia, it probably has a
basis in a form of
sensory extinction and a
vated by the damaged loss of appreciation of
parietal lobe or by a extrapersonal space.
deep lesion. It is the These issues are
dominant parietal lobe discussed further in
that still embodies the Chap. 23.
prop erty of praxis. Testing for apraxia is
Of a somewhat carried out in several
different nature is an ways. First, one observes
oral-buccal-lingual apraxia, the actions of the patient
which is probably the as he engages in such
most common of all tasks as dressing,
aprax ias in practice. It washing, shaving, and
may occur with lesions using eating utensils.
that undercut the left Second, the patient is
supramarginal gyrus or asked to carry out
the left motor association familiar symbolic acts—
cor tex and may or may wave goodbye, salute the
not be associated with flag, shake a fist as
the apraxia of the limbs though angry, or blow a
described above. Such kiss. If he fails, he is
patients are unable to asked to imitate such
carry out facial acts made by the
movements on examiner. Finally, he is
command (lick the lips, asked to show how he
blow out a match, etc.), would hammer a nail,
although they may do brush his teeth, take a
better when asked to comb out of his pocket
imitate the examiner or and comb his hair, or to
when holding a lighted execute a more complex
match. With lesions that act, such as lighting and
are restricted to the facial smok ing a cigarette or
area of the left motor opening a bottle of soda,
cortex, the apraxia will pouring some into a
be limited to the facial glass, and drinking it.
musculature and may be These last actions,
associated with a verbal involving more complex
apraxia or cortical sequences, are said to be
dysarthria (Broca’s tests of ideational
aphasia). apraxia; the simpler and
So-called apraxia of familiar acts are
gait is considered in considered tests of
Chap. 7, but, strictly ideomotor apraxia. To
speaking, this not an perform these tasks in
apraxia as walking is not the absence of the tool or
a learned act. The terms utensil is always more
dressing apraxia and demanding because the
constructional apraxia are patient must mentally
used to describe special formulate a plan of
manifestations of non action rather than
dominant parietal lobe engage in a habitual
disease, in contrast to the motor sequence. The
above described forms of patient may fail to carry
apraxia that result from out a commanded or sug
lesions on the dominant gested activity (e.g., to
side. Although dressing
take a pen out of his
pocket), yet a few
minutes later he may
perform the same motor
sequence automatically.
One may think of such
an ideo motor deficit, if it
can be singled out from
confusion or a defect in
comprehension, as a
kind of amnesia for
certain learned patterns
of movement, analogous
to the amnesia for words
in aphasia.
Children with cerebral
diseases that retard
mental development are
often unable to learn the
sequences of movement
required in hopping,
jumping over a barrier,
hitting or kicking a ball,
or dancing. They suffer a
devel opmental motor
apraxia. Certain tests
quantitate failure in
these age-linked motor
skills (see Chap. 28).
In the authors’
opinion, the time-
honored division of
apraxia into ideational,
ideomotor (ideokinetic),
and kinetic
CHAPTER 3 Motor Paralysis
55
types is not entirely
satisfactory because of
the difficulty separating
them in practice. It is
more helpful to think of
the apraxias in an
anatomic sense, as
disorders of associa tion
between different parts
of the cerebral cortex, as
described above. We
have been unable to
confidently sepa rate
ideomotor from
ideational apraxia. The
patient with a severe
ideomotor apraxia
nearly always has
difficulty at the
ideational level and, in
any case, similarly
situated left pari etal
lesions give rise to both
types. Furthermore, in
view of the complexity
of the motor system, we
are frequently uncertain
whether the clumsiness
or ineptitude of a hand
in performing a motor
skill represents a kinetic
apraxia or some other
subtle fault in hand
control by the
corticospinal or one of
the other parallel motor
systems.
A related but poorly
understood disorder of
movement has been
termed the alien hand. In
the absence of volition,
the hand and arm
undertake complex and
seemingly pur poseful
movements such as
reaching into a pocket or
handbag, placing the
hand behind the head,
tugging on the opposite
hand or other body part,
and rebuttoning the shirt
immediately after it has
been unbuttoned by the
other hand. These
activities may occur even
during sleep. The patient
is aware of the
movements but has the
sense that the actions are
beyond his control, and
there is often an
impression that the hand
is estranged, as if com
manded by an external
agent (although the limb
is recog nized as one’s
own—there is no
anosognosia); a grasp
reflex and a tendency to
grope are usually added.
Most instances arise as a
result of infarction in the
territory of the opposite
anterior cerebral artery,
including the corpus
callosum. When the
callosum is involved,
Feinberg and colleagues
find that there frequently
 appears to be a con flict
between the actions of
the hands, the normal
one sometimes even
restraining the alien one.
Damage in the left
supplementary motor
area from any cause, as
well as from the
degenerative disease
called corticobasal gangli
onic degeneration
(corticobasal-ganglionic
syndromes), is
associated with a similar
alien hand syndrome. A
form that results from a
stroke in the posterior
cerebral artery territory
with associated sensory
loss has also been
observed by Ay and
colleagues.
A possibly related
phenomenon has been
described by Lhermitte
as “utilization behavior,”
in which the patient
obligatorily seizes and
uses objects in the
surrounding
environment. It is
associated with
extensive bilateral fron
tal lobe damage and has
been likened,
unsatisfactorily in our
view, to a bilateral alien
hand phenomenon.
56 Part 2 CARDINAL MANIFESTATIONS OF
NEUROLOGIC DISEASE
grally of the basal
ganglia, cerebellum, and
reticular forma tion of
the brainstem. All are
continuously integrated
and controlled by
feedback mechanisms
from the sensory and
spinal motor neurons.
Even the spinal stretch
reflex has con nections
with the motor cortex.
These points, already
touched upon in this
chapter, are elaborated
in the following three
chapters.
Finally, it should be
remarked again that the
complexity of motor
activity is almost beyond
imagination. Reference
was made earlier to the
reciprocal innervation
involved in an act as
simple as making a fist.
Scratching one’s
shoulder has been
estimated to recruit
about 75 muscles. But
what must be involved
in playing a piano
concerto? Over a century
ago Hughlings Jackson
commented that “There
are, we shall say, over
thirty muscles in the
hand; these are
represented in the
nervous centers in
thousands of different
combinations, that is, as
very many movements;
it is just as many chords,
musi cal expressions,
and tunes can be made
out of a few notes.” The
execution of these
complex movements,
many of them learned
and habitual, is made
possible by the
cooperative activities of
not just the motor and
sensory cortices but inte-
A historical
perspective that outlines
the development of these
concepts is given by
Faglioni and Basso and
an authoritative review
of the subject of apraxia
can be found in the
chapter by Heilman and
Gonzalez-Rothi.
PATTERNS OF
PARALYSIS
AND THEIR
DIAGNOSIS
The diagnostic in the cervical cord,
considerations in cases brain stem, or
of paralysis can be cerebrum. Diplegia is
simplified by using the a special form of
following subdivision, quad riplegia in
based on the location which the legs are
and distribution of the affected more than
muscle weakness: the arms. Triplegia
occurs most often as
1. Monoplegia refers to
a transitional con
weakness or
dition in the
paralysis of all the
development of or
muscles of one leg
partial recovery
or arm. This term
from tetraplegia.
should not be
5. Isolated paralysis of
applied to paralysis
one or more muscle
of isolated muscles
groups. 6. Nonparalytic
or groups of muscles
disorders of movement
supplied by a single
(e.g., apraxia, ataxia).
nerve or motor root.
7. Diseases of
2. Hemiplegia, the
muscle
commonest form of
neurons,
paralysis, involves
roots, or
the arm, the leg, and
nerves. 8.
sometimes the face
Hysterical
on one side of the
paralysis.
body. With rare
exceptions,
mentioned further Monoplegia
on, hemiplegia is The examination of
attributable to a patients who complain
lesion of the corti of weakness of one limb
cospinal system on often discloses an
the side opposite to asymptomatic weakness
the paralysis. of another, and the
3. Paraplegia indicates condition is actually a
weakness or hemiparesis or
paralysis of both paraparesis. Or, instead
legs. It is most often of weakness of all the
the result of diseases muscles in a limb, only
of the tho racic isolated groups are
spinal cord, cauda found to be affected.
equina, or Ataxia, sensory
peripheral nerves, disturbances, or
and, rarely, both reluctance to move the
medial frontal limb because of pain
cortices. must not be
4. Quadriplegia misinterpreted as
(tetraplegia) denotes weakness. Parkinsonism
weakness or paraly may give rise to the same
sis of all four error, as can rigid ity or
extremities. It may bradykinesia of other
result from disease causation or a
of the peripheral mechanical lim itation
nerves, muscles, or because of arthritis and
myoneural junc bursitis. The presence or
tions; gray matter of absence of atrophy of
the spinal cord; or muscles in a monoplegic
the upper motor limb is of particular
neurons bilaterally diagnostic help, as
indicated below.
Monoplegia without
Muscular Atrophy
This is most often caused
by a lesion of the
cerebral cortex. Only
infrequently does it
result from a subcortical
lesion that interrupts the
motor pathways. A tion of muscles, there
cerebral vascular lesion
(thrombotic or embolic
infarction) is the most
com mon cause; a
circumscribed tumor or
abscess may have the
same effect. A small
cortical lesion may
paralyze half the hand or
even just the thumb.
Multiple sclerosis and
spinal cord tumor, early
in their course, may
cause weak ness of one
limb, usually the leg.
Monoplegia caused by a
lesion of the upper
motor neuron is usually
accompanied by
spasticity, increased
reflexes, and an extensor
plantar reflex (Babinski
sign); exceptionally, a
small lesion of the motor
cortex will not result in
spasticity. In either
event, nerve conduction
studies are normal. In
acute diseases of the
lower motor neurons,
the tendon reflexes are
reduced or abolished,
but atrophy may not
appear for several
weeks. Hence, before
reaching an anatomic
diagnosis, one must take
into account the mode of
onset and duration of the
disease.
Monoplegia with
Muscular Atrophy
This is more frequent
than monoplegia
without muscular
atrophy. Long-continued
disuse of one limb may
lead to atrophy, but it is
usually of lesser degree
than atrophy caused by
lower motor neuron
disease (denervation atro
phy). In disuse atrophy,
the tendon reflexes are
retained and nerve
conduction studies are
normal. With denerva
may be visible
fasciculations and
reduced or abolished
tendon reflexes in
addition to paral ysis. If
the limb is partially
denervated, the EMG
shows reduced numbers
of motor unit potentials
(often of large size) as
well as fasciculations
and fibrillations. The
loca tion of the lesion (in
nerves, spinal roots, or
spinal cord) can usually
be determined by the
pattern of weakness, by
the associated neurologic
symptoms and signs,
and by special tests—
MRI of the spine,
examination of the cere
brospinal fluid (CSF),
and electrical studies of
nerve and muscle.
A complete atrophic
brachial monoplegia is
uncommon; more often,
only parts of a limb are
affected. When present
in an infant, it should
suggest brachial plexus
trauma from birth; in a
child, poliomyelitis or
other viral infection of
the spinal cord; and in
an adult, poliomyelitis,
syringomyelia,
amyotrophic lateral
sclerosis, or a brachial
plexus lesion. Crural (leg)
monoplegia is more
frequent than brachial
monoplegia and may be
caused by any lesion of
the thoracic or lumbar
cord—i.e., trauma,
tumor, myelitis, multiple
 sclerosis, progressive lower face on the
muscular atro phy, late opposite side. The occur
radiation effect, etc. rence of seizures or the
These disorders rarely presence of a language
cause severe atrophy; disorder (aphasia), a loss
neither does infarction in of discriminative
the territory of the sensation (e.g., astereog
anterior cerebral artery. nosis, impairment of
A prolapsed tactile localization),
intervertebral disc and anosognosia, or a
the several varieties of homonymous visual
mononeuropathy almost field defect suggests a
never paralyze all or contralateral cortical or
most of the muscles of a subcortical location.
limb. The effects of a Damage to the
centrally prolapsed disc corticospinal and
or other compressive corticobulbar tracts in
lesion of the cauda the upper portion of the
equina are rarely brainstem also causes
confined to one leg. paralysis of the face,
However, a unilateral arm, and leg of the
retroperitoneal tumor or opposite side (see Fig. 3-
hematoma 2). The lesion in such
cases may in some
patients be localized by
the presence of a third
may paralyze the leg by nerve palsy (Weber
compressing the syndrome) or other
lumbosacral plexus. The segmental abnormality
mode of onset and on the same side as the
temporal course differen lesion (opposite the
tiate these diseases. hemiplegia). With low
pontine lesions, an
Hemiplegia ipsilateral abducens or
facial palsy is combined
This is the most frequent
with a contralateral
form of paralysis. With
weakness or paralysis of
rare exceptions (a few
the arm and leg (Millard-
unusual cases of
Gubler syndrome).
poliomyelitis or motor
Lesions in the medulla
system disease), this
affect the tongue and
pattern of paralysis is a
sometimes the pharynx
result of involvement of
and larynx on one side
the corticospinal
and the arm and leg on
pathways.
the other. These “crossed
The site or level of the
paralyses,” so
lesion—i.e., cerebral
characteristic of
cortex, corona radiata,
brainstem lesions, are
capsule, brainstem, or
described further in
spinal cord—can usually
Chap. 34.
be deduced from the
Even lower in the
associated neurologic
medulla, a unilateral
find ings. Diseases
infarct in the pyramid
localized to the cerebral
causes a flaccid paralysis
cortex, cerebral white
followed by slight spas
matter (corona radiata),
ticity of the contralateral
and internal capsule usu
arm and leg, with
ally manifest themselves
sparing of the face and
by weakness or paralysis
tongue. Some motor
of the leg, arm, and
function may be
retained, as in the case
described by Ropper and
colleagues; interest
ingly, in this case and in
others previously
reported, there was
considerable recovery of
voluntary power even
though the pyramid was
almost completely
destroyed.
Rarely, an ipsilateral
hemiplegia may be
caused by a lesion in the
lateral column of the
cervical spinal cord. In
this location, however,
the pathologic process
more often induces
bilateral signs, with
resulting quadriparesis
or quadriplegia. A hemorrhage)
homolateral paralysis
that spares the face, if
combined with a loss of
vibratory and position
sense on the same side
and a contralateral loss
of pain and temper
ature, signifies disease of
one side of the spinal
cord (Brown-Séquard
syndrome, as discussed in
Chap. 44).
As indicated above,
muscle atrophy that
follows upper motor
neuron lesions never
reaches the proportions
seen in diseases of the
lower motor neuron. The
atrophy in the former
cases is a consequence of
disuse. When the motor
cortex and adjacent parts
of the parietal lobe are
damaged in infancy or
childhood, normal
development of the mus
cles, as well as the
skeletal system in the
affected limbs, is
retarded. The limbs and
even the trunk are
smaller on one
CHAPTER 3 Motor Paralysis
57
side than on the other.
This does not happen if
the paraly sis occurs
after puberty, by which
time the greater part of
skeletal growth has been
attained. In hemiplegia
caused by spinal cord
lesions, muscles at the
level of the lesion may
atrophy as a result of
damage to anterior horn
cells or ventral roots.
In the causation of
hemiplegia, ischemic
and hemor rhagic
vascular diseases of the
cerebrum and brainstem
exceed all others in
frequency. Trauma
(brain contusion,
epidural and subdural
ranks
second. Other important
causes, less acute in
onset, are, in order of fre
quency, brain tumor,
brain abscess,
demyelinating dis eases,
and the vascular
complications of
meningitis and
encephalitis. Most of
these diseases can be
recognized by their
mode of evolution and
characteristic clinical and
lab oratory findings,
which are presented in
the chapters on
neurologic diseases.
Alternating transitory
hemiparesis may be the
result of a special type of
migraine (see discus sion
in Chap. 10). From time
to time, hysteria is found
to be the cause of a
hemiplegia, as discussed
further on.
Paraplegia
Paralysis of both lower
extremities may occur
with dis eases of the
spinal cord, nerve roots,
or, less often, the
peripheral nerves. If the
onset is acute, it may be
 difficult to distinguish
spinal from neuropathic
paralysis because of the
element of spinal shock,
which results in
abolition of reflexes and
flaccidity. In acute spinal
cord diseases with
involvement of
corticospinal tracts, the
paralysis or weakness
affects all muscles below
a given level; usually, if
the white matter is
extensively damaged,
sensory loss below a
particular level is
conjoined (loss of pain
and tem perature sense
because of spinothalamic
tract damage, and loss of
vibratory and position
sense from posterior
column involvement).
Also, in bilateral disease
of the spi nal cord, the
bladder and bowel and
their sphincters are
usually affected. These
abnormalities may be the
result of an intrinsic
lesion of the cord or to
an extrinsic mass that
narrows the spinal canal,
both types of lesions
being evi dent on MRI.
In peripheral nerve
diseases, motor loss
tends to involve the
distal muscles of the legs
more than the proximal
ones (exceptions are
certain varieties of the
58 Part 2 CARDINAL MANIFESTATIONS OF
NEUROLOGIC DISEASE
branches of the aorta
(because of dissecting
aneurysm or atheroma,
vasculitis, or nucleus
pulposus embolism). A
special syndrome occurs
in older men where
chronic lum bar pain is
followed after some
months or years by the
rapid development of
paraplegia. This is
caused by an
Guillain-Barré syn
drome and certain types
of diabetic neuropathy
and por phyria);
sphincteric function is
usually spared or
impaired only
transiently. Sensory loss,
if present, is also more
prominent in the distal
segments of the limbs,
and the degree of loss is
often more for one
modality than another.
For clinical purposes it
is helpful to separate the
acute paraplegias from
the chronic ones and to
divide the latter into two
groups: those beginning
in adult life and those
occurring in infancy.
The most common
cause of acute paraplegia
(or quadriple gia if the
cervical cord is involved)
is spinal cord trauma,
usually associated with
fracture–dislocation of
the spine. Less-common
causes are hematomyelia
because of a vas cular
malformation, an
arteriovenous
malformation of the cord
that causes ischemia by
an obscure mechanism,
and infarction of the
cord as a result of
occlusion of the ante rior
spinal artery or, more
often, to occlusion of
segmental
arteriovenous
malformation or fistula
in the cord or over lying
dura of the lumbar
region. Closure of the
shunt leads to rapid
reversal of paraplegia—a
truly treatable form of
paraplegia.
Paraplegia or
quadriplegia caused by
postinfectious myelitis,
demyelinating or
necrotizing myelopathy,
or epi dural abscess or
tumor with spinal cord
compression tends to
develop somewhat more
slowly, over a period of
hours, days, or longer.
Epidural or subdural
hemorrhage from
diseases that cause a
hemorrhagic diathesis or
warfarin therapy causes
an acute or subacute
paraplegia; in a few
instances the bleeding
has followed a lumbar
puncture. Paralytic
poliomyelitis and acute
Guillain-Barré syn
drome—the former a
purely motor disorder
with mild meningitis,
the latter predominantly
motor but often with
sensory disturbances—
must be distinguished
from the acute and
subacute myelopathies
and from each other.
In adult life, multiple
sclerosis and tumor
account for most cases of
subacute and chronic
spinal paraplegia, but a
wide vari ety of extrinsic
and intrinsic processes
may produce the same
effect: protruded cervical
disc and cervical
spondylosis (often with a
congenitally narrow
canal), epidural abscess
and other infections
(tuberculous, fungal, and
other granulomatous
diseases), syphilitic
meningomyelitis, motor
system disease, subacute
combined degeneration
(vitamin B12 deficiency),
syringomyelia, and
degenerative disease of
the lateral and posterior
columns of unknown
cause. (See Chap. 44 for
dis cussion of these
spinal cord diseases.)
In pediatric practice,
delay in starting to walk
and difficulty in walking
are common problems.
These conditions may
indicate a systemic
disease (such as rickets),
mental retarda tion, or,
more commonly, some
muscular or neurologic
pro cess. Congenital
cerebral disease because
of periventricular
leukomalacia accounts
for a majority of cases of
infantile diplegia
(weakness
predominantly of the
legs, with mini mal
affection of the arms).
Present at birth, it
becomes man ifest in the
first months of life and
may appear to progress,
but actually the disease
is stationary and the
progression is only
apparent, being exposed
as the motor system
devel ops; later there
may seem to be slow
improvement as a result
of the normal maturation
processes of childhood.
These disorders fall
under the heading of
cerebral palsy, as
discussed in Chap. 38.
Congenital malformation
or birth injury of the
spinal cord are other
possibilities. Friedreich
ataxia and familial
paraplegia, muscular
dystrophy, tumor, and
the chronic varieties of
polyneuropathy tend to
appear later, during
childhood and
adolescence, and are
slowly progressive.
Transverse
(demyelinative) myelitis
is a cause of acute
paraplegia in childhood.
Quadriplegia
(Tetraplegia)
All that has been said
about the spinal causes
of paraplegia applies to
quadriplegia, the lesion
being in the cervical
rather than the thoracic
or lumbar segments of
the spinal cord. If the
lesion is situated in the
low cervical segments
and involves the anterior
half of the spinal cord, as
typified by the syndrome
resulting from occlusion
of the anterior spinal
artery (but occurring
also in some cases of
myelitis and fracture–
dislocations of the
cervical spine). In all
these processes, the
paralysis of the arms
may be flaccid and
areflexic in type and that
of the legs, spastic. There
is usu ally pain in the
neck and shoulders and
numbness of the hands;
elements of ataxia from
posterior column lesions
accompany the
paraparesis.
Compression of the C1
and C2 spinal cord
segments is caused by
dislocation of the odon
toid process.
Rheumatoid arthritis
and Morquio disease are
causes of special note; in
the latter, there is
pronounced dural
thickening.
A progressive
syndrome of
monoparesis, biparesis,
and then triparesis is
caused by tumors and a
variety of other
compressive lesions in
the region of the foramen
magnum and high
cervical cord. Bilateral
infarction of the medul
lary pyramids from
occlusion of the vertebral
arteries or their anterior
spinal branches is a very
rare cause of quad
riplegia. Repeated
strokes affecting both
hemispheres may lead to
bilateral hemiplegia,
usually accompanied by
pseudobulbar palsy (see
Chap. 23 on spastic
dysarthria and Chap. 25
on pseudobulbar
laughing and crying). In
infants and young
children, aside from
developmental
abnormalities and anoxia
of birth, certain
metabolic cere bral
diseases (metachromatic
and other forms of
leukoen cephalopathy,
lipid storage disease)
may be responsible for a
quadriparesis or
quadriplegia, but always
with severe psychomotor
retardation. Congenital
forms of muscular
dystrophy and muscular
atrophy (Werdnig
Hoffmann disease) may
be recognized soon after
birth or later and may
progress slowly.
Triplegia
Paralysis that remains
confined to three limbs is
observed only rarely;
more often the fourth
limb is weak or hyperre
flexic, and the syndrome
is really an incomplete
tetraplegia. As indicated
earlier, this pattern of
involvement is impor
tant, because it may
signify an evolving
lesion of the upper
cervical cord or
cervicomedullary
junction. A meningioma
of the foramen magnum,
for example, may begin
with spastic weakness of
one limb, followed by
sequential involvement
of the other limbs in an
“around-the-clock”
pattern. There are
usually bilateral Babinski
signs early in the
process, but there may
be few sensory findings.
 We have also seen this is impractical to
pattern in patients with memorize the precise
multiple sclero sis and senso rimotor
other intrinsic distribution of each
inflammatory and peripheral nerve, and
neoplastic lesions. These special manuals, such as
same diseases may Aids to the Examination of
produce triplegia (or the Peripheral Nervous
triparesis) by a System, should be
combination of consulted (see also Table
paraplegia from a 46-1). In addition, it is
thoracic spinal cord important to decide
lesion and a separate whether the lesion is a
unilateral lesion in the temporary one of
cervical cord or higher electrical conduction
that results in a alone or whether there
hemiparesis. has been a structural
interruption of nerve
fibers, requiring nerve
Paralysis of
regeneration or
Isolated Muscle
corrective surgery for
Groups recovery.
This condition usually Electromyography and
indicates a lesion of one nerve conduction
or more peripheral studies are of great
nerves or of several value here.
adjacent spinal roots. If there is no evidence
The diagnosis of an of upper or lower motor
individual peripheral neuron disease but
nerve lesion is made on certain movements are
the basis of weakness or nonetheless imper fectly
paralysis of a particular performed, one should
mus cle or group of look for a disorder of
muscles and impairment posi tion sense or
or loss of sensa tion in cerebellar coordination
the distribution of the or for rigidity with
nerve. Complete or abnormalities of posture
extensive and movement due to
disease of the basal
ganglia (Chap. 4). In the
absence of these disor
interruption of a ders, the possibility of
peripheral nerve is an apraxic disorder
followed by atrophy of should be investigated
the muscles it innervates by the methods outlined
and by loss of tendon earlier.
reflexes of the involved
muscles; abnormalities
of vasomotor and Hysterical Paralysis
sudomotor functions Hysterical paralysis may
and trophic changes in involve one arm or leg,
the skin, nails, and both legs, or all of one
subcutaneous tissue side of the body. Tendon
may also occur. reflexes are of normal
Knowledge of the amplitude and atrophy
motor and sensory is lacking in hysterical
innervation of the paralysis, fea tures that
peripheral nerve in distinguish it from
question is needed for a chronic lower motor
satisfactory diagnosis. It neuron disease.
Diagnostic difficulty
arises only in certain
acute cases of upper
Asanuma H: Cerebral
motor neuron disease
that lack the usual
changes in reflexes and
muscle tone. The
hysterical gait is often
diagnostic. Sometimes
there is loss of sensation
in the paralyzed parts
and loss of sight,
hearing, and smell on
the paralyzed side—a
pattern of sensory
changes that is never
seen in organic disease
of the nervous system.
When the hys terical
patient is asked to move
the affected limbs, the
move ments tend to be
slow, hesitant, and jerky,
often with contraction of
agonist and antagonist
muscles simulta neously
and intermittently
(“give-way” weakness).
Lack of effort is usually
obvious, despite facial
and other expressions to
the contrary. Power of
contraction improves
with encour agement.
The weakness is
inconsistent; some
movements are
performed tentatively
and moments later
another movement
involving the same
muscles is performed
naturally. The Hoover
sign and the trunk–thigh
sign of Babinski are
helpful in distinguishing
hysterical from organic
hemiplegia. To elicit the
Hoover sign, the
examiner places both
hands under the heels of
the recumbent patient,
who is asked to press the
References
Aids to the Examination of the
Peripheral Nervous System.
London, Bal lière
Tindall/Saunders, 1986.
cortical control of
movement. Physiologist
16:143, 1973. [PMID:
4197405]
CHAPTER 3 Motor
Paralysis 59
heels down forcefully.
With organic
hemiplegia, downward
pressure will be felt
from the nonparalyzed
leg. The exam iner then
removes his hand from
under the nonparalyzed
leg, places it on top of
the nonparalyzed one,
and asks the patient to
raise that leg. In true
hemiplegia, no added
pres sure will be felt by
the hand that remained
beneath the heel of the
paralyzed leg. In
hysteria, the heel of the
supposedly paralyzed
leg may press down on
the examiner’s hand. Or,
more useful in our
experience, the normal
leg fails to demon strate
downward pressure
when the hysteric is
asked to ele vate the
supposedly paralyzed
one, thereby indicating a
lack of voluntary effort.
To carry out the
Babinski trunk–thigh
test, the examiner asks
the recumbent patient to
sit up while keeping his
arms crossed in front of
his chest. In the patient
with organic hemiplegia,
there is an involuntary
flexion of the paretic
lower limb; in
paraplegia, both limbs
are flexed as the trunk is
flexed; in hysterical
hemiplegia, only the
normal leg may be
flexed; and in hysterical
paraplegia, neither leg is
flexed. Patients with
apparently paralyzed nerve fibers. Almost any
legs may propel a chair dis ease of the
on wheels by pedaling neuromuscular junction
along the floor (a sign and many diseases of
attributed to Blocq by muscle may cause this
Okun and colleagues). combination. This group
Asking the patient to comprises myasthenia
adduct the thighs gravis; inflammatory
against resistance may myopathies, the
also help to reveal muscular dystrophies,
hysterical weakness. The and myotonia congenita
examiner tells the (Thomsen disease);
patient that he is testing familial periodic
the normal limb, while paralysis; disorders of
asking the patient to try potassium, sodium,
to push the knees calcium, and magnesium
together. In hysterical metabolism; tetany;
weakness, the appar tetanus; poi soning by
ently paralyzed limb Clostridium botulinum;
adducts with normal black widow spider bite;
power. One can take and the thyroid and
advantage of midline other endocrine
motor actions in the myopathies. In these
upper extremity by diseases, each with a
asking the patient to fairly distinctive clinical
push his hands together picture, the abnormality
and telling him that the is essentially
normal side is being biochemical; their
tested. In hys terical investigation requires
weakness, there is special biochemical and
adduction movement of histochemical tests and
the sup posedly electron microscopic
paralyzed limb. study. These subjects are
discussed in the sections
Muscular on muscle disease later
Paralysis and in this book.
Spasm
Unattended by
Visible Changes
in Nerve or Asanuma H: The pyramidal
Muscle tract, in Brooks VB (ed):
A discussion of motor Handbook of Physiology. Sec
1: The Nervous System.
paralysis would be
Vol 2: Motor Control, Part
incomplete with out
2. Bethesda, MD,
some reference to a American Physiological
group of diseases in Society, 1981, pp 702– 733.
which muscle weakness Ash J, Georgopoulos AP:
may be profound but Mechanisms of motor
there are no overt control, in Asbury AK,
structural changes in McKhann GM, McDonald
motor nerve cells or WI, et al (eds): Diseases of
the Nervous
60 Part 2 CARDINAL MANIFESTATIONS OF
NEUROLOGIC DISEASE

System, 3rd ed. Ay H, Buonanno FS, Price

Cambridge, Cambridge BH, et al: Sensory alien hand
University Press, 2002, pp syndrome. J Neurol Neurosurg
447–460. Psychiatry 65:366, 1998.
[PMID: 9728952] Brodal P:
The Central Nervous System:
Structure and Function, 5th ed.
New York, Oxford University
Press, 1992.
Brown P: Pathophysiology of
spasticity. J Neurol
Neurosurg Psychiatry
57:773, 1994. [8021658]
Bucy PC, Keplinger JE,
Siqueira EB: Destruction of
the pyramidal tract in man. J
Neurosurg 21:285, 1964.
[PMID: 14168200] Burke D,
Lance JW: Myotatic unit and
its disorders, in Asbury AK,
McK hann GM, McDonald
WI (eds): Diseases of the
Nervous System: Clinical
Neurobiology, 2nd ed.
Philadelphia, Saunders, 1992,
pp 270–284. Davidoff RA:
Antispasticity drugs:
Mechanisms of action. Ann
Neurol 17:107, 1985. [PMID:
2858176]
Davidoff RA: Skeletal muscle
tone and the
misunderstood stretch
reflex. Neurology 42:951,
1992. [PMID: 1579249]
Denny-Brown D: The Cerebral
Control of Movement.
Springfield, IL, Charles C
Thomas, 1966.
Denny-Brown D: The nature
of apraxia. J Nerv Ment Dis
12:9, 1958. Evarts EV,
Shinoda Y, Wise SP:
Neurophysiological Approaches
to Higher Brain Functions.
New York, Wiley, 1984.
Faglioni PR, Basso A:
Historical perspectives on
neuroanatomical
correlates of limb apraxia,
in Roy EA (ed):
Neuropsychological Studies
of Apraxia and Related
Disorders. Amsterdam,
North Hol land, 1985, pp
3–44.
Feinberg TE, Schindler RJ,
Flanagan NG, Haber LD:
Two alien hand
syndromes. Neurology
42:19, 1992. [PMID:
1734302]
Fulton JF: Physiology of the
Nervous System. New
York, Oxford Univer sity
Press, 1938, chap 20.
Fulton JF, Keller AD: The
Sign of Babinski. A Study in the
Evolution of Cor tical
Dominance in Primates.
Charles C Thomas,
Springfield, 1932. Geschwind
N: The apraxias: Neural
mechanisms of disorders of
learned movement. Am
Sci 63:188, 1975. [PMID:
1115438] Gilman S, Marco
LA: Effects of medullary
pyramidotomy in the
monkey. Brain 94:495, 515,
1971. [PMID: 4255782]
Hallett M, Shahani BT, Young
RR: EMG analysis of
stereotyped vol untary
movements in man. J
Neurol Neurosurg
Psychiatry 38:1154, 1975.
[PMID: 1219079]
Heilman KM, Gonzalez-Rothi
LJ: Apraxia, in Heilman
KM, Valen stein E (eds):
Clinical Neuropsychology,
4th ed. New York, Oxford
University Press, 2003, pp
215–235.
Heilman KM, Vlanestein E:
Clinical Neuropsychology,
4th ed. Oxford, Oxford
University Press, 2003.
Henneman E: Organization
of the spinal cord and its
reflexes, in Mountcastle
VB (ed): Medical
Physiology, 14th ed. Vol 1.
St. Louis, Mosby, 1980, pp
762–786.
Iwatsubo T, Kuzuhara S,
Kanemitsu A, et al:
Corticofugal projections
to the motor nuclei of the
brain stem and spinal
cord in humans.
Neurology 40:309, 1990.
[PMID: 2300253]
Kertesz A, Ferro JM, Shewan
CM: Apraxia and aphasia:
The func tional
anatomical basis for their
dissociation. Neurology
34:40, 1984. [PMID:
6537852]
Kleist K: Leitunsgaphasie
(Nachtsprechaphasie). In
Bonhoffer K (ed):
Handbuch der artzilichen
Erhahrungen im
Welktriege. 1914/ 1918.
Barth, Leipzig, 1934. pp
725–737.
Lance JW: The control of
muscle tone, reflexes and
movement: Robert
Wartenburg Lecture.
Neurology 30:1303, 1980.
 [PMID: 7192811]
Laplane D, Talairach J,
Meininger V, et al: Motor
consequences of motor
area ablations in man. J
Neurol Sci 31:29, 1977.
[PMID: 833609]
Lassek AM: The Pyramidal
Tract. Springfield, IL, Charles
C Thomas, 1954. Lawrence
DG, Kuypers HGJM: The
functional organization of the
motor system in the monkey.
Brain 91:1, 15, 1968. [PMID:
4966860] Lhermitte F:
“Utilization behaviour” and
its relation to lesions of the
frontal lobes. Brain 106:237,
1983. [PMID: 6850269]
Liepmann H: Das
Krankheitsbild der
Apraxie (motorische
Asym bolie auf Grund
eines Falles von
einseitiger Apraxie).
Monatsschr Psychiatr
Neurol 8:15, 102, 182, 1900.
Lorente de Nó R: Cerebral
cortex: Architecture,
intracortical connec tions,
motor projections, in
Fulton JF (ed): Physiology
of the Ner vous System, 3rd
ed. New York, Oxford
University Press, 1949, pp
288–330.
Luria AR: The Working Brain:
An Introduction to
Neuropsychology. New
York, Basic Books, 1973.
Marx JJ, Ianetti GD, Thöme F,
et al: Somatotopic
organization of the
corticospinal tract in the
human brainstem: A MRI-
based map ping analysis.
Ann Neurol 57:824, 2005.
[PMID: 15852473]
Mountcastle VB: Central
nervous mechanisms in
sensation, in Mountcastle
VB (ed): Medical
Physiology, 14th ed. Vol 1:
Part 5. St. Louis, Mosby,
1980, pp 327–605.
Nathan PW, Smith M,
Deacon P:
Vestibulospinal,
reticulospinal and
descending propriospinal
nerve fibers in man. Brain
119:1809, 1996. [PMID:
9009990]
Nyberg-Hansen R, Rinvik E:
Some comments on the
pyramidal tract with
special reference to its
individual variations in
man. Acta Neurol Scand
39:1, 1963.
Okun MS, Rodriquez RL,
Foote KD, et al: The “chair
test” to aid in the
diagnosis of psychogenic
gait disorders. The
Neurologist 13:87, 2007.
[PMID: 17351529]
Pantano P, Formisano R,
Ricci M, et al: Prolonged
muscular flaccidity after
stroke. Morphological and
functional brain
alterations. Brain 118:1329,
1995. [PMID: 7496790]
Pause M, Kunesch F,
Binkofski F, Freund H-J:
Sensorimotor distur
bances in patients with
lesions of the parietal
cortex. Brain 112:1599,
1989. [PMID: 2598000]
Roland PE: Organization of
motor control by the
normal human brain.
Hum Neurobiol 2:205, 1984.
[PMID: 6715206]
Ropper AH, Fisher CM,
Kleinman GM: Pyramidal
infarction in the medulla:
A cause of pure motor
hemiplegia sparing the
face. Neu rology 29:91,
1979. [PMID: 570681]
Russell JR, DeMyer W: The
quantitative cortical
origin of pyramidal axons
of Macaca rhesus, with
some remarks on the slow
rate of axolysis. Neurology
11:96, 1961. [PMID:
13744848]
Terao S, Miura N, Takeda A,
et al: Course and
distribution of facial
corticobulbar tract fibers
in the lower brainstem. J
Neurol Neuro surg
Psychiatry 69:262, 2000.
[PMID: 10896707]
Terakawa H, Abe K,
Nakamura M, et al:
Ipsilateral hemiparesis
after putaminal
hemorrhage due to
uncrossed pyramidal
tract. Neurol ogy 54:1801,
2000. [PMID: 10802787]
Thach WT Jr, Montgomery
EB Jr: Motor system, in
Pearlman AL, Col lins RC
 (eds): Neurobiology of
Disease. New York,
Oxford Univer sity Press,
1990, pp 168–196.
Tower SS: Pyramidal lesion
Abnormalities
of Movement
and Posture
Caused by
Disease of
the Basal
Ganglia
In this chapter, the
disorders of the
automatic, static, pos
tural, and other less-
modifiable motor
activities of the ner vous
system are discussed.
They are an expression
of what has come to be
called the extrapyramidal
motor system, meaning
—according to S.A.K.
Wilson, who introduced
this term—the motor
structures of the basal
ganglia and certain
related thalamic and
brainstem nuclei.
The activities of the
basal ganglia and the
cerebellum are blended
with and modulate the
corticospinal and cor
tical–brainstem–spinal
systems. The static
postural influ ence of the
extrapyramidal system is
in the monkey. Brain 63:36,
1940. Van Gijn J: The Babinski
Sign. A Centenarary.
Universitiet Utrecht. Utrecht,
1996.
4
indispensable to
voluntary corticospinal
movements. This close
association of the basal
ganglia and corticospinal
systems becomes evident
in the course of many
forms of neurologic
disease. Cerebral lesions
that involve the
corticospinal tracts result
not only in a
contralateral paralysis of
volitional move ments
but also in a fixed
posture in which the arm
is flexed and the leg
extended. Similarly, as
noted in Chap. 3,
interruption of the motor
projections by a lesion in
the up per pons or
midbrain may release a
posture in which all four
limbs or the arm and leg
on one side are
extended, and the
cervical and ity related to the term
thoracolumbar portions pyramidal was discussed
of the spine are in Chap. 3,
hyperextended in which it was pointed
(decerebrate rigidity). In out that pure pyramidal
these aberrant motor lesions do not cause total
patterns, one also sees paralysis; when total
evidence of labyrinthine, paralysis exists, there is
tonic neck, and other always some degree of
postural reflexes that are involvement of other
mediated through descending motor
nonpyramidal pathways as well. The
bulbospinal and other term extrapyram idal is
brainstem motor equally imprecise.
systems. Observations Strictly interpreted, it
such as these and the ana refers to all the motor
tomic data presented in pathways except the
Chap. 3 have blurred the pyramidal one, making
classic distinctions this term so all-
between pyramidal and embracing as to be
extrapyramidal mo tor practically meaning less.
systems. Nevertheless, The concept of an
this division remains a extrapyramidal motor
useful, if not an essential, system becomes more
concept in clinical work, meaningful if it is
because it compels a subdivided into two
distinction between parts: (1) the
several motor striatopallidonigral
syndromes— one that is system (basal ganglia)
characterized by a loss of and (2) the cerebellum,
volitional movement and it is the former that
accompanied by is cur rently referred to
spasticity—the as “extrapyramidal.”
corticospinal syndrome; These parts func tion
a second by akinesia, very differently in the
rigidity, and tremor control of movement and
without loss of voluntary posture, and disease in
movement—the each of them results in
hypokinetic basal particular disturbances
ganglionic syndrome; a of movement and
third by involuntary posture without
movements (choreo paralysis. The basal
athetosis and dystonia) ganglia and the
—the hyperkinetic basal symptoms that result
gangli onic syndrome; when they are diseased
and yet another by are described in the
incoordination (ataxia)— pages that follow and in
the cerebellar syndrome. Chap. 6. The disorders of
Table 4-1 summarizes movement and posture
the main clinical strictly as a consequence
differences between of cerebellar disease are
corticospinal and ex described in Chap. 5.
trapyramidal
syndromes.
Much of the criticism THE
of the pyramidal– STRIATOPAL
extrapyramidal concept LIDONIGRAL
derives from the terms SYSTEM
themselves. The ambigu (BASAL
GANGLIA)
 Anatomic masses into the striatum
Considerations (or neostriatum),
comprising the caudate
As an anatomic entity,
nucleus and putamen,
the basal ganglia have no
and the paleostriatum or
precise definition.
pallidum, which has a
Principally they include
medial (internal) and a
the caudate nucleus and
lateral (external) portion.
the lentiform (lenticular,
The putamen and
from its lens-like shape)
pallidum lie on the
nucleus with its two
lateral aspect of the
subdivisions—the
internal capsule, which
putamen and glo bus
separates them from the
pallidus. Insofar as the
caudate nucleus,
caudate nucleus and
thalamus, subthalamic
putamen are really a
nucleus, and substantia
continuous structure
nigra on its medial side
(separated only incom
(Figs. 4-1 and 4-2). By
pletely by fibers of the
virtue of their close
internal capsule) and are
connections with the
cytologi cally and
caudate and lenticular
functionally distinct
nuclei, the subthalamic
from the pallidum, it is
nucleus (nucleus of
more meaningful to
Luys) and the
divide these nuclear

61
62 Part 2 CARDINAL MANIFESTATIONS OF
NEUROLOGIC DISEASE

Table 4-1
ORTICOSPINAL AND EXTRAPYRAMIDAL
SYNDROMES CORTICOSPINAL
EXTRAPYRAMIDAL

qual throughout passive movement (rigidity), or intermittent

(cogwheel rigidity)
Distribution of hypertonus Flexors of arms, extensors
of legs Generalized but predominates in flexors of
limbs and of trunk
Involuntary movements Absent Presence of
tremor, chorea, athetosis, dystonia Tendon
reflexes Increased Normal or slightly increased
Babinski sign Present Absent
Paralysis of voluntary movement Present Absent or slight

substantia nigra are physiologists have

included as parts of the expanded the list of
basal ganglia. The basal ganglionic
claustrum and structures to include the
amygdaloid nuclear red nucleus, the
complex, because of intralaminar thalamic
their largely different nuclei, and the reticular
connections and formations of the upper
functions, are usually brainstem. These
excluded. structures receive direct
For reasons indicated cortical projections and
further on, some give rise to rubrospinal
and reticulospinal tracts Whittier and Mettler and
that run parallel to the of Carpenter, in the late
corticospinal 1940s. These
(pyramidal) ones; hence investigators demon
they also were once strated, in monkeys, that
referred to as a characteristic
extrapyramidal. However, movement disor der,
these nonpyramidal which they termed
linkages are structurally choreoid dyskinesia, could
indepen dent of the be brought about in the
major extrapyramidal limbs of one side of the
circuits that include the body by a lesion
striatum, pallidum, localized to the opposite
thalamus, and premotor subthalamic nucleus.
and supple mentary They also showed that
motor cortices. Insofar as for such a lesion to
the final links in this provoke dyskinesia, the
circuit—the premotor adjacent pallidum and
and supplementary pallidofugal fibers had to
motor corti ces— be preserved; that is, a
ultimately project onto second lesion—placed in
the motor cortex, the the medial segment of
afore mentioned circuit the pallidum, in the
is more aptly referred to fasciculus lenticularis, or
as prepyramidal (Thach in the ventrolateral
and Montgomery). thalamus—abolished the
dyskinesia. This
experimental
hyperkinesia could also
Caudate be abolished by
nucleus
interruption of the lateral
Puta
corticospinal tract but
men
not by interruption of the
other motor or sensory
pathways in the spinal
cord. These observations
were interpreted to mean
that the subthalamic
nucleus exerts an
inhibitory or regu
Corpus
callosum

Lateral
ventricle

Thalamus
Earlier views of basal
ganglionic organization
empha sized serial
connectivity and the
funneling of efferent pro
jections to the
ventrolateral thalamus
and thence to the motor
cortex (Fig. 4-3). This
concept was based Caudate nucleus
largely on the classic
Putamen
experimental work of

Internal capsule Claustrum Amygdala

Globus pallidus: Basal The main nuclei from Kandel
External ganglia
segment Internal Figure 4-1.
of the basal ER, Schwartz
segment ganglia are JH, Jessell TM:
Overview of the represented in Principles of
compo nents of blue, as labeled Neural Science,
Subthalamic
the basal
nucleus on the right. 4th ed. New
ganglia in (Reproduced York: McGraw-
Substantia nigra
coronal view. with permissionHill, 2000.)
CHAPTER 4 Abnormalities of Movement and Posture
Caused by Disease of the Basal Ganglia 63

Caudate
nucleus
Ventricle

Thalamus
Dopamine

Direct
D1 D2 Indirect
 Thalamus
pathway
facilitates
movement

From
SNc
pathway
inhibits
movement

Putamen pallidus Nucleus of Substantia

Globus Luys nigra
Putamen

Figure 4-2. destruction cal fibers to STN

Diagram of the
of the the ipsilateral
basal ganglia in
the coronal
subthalamic premotor
plane, illus nucleus is cortex, and Pedunculo
trating the main expressed from there, to pontine
interconnection physiological the motor nucleus
s (see text for ly by an cortex, all in
details). The
irregular a serial
pallido thalamic
connections are
activity that manner. New
illustrated in is now observations
Fig. 4-3. identified as have made it
chorea, pre apparent that
sumably there are,
arising from instead, a
lating
influence on the intact number of
the globus pallidum and parallel
pallidus and conveyed to circuits as
ventral thala the detailed
mus. ventrolateral further on. A Spinal
cord
Removal of thalamic gen
Direct GPe
this influence nuclei, t

by selective thence by
c

ire
d

thalamocorti GPi In
eral principle that has from it anatomically and
withstood the test of physiologically. At least
time is the cen tral role of
Figure 4-3. Schematic
the ventrolateral and
illustration of major efferent
ventroanterior nuclei of
and afferent con nections of
the thalamus. Together, the basal ganglia. The blue
they form a vital link in lines indicate neurons with
an ascend ing fiber excitatory effects, whereas the
system, not only from black lines indicate inhibitory
the basal ganglia but also influ ences. (See text for
details; also Fig. 4-2.)
from the cerebellum, to
(Reproduced with permis
the motor and premotor sion from Kandel ER,
cortex. Thus both basal Schwartz JH, Jessell TM:
ganglionic and cerebellar Principles of Neural Science,
influences are brought to 4th ed. New York: McGraw-
bear, via thalamocortical Hill, 2000.)
fibers, on the cortico
spinal system and on
five such anatomic
other descending
circuits have been
pathways from the
described, each pro
cortex. Direct
jecting to a different
descending pathways
portion of the frontal
from the basal ganglia to
lobe: (1) the pro totypical
the spinal cord are
motor circuit,
relatively insignificant.
converging on the
The foregoing view of
premotor cortex; (2) the
basal ganglionic
oculomotor circuit,
organization has been
projecting onto the fron
broadened considerably
tal eye fields; two
as a result of new
prefrontal circuits: (3)
anatomic, physiologic,
one ending in the
and pharmacologic data
dorsolateral prefrontal
(see in particular the
and (4) the other on the
reviews of Gombart and
lateral orbitofrontal
colleagues, of DeLong,
cortex; and (5) a limbic
and of Penney and
circuit that projects to
Young). Whereas earlier
the anterior cingulate
concepts emphasized the
and medial orbitofrontal
serial connectivity of the
cortex.
basal ganglionic
An additional and
structures and the
essential feature of basal
funneling of efferent
ganglionic structure, also
projections to the
relatively recently
thalamus, current
appreciated, is the non
evidence indicates an
equivalence of all parts
organization into several
of the striatum.
parallel basal
Particular cell types and
ganglionic–cortical
zones of cells within this
circuits. Although these
structure appear to
circuits run parallel to
mediate different aspects
the premotor pathway,
of motor control and to
they remain separate
utilize
64 Part 2 CARDINAL MANIFESTATIONS OF
NEUROLOGIC DISEASE

specific neurochemical “Pharmacologic

transmitters, as detailed Considerations” (see
below under also Albin et al and
DeLong). This
specialization has taken
on further importance
with the observation that
one or another cell type
is destroyed
preferentially in
degenerative diseases
such as Huntington
chorea.
The most important
basal ganglionic
connections and circuitry
are indicated in Figs. 4-1,
4-2, and 4-3. Conven
tionally it has been
taught that the striatum,
mainly the putamen, is
the receptive part of the
basal ganglia, receiv ing
topographically
organized fibers from all
parts of the cerebral
cortex and from the pars
compacta (pigmented
neurons) of the
substantia nigra, and
that the output nuclei of
the basal ganglia consist
of the medial (internal)
palli dum and the pars
reticulata
(nonpigmented portion)
of the substantia nigra
(Fig. 4-3).
Furthermore, it has
been proposed on the
basis of physio logic,
lesional, and
pharmacologic studies,
that there are two main
efferent projections from
the putamen; but these
models, being quite
incomplete, should be
viewed as provi sional.
Nonetheless, there are
reasons to conceptualize
a direct efferent system
from the putamen onto
the medial (internal)
pallidum and then onto
the substantia nigra
again, particularly to the
pars reticulata cells, and
an indirect system that
traverses the lateral
(external) pallidum and
continues on to the
subthalamic nucleus,
with which it has strong
to-and-fro connections.
In most ways, the subtha
lamic nucleus and lateral
pallidum operate as a
single func tional unit (at
least in terms of the
effects of lesions in those
locations on
parkinsonian symptoms
and the neurotrans
mitters involved; see
further on). The medial
pallidum and reticular
part of the nigra can be
viewed in a similar
unitary way, sharing the
same input and output
patterns. Within the
indirect pathway, an
internal loop is created
by projec tions from the
subthalamic nucleus to
the medial segment of
the pallidum and pars
reticulata. A second
offshoot of the indirect
pathway, recently
uncovered, consists of
projec tions from the
lateral pallidum to the
medial pallidonigral
output nuclei. These
anatomic and
physiologic concepts are
continuously being
revised on the basis of
clinical and neu
rochemical observations.
A complete account of
this intri cate
connectivity cannot be
given, but the main
themes outlined here
seem to have been
accepted. The relative
importance of the direct
and indirect pathways is
being altered by recent
experience, as discussed
below.
From the internal
pallidum, two bundles of
fibers reach the thalamus
—the ansa lenticularis
and the fasciculus len
ticularis. The ansa
sweeps around the
internal capsule; the sensorimotor cortex and
fasciculus traverses the by dopaminergic nigral
internal capsule in a (pars compacta)–striatal
number of small fascicles projections. Activation of
and then continues this direct pathway
medially and caudally to inhibits the medial palli
join the ansa in the dum, which, in turn,
prerubral field. Both of disinhibits the
these fiber bundles join ventrolateral and ven
the thalamic fasciculus, troanterior nuclei of the
which then contains not thalamus. As a
only the pallidothalamic consequence,
projections but also thalamocortical drive is
mesotha lamic, enhanced and cortically
rubrothalamic, and initiated movements are
dentatothalamic ones. facilitated. The indirect
These projections are circuit arises from
directed to separate putaminal neurons that
targets in the ventro contain gamma-
lateral nucleus of the aminobutyric acid (GABA)
thalamus and to a lesser and smaller amounts of
extent in the ventral enkephalin. These stri
anterior and atal projections have an
intralaminar thalamic inhibitory effect on the
nuclei. The lateral pal lidum, which,
centromedian nucleus of in turn, disinhibits the
the intralaminar group subthalamic nucleus
projects back to the through GABA release,
putamen and, via the providing subthalamic
parafascicular nucleus, drive to the medial
to the caudate. A major pallidum and substantia
projection from the nigra pars reticulata. The
ventral tha lamic nuclei net effect is thalamic
to the ipsilateral inhibition that reduces
premotor cortex thalamo cortical input to
completes the precentral motor
the large cortical–striatal– fields and impedes
pallidal–thalamic–cortical voluntary movement.
motor loop, with These complex anatomic
conservation of the and physi ologic
somatotopic relationships have been
arrangement of motor summarized in
fibers, again numerous schematic
emphasizing the nexus diagrams similar to Fig.
at the tha lamic nuclei. 4-4 and those by Lang
and Lozano and by
Physiologic Standaert and Young.
Considerations Restated, the current
view is that enhanced
Physiologic evidence conduction through the
indicates that a balanced indirect pathway leads
functional architecture, to hypokinesia by
one excitatory and the increasing
other inhibitory, is pallidothalamic
operative within the inhibition, whereas
individual circuits. The enhanced conduction
direct stri atomedial through the direct
pallidonigral pathway is pathway results in
activated by glutamin hyperki nesia by
ergic projections from the
 reducing pallidothalamic
inhibition. The direct
pathway has been
perceived by Marsden
and Obeso as facilitating
cortically initiated
movements and the
indirect pathway as
suppressing potentially
conflicting and
unwanted motor
patterns. In Parkinson
disease, for exam ple,
loss of dopaminergic
input from the
substantia nigra
diminishes activity in the
direct pathway and
increases activity in the
indirect pathway; the net
effect is to increase
inhibition of the thalamic
nuclei and to reduce
excitation of the cortical
motor system.
Further insight into
these systems and into
the mecha nism of
Parkinson disease has
come from the discovery
that the parkinsonian
syndrome can be
reproduced in humans
and primates by the
toxin 1-methyl-4-phenyl-
CHAPTER 4 Abnormalities of Movement and Posture
Caused by Disease of the Basal Ganglia 65
1,2,3,6-tet
rahydropyridine
(MPTP). This toxin was
discovered acci dentally
in drug addicts who self-
administered an
analogue of meperidine.
The toxin binds with
high affinity to mono
amine oxidase (MAO),
an extraneural enzyme
that trans forms it to
pyridinium, a toxic
metabolite that is bound
by melanin in the
dopaminergic nigral
neurons in sufficient
quantities to destroy the
cells, probably by
interfering with
mitochondrial function.
In monkeys made
parkinsonian by the
administration of MPTP,
electrophysiologic
studies have shown
increased activity in the
medial globus pallidus
and decreased activity in
the lateral globus
pallidus, as pre dicted
from the previously
described models. This
comes about because of
the differential loss of
activity of dopamin-

Normal Functional Anatomy of Functional Anatomy of Motor

Motor Cortex Basal Ganglia and Cortex Basal Ganglia and
Thalamus Thalamus in Parkinson Disease

Cortex Cortex
Glutamate
Striatum Striatum
DA D1 DA Excitatory
t

(Glutamate,
DA t

D2 DA
D2 Excitatory
D1 (Glutamate,
Inhibitor
t

SNpc LGP STN

i r

c
D
i

DA: D1)
DA: D1) y (GABA,
d
e c

Inhibitory
r n
e
i I

DA: D2)
r

(GABA,
i

SNpc
D

GABA
d
t
LGP
DA: D2)
n
c

STN
I c

e
r

GABA Glutamate

SNpr MGP VL/VA SNpr MGP VL/VA

GABA Thalamus Thalamus

A Motor Output B Motor Output

F
u
n
c
t
 i
o
n
a
l

A
n
a
t
o
m
y

o
f

M
o
t
o
r

C
o
r
t
e
x

B
a
s
a
l

G
a
n
g
l
i
a

a
n
d

T
h
a
l
a
m
u
s

i
n

H
u
n
t
i
n
g
t
o
n

D
i
s
e
a
s
e

C
o
r
t
e
x
 St
ria
tu
m
DA D2 Excitatory
(Glutamate,
DA D1
t
t

SNpc
n

e
I

DA: D1)
LGP
c

Inhibitory (GABA,
r

i
e

STN
r
D

DA: D2)
i

SNpr

MGPVL/VA
Thalamu
s

C Motor Output
Figure 4-4. A. Schematic diagram of the main
neurotransmitter pathways and their effects in the
cortical–basal ganglia–thalamic circuits. The blue lines
indicate neurons with excitatory effects; the black lines
indicate inhibitory influences. The internal (medial)
segment of the globus palli dus (MGP) and the zona
reticulata of the substantia nigra (SNpr) are believed to
act as one entity that projects via GABA-containing
neurons to the thalamus (ventrolateral and ventroanterior
nuclei) and to the pedunculopontine nuclei (not shown).
Dopaminergic neurons (DA) arising in the pars compacta
of the substantia nigra (SNpc) have an excitatory
influence on the direct striatopallidal fibers (via D1
receptors) and an inhib itory effect on the indirect
striatopallidal fibers (via D2 receptors) that project to the
external (lateral) pallidum (LGP) and subthalamic
nucleus (STN). Dotted lines in the subsequent figures
denote a reduction in activity of the pathway. (See text.)
B. Corresponding physiologic state as con ceptualized in
Parkinson disease, in which hypokinesia is the main
finding as a result of reduced dopamine input from the
substantia nigra and pars compacta to the striatum via
the direct pathway, which results in withdrawal of
inhibitory activity of the globus pallidus and, in turn,
increased inhibitory drive on the thalamic nuclei, which
reduces input to the cortical motor system. C. Schematic
diagram of the theorized mechanism in Huntington
disease, a hyperkinetic movement disorder resulting from
reduced inhibition by the striatum within the indirect
pathway, overdriving of the subthalamic nucleus, and
causing excess activity in thalamocortical circuits. (See
text.)

ergic striatal neurons disease is not

that project to each of reproduced. This
these parts of the subtlety may also ex
pallidum. The end result plain why crude lesions,
is increased inhibition of such as infarcts,
thalamocortical neurons. hemorrhages, and
It is, however, difficult to tumors, rarely produce
explain why medial the complete
pallidal lesions do not parkinsonian syn drome
regularly cause parkin of tremor, bradykinesia,
sonism. Perhaps it is and rigidity. Indeed,
because the subtle strik ing improvements
imbalance between the in parkinsonian
medial and lateral symptoms are obtained,
pallidal circuits that paradoxically, by placing
exists in Parkin son lesions in the medial
pallidum (pallidotomy) disease. To further
as discussed in Chap. 39. complicate mat ters, the
It is likely that the various subtypes of
static model of inhibitory dopamine receptors act
and excita tory pathways in both excitatory and
and the parsing of a inhibitory ways under
direct and an indirect different cir cumstances
pathway, as useful as it depending on their
is as a mnemonic, does location as discussed
not below. The complexity of
account well for the basal ganglionic
dynamic activities of the interactions can hardly
basal gan glia. In be explained in these
particular, the electrical simplified models, but
activity of the neurons in they remain reasonable
these systems oscillate prototypes for
and influence the understanding abnor
frequency of oscillations mal hyperkinetic and
in other parts of the hypokinetic movements.
system, as well as bring In more conventional
ing individual cells and not yet antiquated
closer to firing. One physio logic terms,
deficiency of cur rently Denny-Brown and
conceived models is that Yanagisawa, who
they do not account for studied
the tremor of Parkinson
66 Part 2 CARDINAL MANIFESTATIONS OF
NEUROLOGIC DISEASE

the effects of ablation of structs focus on the role

individual of the basal ganglia in
extrapyramidal struc the initia tion,
tures in monkeys, sequencing, and
concluded that the basal modulation of motor
ganglia func tion as a activity (“motor
kind of clearinghouse programming”). Also, it
where, during an appears that the basal
intended or projected ganglia participate in the
movement, one set of constant priming of the
activities is facilitated motor system, enabling
and all other the rapid execution of
unnecessary ones are motor acts with out
suppressed. They used premeditation—e.g.,
the analogy of the basal hitting a baseball. In
ganglia as a brake or most ways, these
switch, the tonic conceptualizations
inhibitory (“brake”) restate the same notions
action preventing target of bal ance and
struc tures from selectivity imparted to
generating unwanted all motor actions by the
motor activity and the basal ganglia. The
“switch” function manner in which
referring to the capacity excessive or depleted
of the basal ganglia to activity of various
select which of many components of the basal
available motor ganglia gives rise to
programs will be active hypokinetic and
at any given time. Still hyperkinetic movement
other theoretical con disorders is discussed
further on, under glutamate, GABA,
“Symptoms of Basal Gan dopamine, acetylcholine,
glia Disease.” and seroto nin. Figure 4-
4 summarizes their roles.
Pharmacologic A more complete
Considerations account of this subject
than is possible here
During the past decades, may be found in the
a series of pharmacologic reviews of Penney and
obser vations have Young, of Alexander and
considerably enhanced Crutcher, and of Rao.
our understanding of The following is what
basal ganglionic function is known with a fair
and led to a rational degree of certainty.
treatment of Parkinson Glutamate is the
disease and other neurotransmitter of the
extrapyramidal excita tory projections
syndromes. Whereas from the cortex to the
physiologists had for striatum and of the
years failed to discover excitatory neurons of the
the functions of the basal subthalamic nucleus.
ganglia by stimulation GABA is the inhibitory
and crude ablation neurotransmitter of
experiments, clinicians striatal, pallidal, and
became aware that the substantia nigra (pars
use of certain drugs, reticulata) projection
such as reserpine and the neurons. Ace tylcholine
phenothiazines, (ACh), long established
regularly produced as the neurotransmit ter
extrapyramidal at the neuromuscular
syndromes (e.g., par junction and the
kinsonism, autonomic ganglia, is
choreoathetosis, also physiologically
dystonia). These observa active in the basal
tions greatly stimulated ganglia.
the study of central The highest
nervous system (CNS) concentration of ACh, as
transmitter substances in well as of the enzymes
general. The cur rent necessary for its
view is that the synthesis and
integrated basal degradation (choline
ganglionic control of acetyl transferase and
movement can be best acetylcholinesterase), is
understood by in the striatum.
considering, in the Acetylcholine is
context of the anatomy synthesized and released
described above, the by the large but sparse
physiologic effects of (Golgi type 2) nonspiny
neurotransmitters that striatal neurons. It has a
convey the signals mixed but mainly
between cortex, striatum, excitatory effect on the
globus pallidus, more numerous spiny
subthalamic nucleus, neurons within the
substantia nigra, and putamen that constitute
thalamus. the main origin of the
The most important direct and indirect
neurotransmitter pathways described
substances from the above. Dopamine, by
point of view of basal contrast, has both
ganglionic function are
inhibitory and excitatory the most simplified
effects on these neurons, models, stimulation of
as detailed below. It is the dopaminergic
likely that the neurons of the substan
effectiveness of atro tia nigra induces a
pinic agents—which specific response in the
have been used striatum— namely, an
empirically for many inhibitory effect on the
years in the treatment of already low firing rate of
Parkinson disease and neostriatal neurons.
dystonia—depends on However, the effects of
their capacity to dopamine have proved
antagonize ACh at sites more difficult to resolve,
within the basal ganglia in large part because
and in projections from there are now five
the pedunculopontine known types of
nuclei. Acetylcholine postsynaptic dopamine
appears also to act on the receptors (D1 to D5),
presynaptic membrane each with its particular
of striatal cells and to anatomic distribution
influence their release of and pharmacologic
neurotransmitters, as action. This
discussed below. In heterogeneity is
addition, the basal exemplified in the
ganglia contain other excitatory effect of
biolog ically active dopamine on the small
substances—substance P, spiny neurons of the
enkephalin, chole putamen and an
cystokinin, somatostatin, inhibitory effect on
and neuropeptide Y— others.
which enhance or The five types of
diminish the effects of dopamine receptors are
other neurotransmit ters, found in dif fering
i.e., they act as concentration
neuromodulators. throughout various parts
Of the catecholamines, of the brain, each
dopamine has the most displaying differing
perva sive role. It can be affinities for dopamine
said that it is among the itself and for various
most impor tant in brain drugs and other agents
disease, because (Table 4-2; also see
disturbances of Jenner). The D1 and D2
dopamine signaling are receptors are highly con
essential abnormalities centrated in the striatum,
of several CNS dis D3 in the nucleus
orders including accumbens, D4 in the
parkinsonism, frontal cortex and certain
schizophrenia, attention limbic structures, and D5
deficit hyperactivity in the hippocampus. In
disorder, and drug the striatum, the effects
abuse. Within the basal of dopamine act as a
ganglia, the areas richest class of “D1-like” (D1
in dopamine are the sub and D5 sub types) and
stantia nigra, where it is “D2-like” (D2, D3, and
synthesized in the nerve D4 subtypes) recep tors.
cell bodies of the pars Activation of the D1
compacta, and the class stimulates adenyl
termination of these cyclase, whereas D2
fibers in the striatum. In receptor binding inhibits
 this enzyme. Whether earlier, excitatory D1
dopamine functions in recep tors predominate
an excitatory or inhibi on the small spiny
tory manner at a putamenal neurons that
particular synapse is are the origin of the
determined by the local direct striatopallidal
receptor. As mentioned output
CHAPTER 4 Abnormalities of

Movement and Posture Caused by Disease

of the Basal Ganglia 67 Table 4-2

PROPERTIES AND LOCALIZATION OF DOPAMINE

RECEPTORS
Classes of Dopaminergic
Receptors
D1 D2 D3 D4 D5

Within basal ganglia

a b
Striatum + + + ++ Lateral GP + +
Subthalamic nucleus + + +
Medial GP/SN pars reticulata +
SN pars compacta + + +
Outside basal ganglia
Nucleus accumbens + +
Frontal cortex + + Limbic structures +
Hippocampus + Hypothalamus + +
Olfactory tubercle +
Pituitary +
Brainstem + Drug
affinities
Dopamine ++ +++ ++++ N/A N/A
Bromocriptine — ++ ++ N/A N/A Pergolide +
++++ +++ N/A N/A Ropinirole 0 +++ ++++ N/A
N/A Pramipexole 0 +++ ++++ N/A N/A
a
Acts through direct striatal projection neurons.
b
Acts through indirect striatal projection neurons.
GP, globus pallidus; SN, substantia nigra.

pathway, whereas D2 further on) are prone to

receptors mediate the occur when drugs are
inhibitory influence of administered that
dopamine on the indirect competi tively bind to
striatopallidal out put, as the D2 receptor, but that
indicated in Fig. 4-4. the newer antipsy chosis
Some of the clinical drugs, which produce
and pharmacologic fewer of these effects,
effects of dopa mine are have a stronger affinity
made clear by for the D4 receptor.
considering both the However, the situa tion
anatomic sites of various is actually far more
receptors and their complex, in part because
physiologic effects. For of the synergistic
example, it appears that activities of D1 and D2
drug-induced receptors, each potenti
parkinsonian syn ating the other at some
dromes and tardive sites of convergence, and
dyskinesias (described the pres ence on the
presynaptic terminals of striatum.
nigrostriatal neurons of The basic validity of
D2 receptors, which the physiologic
inhibit dopamine pharmacologic model
synthesis and release. outlined here is
Even these intricacies supported by the
do not capture the observation that excess
complexity of neural doses of L-dopa or of a
transmission in the basal direct-acting dopamine
ganglia. In contrast to receptor agonist lead to
the almost instantaneous excessive motor activity.
actions of glutamate and Further more, the
its antago nist, GABA, at therapeutic effects of the
synapses, the main drugs used in the
monoamines have more treatment of Parkinson
pro tracted effects, disease become
lasting for seconds or as understandable in the
long as several hours. context of
And they influence rapid neurotransmitter
as well as slower function. To correct the
synaptic activities. basic dopamine
Dopamine and related deficiency from a loss of
neurotransmitters have a nigral cells that underlies
slower influence through Parkinson disease,
the “second messenger” attempts were at first
cyclic adenosine made to administer
monophosphate (cAMP), dopamine directly.
which, in turn, con trols However, dopamine as
the phosphorylation or such cannot pass the
dephosphorylation of blood–brain barrier and
numer ous intraneuronal therefore has no
proteins. These therapeutic effect. But its
intracellular effects have immediate dopamine
been summarized by precur sor, L-dopa, does
Greengard. cross the blood–barrier
The effects of certain and is effective in
drugs are best decreasing the
comprehended by symptoms of Parkinson
understanding the disease as well as of the
manner in which they above-described MPTP-
alter neu induced parkinsonism.
rotransmitter function. This effect is enhanced
Several drugs—namely by the addition of an
reser pine, the inhibitor of dopa
phenothiazines, and the decarboxylase, an
butyrophenones important enzyme in the
(notably haloperidol)— catabolism of dopamine.
induce prominent The addition of an
parkinsonian syndromes enzyme inhibitor of this
in humans. Reserpine, type (carbidopa or
for example, depletes the benserazide) to L-dopa
stria tum and other parts results in an increase of
of the brain of dopamine concentration
dopamine; halo peridol in the brain while
and the phenothiazines sparing other organs
work by a different from exposure to high
mechanism, probably by levels of the drug.
blocking dopamine Similarly, drugs that
receptors within the inhibit catechol O-
methyltrans ferase
(COMT), another
enzyme that breaks
down dopa mine,
prolong the effects of
administered L-dopa.