Professional Documents
Culture Documents
BLUEPRINTS
NEUROLOGY
Third Edition
12887_FM.qxd 10/9/08 9:51 PM Page ii
12887_FM.qxd 10/9/08 9:51 PM Page iii
BLUEPRINTS
NEUROLOGY
Third Edition
The publishers have made every effort to trace the copyright holders for borrowed mate-
rial. If they have inadvertently overlooked any, they will be pleased to make the necessary
arrangements at the first opportunity.
To purchase additional copies of this book, call our customer service department at
(800) 638-3030 or fax orders to (301) 824-7390. International customers should call
(301) 714-2324.
Visit Lippincott Williams & Wilkins on the Internet: http://www.LWW.com. Lippincott
Williams & Wilkins customer service representatives are available from 8:30 am to
6:00 pm, EST.
12887_FM.qxd 10/9/08 9:51 PM Page v
Contents
Reviewers . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .vii
Preface . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . x
Acknowledgments . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . xi
Abbreviations . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . xii
PART ONE: Basics of Neurology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .1
1 The Neurologic Examination . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .3
2 Neurologic Investigations . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .10
PART TWO: Common Neurologic Symptoms . . . . . . . . . . . . . . . . . . . . . . . . . . . . .19
3 The Approach to Coma and Altered Consciousness . . . . . . . . . . . . . . . . . . . .21
4 Neuro-Ophthalmology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .29
5 The Approach to Weakness . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .40
6 The Sensory System . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .48
7 Dizziness, Vertigo, and Syncope . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .54
8 Ataxia and Gait Disorders . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .58
9 Urinary and Sexual Dysfunction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .63
10 Headache and Facial Pain . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .69
PART THREE: Neurologic Disorders . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 75
11 Aphasia and Other Disorders of Higher Cortical Function . . . . . . . . . . . . . .77
12 Dementia . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .84
13 Sleep Disorders . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .92
14 Vascular Disease . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .96
15 Seizures . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .103
16 Movement Disorders . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .111
17 Head Trauma . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .119
18 Systemic and Metabolic Disorders . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .124
19 Central Nervous System Tumors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .131
20 Demyelinating Diseases of the Central Nervous System . . . . . . . . . . . . . . .139
12887_FM.qxd 10/9/08 9:51 PM Page vi
vi • Contents
Reviewers
Catarina Castaneda, MD
Class of 2004
Drexel University College of Medicine
Philadelphia, Pennsylvania
Maureen Chase, MD
Resident, Emergency Medicine
Hospital of University of Pennsylvania
Jefferson Medical College
Thomas Jefferson University Hospital
Philadelphia, Pennsylvania
Suzanne Crandall
Class of 2005
Kansas City University of Medicine and Biosciences
Kansas City, Missouri
Alexis Dang, MD
Class of 2004
University of California—San Francisco
San Francisco, California
Merritt Fajt, MD
Class of 2004
Temple University School of Medicine
Philadelphia, Pennsylvania
R1- Internal Medicine, Penn State University
Milton S. Hershey
Hershey Medical Center
Hershey, Pennsylvania
Baback Gabbay, MD
Class of 2005
David Geffen School of Medicine at UCLA
Los Angeles, California
12887_FM.qxd 10/9/08 9:51 PM Page viii
viii • Reviewers
Amir A. Ghaferi
Class of 2005
Johns Hopkins School of Medicine
Baltimore, Maryland
Hoda Ghanem, MD
Intern
UC Irvine—Internal Medicine
Irvine, California
Sarah Harper
Class of 2005
University of Pittsburgh School of Medicine
Pittsburgh, Pennsylvania
Gloria Hsu
Class of 2005
Stanford University School of Medicine
Stanford, California
Mark Lassoff, MD
Class of 2004
UMDNJ—New Jersey Medical School
Newark, New Jersey
Urology Resident
LAC⫹USC Medical Center
Los Angeles, California
Ryan Ley
Class of 2005
University of Nevada School of Medicine
Reno, Nevada
Meredith M. LeQuear, DO
Class of 2004
New York College of Osteopathic Medicine
Old Westbury, New York
Mark Naftanel
Class of 2005
Duke University School of Medicine
Durham, North Carolina
David J. Nusz, MD
Class of 2004
SUNY Downstate College of Medicine
Brooklyn, New York
12887_FM.qxd 10/9/08 9:51 PM Page ix
Reviewers • ix
Christi Otten
Class of 2005
University of Oklahoma Health Sciences Center—Physician Assistant program
Oklahoma City, Oklahoma
Pulak Ray
Class of 2005
University of Maryland School of Medicine
Baltimore, Maryland
Chris Reed
Class of 2005
Medical College of Wisconsin
Milwaukee, Wisconsin
Matheni Sathananthan
Class of 2006
SUNY at Buffalo School of Medicine
Buffalo, New York
Kamran Shamsa, MD
Class of 2004
University of California—San Diego
La Jolla, California
Victor Sung
Class of 2005
University of Texas Southwestern Medical Center
Dallas, Texas
Ahmet Tural, MD
Department of Infectious Diseases
Providence Physician Group
Everett, Washington
Alyssa Tzoucalis
Class of 2004
Hofstra University—Physician Assistant program
Hempstead, New York
Parham Yashar, MD
Neurological Surgery PGY-1
Albert Einstein College of Medicine
Bronx, New York
Ming Zhou, MD
Class of 2004
University of Nevada School of Medicine
Las Vegas, Nevada
12887_FM.qxd 10/9/08 9:51 PM Page x
x • Blueprints Psychiatry
Preface
n 1997, the first five books in the Blueprints series were published as board review for
I medical students, interns, and residents who wanted high-yield, accurate clinical content
for USMLE Steps 2 and 3. Nearly a decade later, the Blueprints brand has expanded into
a high-quality, trusted resource covering the broad range of clinical topics studied by med-
ical students and residents during their primary, specialty, and subspecialty rotations.
The Blueprints were conceived as study aids created by students, for students. In keep-
ing with this concept, the editors of the current editions of the Blueprints books have
recruited resident contributors to ensure that the third edition of the series continues to
offer the information and approach that made the original Blueprints a success.
Now in their third editions, each of the five specialty Blueprints—Blueprints Emergency
Medicine, Blueprints Family Medicine, Blueprints Neurology, Blueprints Cardiology, and
Blueprints Radiology—has been completely revised and updated to bring you the most cur-
rent treatment and management strategies. The feedback we’ve received from our readers
has been tremendously helpful in guiding the editorial direction of the second editions; for
that, we are grateful to the hundreds of medical students and residents who have responded
with in-depth comments and highly detailed feedback.
Each book has been thoroughly reviewed and revised accordingly, with new features
being included across the series. An evidence-based resource section has been added to
provide current and classic references for each chapter, and an increased number of cur-
rent board-format questions with detailed explanations for correct and incorrect answer
options are included in each book. All revisions to the Blueprints series have been made
in order to offer you the most concise, comprehensive, and cost-effective information
available.
Our readers report that Blueprints are useful for every step of their medical career,
from their clerkship rotations and subinternships to a board review for USMLE Steps 2
and 3. Residents studying for USMLE Step 3 often use the books to review areas that were
not their specialty. Students from a wide variety of health care specialties, including those
in physician assistant, nurse practitioner, and osteopathic programs, use Blueprints either
as a course companion or to review for their licensure examinations.
However you use Blueprints, we hope that you find the books in the series informative
and useful. Your feedback and suggestions are essential to our continued success.
The Publisher
Lippincott Williams & Wilkins
12887_FM.qxd 10/9/08 9:51 PM Page xi
Acknowledgments
e thank our patients for the opportunity of working with them and learning
W Neurology, our colleagues and teachers in the Beth Israel Deaconess Medical Center
Neurology department for teaching us more fascinating concepts about the nervous sys-
tem, and our families for tolerating the many hours spent writing and revising this book.
12887_FM.qxd 10/9/08 9:51 PM Page xii
Abbreviations
A() amyloid-beta DM dermatomyositis
ABP abductor pollicis brevis DMD Duchenne muscular dystrophy
Abs antibodies DSD detrusor-sphincter dyssynergia
APP amyloid–beta protein precursor DTRs deep tendon reflexes
ACA anterior cerebral artery DWI diffusion-weighted imaging
ACE angiotensin converting enzyme EA episodic ataxia
AD Alzheimer disease ED erectile dysfunction
ADEM acute disseminated encephalomyelitis EEG electroencephalogram
ADHD attention deficit–hyperactivity disorder EMG electromyography
ADM abductor digiti minimi ER emergency room
AED antiepileptic drug ESR erythrocyte sedimentation rate
AICA anteroinferior cerebellar artery ET essential tremor
AIDP acute inflammatory demyelinating EWN Edinger-Westphal nuclei
polyradiculoneuropathy FDI first dorsal interosseus
AIDS acquired immunodeficiency syndrome FEV1 forced expiratory volume in 1 second
AION anterior ischemic optic neuropathy FLAIR fluid-attenuated inversion recovery
ALS amyotrophic lateral sclerosis FTA fluorescent treponemal antibody
ANA antinuclear antibody FTD frontotemporal dementia
APP amyloid precursor protein FVC forced vital capacity
APS antiphospholipid syndrome GAD glutamic acid decarboxylase
AVM arteriovenous malformation GBS Guillain-Barré syndrome
AZT zidovudine GCS Glasgow Coma Scale
BMD Becker muscular dystrophy GTC generalized tonic-clonic
BPPV benign positional paroxysmal vertigo HD Huntington’s disease
CBC complete blood count HIV human immunodeficiency virus
cGMP cyclic guanosine monophosphate HNPP hereditary neuropathy with
CIDP chronic inflammatory demyelinating liability to pressure palsies
polyradiculoneuropathy HS Horner’s syndrome
CJD Creutzfeldt-Jakob disease HSAN hereditary sensory and autonomic
CK creatine kinase neuropathy
CMAP compound muscle action potential HSV herpes simplex virus
CMT Charcot-Marie-Tooth disease IBM inclusion body myositis
CN cranial nerve ICA internal cerebral artery
CNS central nervous system ICP intracranial pressure
COMT catechol O-methyl transferase ICU intensive care unit
CP cerebral palsy IIH idiopathic intracranial hypertension
CPAP continuous positive airway pressure INO internuclear ophthalmoplegia
CSF cerebrospinal fluid INR international normalized ratio
CT computed tomography IVIg intravenous immunoglobulin
DH detrusor hyperreflexia LEMS Lambert-Eaton myasthenic syndrome
DI detrusor instability LGN lateral geniculate nucleus
DLB dementia with Lewy bodies LMN lower motor neuron
12887_FM.qxd 10/9/08 9:51 PM Page xiii
Abbreviations • xiii
Part 1
Basics of Neurology
1
12887_CH01.qxd 10/4/08 3:15 PM Page 2
12887_CH01.qxd 10/4/08 3:15 PM Page 3
Chapter
The Neurologic
1 Examination
To practicing neurologists, the neurologic exam re- when they have difficulty rising from a chair. It is
flects the uniqueness of the specialty. In a world of often more useful to describe a patient’s observed
technology, it remains a purely clinical tool still un- activities and capabilities than to describe the find-
matched in its ability to identify and localize abnor- ings obtained upon formal testing. Confrontation
malities of the nervous system. To students, however, testing is subjective and variable; the grading of
the exam can be both mystifying and bemusing, an muscle strength depends on the examiner’s effort
endless series of maneuvers designed to elicit seem- and expectations of what the patient’s “normal”
ingly obscure and inexplicable findings. strength should be. The observation of a pronator
When its principles and elements are presented drift, for example, is less subjective.
simply, though, the exam is logical and elegant, re- 3. The object is to localize. The extent and com-
flecting the rational diagnostic process that character- plexity of the nervous system require that any at-
izes not just Neurology but all of medicine. tempt to formulate a concise differential diagno-
sis must begin with an accurate localization of
the problem to a specific region of the nervous
PRINCIPLES system. Left hand weakness may stem from
carpal tunnel syndrome, a brachial plexus injury,
1. The neurologic exam is not a standardized check- cervical spondylosis, or a right middle cerebral
list. Part of the intimidation of performing the artery stroke, all of which have different diagnos-
exam is its sheer length; hours could be spent on tic workups, treatments, and prognoses. The alert
examining the mental status alone. In reality, how- physician thinks, “What signs would be present in
ever, the exam is used in a focused and thoughtful a carpal tunnel problem that would not be pres-
way, depending on what hypotheses have been ent in a brachial plexus problem (and vice
generated about the patient’s disease from the his- versa)?” Those signs are then sought and the
tory. A patient presenting with confusion may exam further refined if necessary.
need quite a comprehensive mental status exam, 4. Not all findings have equal importance. A com-
whereas a patient presenting with a left foot drop mon difficulty is that completion of the exam re-
may need detailed motor, sensory, and reflex test- sults in a long list of many minor abnormalities of
ing of the left leg. In both cases general screening questionable importance, such as a 20% decrease
elements of the remaining parts of the exam may in temperature sensation over a patch on the left
be sufficient. thigh. Though certainly in some cases incidental
2. Observation is more important than confronta- findings may be the clue to a previously unsus-
tion. Most abnormalities of the nervous system pected diagnosis, in most cases the highest impor-
manifest themselves in ways visible to the obser- tance must be given to findings directly related to
vant examiner. A significant anomia becomes evi- the patient’s symptoms and to “hard” findings that
dent when a patient uses circumlocutions to relate require definitive explanation, such as a dropped
the history, and proximal weakness is obvious reflex or a Babinski sign.
3
12887_CH01.qxd 10/4/08 3:15 PM Page 4
4 • Blueprints Neurology
MENTAL STATUS
6 • Blueprints Neurology
object, which is more sensitive), and the pupillary tongue is mediated by this nerve and can be evalu-
light reflex, the afferent limb of which is mediated by ated with sugar or another nonnoxious stimulus.
this nerve. Funduscopic examination is the only Hearing (VIII) may be evaluated in each ear simply
means by which a part of the central nervous system by whispering or rubbing fingers; more detailed assess-
(the retina) can be directly visualized. ment of hearing loss may be accomplished with the
Extraocular movements (III, IV, and VI) are tested Weber or Rinne tuning fork (512 Hz) test. Vestibular
in three ways: by having the patient pursue a moving function can be tested in many ways, including evalua-
target that is a drawing of the letter “H” in front of tion of eye fixation while the patient’s head is rapidly
their face (pursuit), by directing their gaze rapidly to turned or by observation for drift in one direction while
various stationary targets (saccades), and by fixating the patient is walking in place with the eyes closed.
on an object while the head is being turned passively Palatal elevation should be symmetric and the voice
(vestibulo-ocular movements). The presence of nys- should not be hoarse or nasal (IX and X). Failure of
tagmus should be noted. the right palate to elevate implies pathology of the
Muscles of mastication (V) are tested by assessing right glossopharyngeal nerve. The gag reflex is also me-
strength of jaw opening and palpating over the mas- diated by these nerves.
seters bilaterally while the jaw is clenched. Facial Sternocleidomastoid strength is tested by having
sensation can be tested to all modalities over the fore- the patient turn the head against resistance; weakness
head (V1), cheek (V2), and jaw (V3). The afferent on turning to the left implies a right accessory nerve
limb of the corneal reflex is mediated by this nerve. (XI) problem. The trapezius muscle is tested by hav-
Muscles of facial expression (VII) are tested by ing the patient shrug their shoulders.
having patients raise their eyebrows, squeeze their Tongue protrusion should be in the midline. If the
eyes shut, or show their teeth. Though uncommonly tongue deviates toward the right, the problem lies
tested, taste over the anterior two-thirds of the with the right hypoglossal nerve (XII).
12887_CH01.qxd 10/4/08 3:15 PM Page 7
Figure 1-2 • Power testing of individual movements. For each movement, the predominant muscle, peripheral nerve, and nerve
root are given.
(Reproduced with permission from Ginsberg L. Lecture Notes: Neurology, 8th ed. Oxford: Blackwell Publishing, 2005:40–41.)
12887_CH01.qxd 10/4/08 3:15 PM Page 8
8 • Blueprints Neurology
SENSORY EXAM
REFLEXES
The sensory exam can be frustrating to perform be-
Muscle stretch (or “deep tendon”) reflexes can be cause of the tedium of potentially examining the en-
useful aids in localizing or diagnosing both central tire body surface (see dermatome map in Chapter 6)
and peripheral nervous system problems (Fig. 1-3). as well as the inherent subjectivity and all-too-
In the upper extremities, the biceps, brachioradi- frequent inconsistencies in patients’ responses.
alis, and triceps reflexes are the ones commonly In general, sensation should be tested in detail in
tested. Pectoral and finger flexor reflexes can also be areas relevant to a patient’s complaints, especially if
tested. Hoffmann’s sign is sought by flicking the dis- the complaints are sensory in nature. Otherwise,
tal phalanx of the middle finger while observing for screening elements of the sensory exam that are tar-
flexion of the thumb. geted at the distal lower extremities, where most
12887_CH01.qxd 10/4/08 3:15 PM Page 9
Chapter
Neurologic
2 Investigations
either a supratentorial or infratentorial mass lesion. cistern. Low-pressure headache is the most common
A computed tomography (CT) scan should be per- complication of lumbar puncture and is most effec-
formed prior to an LP except in cases of suspected tively treated by having the patient lie flat and in-
meningitis and when a CT scan cannot be per- crease her intake of liquids and caffeine. Rarely, it
formed. Radiologic contraindications to LP include may be necessary to administer an epidural blood
closure of the fourth ventricle and quadrigeminal patch (see Chapter 10).
12 • Blueprints Neurology
KEY POINTS
• A CT scan should be performed prior to lumbar
puncture except when bacterial meningitis is
suspected.
• Lumbar puncture is performed at or below the L2-3
interspace.
• Xanthochromia indicates recent intrathecal hemor-
rhage.
TECHNICAL CONSIDERATIONS
CT measures the degree of x-ray attenuation by tissue.
Attenuation is defined simply as the removal (by ab-
sorption or scatter) of x-ray photons and is quantified
on an arbitrary scale (in Hounsfield units) that is rep- Figure 2-1 • T2-weighted MRI of the cervical spine.
resented in shades of gray. Differences in the shades
directly reflect the differences in the x-ray attenuation
of different tissues, a property that depends on their useful in evaluating the spinal cord (Fig. 2-1).
atomic number and physical density. Images are usu- Gadolinium is the contrast agent used in MRI, and
ally obtained in either an axial or a coronal plane. gadolinium-enhanced images are usually acquired
Three-dimensional reconstruction and angiography with a T1-weighted sequence. Contrast-enhanced
are possible with new-generation spiral CT scanners. images are invaluable in determining the presence of
Magnetic resonance imaging (MRI) is similar to brain tumors, abscesses, other areas of inflammation,
CT in that radiant energy is directed at the patient and new multiple sclerosis lesions (see Fig. 19-2).
and detected as it emerges from the patient. MRI dif- Other commonly used MRI sequences are fluid-
fers, however, in its use of radiofrequency (RF) attenuated inversion recovery (FLAIR) and suscep-
pulses rather than x-rays. The images in MRI result tibility- and diffusion-weighted imaging (DWI).
from the varying intensity of radio-wave signals ema- FLAIR is a strong T2-weighted image, but one in
nating from tissue in which hydrogen ions have been which the signal from CSF has been inverted and is
excited by an RF pulse. A detailed understanding of thus of low rather than high intensity. FLAIR is the
magnetic resonance physics is not necessary for the single best screening image sequence for most
interpretation of routinely used MRI sequences. It is pathologic processes of the central nervous system
sufficient to understand that the patient is placed in (CNS). It is very useful in assessing the chronic le-
a magnet and that an RF pulse is administered. Signal sion burden in multiple sclerosis (see Fig. 20-2). A
intensity is measured at a time interval, known as susceptibility-weighted sequence is one that is sen-
time to echo (TE), following RF administration. The sitive to the disruptive effect of a substance on the
RF pulse is administered many times in generating an local magnetic field. Examples of substances that
image; the time to repetition (TR) is the time be- exert such a susceptibility effect are calcium, bone,
tween these RF pulses. and the blood breakdown products ferritin and he-
Two basic MRI sequences in common usage are mosiderin. Areas of increased susceptibility appear
T1- (short TE and TR) and T2- (long TE and long black on these images.
TR) weighted images. Fat is bright on a T1-weighted DWI demonstrates cellular toxicity with high sen-
image, which imparts a brighter signal to the myelin- sitivity and is most commonly employed in the diag-
containing white matter. Water (including CSF) is nosis of acute stroke, where it can be positive within
dark on T1 and bright on T2. T2 images are most half an hour of symptom onset. Areas of restricted
12887_CH02.qxd 10/4/08 3:15 PM Page 13
Figure 2-2 • Normal T1, T2, FLAIR, and DWI images of the brain.
diffusion appear bright on DWI. Figure 2-2 provides available for demonstrating early tissue ischemia and
examples of T1, T2, FLAIR, and DWI images. is therefore extremely useful in the evaluation of pa-
tients with suspected stroke.
CLINICAL UTILITY
SAFETY, TOLERABILITY, AND
Head CT is often the initial investigation used in a va- COMPLICATIONS
riety of neurologic disorders, including headache,
trauma, seizures, subarachnoid hemorrhage, and CT scanning employs x-rays and is thus relatively
stroke. The sensitivity of a CT scan for detecting le- contraindicated during pregnancy. The use of RF
sions depends on many factors, including the nature waves in MRI makes this the imaging modality of
and duration of the underlying disease process. The choice in pregnant women. There is no cross-reactiv-
sensitivity for detecting areas of inflammation, infec- ity between the iodinated contrast agents used in CT
tion, or tumor may be increased by the administra- and the gadolinium used as a contrast agent in MRI.
tion of intravenous contrast. Contrast enhancement When contrasted imaging is required, MRI may
indicates local disruption of the blood-brain barrier. therefore be preferable when there is a history of al-
CT is the investigation of choice for demonstrating lergy to intravenous contrast. Similarly, gadolinium
fresh blood. does not have the nephrotoxicity of iodinated con-
Apart from providing better anatomic definition, trast. MRI may be used safely only in the absence of
MRI is particularly useful for imaging the contents of metal objects (foreign bodies, plates, and screws) and
the posterior fossa and craniocervical junction, which pacemaker and defibrillator devices. Some people
are seen poorly on CT because of artifact from sur- with claustrophobia cannot tolerate MRI; under
rounding bone. DWI is the most sensitive technique these circumstances, CT is preferred.
12887_CH02.qxd 10/4/08 3:16 PM Page 14
14 • Blueprints Neurology
KEY POINTS
• CT is the imaging modality of choice for demon-
strating acute intracranial bleeding.
• MRI is required for adequate imaging of the poste-
rior fossa and craniocervical junction.
• DWI is the most sensitive MRI sequence for demon-
strating early cerebral ischemia or infarction.
KEY POINTS
• Conventional angiography is the gold standard for
evaluating cerebrovascular anatomy.
• MRA is less invasive but also less accurate than con-
ventional angiography.
Figure 2-3 • Conventional cerebral angiogram demonstrating
aneurysm of the right middle cerebral artery (arrow). • MRV is useful for assessing the presence of venous
(Reproduced with permission from Patel PR. Lecture Notes: Radiology, 2nd sinus thrombosis.
ed. Oxford: Blackwell Publishing, 2005:278.)
12887_CH02.qxd 10/4/08 3:16 PM Page 15
OTHER IMAGING STUDIES regions in the relaxed awake state with the eyes closed.
Lower-amplitude beta activity is more prominent
Positron emission tomography (PET) scans measure over the frontal regions. Theta and delta activity is
regional brain metabolism. Hypermetabolism can be normal during drowsiness and sleep, and the different
demonstrated during seizures (though it is rare to get stages of sleep are defined by the relative propor-
the scan during a seizure), while hypometabolic re- tions and amplitudes of theta and delta activity (see
gions may be evident interictally. Such a finding can Chapter 13).
be very useful in planning epilepsy surgery, especially
in the temporal areas. Single-photon emission com- TECHNIQUE
puted tomography (SPECT) uses a radioactive iso-
tope to demonstrate increased blood flow during The standard EEG is recorded from electrodes
seizures. Both PET and SPECT scans have been stud- attached to the scalp in a symmetric array. The pat-
ied in the evaluation of dementia. While regional pat- tern in which these electrodes are connected to each
terns of abnormality help study disease processes, other is referred to as the montage, of which there are
they are not specific enough for diagnosis in individ- essentially two types: bipolar and referential. In a
ual patients. Magnetic resonance spectroscopy is pri- bipolar montage, all electrodes are active and a
marily a research tool used to demonstrate areas of recording is made of the difference in electrical activ-
neuronal damage or dysfunction and has been studied ity between two adjacent electrodes. In a referential
in the assessment of brain tumors, demyelinating dis- montage, the electrical activity is recorded beneath
ease, and infections of the CNS. the active electrode relative to a distant electrode or
common average signal. The signal recorded by an
ELECTROENCEPHALOGRAPHY EEG is a sum of excitatory and inhibitory postsynap-
tic potentials of cortical neurons.
The electroencephalogram (EEG) provides a record of
the electrical activity of the cerebral cortex. Normal CLINICAL UTILITY
EEG patterns are characterized by the frequency and
amplitude of the recorded electrical activity, and the To appreciate the utility of the EEG, it is important
patterns of activity correlate with the degree of wake- to understand its limitations. First, the patterns of
fulness or sleep. The normally observed frequency pat- electrical activity recorded by the EEG are rarely
terns are divided into four groups: alpha (8 to 13 Hz), (if ever) specific to their cause. For example, the
beta (14 to 30 Hz), theta (4 to 7 Hz), and delta (0.5 presence of diffuse theta or delta activity during the
to 3.0 Hz) (Fig. 2-5). Under normal circumstances, awake state suggests an encephalopathy but does not
alpha waves are observed over the posterior head indicate the etiology. Second, the EEG records the
electrical activity of cortical neurons. Although sub-
cortical structures influence cortical activity, the
surface EEG may be insensitive to dysfunction of
deep structures. For example, seizures originating in
the medial frontal or temporal lobes may not be read-
ily apparent on the surface EEG. Furthermore, the
EEG provides a measure of the electrical activity of
the cortex at the time of the recording and is there-
fore frequently normal in paroxysmal conditions such
as seizures. The interictal EEG, for example, may be
abnormal in only about 50% of adults with epilepsy.
The frequency of interictal EEG abnormalities may
be higher in certain forms of epilepsy.
Several common patterns of abnormal activity are
recognized. Focal arrhythmic or polymorphic slow
activity in the theta or delta range suggests local dys-
function in the underlying brain. Vascular disease is a
Figure 2-5 • Electroencephalographic frequencies. common cause of such findings, but the slowing
12887_CH02.qxd 10/4/08 3:16 PM Page 16
16 • Blueprints Neurology
cannot specify the etiology. Generalized arrhythmic are placed over the endplate of a muscle innervated by
slow activity often indicates a diffuse encephalopa- the nerve being stimulated. The nerve is stimulated in
thy. Interictal epileptiform findings include sharp- at least two locations (distal and proximal), and the
and spike-wave discharges, with or without an distance between the two sites of stimulation is meas-
accompanying slow wave. Electrographic seizures ured carefully. The distal latency, compound muscle
may take various forms. The most common are action potential (CMAP), and conduction velocity are
rhythmic spike- or sharp- and slow-wave discharges recorded. The CMAP is a recording of the contraction
or rhythmic slow waves. They may be focal or gener- of the underlying muscle. The distal latency is the time
alized. Activation procedures can be used to enhance interval between stimulation over the distal portion of
the likelihood of finding abnormal EEG patterns: the nerve and the initiation of the CMAP. Conduction
hyperventilation is useful for provoking EEG changes velocity is calculated by measuring the difference in la-
in patients with absence seizures, while photic stim- tency to CMAP initiation between proximal and distal
ulation can induce EEG changes in patients with sites of stimulation. For sensory studies, the nerve is
myoclonic seizures. stimulated at one site and the sensory nerve action po-
tential (SNAP) is recorded either at a more proximal
site (orthodromic study) or at a more distal site (an-
tidromic study). Repetitive nerve-stimulation studies
KEY POINTS are used to demonstrate either decremental or
• Alpha frequency (8 to 13 Hz) is the dominant poste- incremental CMAP responses in disorders of the neu-
rior rhythm on the EEG in the awake restful state romuscular junction.
with the eyes closed. Electromyography involves the insertion of a needle
• Epilepsy is a clinical diagnosis; interictal epilepti-
into individual muscles. Recordings are made of the
form EEG findings are demonstrable in about half of muscle electrical activity upon insertion (insertional
patients with epilepsy. activity), while the muscle is at rest (spontaneous ac-
tivity), and during contraction (volitional motor unit
potentials). To increase the strength of muscular con-
traction, motor units can fire more quickly (activation)
or more motor units can be added (recruitment).
NERVE CONDUCTION STUDIES AND Reduced activation is seen in CNS disease. Reduced
ELECTROMYOGRAPHY recruitment suggests a lower motor neuron lesion,
while early recruitment can be seen in myopathic dis-
Nerve conduction studies (NCS) and electromyogra- ease. For routine EMG studies, activity is recorded
phy (EMG) are appropriately used as an extension of from a group of muscle fibers simultaneously. Single-
the clinical examination. fiber EMG is the technique used in the investigation of
disorders of the neuromuscular junction.
TECHNIQUE
CLINICAL UTILITY
In performing NCS, an electrical stimulus is applied
over a nerve and recordings are made from surface skin NCS and EMG are used primarily to assist in the
electrodes. For motor studies, the recording electrodes localization of dysfunction within the peripheral
nervous system and to define pathophysiology distinguish primary demyelinating from axonal
more clearly. For example, NCS and EMG may disease (Table 2-4).
help to differentiate a C8–T1 radiculopathy from a
lower brachial plexopathy or an ulnar neuropathy
in the patient who presents with numbness of
the fourth and fifth fingers and weakness of KEY POINTS
the hand. Similarly, the combination of motor
NCS, repetitive nerve stimulation, and EMG may • The goal of NCS and EMG is to localize the neurologic
help to localize motor dysfunction (i.e., weakness) dysfunction within the peripheral nervous system.
to the peripheral nerve, the neuromuscular junc- • Repetitive nerve stimulation and single-fiber EMG
tion, or the muscle (Table 2-3). In a patient with a are useful in the diagnosis of disorders of the neu-
polyneuropathy, NCS may help to define the rela- romuscular junction.
tive degree of motor and sensory involvement and to
12887_CH02.qxd 10/4/08 3:16 PM Page 18
12887_CH03.qxd 10/4/08 3:16 PM Page 19
Part 2
Common Neurologic
Symptoms
19
12887_CH03.qxd 10/4/08 3:16 PM Page 20
12887_CH03.qxd 10/4/08 3:16 PM Page 21
21
12887_CH03.qxd 10/4/08 3:16 PM Page 22
22 • Blueprints Neurology
Focal Focal
signs signs
present absent
such as diabetes, hepatic failure, alcoholism, or a 3. Try reversing common reversible etiologies. Most
seizure disorder may be provided by the family, emergency rooms (ERs) make it standard practice
noted on a medical alert bracelet, or deduced to administer naloxone, thiamine, and dextrose to
from prescription labels. The circumstances in any patient with depressed consciousness and no
which the patient was found can offer clues to obvious etiology. Note that thiamine should
the onset or etiology of depressed consciousness. always be given before glucose, because the latter
The general exam may yield telling signs, such can precipitate Wernicke encephalopathy if given
as an odor on the breath, needle tracks on the alone.
skin, or a tongue laceration. It is important to 4. Check brainstem reflexes and look for focal signs.
check for meningeal signs in any unconscious pa- These are the two primary goals of the neurologic
tient because both bacterial meningitis and sub- exam in this setting, because the subsequent diag-
arachnoid hemorrhage may lead to depressed nostic and therapeutic steps will depend on these
consciousness. clinical findings.
12887_CH03.qxd 10/4/08 3:16 PM Page 23
24 • Blueprints Neurology
DIFFERENTIAL DIAGNOSIS
In theory, there are two main ways in which con-
sciousness can be depressed: the brainstem can be
dysfunctional or both cerebral hemispheres can be
dysfunctional simultaneously. In fact, acute disease in
the brainstem (e.g., pontine hemorrhage) can lead to
coma, as can processes affecting both cerebral hemi-
spheres at once (e.g., hypoglycemia). Unilateral cere-
bral hemispheric lesions, however, can also lead to
coma if they are large or severe enough to cause
swelling and compression of the opposite hemisphere
or downward pressure on the brainstem.
Therefore most neurologists interpret the informa-
tion obtained from the exam of the comatose patient
using the following principle: the presence or absence
of brainstem reflexes suggests how deep the coma is,
Figure 3-2 • Decorticate (above) and decerebrate (below) pos-
turing in response to noxious stimuli. Both indicate brainstem while the presence or absence of focal signs narrows
dysfunction, although decorticate posturing suggests dysfunc- the differential diagnosis and guides the workup.
tion slightly more superior than decerebrate posturing. Thus, in milder cases of depressed consciousness,
(Reproduced with permission from Kandel ER, Schwatz JH, Jessell TM. the pupillary, corneal, and gag reflexes may all be pre-
Principles of Neural Science, 4th ed. New York: McGraw-Hill, 2000:903.)
served. In more severe cases, some or all of these brain-
stem reflexes may be lost, no matter what the etiology.
to each limb and the speed and strength of with- (Note that if a brainstem reflex is abnormal in an asym-
drawal noted, although abnormalities here may result metric fashion, such as a unilateral unreactive pupil,
from sensory loss as well as motor dysfunction. this would be interpreted as a focal sign and suggests
Decorticate and decerebrate posturing, signs of brain- compression of or primary disease in the brainstem.)
stem dysfunction, may be seen either spontaneously The presence of focal signs either on cranial nerve
or in response to noxious stimuli (Fig. 3-2). testing or in the remainder of the examination—
Muscle stretch reflexes can be tested in the usual including such findings as hemiparesis, aphasia, reflex
manner, and a Babinski sign should be sought. asymmetry, facial droop, or a unilateral Babinski
Sensory testing in most patients with altered con- sign—suggests a structural cause of depressed con-
sciousness is limited to testing of light touch or pain sciousness (Box 3-1). Examples include a large unilat-
sensation. Noxious stimulation to each limb, as
described previously, may be useful in looking for
䊏 BOX 3-1 Structural Causes of Depressed
gross sensory abnormalities.
Consciousness
Coordination and gait may be tested in patients
who are arousable enough. Acute ischemic stroke
Brainstem
Unilateral cerebral hemisphere (with edema)
KEY POINTS
Acute intracranial hemorrhage
• The mental status exam in patients with altered Intraparenchymal
consciousness primarily assesses the level of
Subdural
responsiveness.
Epidural
• The cranial nerve exam includes the testing of im-
portant brainstem reflexes, including the pupillary, Brain tumor (with edema or hemorrhage)
corneal, and oculocephalic reflexes. Primary
• The remainder of the examination should be dedi- Metastatic
cated to looking for focal abnormalities.
Brain abscess
12887_CH03.qxd 10/4/08 3:17 PM Page 25
eral stroke or intracranial hemorrhage. The absence of 䊏 BOX 3-2 Diffuse Causes of Depressed
focal signs suggests a diffuse cause of depressed con- Consciousness
sciousness, including metabolic, toxic, or hypoxic-
ischemic etiologies (Box 3-2). Examples include coma Metabolic
from fulminant hepatic failure, barbiturate overdose, Electrolyte abnormality
or anoxia following prolonged cardiac arrest. Hyponatremia, hypernatremia, hypocalcemia,
hypercalcemia, hypomagnesemia, hypermagne-
semia, hypophosphatemia
KEY POINTS Glucose abnormality
• In theory, consciousness can be depressed either Hypoglycemia, nonketotic hyperosmolar coma,
by dysfunction of the brainstem or dysfunction of diabetic ketoacidosis
both cerebral hemispheres simultaneously; in real- Hepatic failure
ity, large unilateral hemispheric lesions (with pres-
Uremia
sure on the other side) qualify as well.
• The presence or absence of brainstem reflexes Thyroid dysfunction
Myxedema coma, thyrotoxicosis
suggests how deep the coma is.
• The presence of focal signs suggests a structural Adrenal insufficiency
cause of coma. Toxic
• The absence of focal signs suggests a diffuse cause Alcohol
of coma, such as metabolic, toxic, infectious or Sedatives
hypoxic-ischemic etiologies.
Narcotics
Psychotropic drugs
Other exogenous toxins (carbon monoxide, heavy
LABORATORY AND RADIOGRAPHIC metals)
STUDIES Infectious
Meningitis (bacterial, viral, fungal)
The distinction between structural and diffuse causes
of depressed consciousness, arrived at by interpreting Diffuse encephalitis
the findings on exam, suggests different pathways of Hypoxic-ischemic
diagnostic workup. Respiratory failure
The presence of focal findings on examination,
Cardiac arrest
suggesting a structural cause, demands urgent head
imaging, almost always a noncontrast computed Other
tomography (CT) scan. One should be looking for Subarachnoid hemorrhage
signs of a large acute stroke, an intracranial hemor- Carcinomatous meningitis
rhage, or a mass lesion that may have enlarged rapidly
Seizures or postictal state
or had hemorrhage within it. (Contrast-enhanced CT
should be avoided if acute hemorrhage is possible.)
Even in cases where focal brainstem signs are found,
the initial choice of head imaging may have to be a CT toxicologic screen—may be necessary. If infection is
scan rather than magnetic resonance imaging (MRI), suspected, a chest x-ray, urinalysis, and blood or
despite the poor quality of the former in evaluating the urine cultures may be called for. There should be a
brainstem, because of the possibility of a large cerebral low threshold for obtaining a lumbar puncture (LP).
hemispheric lesion compressing the brainstem as well If a basic workup is unrevealing, one should search
as because of the more immediate availability of CT. for more unusual causes (such as myxedema coma,
The absence of focal findings on examination, sug- by checking thyroid function tests). Head imaging is
gesting a diffuse cause, warrants an extensive workup usually needed even in these cases of suspected
for causes of metabolic, toxic, or infectious etiologies. diffuse cause because it may demonstrate signs of
Blood testing—including complete blood count global hypoxic-ischemic injury, diffuse cerebral
(CBC), electrolytes, glucose, liver function tests, and edema, or bilateral lesions mimicking a diffuse
12887_CH03.qxd 10/4/08 3:17 PM Page 26
26 • Blueprints Neurology
process, although the urgency is not as high as for pa- hemorrhages, Chapter 17 for head trauma, Chapter
tients with focal findings. Of course, a head CT 18 for systemic and metabolic disorders, Chapter 19
should be performed before obtaining an LP almost for brain tumors, and Chapter 21 for central nervous
without exception in the evaluation of a patient with system (CNS) infections.
depressed consciousness, given the risk of precipitat- When increased intracranial pressure (ICP) is sus-
ing brain herniation if a large intracranial mass pected clinically or radiographically, treatments
(particularly in the posterior fossa) is present. (If bac- aimed at lowering ICP should be applied. These
terial meningitis is suspected, empiric antibiotic include raising the head of the bed, hyperventilation,
treatment can be started if CT scanning is delayed.) and the use of an osmotic diuretic such as mannitol.
Frequently, an electroencephalogram (EEG) is or- Corticosteroids tend to be useful only in cases of
dered in patients with coma or altered consciousness. edema associated with brain tumors. The lowering of
Although many of its findings may be nonspecific, ICP may be a neurologic or neurosurgical emergency
the EEG can help to assess how deep a coma is based if the patient shows signs of brain herniation, which
on the degree of background slowing. In addition, is discussed in more detail in Chapter 17.
there are occasionally more specific patterns on EEG The prognosis of depressed consciousness is mostly
that suggest a particular diagnosis, such as hepatic en- dependent on etiology—the patient with a barbiturate
cephalopathy or anoxic brain injury. Finally, the EEG overdose may recover completely, whereas one with a
can rule out nonconvulsive status epilepticus as a severe anoxic injury likely will not. Age is an important
cause of coma in cases in which this is (or is not) clin- prognostic factor as well. One of the most frequent
ically suspected. reasons for admission to an intensive care unit (ICU)
or neurologic consultation is to estimate the prognosis
of a patient in coma following cardiopulmonary arrest.
KEY POINTS In these cases the circumstances and duration of the
arrest are important, and published studies have corre-
• If a structural cause of coma is suspected, urgent lated outcome with findings on neurologic examina-
head imaging, usually with a noncontrast head CT, tion performed at least 24 hours after the arrest.
should be performed.
• If a diffuse cause is suspected, an extensive workup
for metabolic, toxic, or infectious causes should be
undertaken.
KEY POINTS
• Head imaging in suspected diffuse cases may
demonstrate cerebral edema, signs of global • The treatment of coma or altered consciousness
hypoxic-ischemic injury, or bilateral lesions mimick- depends on etiology.
ing a diffuse process. • The lowering of intracranial pressure may be a neu-
• Almost without exception, head CT should be per- rologic emergency if the patient shows signs of
formed before LP. brain herniation.
• EEG can assess the depth of coma and can occa- • Prognostic factors for coma or altered conscious-
sionally suggest a specific diagnosis. ness include both etiology and patient age.
being in coma for a prolonged period if their vital ACUTE CONFUSIONAL STATE
functions have been supported.
Definition
LOCKED-IN SYNDROME
The terms confusion, delirium, and encephalopa-
thy are often used nonspecifically to indicate a dis-
Although a locked-in syndrome can be confused with
turbance of mental status in which the patient is
coma at first glance, a patient with locked-in syn-
unable to carry out a coherent plan of thought or
drome is awake and may be intact cognitively, with
action. Most neurologists employ the terms confu-
no abnormality of consciousness. Usually a conse-
sion or encephalopathy, while delirium (commonly
quence of large lesions in the base of the pons, the
used by psychiatrists) often implies a state of en-
locked-in syndrome leaves patients unable to move
cephalopathy characterized by a waxing and waning
the extremities and most of the face. If all other
level of alertness.
motor function is lost, they may be limited to com-
At its core, an acute confusional state results
municating by vertical eye movements or blinks.
from a problem of attention. Thus, a patient’s fail-
ure to answer questions in a coherent manner or to
BRAIN DEATH carry out an intended series of actions in an ex-
pected way derives from an inability to maintain
Death can be declared either when there has been
attention for long enough to proceed through the
irreversible cessation of cardiopulmonary function or
cognitive or motor steps required for the task. On
there has been irreversible cessation of all functions
formal mental status testing, therefore, patients
of the entire brain, including the brainstem. A decla-
with confusion typically do poorly on standard tests
ration of death based on the latter criterion is com-
of attention, such as spelling the word “world” in re-
monly referred to as brain death. Many institutions
verse, reciting the months of the year backward, or
have specific guidelines for how brain death must be
completing serial subtractions. Such inattention
determined, but in general the patient must be com-
may be significant enough to make impossible the
atose, have absent brainstem reflexes, and have no
performance of more detailed mental status testing.
spontaneous respirations even when the PCO2 has
Depending on the underlying etiology of the acute
been allowed to rise (the apnea test). Confounding
confusional state, other associated features may be
factors such as hypothermia or drug overdose must
present on neurologic or general physical examina-
not be present. Confirmatory tests most commonly
tion as well.
include an EEG, which can demonstrate electrocere-
bral silence (“flat line”), or cerebral angiography,
which can demonstrate absence of blood flow to the Differential Diagnosis
brain. Local institutional guidelines for declaration of
The differential diagnosis of acute confusion in-
brain death should always be consulted.
cludes a number of different disorders, among them
aphasia (particularly Wernicke), psychosis, and
KEY POINTS complex partial seizures. Patients with Wernicke
aphasia may appear “confused” but in fact are atten-
• A persistent vegetative state may follow prolonged tive and able to carry out coherent series of actions;
coma and is characterized by preserved sleep-wake their deficit lies solely in their ability to communi-
cycles and maintenance of autonomic functions, cate. Although patients with psychosis may also
with absence of awareness and cognition. behave as if they were acutely confused, pure con-
• Locked-in syndrome, in which awareness and cog- fusional states do not result in frank psychotic
nitive function are preserved but almost complete symptoms like hallucinations or delusions. Complex
paralysis occurs, is often caused by large lesions in partial seizures can be characterized by behavior
the base of the pons. that appears “confused,” but seizures are typically
• Brain death is a declaration of death based on self-limited in duration and may be associated with
irreversible cessation of all brain functions. clonic motor movements or automatisms such as
lip-smacking.
12887_CH03.qxd 10/4/08 3:17 PM Page 28
28 • Blueprints Neurology
Chapter
Neuro-
4
Blueprints Neurology
Chapter 4 / Neuro-
Ophthalmology
Chapter
Ophthalmology
An understanding of visual impairment, pupillary dis- to many higher-order centers in the posterior parietal
turbances, and oculomotor control is essential in the and inferior temporal cortices, where the perception of
diagnosis of neurologic disorders. Maximal interpre- motion, depth, color, location, and form takes place.
tation of our environment is accomplished through
the integration of visual, somatosensory, motor, and
auditory information. SYMPTOMS APPROACH TO
A systematic approach to evaluating patients with NEURO-OPHTHALMOLOGIC
“visual” problems includes the analysis of: vision, eye DISTURBANCES
movements, and integration of visual information.
This chapter covers the first two; the third consti- The most common neuro-ophthalmologic symptoms
tutes part of higher cortical function, discussed else- are loss of vision and diplopia. Other symptoms in-
where (see Chapter 11). clude eye pain, visual hallucinations, and oscillopsia.
Two important signs discussed in this chapter are the
abnormal optic disc and anisocoria (unequal pupils).
ANATOMY
VISUAL LOSS
Light enters the cornea and stimulates the rods and
cones in the retina, where the visual stimuli are con-
Visual disturbances can be described as positive or
verted into electrical signals that are sent through the
negative phenomena. Positive visual phenomena in-
optic nerve to centers in the brain for further pro-
clude brightness, shimmering, sparkling, hallucina-
cessing and visual perception. The visual pathway
tions, shining, flickering, or colors, often suggesting
(with various field defects) is shown in Figure 4-1.
migraine or seizures. Negative visual phenomena
The more posterior parts of the cerebral hemi-
can be described as blackness, grayness, dimness, or
spheres are involved in seeing and analyzing visual in-
shade-obscuring vision, as seen in patients with
formation, including written language, and the more
strokes or transient ischemic attacks.
anterior parts control looking at and exploring visual
When the complaint is loss of vision, ask the fol-
space.
lowing questions:
Ninety percent of retinal axons terminate in a
retinotopic fashion in the lateral geniculate nucleus, the 1. Is this a monocular or binocular problem? Does
principal subcortical structure that carries visual infor- the problem go away when one eye is closed?
mation to the cerebral cortex through the optic radia- 2. Does it affect a portion or the entire visual field?
tions. The primary visual cortex is visual area 1 (V1), 3. Is it transient or persistent?
corresponding to Brodmann’s area 17, or striate cortex, 4. Are there associated symptoms, such as headache,
which receives information from the contralateral vi- visual auras, motor or sensory disturbances, changes
sual hemifield. This information is then transferred to in mentation, seizures, or eye pain (e.g., with optic
associative visual cortex, including areas 18 and 19, and neuritis)?
29
12887_CH04.qxd 10/4/08 3:17 PM Page 30
30 • Blueprints Neurology
L R
1
L R
1
2
2
L R
3
L R
3 4
L R
5
LGN 4 L R
6
5
6 L R
7
7
Occipital Cortex
Figure 4-1 • The visual pathway, with lesions and resultant visual field defects.
Chapter 4 / Neuro-Ophthalmology • 31
Retina Chiasm
Detachment Tumor: pituitary tumors such as adenoma,
Infectious: CMV, toxoplasmosis craniopharyngioma, and glioma
32 • Blueprints Neurology
ipsilateral posterolateral hypothalamus (first-order near stimulation. If the anisocoria is not physiologic,
neuron) and projects down the brainstem to the the next question to be answered is which pupil is ab-
intermediolateral cell column at the C8–T1 spinal normal, the dilated or the constricted one.
level. The second-order neurons synapse in the supe- First, examine the pupils in the dark (turn the lights
rior cervical ganglion and represent the preganglionic off and look at the pupils during the first 5 to 10 sec-
neurons. Third-order neurons (postganglionic) travel onds). A dilation lag in the small pupil and anisocoria
along the internal carotid artery into the cavernous greater in darkness means a sympathetic defect in that
sinus and from there into the orbit to the pupil- pupil. Horner’s syndrome (HS) is characterized by uni-
lodilator muscles. lateral miosis, ptosis, and (sometimes) ipsilateral facial
anhidrosis as a result of impaired sympathetic innerva-
tion. There are many different causes of HS, but in all
DIAGNOSTIC EVALUATION of them cocaine eyedrops fail to dilate the abnormal
pupil. If the cocaine test is negative, hydroxyampheta-
Document pupil reactivity and size in bright and dim mine eyedrops will help to distinguish a preganglionic
illumination. Remember that up to 25% of normal from a postganglionic HS (the pupil with a postgan-
people have asymmetric pupils without pathologic glionic HS fails to dilate with hydroxyamphetamine).
significance. In physiologic anisocoria, the amount of The different causes of HS are summarized in Box 4-2.
anisocoria does not change with different illumina- Once you have established that the abnormal pupil
tion. Pupils should respond normally to light and is the larger one (mydriatic), localization of the prob-
12887_CH04.qxd 10/4/08 3:17 PM Page 33
Chapter 4 / Neuro-Ophthalmology • 33
䊏 BOX 4-2 Etiology of Horner’s Syndrome An Argyll Robertson pupil is classically associated
with syphilis. Usually both pupils are small and irreg-
First-order Horner’s, or central Horner’s: ular, with impaired light reaction and intact near re-
Hypothalamic infarcts, tumor sponse (light-near dissociation); pupils also dilate
Mesencephalic stroke poorly to mydriatic agents.
Brainstem: ischemia (Wallenberg syndrome),
tumor, hemorrhage
KEY POINTS
Spinal cord: syringomyelia, trauma
• Horner’s syndrome (HS) is characterized by ipsilateral
Second-order Horner’s, or preganglionic:
miosis, ptosis, and facial anhidrosis.
Cervicothoracic cord/spinal root trauma
• A complete third nerve palsy presents with mydria-
Cervical spondylosis sis, ptosis, and ophthalmoplegia.
Pulmonary apical tumor: Pancoast tumor • An Adie’s pupil is dilated, with segmental contrac-
Third-order Horner’s, or postganglionic: tion and light-near dissociation.
Superior cervical ganglion (tumor, iatrogenic, etc.) • Argyll Robertson pupils are small and poorly reac-
tive to light but have preserved near response; they
Internal carotid artery: dissection, trauma,
are typically associated with syphilis.
thrombosis, tumor, etc.
• Light-near dissociation (LND): Normally the pupil-
Base of skull: tumor, trauma
lary constriction to light is greater than to a near
Middle ear problems stimulus. The opposite is called LND. It implies a de-
Cavernous sinus: tumor, inflammation (Tolosa- fect in light response, as in optic neuropathy, or the
Hunt syndrome), aneurysm, thrombosis, fistula presence of aberrant regeneration, as in the Adie
pupil. Other causes of LND include dorsal midbrain
lesions and severe bilateral visual loss.
34 • Blueprints Neurology
Chapter 4 / Neuro-Ophthalmology • 35
36 • Blueprints Neurology
Figure 4-2 • Damage to the PPRF, sixth nerve nucleus, and both MLF produces the “one-and-a-half syndrome
syndrome” (patterned oval). The only eye movement present in the horizontal plane in this case is the abduc-
tion of the left eye. INO occurs after damage of the MLF. In this graphic, damage to the left MLF alone would
produce a left INO, i.e., an inability to adduct the left eye and nystagmus in the right eye with right lateral gaze.
reticular formation (PPRF), or sixth nerve nucleus tagmus on attempted upgaze, and light-near dissoci-
and the adjacent ipsilateral MLF. These produce an ation of the pupils. It is generally produced by a
ipsilateral gaze palsy and INO on the contralateral pineal tumor compressing the dorsal midbrain.
side (the only eye movement present in the lateral Finally, skew deviation is a vertical tropia, generally
plane is abduction of the contralateral eye) (Fig. 4-2). caused by brainstem or cerebellar lesions. The hy-
Vertical eye movements are controlled by the ros- potropic (lower) eye is often on the side of the lesion.
tral interstitial nucleus of the MLF (riMLF) located in
the pretectal midbrain area, near the CN III nucleus.
Fibers controlling upgaze from the riMLF cross to the
DIAGNOSTIC EVALUATION
contralateral side using the posterior commissure to
The evaluation includes a careful history and a de-
communicate with the inferior oblique and superior
tailed neurologic exam. Some tests done to evaluate
rectus subnuclei of the CN III complex. The
diplopia include the following:
downgaze pathway is less well understood but does
not travel in the posterior commissure. Abnormal • Cover test: Ask the patient to fixate on a small tar-
vertical gaze movements can be found in dorsal mid- get. Cover one eye and watch the other eye. If the
brain syndromes. Parinaud syndrome is characterized eye makes a refixation movement, this means that
by upgaze disturbance, convergence-retraction nys- it was not aligned on the target. If the eye moves
12887_CH04.qxd 10/4/08 3:17 PM Page 37
Chapter 4 / Neuro-Ophthalmology • 37
38 • Blueprints Neurology
Chapter 4 / Neuro-Ophthalmology • 39
Chapter
The Approach
5 to Weakness
Weakness is one of the most common presenting which muscles in the left leg are weak or, if they are
neurologic complaints. Many patients may tolerate all diffusely weak, which are weaker than others.
some degree of numbness, tingling, or even pain, but 3. Determine the pattern of weakness. This is fre-
often it is when weakness sets in that medical atten- quently the crux of the entire diagnosis. It is the
tion is finally sought. Similarly, friends or family pattern of weakness that will reveal when left leg
members will not notice a patient’s sensory prob- weakness is due to a peroneal nerve problem and
lems, but significant weakness will be obvious to all. not a right hemispheric stroke. Needless to say,
At the same time, weakness can be one of the most one must be familiar with the different patterns of
difficult neurologic problems to sort out, because the weakness and their implications.
pathways that control motor function span the entire 4. Look for associated signs and symptoms. If a leg is
axis of the nervous system. Left leg weakness can arise weak, determine whether it is also numb, tingling,
from a peripheral nerve lesion, a lumbosacral plexus or painful. Check the reflexes carefully. Often the
problem, or a stroke in the right cerebral hemisphere. motor deficit overshadows other problems, whose
Each of these has a different workup, prognosis, and presence may be helpful in supporting or exclud-
treatment, and it is the job of the physician to use the ing certain diagnoses.
history and examination to distinguish among them. 5. Use laboratory and electrophysiologic tests wisely.
Blood tests or neuroimaging studies can be useful
in the appropriate settings, and electromyogra-
PRINCIPLES phy/nerve conduction studies (EMG/NCS) can
act as an extension of the clinical exam in localiz-
Figure 5-1 presents a flowchart to aid in the diagno- ing the problem to a particular segment of the
sis of weakness. The key steps in the clinical approach peripheral nervous system. Tests are most useful
are outlined below. in the setting of a complete clinical evaluation and
formed diagnostic hypothesis, however.
1. Make sure that true weakness is the complaint.
Sometimes patients will use the term weak to mean
a general sense of fatigue; others will say a limb is
“weak” when it is clumsy or numb. Having the pa- KEY POINTS
tient confirm that decreased strength is the symp-
tom may be useful. Likewise, a limb that is painful • Weakness can be caused by lesions along the entire
to move may seem “weak”; whether there is true neuraxis, from brain to muscle.
underlying weakness may be difficult to discern. • The diagnosis rests on determining what the pat-
2. Identify which muscles are weak. This seems like an tern of weakness is, searching for associated signs
obvious point but must be emphasized. It is not suf- and symptoms, and using laboratory tests and
ficient to know that a patient has left leg weakness. EMG/NCS to confirm clinical hypotheses.
Testing must be done in enough detail to know
40
12887_CH05.qxd 10/4/08 3:18 PM Page 41
Consider the
differential diagnosis
of disorders within your
localization
42 • Blueprints Neurology
fashion. Distal muscles are affected later or not as change from hour to hour. Depending on the specific
severely. In addition, neck flexors and extensors, disease, strength may be worse after using the muscles
which are not affected in most nerve or brain lesions, or toward the end of the day; it may improve after
may be weak in a muscle disorder. resting or in the morning (fatigability). Alternatively,
strength may paradoxically improve after exercise in
Associated Signs and Symptoms other conditions.
KEY POINTS
KEY POINTS
• NMJ disorders can cause weakness of proximal mus-
• Primary muscle disorders typically cause symmetric cles; some characteristically affect extraocular and
proximal weakness and can affect neck muscles. bulbar muscles.
• Sensory signs and symptoms are not present in • The key to diagnosing NMJ disorders is fluctuation
myopathies. in the degree of weakness.
• Serum CK level is elevated in some muscle disor- • Sensory signs and symptoms are not present in
ders, and EMG may show a characteristic “myo- NMJ disorders.
pathic” pattern. • EMG/NCS can be nearly pathognomonic in some
cases of NMJ disorders.
NEUROMUSCULAR JUNCTION
DISORDERS PERIPHERAL NERVE DISORDERS
conditions can lead to dysfunction of multiple EMG may yield insight as to the relative acuity or
peripheral nerves in succession, a disorder known as chronicity of a nerve disorder.
mononeuropathy multiplex. Finally, when pe-
ripheral nerves are all affected diffusely, in a poly- Differential Diagnosis
neuropathy, dysfunction typically occurs in the
longest nerves first. Thus, weakness from a polyneu- Mononeuropathies most commonly occur as a result
ropathy usually appears first in the distal muscles, of entrapment (as in carpal tunnel syndrome).
symmetrically. Mononeuropathy multiplex is associated with systemic
vasculitis and other metabolic or rheumatologic dis-
eases. Demyelinating polyneuropathies can be heredi-
Associated Signs and Symptoms
tary (such as Charcot-Marie-Tooth disease) or acquired
Mononeuropathies may cause sensory symptoms— (as in Guillain-Barré syndrome), while axonal polyneu-
such as numbness, tingling, or pain—in the distribu- ropathies have many potential underlying causes.
tion of the relevant peripheral nerve. Mononeu- Peripheral nerve disorders are discussed in Chapter 23.
ropathy multiplex is characteristically associated with
pain. Polyneuropathies, depending on etiology, usu-
ally have associated sensory loss and depressed or KEY POINTS
absent reflexes, particularly in the distal extremities.
• Mononeuropathies lead to weakness in muscles
innervated by a single peripheral nerve.
Laboratory Studies • Polyneuropathies first affect the muscles of the dis-
EMG/NCS can confirm the clinical suspicion of a tal extremities symmetrically.
problem localized to the peripheral nerves. NCS can • EMG/NCS can confirm peripheral nerve involvement,
identify whether the pathologic process affects pri- identify axonal or demyelinating features, and evalu-
marily the axons or the myelin of the nerve, an ate the relative chronicity of a nerve disorder.
essential step in formulating a differential diagnosis.
12887_CH05.qxd 10/4/08 3:18 PM Page 44
44 • Blueprints Neurology
C5 Musculocutaneous
Upper Lateral
C6 Median
C8 Axillary
Lower Posterior
Laboratory Studies
KEY POINTS
MRI of the spine can rule out structural etiologies or
• A plexus problem should be suspected when multi- demonstrate intrinsic inflammation within the cord.
ple muscles in a limb are weak and do not conform LP may be needed to evaluate infectious, inflamma-
to a particular nerve root or peripheral nerve pattern. tory, or neo-plastic possibilities.
• There may be associated sensory signs or reflex loss
in plexus disorders.
Differential Diagnosis
• Plexopathies can be confirmed by EMG/NCS and
have many potential causes. Spinal cord disorders are discussed in Chapter 22; they
may stem from inflammation (transverse myelitis),
12887_CH05.qxd 10/4/08 3:18 PM Page 46
46 • Blueprints Neurology
Figure 5-3 • Upper motor neuron (UMN) versus lower motor neuron (LMN).
12887_CH05.qxd 10/4/08 3:18 PM Page 47
KEY POINTS
• Spinal cord disorders lead to weakness in a UMN pat-
tern below the lesion and weakness in a nerve root
pattern at the level of the lesion.
• There may be sensory loss below the level of the
lesion due to interruption of ascending tracts.
• Reflexes below the level of the lesion are typically
increased, and Babinski signs may be present.
• Bladder and bowel incontinence may occur.
Pattern of Weakness
Laboratory Studies
Lesions in the cerebral hemispheres lead to weakness
of the contralateral body in a UMN pattern (see Fig. Imaging of the brain is important to evaluate almost
5-3). Knowledge of the homunculus of the motor all of the potential etiologies in this category. The
strip (Fig. 5-4) explains why lesions in the parasagit- choice of MRI or CT depends on the suspected etiol-
tal part of the cerebral hemisphere cause weakness ogy and relative acuity.
primarily in the leg, whereas lesions more laterally in
the hemisphere cause weakness primarily in the face Differential Diagnosis
and arm. Deep hemispheric lesions, as in the internal
capsule, may lead to weakness of all three parts of The differential diagnosis includes such diverse eti-
the contralateral body (face, arm, and leg), because ologies as stroke (Chapter 14), demyelinating disease
motor fibers from all areas of the motor strip join (Chapter 20), traumatic injury (Chapter 17), brain
together as they travel toward the brainstem. tumor (Chapter 19), and infection (Chapter 21).
Lesions in the base of the pons may lead to weak-
ness of the ipsilateral face and contralateral arm and
leg (crossed signs), because descending motor fibers KEY POINTS
to the face have crossed at that level but those to the
body have not. • Cerebral hemispheric lesions lead to weakness of the
contralateral side in a UMN pattern.
• Parasagittal lesions lead primarily to leg weakness,
Associated Signs and Symptoms more lateral lesions lead primarily to face and arm
Lesions of the cerebral hemispheres frequently have weakness, and deep lesions may lead to weakness
associated cognitive signs, such as those described in of all three parts.
Chapter 11. Left hemispheric lesions may cause apha- • Cerebral hemispheric lesions may have accompa-
sia or apraxia, while right hemispheric lesions may nying cognitive signs, such as aphasia or neglect.
cause neglect or visuospatial dysfunction. Lesions of • Brainstem lesions may have accompanying CN
the brainstem may cause cranial nerve problems, such findings.
as extraocular movement disorders.
12887_CH06.qxd 10/4/08 3:19 PM Page 48
Chapter
The Sensory
6 System
The sensory system includes somatosensory and spe- • Spinothalamic tract: At the level of the spinal
cial senses: smell, vision, taste, hearing, and vestibu- cord, sacral segments are located laterally, lumbar
lar sensation. The common characteristic in all is the fibers more medially, and cervical segments in the
presence of a receptor, an afferent nerve, and a dor- most medial locations.
sal root or cranial nerve ganglion that carries the • The dorsal columns: The medial fibers are from the
information to the CNS. legs and lateral fibers from the arms. At the level of
Somatosensory abnormalities may be character- the medial lemniscus, the upper body fibers
ized by increase, alteration, impairment, or loss of become medial and those of the lower body lateral.
feeling. The diagnosis of these problems includes
Facial sensation is carried to the brainstem by the
analysis of the nature, location, characteristics, and
trigeminal nerve. The STT and the trigeminal tract
distribution of symptoms.
terminate in the thalamus (ventroposterolateral and
ventroposteromedial, respectively), with further cor-
ANATOMY OF THE SENSORY tical projections through the third-order neurons to
PATHWAYS the postcentral cortex in a somatotopic arrangement
similar to that in the motor cortex, with the face in
Each sensory modality has a receptor. Information the lowest area and the leg in the parasagittal area.
from the receptor is then carried to the CNS by in- Fine sensory discrimination and localization of pain,
dividual fibers in the nerve (peripheral or cranial) temperature, touch, and pressure require normal
known as first-order neurons. Pain and temperature functioning of the sensory cortex.
are carried by thinly myelinated and unmyelinated
slowly conducting fibers (A-delta and C fibers,
respectively) that synapse at the level of the dorsal EXAMINATION OF THE
horn of the spinal cord. From here, the axons from SENSORY SYSTEM
the second-order neurons cross and travel contralat-
erally in the spinothalamic tract (STT), also called This is a difficult part of the neurologic exam and
the anterolateral system (Fig. 6-1). Proprioception, requires the patient’s cooperation. The evaluation of
vibration, and light touch run ipsilaterally in heavily different primary sensory modalities (temperature,
myelinated fibers (A-alpha and A-beta fibers) in the pain [pinprick], light touch, vibration, and propio-
dorsal column system, reaching the second-order ception) is necessary to characterize sensory loss and
neuron at the level of the medulla in the nuclei gra- its extent. In some instances, it is difficult to demon-
cilis and cuneatus. Axons from these nuclei cross at strate sensory abnormalities in a patient with sensory
the lower medulla to form the medial lemniscus symptoms; in others, the exam shows sensory find-
(Fig. 6-2). ings in an asymptomatic patient. Whatever the situa-
There is a somatotopic arrangement of fibers in tion, the sensory examination must be organized and
these tracts. methodical.
48
12887_CH06.qxd 10/4/08 3:19 PM Page 49
50 • Blueprints Neurology
Touch sensation is tested with a wisp of cotton, The next step is to record the sensory abnormali-
using a very soft stimulus. Pain sensation is tested ties using accepted definitions. It is important to reg-
with a pin. Thermal modalities are tested using ob- ister the patient’s own words rather than using the
jects with a temperature range between 10° and terms below. Not only the presence or absence of
50°C, because beyond those limits the stimulus be- sensation but also slight differences and gradations
comes painful. Moving the great toe up and down should be recorded. The following list defines some
and asking the patient to indicate the direction of of the terminology used to describe sensory abnor-
movement test joint position sense. Proprioception malities:
can also be tested by moving an object up or down on • Paresthesias are abnormal sensations described
the skin and asking the patient the direction of the by the patient as tingling, prickling, pins, and nee-
movement. The testing of vibration sense requires a dles, etc.
tuning fork (128 Hz) to be applied to toes and other • Dysesthesias are unpleasant sensations triggered
bony prominences. by painless stimuli.
12887_CH06.qxd 10/4/08 3:19 PM Page 52
52 • Blueprints Neurology
AVM, arteriovenous malformation; INO, internuclear ophthalmoplegia; LT, light touch; PP, pinprick; T, temperature.
• Hyperesthesia is increased sensitivity to sensory to light touch and normal proprioception. This
stimuli. The opposite is hypesthesia. occurs frequently with central cord syndromes
• Allodynia is pain provoked by normally innocuous (see Chapter 22).
stimuli.
• Dissociated sensory loss refers to the loss of one of APPROACH TO THE PATIENT WITH
the sensory systems with preservation of another. SENSORY LOSS
For example, in a syrinx, the STT is compromised
early, with loss of pain and temperature in the der- Sensory dysfunction becomes manifest through two
matomes involved but preservation of posterior types of symptoms: negative, such as numbness, loss
column function and therefore a normal response of cold or warm sensation, blindness, and deafness; or
12887_CH06.qxd 10/4/08 3:19 PM Page 53
positive, such as pain, paresthesias (tingling, pins and The last step in evaluating these sensory abnor-
needles), visual sparkles, and tinnitus. The former malities is to establish the cause. There are many pri-
usually means disruption of nerve excitation; the latter mary neurologic diseases as well as systemic diseases
in general means excitation or disinhibition. that can present with sensory symptoms. They are
In a patient complaining of sensory disturbances, explored in more detail in Chapter 23 on peripheral
the first goal is to establish the presence or absence of neuropathies.
a neurologic lesion and then, if present, to establish its The different patterns of sensory loss and the loca-
location. Sometimes the sensory problems accompany tion of the respective neurologic problem are repre-
other symptoms—such as weakness, neglect, visual sented in Table 6-1. This table provides a guide to the
field cuts, behavioral problems, or seizures—that may process of diagnosis based on clinical symptoms and
help to determine the lesion’s location. the physical exam, without the need for further tech-
The goal is to recognize sensory abnormalities by nologic resources.
modality and to judge the level at which they are
produced. Although in theory it is easy to distinguish
peripheral nerve from segmental nerve or root,
spinal cord, or other CNS locations, this is in fact
often not possible or at best imprecise. In general, KEY POINTS
compression of a peripheral nerve has a distribution
of sensory loss in the territory of that specific nerve. • It is important to obtain a good history of the
Root problems give a dermatomal pattern of loss sensory abnormalities and direct the exam accord-
(Fig. 6-3). Spinal cord disease leads to a characteris- ing to it.
tic loss of sensation below a certain level. In brain- • Nerve damage produces sensory problems in the
stem lesions, the sensory abnormalities may occur on distribution of the damaged nerve; root damage
the ipsilateral side of the face and contralateral side produces sensory problems in a dermatome; and
of the body. Central sensory loss involving the tha- plexus damage produces sensory problems in a
lamus or sensory cortex will generally affect the con- group of nerves in the same limb.
tralateral face, arm, and leg. • Spinal cord lesions produce a sensory level; brain-
Once the location of sensory loss has been charac- stem lesions cause a crossed sensory loss; and thal-
terized, it is important to determine what sensory amus and cortex lesions produce sensory loss in the
modality is involved, because different pathologic contralateral face, arm, and leg.
processes can affect different sensory systems.
12887_CH07.qxd 10/4/08 3:20 PM Page 54
Chapter Dizziness,
Vertigo, and
7 Syncope
Because “dizziness” means different things to differ- cause, whereas diplopia, dysarthria, dysphagia, or
ent people, it is not a useful term in describing one’s other symptoms of brainstem dysfunction indicate a
symptoms. Broadly speaking, the possibilities in- central process. Accompanying nausea and vomiting
clude vertigo, light-headedness, dysequilibrium, and is often more prominent with peripheral causes of
a fourth category of ill-defined dizziness. Vertigo is vertigo, and the ability to walk or maintain posture
an illusion or hallucination of movement that is usu- may be more impaired with central disease. Neither
ally rotatory but may be linear. Light-headedness of these latter features, however, is very reliable.
may also be described as feeling faint and may refer Finally, the nature of the nystagmus may suggest the
to a presyncopal state. This chapter focuses on these source of the vertigo. Vertical and direction-changing
two categories. gaze-evoked nystagmus indicates a central process.
Dysequilibrium is a sensation of imbalance or Unidirectional nystagmus may arise from either cen-
unsteadiness that is usually referable to the legs rather tral or peripheral dysfunction.
than to a feeling inside the head. The neurologic ab- Vestibular neuronitis presents as an acute unilat-
normalities responsible for this symptom are outlined eral (complete or incomplete) peripheral vestibu-
in detail in Chapter 8. Finally, there are people who lopathy. The designation neuronitis is inaccurate
simply cannot define their symptoms accurately, as because there is no evidence of inflammation, but
well as those with anxiety. the term is retained here because of its common
usage. Patients develop a sudden and spontaneous
onset of vertigo, nausea, and vomiting. The onset is
VERTIGO usually over minutes to hours; symptoms peak
within 24 hours and then improve gradually over
Most vertigo is caused by an acute asymmetry or several days or weeks. Complete recovery may not
imbalance of neural activity between the left and occur for months. Nystagmus is strictly unilateral
right vestibular systems. Vertigo does not result from and may be suppressed by visual fixation. Recovery
symmetric bilateral loss of vestibular function (as represents central compensation for the loss of pe-
with ototoxic drugs) or from a slow unilateral loss of ripheral vestibular function.
vestibular function (e.g., with an acoustic neuroma); Labyrinthine concussion may result from head
the brain appears to habituate to slow changes. A injury irrespective of whether there is an associated
useful approach (Box 7-1) to sorting out the etiology skull fracture. Vertigo is sometimes accompanied by
is to determine the periodicity and duration of the hearing loss and tinnitus.
symptoms and whether they are positional or sponta- Infarction of the labyrinth, brainstem, or cerebel-
neous. A determination should also be made as to lum. The blood supply to the central and peripheral
whether the vertigo is of peripheral or central origin; vestibular apparatus and the cerebellum is via the
the most helpful features in this regard are the pres- vertebrobasilar system (posterior and anterior infe-
ence and nature of the associated symptoms and rior cerebellar arteries and the superior cerebellar ar-
signs. Tinnitus or hearing loss suggests a peripheral tery). Blood supply to the inner ear is via the internal
54
12887_CH07.qxd 10/4/08 3:20 PM Page 55
䊏 BOX 7-1 Approach to the Patient With change in position. Attacks occur most frequently
Vertigo when the individual is reclining in bed at night or
upon awakening in the morning. There may be asso-
Spontaneous vertigo ciated severe nausea and vomiting. Attacks may
Single prolonged episode occur in clusters, with patients remaining asympto-
Vestibular neuronitis matic for months or years in between.
BPPV results from freely moving crystals of cal-
Labyrinthine concussion
cium carbonate within one of the semicircular canals.
Lateral medullary or cerebellar infarction When the head is stationary, these crystals settle in
Recurrent episodes the most dependent part of the canal (usually poste-
Ménière disease rior). With head movements, the crystals move more
slowly than the endolymph within which they lie;
Perilymph fistula
once the head comes to rest, their inertia causes
Migraine ongoing stimulation of the hair cells, resulting in the
Posterior circulation ischemia illusion of movement (vertigo). Diagnosis is estab-
Positional vertigo lished by demonstrating the characteristic downbeat-
ing and torsional nystagmus with the Dix-Hallpike
Peripheral
test (Fig. 7-1, upper). The offending ear is the one
Benign positional paroxysmal vertigo (BPPV) that is toward the ground when vertigo occurs during
Central the test. A positioning (Epley) maneuver (Fig. 7-1,
lower) can be used to remove the crystals from the
posterior semicircular canal. The head is turned in
auditory artery, a branch of the anteroinferior cere- the direction of the offending ear. The illustration
bellar artery. Infarction of the inner ear presents with demonstrates treatment for BPPV originating from
a sudden onset of deafness, vertigo, or both. the left ear.
Brainstem or cerebellar stroke is the most impor-
tant differential diagnosis in patients with suspected
acute vestibular neuronitis. The type of nystagmus and
KEY POINTS
the presence of associated neurologic signs are the • Vertigo is a hallucination of movement that results
main distinguishing factors. A central-type nystagmus from acute unilateral vestibular dysfunction.
results from cerebellar or brainstem infarction, and • Tinnitus and hearing loss often accompany periph-
almost invariably there are associated cranial nerve eral vertigo; diplopia, dysarthria, or other symptoms
signs, weakness, ataxia, or sensory changes that clearly of brainstem dysfunction indicate a central cause.
indicate a central process.
• Isolated vertigo is almost never caused by brain-
Ménière disease is characterized by episodic stem ischemia.
vertigo with nausea and vomiting; fluctuating, but
progressive hearing loss; tinnitus; and a sensation of • Recurrent episodes of vertigo lasting seconds to
minutes triggered by a change in head position are
fullness or pressure in the ear. It is caused by an
typical of benign positional paroxysmal vertigo.
intermittent increase in endolymphatic volume.
A perilymph fistula results from disruption of the
lining of the endolymphatic system. Typically, the
patient reports hearing a “pop” at the time of a sud- SYNCOPE
den increase in middle ear pressure, with sneezing,
nose-blowing, coughing, or straining. This is followed Syncope is a transient loss of consciousness and pos-
by the abrupt onset of vertigo. tural tone that results from brain hypoperfusion.
Patients with benign positional paroxysmal ver- Prior to losing consciousness, patients often report
tigo (BPPV) have episodes of vertigo that are precip- light-headedness and a variety of visual symptoms
itated by changes in position, such as turning over in (blurred or tunnel vision, graying or blacking out).
bed or looking upward. The attacks are brief, usually The term presyncope is used when patients experi-
lasting seconds to minutes, and symptoms typically ence this prodrome of symptoms but do not subse-
begin after a few seconds’ latency following the quently lose consciousness. Observers may note that
12887_CH07.qxd 10/4/08 3:20 PM Page 56
56 • Blueprints Neurology
Figure 7-1 • The Dix-Hallpike maneuver is illustrated in the first two frames of the figure. The patient’s head is rotated 45 degrees
to one side and then extended 30 degrees over the edge of the bed. The examiner looks for a rotatory and down-beating
nystagmus. The Epley positioning maneuver begins with the positioning used for the Dix-Hallpike maneuver and continues with
a series of other positions, as illustrated.
(Reproduced with permission of the Department of Neurology, Charité, Humbolt University, Berlin.)
the patient appears pale or is sweating. Syncope is charges from arterial (including cardiac or great ves-
most commonly a manifestation of hypotension due sel) or visceral mechanoreceptors. Afferent impulses
to cardiac causes, low intravascular volume, or exces- via the vagus nerve lead to cardioinhibition and
sive vasodilation. Cardiac causes include asystole, vasodepression, resulting in hypotension and brady-
third-degree heart block, tachyarrhythmias, outflow cardia. Different terms are used to describe this
obstruction, valvular disease, or myocardial infarc- reflex, depending on the trigger (Table 7-1).
tion. Low intravascular volume can result from Autonomic failure is characterized by an inability
dehydration, blood loss, or Addison disease and can to activate efferent sympathetic fibers appropriately,
result in either syncope or orthostatic hypotension. particularly on assumption of the upright posture.
Excessive vasodilation usually has a neurologic cause.
There are essentially two neurologic varieties of syn-
cope, both involving some dysfunction of the auto- 䊏 TABLE 7-1 Reflex Syncope
nomic nervous system that results in excessive
vasodilation. The more common is neurogenic syn- Type of Syncope Pathophysiologic Trigger
cope, in which acute hypotension results from a Micturition syncope Rapid emptying of a distended
sudden reflex change in autonomic cardiovascular bladder
control. Less commonly, orthostatic hypotension and Carotid sinus Compression of the carotid
syncope may result from autonomic failure. hypersensitivity sinus
Neurogenic syncope is an acute hemodynamic Neurocardiogenic Vigorous contraction of an
reaction produced by a sudden change in the activity syncope underfilled ventricle
of the autonomic nervous system. Its pathophysiology
Vasovagal syncope Strong emotions or acute pain
involves a reflex triggered by excessive afferent dis-
12887_CH07.qxd 10/4/08 3:20 PM Page 57
This usually leads to orthostatic hypotension, but In managing patients with symptomatic orthostatic
syncope can also result. The underlying pathologic hypotension or syncope, it is important to recognize
process can be either central (e.g., spinal cord injury the potential contribution of drugs such as diuretics,
or degenerative neurologic conditions that affect the antihypertensives, vasodilators, and antidepressants.
autonomic nervous system, such as multiple system Raising the head of the bed will reduce nocturnal
atrophy and Parkinson disease) or peripheral (e.g., diuresis, and patients should be advised to move grad-
diabetes resulting in autonomic neuropathy), but the ually from the supine to standing position. A variety of
hallmark of both is the failure to release norepineph- drugs are available to ameliorate the symptoms of
rine on standing. Patients usually complain of light- orthostatic hypotension, with midodrine and fludro-
headedness and presyncopal symptoms in response to cortisone being most commonly used. Beta blockers
a sudden change in posture or prolonged standing. can be used to treat neurogenic syncope by suppress-
There may be associated weakness, fatigue, cognitive ing overactive cardiac mechanoreceptors.
slowing, headache, neck pain, or buckling of the legs.
In evaluating patients with syncope or orthostatic
hypotension, a thorough history and medical and
neurologic examinations are warranted. The history KEY POINTS
is critical in detailing the precipitating circumstances • Presyncopal symptoms include light-headedness,
of the event and excluding other conditions, such as headache, neck pain, blurring of vision, cognitive
seizures, that can be confused with syncope. If a car- slowing, and buckling of the knees.
diac cause is suspected, an electocardiogram or more
• Syncope results from cerebral hypoperfusion.
prolonged cardiac monitoring with a Holter monitor
may be indicated in order to exclude an underlying • The two main neurologic causes of syncope are
arrhythmia. An echocardiogram is indicated if a neurogenic syncope and autonomic failure (central
or peripheral).
structural cardiac lesion (e.g., valvular) is suspected.
In addition, clinical findings, orthostatic signs, and • Neurogenic syncope results from inappropriate
blood work (hemoglobin, hematocrit, blood urea activation of a cardioinhibitory and vasodepressor
nitrogen, and creatinine) can indicate intravascular reflex, which may be triggered by micturition, de-
volume depletion and its causes, such as blood loss or glutition, carotid sinus compression, sudden under-
dehydration. If a neurologic cause for syncope is sus- filling of the ventricle, or heightened vagal tone.
pected, the exam can demonstrate a degenerative • The hallmark of autonomic failure is the failure to
neurologic condition or a peripheral neuropathy. If release norepinephrine on standing.
no clear cause for syncope can be identified, tilt-table • Orthostatic hypotension may result from intravas-
testing may be helpful in documenting autonomic cular volume depletion, autonomic failure, or
dysfunction and diagnosing neurogenic syncope, par- medications.
ticularly when the clinical history is unclear.
12887_CH08.qxd 10/4/08 3:21 PM Page 58
Chapter
Ataxia is a term derived from Greek meaning “irreg- lesions, however, typically manifest with ipsilateral
ularity” or “disorderliness”; it is a general term often limb ataxia.
used to describe the manifestations of diseases of the
cerebellum or its connections. It is important, how-
ever, to recognize that not all ataxia is cerebellar in
CEREBELLAR HEMORRHAGE
origin. For example, the deafferentation due to the OR INFARCTION
loss of position sense also results in an ataxia. Hence
it is appropriate to distinguish cerebellar ataxia from Cerebellar hemorrhage or infarction typically pre-
sensory ataxia. sents with the abrupt onset of vertigo, vomiting, and
The cerebellum controls the force, direction, range, inability to walk. Level of arousal may be depressed
rate, and rhythm of movements; a disturbance of these if there is compression of the fourth ventricle with
elements results in the signs and symptoms character- hydrocephalus or if there is pressure on the brain-
istic of cerebellar disease (Box 8-1). Ataxia is not the stem. Cerebellar stroke should be considered a med-
only process that may underlie a gait disorder; these ical emergency because neurosurgical intervention
other causes are described separately below. may be required for decompression if there is brain-
stem compression or risk of herniation.
䊏 BOX 8-1 Signs and Symptoms of 䊏 BOX 8-2 Classification of the Ataxias
Cerebellar Disease
Acute or subacute onset with resolution or
Dysmetria: Abnormality of the range and force of a episodic course
movement; manifests as erratic, jerky movements Postinfectious and infectious cerebellitis
with over- and undershooting the target (hence limb
Cerebellar hemorrhage or infarction
or ocular dysmetria)
Drugs (e.g., phenytoin, barbiturates, antineoplastic
Intention tremor: Rhythmic side-to-side oscillations
agents)
of the limb as it approaches the target
Multiple sclerosis
Dysdiadochokinesia: Abnormality of the rate
and rhythm of a movement demonstrated by Hydrocephalus*
asking the patient to perform a rapid alternating Posterior fossa mass*
movement
Foramen magnum compression*
Gait ataxia: Broad-based and unsteady, with an in-
ability to walk in a straight line and a tendency to Dominantly inherited episodic ataxias
lurch from side to side Childhood metabolic disorders (e.g., aminoacidurias,
Truncal ataxia: Impaired control of truncal posture; disorders of pyruvate and lactate metabolism)
when severe, unable to even sit unsupported Acute or subacute onset with progressive course
Dysarthria: Slow scanning and monotonous speech Paraneoplastic cerebellar degeneration
Nystagmus Alcoholic or nutritional cerebellar degeneration
Chronic onset and progressive course
Autosomal dominant spinocerebellar degenerations
varicella or other viral infection. Children present Autosomal recessive cerebellar degenerative
with acute onset of limb and gait ataxia as well as disorders
dysarthria. Severity ranges from mild unsteadiness to Infectious (e.g., Creutzfeldt-Jakob disease)
complete inability to walk. The diagnosis is one of ex- Vitamin E deficiency
clusion; this usually requires a careful search for un- Hypothyroidism
derlying drug intoxication and for a mass lesion in the
posterior fossa. The illness lasts a few weeks and re- Childhood metabolic disorders (e.g., mitochondrial
encephalomyelopathies, Wilson disease, ataxia-
covery is usually complete.
telangiectasia)
*May also cause insidious onset and chronically progressive ataxia.
PARANEOPLASTIC CEREBELLAR
DEGENERATION
60 • Blueprints Neurology
potassium channel. Episodes are brief, and an interat- ophthalmoplegia. The ataxia is due to propriocep-
tack skeletal muscle myokymia is associated. EA-2 is tive loss rather than to cerebellar dysfunction. MFS
caused by mutations in the pore-forming ␣1 subunit of is thought to be a variant of the Guillain-Barré syn-
the P/Q-type voltage-gated calcium channel. Attacks drome; as such, it is most likely mediated by a
are longer, lasting several minutes; there is interictal postinfectious immune process. IgG anti-GQ1b anti-
nystagmus; and a progressive irreversible ataxia may bodies are detectable in the serum of over 90% of
develop late in the disease. patients with this syndrome. It is usually a self-
limiting disorder with a relatively good prognosis for
AUTOSOMAL DOMINANT full recovery.
SPINOCEREBELLAR DEGENERATIONS
Abnormalities of gait are common and frequently Posture is stooped, with flexion of the shoulders,
multifactorial. This is especially true in the elderly, in neck, and trunk. Gait is narrow-based, slow, and shuf-
whom falls often result. Not all gait disorders are the fling with small steps and reduced arm swing. Instead,
result of disease of the nervous system. For example, the arms are carried flexed and slightly ahead of the
local mechanical factors such as pain and arthritis body. There is often difficulty with gait initiation.
may impair ambulation. These factors are not dis- Postural reflexes are impaired, and the patient may
cussed further here. take a series of rapid small steps (festination) forward
Clues to the etiology of the gait disorder may (propulsion) or backward (retropulsion) in an effort
be derived from the presence of other neurologic to preserve equilibrium. The foregoing description is
abnormalities, such as weakness, spasticity, rigidity, typical of patients with idiopathic Parkinson disease,
bradykinesia, ataxia, or frontal lobe dysfunction. but these features may also be seen in other ex-
Sometimes, however, an abnormal gait is suffi- trapyramidal disorders. One difference in progressive
ciently characteristic to permit identification of the supranuclear palsy is that posture tends toward exten-
underlying disorder based solely on the features of sion rather than flexion.
the gait. The following sections are devoted to de-
scriptions of the different types of gait disorders. FRONTAL GAIT
The differential diagnosis of each type of gait is pre-
sented in Table 8-2. Posture is flexed, and the feet may be slightly apart.
Gait initiation is impaired; the word “magnetic” is
HEMIPARETIC GAIT used to describe the patient’s difficulty in lifting the
feet off the ground. The patient advances with small,
The affected leg is stiff and does not flex at the hip, shuffling, and hesitant steps. With increasing severity,
knee, or ankle. The leg is circumducted, with a ten- the patient may make abortive stepping movements
dency to scrape the floor with the toes. The arm is in one place without being able to move forward.
held in flexion and adduction and does not swing
freely. A spastic (paraparetic) gait is essentially that WADDLING GAIT
of a bilateral hemiparesis. The adductor tone is in-
creased, and the legs tend to cross during walking A waddling gait is characteristic of hip-girdle
(scissoring gait). weakness. During normal walking, the hip abductors
12887_CH08.qxd 10/4/08 3:21 PM Page 62
62 • Blueprints Neurology
contract to fix the weight-bearing leg and thus allow hemigait (described earlier) is absent. Another
the opposite leg to rise and the trunk to tilt toward feature is that the patient may adopt extreme pos-
the fixed leg. Weakness of the abductors and con- tures and lurch wildly in all directions but without
sequent failure to stabilize the weight-bearing hip falling, thus demonstrating good strength and more
cause the pelvis and trunk to tilt toward the opposite than adequate postural reflexes. The term astasia-
side during walking. abasia is used to describe this sort of acrobatic psy-
chogenic gait.
SENSORY ATAXIA
Urinary bladder dysfunction is associated with a intermediolateral columns of the sacral cord. The lat-
wide variety of neurologic diseases including stroke, eral (L) region is at the same level of the pons; its
dementia, Parkinson disease, multiple sclerosis, and stimulation produces a powerful contraction of the
diabetes. An understanding of how these diseases urethral sphincter (storage). Damage at the level of
cause incontinence is important in both diagnosis the pontine micturition center will produce a loss of
and management. inhibitory control over spinal reflexes. As the bladder
becomes distended, the micturition reflex is auto-
matically activated without the patient’s awareness
BLADDER INCONTINENCE or control, and detrusor hyperreflexia and inconti-
nence occur.
ANATOMY AND PHYSIOLOGY
DIAGNOSTIC EVALUATION
Neural circuits in the brain and spinal cord coordi-
nate the activity of visceral smooth muscle (bladder The first objective in the evaluation of bladder incon-
and urethra) and striated muscle (external urethral tinence is to determine if the problem is neurogenic or
sphincter) to control micturition (voiding). These cir- not. A detailed history is essential. It is important to
cuits act as on-off switches to shift the lower urinary obtain information about initiation; voiding problems
tract between storage (sympathetic) and elimination such as frequency, stream characteristics, urine vol-
(parasympathetic) modes (Fig. 9-1). ume, fullness, and urgency; effects of posture, cough,
Bradley has defined the different neuroanatomic Valsalva maneuver, and medications; and associated
connections important for bladder control as “cir- bowel and sexual dysfunction.
cuits.” The first circuit connects the dorsomedial Thorough physical and neurologic examinations are
frontal lobe to the medial (M) region in the pons, necessary. The examiner seeks signs of frontal lobe
providing the volitional control of micturition. The dysfunction, parkinsonian features, sensory level,
second, or spinobulbospinal circuit, is a reflex arc myelopathy, and so forth. Laboratory evaluation
that starts in the urinary bladder and projects to the includes basic urinalysis to rule out infection.
M region of the pons, with outflow connections to Measurement of the postvoid residual (PVR) by blad-
the parasympathetic sacral spinal motor nuclei. The der ultrasound or catheterization is important in the
third circuit is a spinal segmental reflex arc with af- characterization of bladder dysfunction. The PVR
ferent fibers from the detrusor muscle to the puden- represents the residual volume in the bladder after
dal nucleus in the sacral spinal cord and efferent voiding. A normal PVR is less than 50 mL.
fibers to the striated sphincter muscles (see Fig. 9-1). Urodynamic studies can clarify the characteristics of
M-region stimulation produces a decrease in ure- the incontinence, determine the underlying neurologic
thral pressure, followed by a rise in detrusor muscle abnormality, categorize the vesicourethral dysfunc-
pressure and voiding. The M region projects to the tion, and provide a basis for appropriate therapy.
63
12887_CH09.qxd 10/4/08 3:21 PM Page 64
64 • Blueprints Neurology
Cortex
Volitional
Control Hypothalamus
Supraspinal
Pons
M-region
Spinal Cord
Sympathetic
–
T10
T11
Multiple Sclerosis T12
L1
Spinal Cord
Parasympathetic +
S2
Hypogastric Nerve
S3
S4
Pudendal Nerve (somatic)
Pelvic Nerve
Bladder
+ –
Peripheral
+
Internal Sphincter
– External Sphincter
Some urodynamic studies include the following: physical activities that increase intra-abdominal
pressure (in the absence of detrusor contraction or
• Cystometry: Provides information about bladder
an overdistended bladder). This is common in mul-
compliance, capacity, and volume at first sensation
tiparous women who have cystoceles or weakened
and at urge to void; voiding pressure; and the pres-
muscles of the pelvic floor. Other causes include
ence of uninhibited detrusor contractions.
urethral hypermobility; significant displacement of
• Cystourethroscopy: Assesses the integrity of the
the urethra and bladder neck; and intrinsic urethral
lower urinary system and identifies important ure-
sphincter deficiency due to congenital weakness in
thral and bladder lesions.
patients with myelomeningocele or epispadias or
• Retrograde urethrography
who have had prostatectomy, trauma, or radiation.
• Neurophysiologic studies: These include EMG of
Mixed incontinence is a combination of urge and
the sphincter and pelvic floor.
stress incontinence.
Urodynamic findings in various types of neuro- Overflow incontinence is an involuntary loss of
genic bladder dysfunctions are listed in Table 9-1. urine associated with overdistention of the bladder,
reflecting a lower motor neuron problem. Patients
report constant dribbling or urge or stress inconti-
KEY POINTS nence symptoms. The resultant atonic bladder can be
• The M region in the pons is the site of activation of produced by an underactive or acontractile detrusor
micturition. (due to drugs, diabetic neuropathy, lower spinal cord
injury, or radical pelvic surgery that interrupts inner-
• History and a complete neurologic exam are impor-
vation to the detrusor muscle). Bladder outlet and
tant in the evaluation of bladder incontinence.
urethral obstruction can also cause overdistention
• PVR should be less than 50 mL. Increased PVR im- and overflow.
plies poor bladder emptying. Sphincter dyssynergia
and atonic bladder are common neurogenic causes
of elevated PVR.
KEY POINTS
• Spastic bladder implies an upper motor neuron
CLASSIFICATION problem due to lesions involving the frontal lobes,
pons, or suprasacral spinal cord. Symptoms include
This classification is based on symptoms. incontinence with urgency. Urodynamics show de-
Urge incontinence is an involuntary loss of urine as- creased capacity and reduced compliance.
sociated with a strong desire to void (urgency), usually • Atonic bladder implies a lower motor neuron lesion
associated with detrusor instability (DI). When the DI at the level of the conus medullaris, cauda equina,
is the result of a neurologic problem, the term detru- or sacral plexus; or it may reflect peripheral nerve
sor hyperreflexia (DH) is used; its clinical expression dysfunction. It is characterized by overflow inconti-
is a spastic bladder. DH is common in patients with nence and increased capacity and compliance.
strokes, suprasacral spinal cord lesions, and multiple • Sphincter dyssynergia produces an increased PVR
sclerosis. It is usually accompanied by detrusor-sphinc- with fluctuating voiding pressures and varying
ter dyssynergia (DSD), which is inappropriate flow rate.
contraction of the external sphincter with detrusor • A small PVR is good; a large PVR with spastic or
contraction. This can result in urinary retention, vesi- atonic bladder is not. It can cause increased intra-
coureteral reflux, and subsequent renal damage. bladder pressure with deleterious effect on the
Stress incontinence is an involuntary loss of ureters and kidneys.
urine during coughing, sneezing, laughing, or other
12887_CH09.qxd 10/4/08 3:21 PM Page 66
66 • Blueprints Neurology
68 • Blueprints Neurology
KEY POINTS
CAUSES OF SEXUAL DYSFUNCTION
• ED is often multifactorial. Many neurogenic dis-
The etiology of sexual dysfunction can be multifacto- eases can produce ED, including strokes, multiple
rial. Neurogenic causes include neuropathy, myelopa- sclerosis, and diabetes.
thy, cauda equina lesions, and CNS dysfunction. • Medical and surgical therapies are available.
Other causes include vascular disease, pelvic trauma,
12887_CH10.qxd 10/4/08 3:22 PM Page 69
Chapter
Headache and
10 Facial Pain
Headache is the most common reason for referral to a For most causes of headache, and certainly for the
neurologist. People are often concerned that a primary headache disorders, the examination will be
headache is symptomatic of an underlying brain tumor normal and a judgment about the nature and cause
or some other mass lesion, but these are in fact rare of a headache will be based on the patients’ subjec-
causes of headache. In general, we make a distinction tive description of the headache and associated
between what are referred to as primary and secondary symptoms. It is necessary to ask about the tempo
headache disorders. The latter are conditions in which with which the headache evolves. Did it begin sud-
the headache is due to some other intracranial process denly and reach maximal intensity shortly after it
such as a mass lesion, raised intracranial pressure or began? Or did it evolve gradually over a period of
some inflammatory or infectious process. In consider- many minutes or several hours? The clinician should
ing possible secondary causes of headache it is helpful also ask about the location and quality of the
to recall that the brain parenchyma itself is insensitive headache. Is it unilateral or bilateral? Is the pain
to pain. Pain-sensitive structures include the meninges mostly located behind the eye or does it seem to ra-
(pia mater), the cranial nerves, the arteries that make diate up from the neck? What does the pain feel
up the circle of Willis and its proximal branches, like? Patients often respond to this question with a
meningeal vessels, the external carotid artery, the description of the severity of the pain, but it is nec-
scalp, pericranial muscles, the mucosa of the paranasal essary to emphasize that what is needed is a de-
sinuses, the teeth, and cervical nerve roots. Diseases scription of the quality of the pain. Is the headache
that involve or affect these structures have the throbbing, pressing, or stabbing? As with any com-
propensity to cause a secondary headache. Primary plaint of pain, the physician should ask about factors
headache disorders are those in which the headache is that alleviate and aggravate the pain. Related to
the primary problem rather than due to some other these questions is the matter of the patient’s behav-
disease process. Migraine and tension-type headache ioral response to the headache. Is there a tendency
are the most common primary headache disorders; to go and sit or lie quietly in a room somewhere or
other examples include cluster headache and paroxys- does the patient feel like getting out for some exer-
mal hemicrania. cise when the headache is present? What about the
duration of the headache and its periodicity? Does it
last only a few minutes, several hours, several days,
EVALUATION OF THE HEADACHE or even perhaps persist without relief? How fre-
PATIENT quently does the headache recur? Finally, it is im-
portant to ask about other symptoms that may be
THE HEADACHE HISTORY associated with the headache. Is it accompanied by
nausea, vomiting, or sensitivity to light or sound?
The clinical evaluation of the patient with a What about visual symptoms such as flashing lights
headache begins with a careful and detailed history. or other associated symptoms such as paresthesias,
69
12887_CH10.qxd 10/4/08 3:22 PM Page 70
70 • Blueprints Neurology
prophylactic, i.e., treatment to reduce the frequency paracervical muscle spasm and tenderness may be
of future attacks. Pharmacologic therapy should be present on examination, but it is important to recog-
undertaken in conjunction with an effort to identify nize that tension-type headaches have a particular
and avoid potential environmental triggers. Triptans character, and the term should not be used as a
(drugs that are agonists of the 5-hydroxytryptamine “grab-bag” for all ill-defined headaches. The diagno-
1B, 1D, and 1F receptors) are the mainstay of therapy, sis of tension-type headache is again a clinical one,
and these are available in several formulations (oral, with little need for neuroimaging unless the history
sublingual, nasal, and subcutaneous). They are most is atypical or focal neurologic deficits are identified
effective when administered early in the course of an on examination. Treatment may be challenging
attack and should be used with caution in subjects and includes both nonpharmacologic measures and
with a history of, or at risk for, coronary artery disease. simple forms of analgesia. Over-use of caffeine and
There are, however, several other classes of drugs barbiturate-containing compounds should be avoided,
that may be effective for abortive therapy. These given their propensity to cause medication-withdrawal
include ergotamine derivatives, caffeine containing or rebound headaches.
compounds, and intravenous antiemetics such as
metoclopramide and prochlorperazine. Drugs of many
different classes have been used for prophylactic ther-
CLUSTER HEADACHE
apy, including -blockers, tricyclic antidepressants,
Cluster headache is the best known, albeit rare,
and anticonvulsants. Prophylactic therapy is generally
member of a group of primary headaches known as
indicated when headaches occur more frequently than
the trigeminal autonomic cephalgias (TAC). The
once per month.
TACs are a group of disorders characterized by uni-
lateral trigeminal nerve distribution pain, accompa-
nied by prominent ipsilateral autonomic symptoms.
KEY POINTS Cluster headache derives its name from its temporal
• Migraine headaches are characteristically unilateral pattern—affected individuals experience periods that
and throbbing, accompanied by nausea, photo- may last several days, weeks, or months in which
phobia and/or phonophobia, and a behavioral headaches occur with a high frequency, followed by
response that involves retreat to a quiet dark place. headache-free periods that may last many months or
• Cortical spreading depression is the mechanism even years. Also, the headaches are strictly unilateral
thought to underlie migraine pathophysiology. (although may occasionally alternate sides be-
tween headaches within a cluster) and are most com-
• Triptans are the mainstay of abortive therapy for
acute migraine attacks.
monly located over the orbital or temporal region.
Headaches are almost invariably accompanied by
cranial autonomic symptoms such as lacrimation,
conjunctival injection, facial or forehead swelling,
TENSION-TYPE HEADACHE eyelid edema, nasal congestion, rhinorrhea, and signs
of a Horner syndrome (miosis, ptosis). With the ex-
Tension-type headache is the most common form ception of the Horner syndrome, these symptoms
of headache. This is a specific form of primary and signs occur only in conjunction with a headache.
headache that is characterized by recurrent attacks The pain is typically excruciating, and affected
of bilateral or holocranial headaches of a pressing, individuals are often restless and feel the need to be
squeezing, or tightening sensation. The quality of the up and moving around (in contrast to patients
pain has been likened to that of having a band or vice with migraine who prefer to lie still in a quiet, dark
around the head. The duration of headaches may be place). There are several (often overlapping) ap-
from 30 minutes to several days. In contrast to mi- proaches to management. Triptans are the most ef-
graine, tension-type headaches are not accompanied fective abortive agents. Steroids (e.g., prednisone)
by nausea or neurologic symptoms and are not exac- may shorten the duration of a cluster and the fre-
erbated by physical activity. In the past, tension-type quency of headaches during a cluster. Patients should
headaches have been described as muscle contrac- be advised to avoid alcohol. For those with frequent
tion headaches, but the role of muscle contraction in clusters, agents such as verapamil and lithium may
headache pathogenesis remains unclear. Cervical or offer effective long-term prophylaxis.
12887_CH10.qxd 10/4/08 3:22 PM Page 72
72 • Blueprints Neurology
74 • Blueprints Neurology
teeth, shaving, eating, drinking, or even a gentle (crops of vesicles on an erythematous base) within
breeze against the face. The disorder is thought to the distribution of one or several nerve root seg-
result from compression of the trigeminal nerve root ments. The pain is typically described as burning,
at the cerebellopontine angle, most often by an itching, and hypersensitivity to light touch. There is
aberrant vascular loop. MRI is typically required to good evidence that early treatment of shingles with
exclude other compressive lesions, but is usually antiviral therapy (acyclovir) reduces the risk of PHN.
normal. Carbamazepine is the treatment of choice, Once present, management is symptomatic, with
but if this does not provide adequate relief then tricyclic antidepressants and gabapentin being most
other anticonvulsant drugs may be tried. Surgical efficacious.
measures such as percutaneous radiofrequency abla-
tion and microvascular decompression are usually
reserved for refractory cases.
KEY POINTS
POSTHERPETIC NEURALGIA • Dental and temperomandibular joint diseases are
far more common as causes of facial pain than neu-
Postherpetic neuralgia (PHN) describes the neuro- rologic disease.
pathic pain that may accompany and follow an acute • An important clue to a neurologic cause of facial pain
attack of varicella zoster (shingles). Shingles typically is a history of pain that has a neuropathic quality.
results from re-activation of a dormant infection of Neurologic examination is typically normal in both
the virus that causes chickenpox within the dorsal neurologic and nonneurologic causes of facial pain.
root ganglion and is characterized by a herpetic rash
12887_CH11.qxd 10/4/08 3:23 PM Page 75
Part 3
Neurologic Disorders
75
12887_CH11.qxd 10/4/08 3:23 PM Page 76
12887_CH11.qxd 10/4/08 3:23 PM Page 77
77
12887_CH11.qxd 10/4/08 3:23 PM Page 78
78 • Blueprints Neurology
KEY POINTS
• Broca’s aphasia is a problem of language
production.
• Patients are frustrated and have nonfluent, hesi-
tant, telegraphic speech output, with an inability to
repeat but relatively preserved comprehension.
• Broca’s aphasia is typically caused by lesions in the
posteroinferior frontal lobe (Broca’s area).
Figure 11-1 • Higher cortical centers in the left hemisphere.
12887_CH11.qxd 10/4/08 3:23 PM Page 79
80 • Blueprints Neurology
82 • Blueprints Neurology
Chapter
12 Dementia
Dementia is a common cause of morbidity and mor- problems with short-term memory, followed by an
tality in the elderly and has many different etiologies. indolent deterioration of cognitive functions that
It implies an intellectual and cognitive deteriora- may involve language, praxis, and so forth. Many
tion of sufficient severity to interfere with normal dementing illnesses manifest characteristic symptoms
functioning. Memory, orientation, visuospatial per- and clinical findings that are helpful in establishing an
ception, language, and higher executive functions etiologic diagnosis.
(planning, organizing, and sequencing) may be im-
paired in dementia. DIAGNOSTIC EVALUATION
The terms delirium and acute confusional state
imply a global disturbance of mental functions, in The initial recognition of dementia is difficult.
general reversible, accompanied by altered level of Normal aging can mimic some of its features. Rarely,
consciousness. These conditions are often acute and the patient is aware of cognitive deterioration; in
reversible; they are discussed further in Chapter 3. most cases, the family brings the patient to the doc-
tor months or years after problems have started. The
EPIDEMIOLOGY most important information in the diagnosis of
dementia is the clinical history (including reports by
Dementia is most common in the elderly but can relatives) and the physical exam (with a very detailed
occur at a younger age (particularly in those with a mental status examination). Then, the diagnosis of
hereditary component). Approximately 5% of people the cause of dementia consists of matching the major
between ages 65 and 70 have dementia; this increases clinical features of the individual patient with char-
to more than 45% above age 85. Alzheimer disease acteristics of known dementing illnesses.
accounts for 50% to 70% of cases of dementia. It is important to rule out an underlying depres-
Cerebrovascular disease accounts for about 15% to sion, because depression can mimic dementia
20%, and the other causes presented in Box 12-1 (“pseudodementia”), and the associated cognitive
account for most of the rest. Dementia has a consider- abnormalities of depression can constitute a true
able social cost (over $50 billion in the United States dementia. Not rarely, when a patient complains of
every year). features suggesting dementia, depression is the
problem. Correspondingly, it is often a family mem-
ber who brings a patient with dementia to the
CLINICAL MANIFESTATIONS physician.
The use of laboratory tests depends on the clinical
There is a known cognitive decline with old age, and history and exam, the tentative diagnosis, and the
sometimes the differentiation between a dementing possibility of finding reversible causes. Box 12-2 sum-
illness and age-related cognitive decline is difficult. In marizes some tests to consider. Most are used to rule
general, most patients with dementia start having out reversible causes of dementia.
84
12887_CH12.qxd 10/4/08 3:24 PM Page 85
Chapter 12 / Dementia • 85
86 • Blueprints Neurology
Chapter 12 / Dementia • 87
cellular accumulation of phosphorylated tau protein. • Preventing or delaying progression: This includes
Senile plaques are extracellular deposits of amyloid therapy with acetylcholinesterase inhibitors such as
surrounded by dystrophic axons. donepezil or rivastigmine, as well as the newer agent
memantine, an N-methyl-D-aspartate (NMDA)
Treatment receptor antagonist.
At present there is no satisfactory treatment for • Prophylaxis: No data from randomized clinical
patients with Alzheimer disease. trials are available. Use of vitamin E, NSAIDs, and
Therapy consists of the following: estrogens has been proposed.
• Preventing associated symptoms: Treatment of Table 12-1 provides information regarding therapy
depression, agitation, sleep disorders, hallucina- of AD and other dementias (not all of which have
tions, and delusions. been proven effective).
88 • Blueprints Neurology
Treatment
KEY POINTS The prevention and treatment of vascular dementia
are essentially the same as prevention and treatment
• AD is the most common neurodegenerative dis- of stroke (see Table 12-1 and Chapter 14).
ease of the brain and accounts for 50% to 70% of all
instances of dementia.
• Risk factors for developing AD include older age,
female sex, head trauma, and family history. KEY POINTS
• Potentially treatable causes of dementia should be
• Vascular dementia may be a common cause of
excluded through laboratory testing and brain
dementia, but it often coexists with other causes.
imaging.
• Vascular dementia is associated with Binswanger
• The average length of time from onset of symptoms
disease (microvascular disease), a lacunar state, and
until diagnosis is 2 to 3 years. The average duration
large strokes.
from diagnosis to nursing home placement is 3 to 6
years. AD patients typically spend 3 years in nursing
homes before death. Thus, the total duration of AD
is roughly 9 to 12 years.
DEMENTIAS ASSOCIATED WITH
EXTRAPYRAMIDAL FEATURES
Chapter 12 / Dementia • 89
90 • Blueprints Neurology
Chapter 12 / Dementia • 91
Chapter
13 Sleep Disorders
92
12887_CH13.qxd 10/4/08 3:25 PM Page 93
Figure 13-1 • Stages of sleep. Rapid-eye-movement (REM) sleep and the 4 stages
of nonREM sleep alternate throughout the night in cycles that last approximately
90 minutes. There are typically four to six cycles each night in a healthy young adult.
nucleus of the hypothalamus, with important inputs Dopaminergic agents are the treatment of choice
from melatonin produced by the pineal gland. for RLS. Dopamine agonists such as ropinirole and
Pathological circadian rhythms include advanced sleep- pramipexole are preferred to levodopa, because
phase disorder in which patients sleep or wake earlier levodopa is associated with a higher incidence of aug-
than they desire, and delayed sleep-phase disorder in mentation, i.e., progressive movement of symptoms
which sleep onset is delayed until early morning, with toward an earlier time of day with continued therapy.
consequent awakening later than desired. Bright light Typically, these medications are given half an hour be-
therapy and melatonin can be used to treat sleep- fore the anticipated start of symptoms, and then every
phase disorders by resetting circadian rhythms. 2 to 3 hours afterward. Side effects of dopamine ago-
nists include nausea, lightheadedness, and sometimes
sleep attacks (falling asleep suddenly in the daytime).
RESTLESS LEGS SYNDROME/ If augmentation becomes a severe problem or RLS
PERIODIC LIMB MOVEMENTS symptoms worsen despite treatment with dopamin-
OF SLEEP ergic agents, other treatment options include anti-
convulsants (particularly gabapentin), opioids, and
Restless legs syndrome (RLS) is a common sleep dis- benzodiazepines. Iron deficiency should be cor-
order characterized by an urge to move the legs, rected; this can help to relieve symptoms, although
usually during periods of rest or inactivity. Patients dopaminergic agents are often still required.
describe uncomfortable crawling sensations in the
legs, with worsening discomfort if the legs remain
still, and relief when they are moved. Typically, rest- KEY POINTS
less legs symptoms occur in the evening or at night.
They are often accompanied by periodic limb move- • RLS is associated with iron deficiency.
ments of sleep, repetitive involuntary movements of • Dopaminergic agonists such as ropinirole and
the toe, ankle, knee, and hip that last 2 to 3 seconds pramipexole are the agents of choice in the treat-
and are followed by slow recovery of the normal leg ment of RLS.
position. These movements can awaken the patient • Augmentation is the occurrence of RLS symptoms
or bed partner. RLS is more common in women, and earlier in the day upon dopaminergic treatment.
in some families an autosomal dominant inheritance
pattern is suggested.
Diagnosis of RLS is made by clinical history. PSG
may help to confirm the diagnosis but is often not NARCOLEPSY/CATAPLEXY
necessary. Laboratory evaluation of RLS should in-
clude measurement of ferritin levels, as many pa- The four components of the narcolepsy/cataplexy
tients with RLS have iron deficiency. syndrome are: excessive daytime sleepiness with
12887_CH13.qxd 10/4/08 3:25 PM Page 94
94 • Blueprints Neurology
during sleep, which can be provoked by talking to the with OSA are at increased risk of developing car-
patient. diopulmonary disease.
PSG is the standard tool used to investigate OSA: a
OTHER PARASOMNIAS combination of more than 5 apneas, hypopneas, or
respiratory event–related arousals are required to es-
Sleep starts or hypnic jerks are commonly experi- tablish the diagnosis. Apneas are defined as respiratory
enced myoclonic jerks that often occur with sleep pauses with cessation of airflow lasting 10 seconds or
onset. Enuresis is abnormal nocturnal bedwetting, more, while hypopneas are defined as pauses with a
defined as more than three episodes per week. Boys reduction of 50% or more in airflow.
have enuresis more often than girls. Most cases of Continuous positive airway pressure (CPAP) is
enuresis resolve spontaneously, although condition- the standard treatment for OSA. This apparatus de-
ing the child or use of imipramine may hasten this livers air at a predetermined pressure through a tube
resolution. Bruxism is teeth grinding during sleep; connected to a facemask. Patients with a diagnosis
treatment of underlying dental abnormalities or use of OSA may have a “split-night” PSG in which the
of a biteplate is often helpful. first part of the night is spent in diagnosing and
quantifying the severity of the disorder while the
second part of the night is spent titrating the CPAP
SLEEP APNEA pressure to best prevent respiratory events. In addi-
tion to CPAP, patients with OSA benefit from
Obstructive sleep apnea (OSA) is produced by weight loss, alcohol cessation, and sleeping on their
obstruction of the upper airway during sleep. sides rather than on the back. Surgical intervention
Preservation of respiratory effort distinguishes OSA may be indicated should CPAP and behavioral mod-
from central sleep apnea, which is derived from a ification prove ineffective. The operation most com-
central (nervous system) lack of ventilatory effort. monly performed is uvulopalatopharyngoplasty to
Symptoms of OSA include excessive daytime relieve upper airway obstruction.
sleepiness, snoring, cessation of breathing in the
middle of the night, and morning headaches.
Nonspecific cognitive complaints may also occur in KEY POINTS
patients with obstructive sleep apnea. Risk factors
for the development of OSA include obesity (body • Continuous positive airway pressure is the treat-
mass index ⬎30 kg/m2 or neck circumference ment of choice for obstructive sleep apnea.
greater than 17 inches) and advanced age. Patients
12887_CH14.qxd 10/4/08 3:25 PM Page 96
Chapter
14 Vascular Disease
A stroke is a brain injury caused by an abnormality of also become familiar with the frequency of the various
the blood vessels supplying the brain. In the United pathologies that affect blood vessels at various sites.
States, about 750,000 individuals have a stroke and The anterior (carotid) circulation supplies the
150,000 die from stroke annually. Every 45 seconds, cerebral hemispheres except for the medial temporal
someone in the United States has a stroke, and each lobes and a portion of the occipital lobes. The poste-
3 minutes, someone dies of stroke. Stroke is the third rior (vertebro-basilar) circulation supplies the brain-
leading cause of death in the world, surpassed only by stem, thalami, cerebellum, and the posterior portions
heart disease and cancer. Strokes are a very important of the cerebral hemispheres (Fig. 14-1).
cause of prolonged disability. Survivors of strokes
often cannot return to work or assume their former ANTERIOR CIRCULATION
effectiveness as spouses, friends, and parents. The
economic, social, and psychological costs of stroke The right common carotid artery (CCA) branches
are huge. from the innominate artery. The left CCA arises di-
Many general medical conditions and behaviors rectly from the aorta. The CCAs divide in the neck
predispose to stroke. These include: hypertension, di- into the internal carotid artery (ICA) and the external
abetes, obesity, hyperlipidemia, sedentary life style, carotid artery. The ICAs travel behind the pharynx,
smoking, cardiac disease, and heavy alcohol use. entering the skull where they form an S-shaped
Prevention of stroke is very important and can be ac- curve—the carotid siphon. This portion of the ICAs
complished by physicians attending to these stroke risk gives rise to ophthalmic artery branches to the eye.
factors and advising patients about their lifestyles and The ICAs then penetrate the dura and give off anterior
habits, and by prescribing appropriate medications. choroidal and posterior communicating arteries before
Prevention is primary in patients who have never had bifurcating into the anterior cerebral (ACAs), and
a stroke and secondary when preventing a stroke re- middle cerebral arteries (MCAs).
currence. Second and third strokes are most often due The ACAs supply the anterior medial cerebral
to the same stroke subtype as the initial stroke. hemispheres and the caudate nuclei and basal frontal
Recognition of the cause of a stroke is the most im- lobes. The anterior communicating artery connects
portant step in taking measures to avoid a recurrence. the two ACAs. The MCAs course laterally, giving off
lenticulostriate artery branches to the basal ganglia
VASCULAR ANATOMY and internal capsule. The MCAs trifurcate into small
anterior temporal branches and large superior and
The nature of the neurologic symptoms and signs helps inferior divisions. The superior divisions supply the
clinicians localize the findings to a particular location lateral cerebral hemispheres above the sylvian fissure,
within the brain. In order to identify the abnormality and the inferior divisions supply the temporal and
within the blood vessel pathway that supplies that re- inferior parietal lobes below the sylvian fissure.
gion of the brain, it is necessary for clinicians to have an The anterior choroidal arteries arise from the ICAs
intimate knowledge of vascular anatomy. They must after the ophthalmic and posterior communicating
96
12887_CH14.qxd 10/4/08 3:25 PM Page 97
Anterior
cerebral
Circle of Middle
Willis cerebral
Posterior
cerebral
Basilar
Cerebellar
Internal
carotid
Eye
Ophthalmic Vertebral
Common
carotid
arteries and course along the optic tract giving off The vascular supply of the brainstem includes
branches to the globus pallidus and posterior limb of large paramedian arteries and smaller, short circum-
the internal capsule and then supply the medial tem- ferential arteries that penetrate through the basal
poral lobe and the lateral geniculate body. portions of the brainstem into the tegmentum. Long
circumferential arteries course around the brainstem
POSTERIOR CIRCULATION giving off branches to the lateral tegmentum. The
PCAs give off penetrating arteries to the midbrain
The first branch of each subclavian artery is the verte- and thalamus, course around the cerebral peduncles,
bral artery (VA). The VAs enter the transverse foram- and then supply the occipital lobes and inferior sur-
ina of C6 or C5 and run within the intravertebral face of the temporal lobes.
foramina, exiting to course behind the atlas before The circle of Willis allows for connections between
piercing the dura mater to enter the foramen magnum. the anterior circulations of each side, through the an-
The intracranial VAs end at the medullo-pontine junc- terior communicating artery, and between the poste-
tion, where they join to form the basilar artery. rior and anterior circulations of each side through the
The intracranial VAs give off posterior and ante- posterior communicating artery (Fig. 14-2).
rior spinal artery branches, penetrating arteries to the
medulla, and the large posterior inferior cerebellar KEY POINTS
arteries (PICAs). The basilar artery runs in the mid-
line along the clivus giving off bilateral anterior infe- • Each carotid artery supplies two-fifths of the brain;
rior cerebellar artery (AICA) and superior cerebellar the vertebro-basilar circulation, one-fifth.
artery (SCA) branches before dividing at the pon- • The anterior circulation supplies mainly the cere-
tomesencephalic junction into PCA branches. Small brum, while the posterior circulation supplies the
penetrating arteries arise at the basilar artery bifurca- brainstem, cerebellum, and the visual cerebral
tion to supply the medial portions of the midbrain cortex.
and thalami.
12887_CH14.qxd 10/4/08 3:25 PM Page 98
98 • Blueprints Neurology
KEY POINTS
• Acute and preventive treatments should be tai-
lored to the individual patient.
• Maximizing cerebral blood flow to ischemic regions
Figure 14-5 • Bright signal is seen on a diffusion-weighted MR can be facilitated by opening blocked arteries
image (DWI), indicating a recent infarction. chemically or mechanically, and by increasing
blood flow in collateral vessels.
KEY POINTS
INTRACRANIAL HEMORRHAGE
• The course of development of symptoms and re-
sults of brain imaging should allow separation of
Bleeding inside the skull can be divided into subarach-
ischemia from hemorrhage, and in case of ischemia,
noid, intracerebral, epidural, and subdural hemor-
identification of the most likely stroke mechanism:
rhages. The latter two types of hemorrhages are al-
thrombosis, embolism, or systemic hypoperfusion.
most always traumatic and are discussed in Chapter
• Cardiac and brain and vascular imaging should 17. Intracerebral hemorrhage (ICH) and subarachnoid
identify the cause of the stroke.
hemorrhage (SAH) have different causes, clinical find-
ings, and management.
KEY POINTS
• AVMs, DVAs, cavernous angiomas, and telangiecta-
sis are different types of malformations, each with
differing clinical findings and management.
• Medical therapy, surgery, interventional oblitera-
Figure 14-7 • Subarachnoid hemorrhage. A CT scan showing tion, and radiotherapy are all used in treating brain
extensive subarachnoid blood within the sulci of the brain. vascular malformations.
The most bleeding is seen in the left frontal region.
12887_CH15.qxd 10/4/08 3:26 PM Page 103
Chapter
15 Seizures
Seizures are among the most common problems in motor seizures, in which one part of the body may
neurology. Up to 10% of the population will have a stiffen or jerk rhythmically, stem from the motor
seizure at some point in their lives. In addition, cortex in the frontal lobe. The classic jacksonian
seizures can be among the most dramatic forms of march occurs when the electrical discharge spreads
nervous system dysfunction. Although seizures have along the motor strip, leading to rhythmic twitching
many different causes and manifestations, by defini- that spreads along body parts following the organiza-
tion a seizure is an abnormal hypersynchronous elec- tion of the motor homunculus. Simple partial
trical discharge of neurons. Epilepsy is defined as a seizures from other regions of the brain can cause
condition in which there is a tendency toward recur- sensory phenomena (parietal), visual phenomena
rent unprovoked seizures. Practically, the diagnosis of (occipital), or gustatory, olfactory, and psychic phe-
epilepsy is often applied after a patient has had two nomena (temporal). The latter may include déjà vu,
unprovoked seizures. jamais vu, or sensations of depersonalization (“out of
body”) or derealization.
CLASSIFICATION
COMPLEX PARTIAL SEIZURES
Seizures can arise from one portion of the brain (par-
Complex partial seizures have a focal onset and
tial) or from the entire brain at once (generalized).
involve an impairment of awareness. They commonly
Those that arise from one portion of the brain can
arise from the temporal lobe, although some may orig-
evolve and spread to involve the whole brain (sec-
inate in the frontal lobe as well. Complex partial
ondarily generalized). Among partial seizures, those
seizures may include automatisms (stereotyped motor
in which awareness is impaired are termed complex,
actions without clear purpose) such as lip-smacking,
whereas those in which awareness is preserved are
chewing movements, or picking at clothing. The
termed simple.
patient may have speech arrest or may speak in a non-
sensical manner. By definition the patient does not
SIMPLE PARTIAL SEIZURES respond normally to the environment or to questions
or commands. Occasionally, patients may continue
By definition, simple partial seizures begin in a focal the activities they were participating in at the onset of
area of the brain and do not impair awareness. In the seizure, sometimes to remarkable lengths: patients
general, such seizures lead to positive rather than may continue folding the laundry during a seizure or
negative neurologic symptoms (e.g., tingling rather even finish driving home. Complex partial seizures of
than numbness, hallucinations rather than blind- frontal lobe origin may involve bizarre bilateral move-
ness). The manifestations of simple partial seizures ments, such as bicycling or kicking, or behavior such as
depend on their site of origin in the brain. Focal running in circles.
103
12887_CH15.qxd 10/4/08 3:26 PM Page 104
Incidence
Childhood Elderly
䊏 TABLE 15-2 Characteristics of Partial Seizures and Other Paroxysmal Neurologic Events
Transient Ischemic
Partial Seizures Attacks (TIAs) Migraines
Onset Progression of symptoms over Sudden onset of symptoms Progression of symptoms
seconds over 15 to 20 minutes
Neurologic symptoms Positive motor or sensory Negative motor, sensory, Positive sensory or
symptoms, “psychic” or visual symptoms especially visual
symptoms such as déjà vu symptoms, such as
scintillating scotomata
Duration Usually less than a few Usually less than 30 Symptoms for 15 to 20
minutes minutes, always less than minutes, followed by
24 hours headache for up to hours
Consciousness Impaired (if complex) Preserved Preserved
Headache Occasionally postictal None Throbbing pain following
progression of symptoms
Recovery Postictal confusion, sleepiness Immediate Fatigue common
Risk factors Structural brain lesion, family Hypertension, Family history of
history of seizures hyperlipidemia, smoking, migraines
diabetes
12887_CH15.qxd 10/4/08 3:26 PM Page 107
LABORATORY STUDIES
required, or the seizures may remain refractory to programmed electrical impulses delivered through
all medical therapy. leads placed in the neck.
All physicians should be familiar with first aid mea- Intubate if not already done
sures for those having a seizure. In general, the goal is
Phenobarbital 20 mg/kg IV
to prevent the patient from becoming injured and to
prevent well-meaning bystanders from intervening un-
If status epilepticus
wisely. The patient with complex partial seizures may
continues
wander or make semipurposeful movements; if neces-
sary, he or she should be gently guided out of harm’s
way. More aggressive attempts at restraint may pro- Induce coma with barbiturates,
voke a violent reaction. The patient with GTC midazolam, or propofol
seizures should be laid on his or her side, if possible, so
Institute continuous bedside EEG
that vomiting does not lead to aspiration. Tight cloth-
monitoring
ing should be loosened. Nothing should be placed in
the mouth. Most GTC seizures stop within 1 to 2 min-
utes; immediate medical attention should be sought if Figure 15-3 • Neurologic emergency: status epilepticus.
a seizure becomes more prolonged.
SEIZURES AND DRIVING drive; exceptions can sometimes be made for purely
nocturnal seizures or those with a prolonged simple
Each state has its own licensing requirements for partial onset that provides the patient with a warning
those with epilepsy; physicians who care for seizure without impaired awareness. A few states require
patients should be aware of these. Most states require physicians to report patients with seizures to the
a specific seizure-free interval before a patient may department of motor vehicles.
12887_CH15.qxd 10/4/08 3:26 PM Page 110
Chapter
Movement
16 Disorders
111
12887_CH16.qxd 10/4/08 3:27 PM Page 112
bid, twice a day; quid, four times a day; tid, three times a day.
䊏 BOX 16-1 Tremor body part to another. Patients are often unaware of
even severe chorea. One of the earliest symptoms
Resting may be clumsiness or incoordination. Involvement
Idiopathic Parkinson disease of bulbar muscles may cause dysarthria and dyspha-
Other parkinsonian syndromes gia. Chorea is usually accompanied by an inability to
maintain a sustained muscle contraction (motor im-
Postural
persistence). Classic examples include an inability
Essential tremor to keep the tongue protruded (serpentine tongue)
Physiological tremor and the inability to maintain a tight handgrip (milk-
Drugs (e.g., theophylline, -agonists) maid grip).
There are many causes of chorea, and it is impos-
Alcohol
sible to determine the etiology based simply on the
Action phenomenology of the abnormal movements. It is
Cerebellum and cerebellar outflow tract dysfunc- necessary to consider the age and relative acuity of
tion (e.g., infarction, multiple sclerosis, tumor, onset, the presence or absence of a family history, the
Wilson disease, drugs) presence of associated symptoms, and the distribu-
tion of the movements. The different causes are sum-
marized in Box 16-2.
For treatment, haloperidol has been used with
causes of the various types of tremors are summarized
greatest success.
in Box 16-1.
Essential tremor (ET) is a condition in which pos-
tural tremor is the only symptom. It may begin at any
age, develops insidiously, and progresses gradually. A 䊏 BOX 16-2 Chorea
family history is common but not invariable. ET al-
most always affects the hands but may also affect the Hereditary
head, face, voice, trunk, or legs. It is almost always Huntington disease
bilateral. Improvement of the tremor with small Neuro-acanthocytosis
quantities of alcohol is a characteristic feature.
Wilson disease
Primidone and propranolol are of proven benefit in
the treatment of ET. Topiramate and gabapentin Drugs
have also been used with some success. Neuroleptics
Antiparkinsonian medications
Toxins
KEY POINTS Alcohol
KEY POINTS
TICS • Tics are abrupt, stereotyped, coordinated move-
ments or vocalizations.
Tics are abrupt, stereotyped, coordinated movements
• Gilles de la Tourette syndrome is a common genetic
or vocalizations. They may vary in intensity and be disorder with onset of motor and vocal tics in
repeated at irregular intervals. The individual will childhood.
frequently describe an inner urge to move, may be
• Dopamine antagonists are often the most effective
able to suppress the movement temporarily at the
therapy for tics.
expense of mounting inner tension, and then obtain
relief from the performance of the movement or
vocalization. Tics may be exacerbated by stress and
relieved by distraction.
Tics may be motor or vocal and are classified as WILSON DISEASE
being either simple or complex. Examples of simple
motor tics include eye blinking, shoulder shrugging, Wilson disease (WD) is an autosomal recessive disor-
and toe curling. Spitting and finger cracking are der of copper metabolism. The clinical presentation
examples of complex motor tics. Simple vocal tics is usually with liver dysfunction and neuropsychiatric
may take the form of sniffing, throat clearing, snorting, symptoms.
12887_CH16.qxd 10/4/08 3:27 PM Page 118
Chapter
17 Head Trauma
119
12887_CH17.qxd 10/4/08 3:28 PM Page 120
lesions and progressive clinical deficits. Anticoagu- and to determine when an athlete can return to
lation should be discontinued to offer the best chance competition:
of resolution.
• Children with no loss of consciousness and con-
cussion symptoms for less than 15 minutes may
CONCUSSION return to play.
• Children with no loss of consciousness and con-
A concussion is an alteration or loss of consciousness cussion symptoms for more than 15 minutes may
produced by head trauma. The symptoms of a con- return to play in 1 week.
cussion are the result of a functional rather than a • Children with loss of consciousness should be
structural change, and brain imaging studies are typ- transported to a hospital for overnight observa-
ically normal. Patients usually have short periods of tion; they may return to play in 1 week if loss of
amnesia for events that occurred before the injury consciousness was brief (seconds), or in 2 weeks if
(retrograde amnesia) and for learning new material loss of consciousness was longer in duration.
after the incident (anterograde amnesia). The sever-
ity of a concussion can be gauged by the duration of
the loss of consciousness and amnesia. Other conse- DIFFUSE AXONAL INJURY
quences of concussion include headache, disorienta-
tion, dizziness and vertigo, nausea, and cortical Diffuse axonal injury is associated with severe head
blindness. Concussions are frequent in sporting trauma and may be seen on CT as multiple areas of
events, particularly in children. Guidelines have punctate hemorrhage in the deep white matter and
been established by the American Academy of corpus callosum (Fig. 17-3). The presence of diffuse
Neurology to determine the severity of a concussion axonal injury is usually associated with poor prognosis.
12887_CH17.qxd 10/4/08 3:28 PM Page 121
HERNIATION SYNDROMES
POSTTRAUMATIC SEIZURES
AND EPILEPSY Brain herniation is a life-threatening condition which
occurs when increased intracranial pressure causes a
Seizures after head trauma can be divided into early shift of brain contents, resulting in compression of
(within 1 week of head trauma) and late (beginning 1 brain parenchyma and ventricles, and, compromise of
week or more later). Approximately 25% of patients cerebral blood vessels.
12887_CH17.qxd 10/4/08 3:28 PM Page 122
CLINICAL MANIFESTATIONS
DIAGNOSTIC EVALUATION
The encephalopathy of fulminant hepatic failure pro-
gresses rapidly, within days, from mild inattention to The diagnosis is usually suspected clinically on the
stupor and coma. The essential feature of portosys- basis of the encephalopathy in the context of liver
temic encephalopathy is the presence of waxing and failure. Hepatic synthetic function is impaired, with
waning cerebral dysfunction in the setting of liver fail- low serum albumin and prolonged prothrombin time
ure. Traditionally, hepatic encephalopathy is graded (PT) and partial thromboplastin time (PTT). The
in severity on a scale from 0 (normal) to 4 (coma). EEG usually shows background slowing and may
The intermediate stages are characterized by impaired demonstrate triphasic waves, and MRI may reveal
attention and concentration, altered sleep patterns, increased T1 signal in the basal ganglia, but these find-
abnormal visuospatial perception, and subtle person- ings are not specific. In a patient with known liver dis-
ality changes. Asterixis (negative myoclonus) is usu- ease who develops encephalopathy, it is important to
ally present. Other neurologic findings may include identify underlying precipitating factors such as gas-
increased muscle tone, hyperreflexia, and extensor trointestinal hemorrhage, infection, increased dietary
plantar responses. protein intake, drugs, constipation, or hypokalemia.
124
12887_CH18.qxd 10/4/08 3:28 PM Page 125
TREATMENT
Steroids are the mainstay of therapy. Although used is the most common. Onset of this neuropathy is
often, there are limited data regarding the use of insidious, and it may often be asymptomatic. There is
steroid-sparing agents such as methotrexate and a predilection for involvement of small myelinated
azathioprine. and unmyelinated fibers, with the result that loss of
temperature and pinprick sensation are the most com-
monly reported symptoms. There may be associated
distal motor neuropathy, but it is invariably minor.
KEY POINTS Once established, this neuropathy is largely irrevers-
• Sarcoidosis is a multisystem granulomatous ible. The incidence of this complication is reduced
disorder. in type 1 diabetic patients by strict glycemic control.
There is frequently an associated autonomic neuropa-
• The nervous system is mostly affected in conjunc-
tion with systemic disease, but it may be affected in
thy, the common symptoms of which include gusta-
isolation. tory sweating, orthostatic hypotension, diarrhea, and
impotence. Neurogenic bladder and gastroparesis
• Cranial neuropathy and basal meningitis are
occur less frequently.
common.
Focal peripheral neuropathies also occur more
commonly in diabetic patients. These include cranial
neuropathies (most commonly affecting cranial nerves
III, IV, and VI) and focal compression neuropathies,
DIABETES MELLITUS such as distal median neuropathies (carpal tunnel) and
meralgia paresthetica (compression of the lateral cuta-
Diabetes mellitus is common in patients with neuro- neous nerve of the thigh). Radiculopathy, especially
logic disease, primarily because the nervous system is thoracic, occurs with greater frequency in diabetic
susceptible to the damaging effects of impaired patients. Typically, these radiculopathies manifest
glycemic control. However, there are also a number with nonradicular pain, truncal sensory loss, and focal
of disorders that are characterized by both diabetes weakness of the muscles of the anterior abdominal
and neurologic symptoms. These include mitochon- wall. Spontaneous recovery usually occurs within a
drial diseases, myotonic dystrophy, Friedreich ataxia, few months.
and the stiff-man syndrome. The entity of proximal diabetic neuropathy is well
Peripheral neuropathy is the most common com- recognized but poorly understood. Another term that
plication of diabetes mellitus and takes many forms has been used to describe at least some of the patients
(Box 18-1). Distal symmetric sensory polyneuropathy with this disorder is diabetic amyotrophy. At least
12887_CH18.qxd 10/4/08 3:28 PM Page 127
vitamin deficiency are presented in more detail the B12 synthetic pathway, its deficiency (theoreti-
below. cally) may cause the same deficits as B12 deficiency,
but typically, hematologic abnormalities occur with-
WERNICKE’S ENCEPHALOPATHY AND out neurologic deficits.
KORSAKOFF’S SYNDROME
䊏 BOX 18-2 Neurologic Manifestations of Neurologic signs and symptoms are very rarely the
only manifestations of thyroid disease. The periodic
Hypothyroidism
paralyses and proximal myopathy associated with
Mental state: Poor concentration and memory, the hyperthyroid state are discussed in Chapter 24.
dementia, psychosis, coma Seizures, chorea, and dysthyroid eye disease may
Seizures also result from hyperthyroidism, and there is an
Headaches: Pseudotumor cerebri association with myasthenia gravis. The range of
neurologic manifestations of hypothyroidism is sum-
Cranial nerves: Papilledema, ptosis, tonic pupil,
marized in Box 18-2.
trigeminal neuralgia, facial palsy, tinnitus, hearing loss
Cerebellar ataxia: Truncal and gait ataxia more than
limb ataxia; dysarthria; nystagmus CENTRAL PONTINE MYELINOLYSIS
Muscles: Cramps, pain and stiffness; proximal more than
distal; creatine kinase level may be markedly increased Central pontine myelinolysis is a rare demyelinating
Neuromuscular junction: Worsening of myasthenia disorder that occurs most often in alcoholic patients
gravis and may be precipitated by too rapid correction of
Nerves: Entrapment neuropathy (e.g., carpal tunnel),
hyponatremia. As the name indicates, the pons is
axonal polyneuropathy (improves with thyroxine most commonly affected, but the basal ganglia, thal-
replacement); delayed relaxation of deep tendon amus, and subcortical white matter may also be
reflexes involved. The clinical presentation includes an acute
Sleep apnea: Obstructive and central
confusional state, spastic quadriparesis, locked-in
syndrome, dysarthria, and dysphagia.
12887_CH19.qxd 10/4/08 3:29 PM Page 131
Chapter
Central Nervous
19 System Tumors
The most common tumors in the central nervous sys- CAUSES AND GENETICS
tem (CNS) are metastases from distant neoplasms.
Primary brain tumors (PBT) are a heterogeneous Primary brain tumors generally originate from genetic
group of neoplasms originating from CNS tissue and disruptions in cells, causing them to bypass normal
meninges and range from benign to aggressive. They growth regulatory mechanisms, with simultaneous
can occur anywhere in the intracranial space and evasion of the immune system. Some brain tumors
are named according to their cellular origin and have a strong hereditary component (Table 19-2).
histologic appearance. In adults, 70% of PBT are Ionizing radiation use in therapeutic dosages has
supratentorial, and of those, 80% to 90% are gliomas been associated with an increased risk of meningiomas,
and meningiomas. The remaining 30% of PBT are astrocytomas, and sarcomas. The use of mobile
infratentorial: medulloblastoma, cerebellar astrocy- phones, low-frequency electromagnetic fields, specific
toma, brainstem glioma, and ependymoma in chil- infections (various viruses, Toxoplasma gondii, etc.),
dren, and schwannoma, hemangioblastoma, and diet (nitrates, aspartame), tobacco, alcohol, and his-
meningioma in adults. In children, approximately tory of head trauma have not been validated in epi-
70% of PBT are infratentorial. Table 19-1 is a con- demiologic studies as risk factors for CNS tumors.
densed version of the World Health Organization
classification of PBT.
CLINICAL FEATURES
EPIDEMIOLOGY
There are no specific clinical symptoms or signs of
About 18,000 new cases of PBT are reported in the brain tumors. The clinical presentation depends on the
United States every year—the most common solid location of the tumor, the rate of growth, and the de-
malignancy in childhood, the second leading cause gree of invasion of surrounding structures. Tumors can
of cancer death in children, and the fifth in adults. mimic many other CNS disorders and should be con-
Metastatic lesions occur in 100,000 to 200,000 sidered part of the differential diagnosis of almost any
cases per year and account for 20% of cancer deaths neurologic dysfunction. In general, tumor symptoms
annually. PBT are more common in males than in tend to present as progressive nonremitting neurologic
females (ratio 1.5:1), except for meningioma symptoms. Nonetheless, a tumor can present as an
(1:1.8). Tumors of cranial and spinal nerves have a acute, subacute, or chronic neurologic problem. The
similar gender distribution to those of PBT. Survival most common symptoms include headaches as the re-
depends on the age of the patient, histologic sub- sult of traction of pain-sensitive structures (arteries
type of the tumor, Karnofsky performance status and veins) or from increased intracranial pressure;
(a measure of functional independence) and pre- focal or generalized seizures, particularly when tumors
senting symptoms. infiltrate the cortex; and altered mental status such as
131
12887_CH19.qxd 10/4/08 3:29 PM Page 132
memory loss, lack of concentration, changes in per- CNS. Glioma is a generic histologic term used
sonality, and apathy. In children, the predilection of for four different CNS tumors: astrocytoma, oligo-
tumors for the posterior fossa may lead to presentation dendroglioma, ependymoma, and choroid plexus
with a decreased appetite and weight loss, reduced papilloma.
school performance, dizziness, ataxia (especially of
gait), neck pain, bulbar weakness, gaze palsy, or GLIOBLASTOMA MULTIFORME
opisthotonos. Clinical findings depend on the location (GRADE IV ASTROCYTOMA)
of the tumor and can include cognitive, motor, sen-
sory, and coordination abnormalities on exam. • Origin: arises from astrocytes.
• Epidemiology: 15% of all intracranial tumors, and
DIAGNOSTIC EVALUATION 50% to 60% of PBT in adults. Peak onset at age 40
to 60.
Imaging studies (MRI and CT) play a central role in • Pathology: highly malignant tumors with ana-
the diagnosis of brain tumors. Blood work, EEG, and plasia, high cellularity, round and pleomorphic
plain x-rays are of limited use. MRI with contrast may cells, nuclear atypia, vascular proliferation, and
show a ring-enhancing mass due to disruption of the necrosis. Necrosis and neovascular proliferation
blood-brain barrier by the infiltrating neoplasm, but a help to differentiate between anaplastic astrocy-
ring-enhancing lesion can also be seen with an abscess, toma (grade III) and glioblastoma (grade IV). On
subacute infarction, resolving hematoma, multiple occasion it is multifocal or infiltrates the entire
sclerosis plaques, thrombosed aneurysms, AVMs, and brain (gliomatosis cerebri). Mitotic activity is
radiation necrosis. Depending on the size and location very high.
of the tumor, MRI features can include hydrocephalus, • Presentation: headaches 30% to 50%, seizures 30%
midline shift, hemorrhages, large areas of edema sur- to 60%, focal neurologic deficits 40% to 60%,
rounding the lesion, meningeal enhancement, etc. MR mental status changes 20% to 40% at the time of
spectroscopy can detect changes in brain tissue that are diagnosis. Symptoms may start when the tumor
associated with the type and grade of the tumor (in- has grown substantially.
cluding a decreased peak of N-acetyl aspartate (NAA)
• Imaging: CT or MRI demonstrates a solitary brain
associated with neuronal loss), but these studies need
lesion (commonly in the deep white matter, basal
further validation. The definitive diagnosis of brain tu-
ganglia and thalamus; rarely infratentorial) with
mors requires histologic examination of samples ob-
contrast enhancement and surrounding edema.
tained either by brain biopsy or open surgery.
About 4% to 10% of GBM do not enhance.
Commonly, the tumor infiltrates white matter
KEY POINTS tracts involving the corpus callosum, producing
the typical “butterfly” pattern (Fig. 19-1).
• The two most important prognostic factors for brain
• Treatment: surgical debulking of tumor (if the
tumors are histologic type and patient age.
location allows), followed by radiation and
• Brain tumors tend to present as progressive non- chemotherapy, often including temozolamide
remitting neurologic symptoms.
and BCNU (Gliadel wafers) implanted in the
• The most common type of brain tumor is metastatic. cavity to slow the delivery of the nitrosourea
The most common primary brain tumors are gliomas drug. Stereotactic radiosurgery can be used for
and meningiomas. local recurrences.
• Headache and seizures are among the most com- • Prognosis: poor 3- and 5-year survival.
mon presenting symptoms.
LOW-GRADE GLIOMAS (GRADE I
AND II ASTROCYTOMA)
PRIMARY BRAIN TUMORS
• Origin: astrocytes (glial cells) or ependymal cells.
GLIOMAS • Epidemiology: up to 10% of PBT; can occur
throughout the brain; in children, more common
Gliomas are a group of tumors that originate from in the cerebellar hemispheres.
glial cells, the supportive nonneuronal cells of the • More common in the fourth decade of life.
12887_CH19.qxd 10/4/08 3:29 PM Page 134
• Epidemiology: 6% to 9% of PBT; 30% of PBT in occur intracranially (with predilection for cerebral
children under age 3. In children, 90% are intracra- convexities, falx cerebri, and the sphenoid wing)
nial (often in the fourth ventricle) with ready sub- or within the spinal canal.
arachnoid spread. In adults, 75% arise within the • Epidemiology: second most common PBT after
spinal canal as intramedullary tumors of the spine. GBM; 15% to 20% of all PBT. More common in
• Pathology: perivascular pseudorosettes (a halo of women at ages 40 to 60. Incidence increases with
cells surrounding a central vascular lumen) are the age. Some genetic conditions are associated with
histologic hallmark. increased susceptibility to develop meningiomas,
• Presentation: intraventricular location can produce as with NF-2 (see Table 19-2), associated with ab-
obstructive hydrocephalus with raised intracranial normalities on chromosome 22.
pressure (papilledema, cranial nerve palsies, cere- • Pathology: histology shows sheets of plump, uni-
bellar dysfunction, etc.). Myxopapillary ependy- form meningothelial cells with the tendency to form
moma of the conus and cauda equina can produce whorls. Progesterone receptors found frequently.
conus medullaris or cauda equina syndromes. • Presentation: low growth; symptoms produced by
• Imaging: MRI enhancement is variable. local impingement on brain (seizures) and nerves
• Treatment: surgery to decrease tumor burden, fol- (weakness) or compression of nearby structures
lowed by radiation and chemotherapy. Recurrence (weakness, headache, apathy).
rates are high; close MRI follow-up is necessary. • Imaging: MRI usually shows a rounded extra-axial
• Prognosis: overall 10-year survival 45% to 55%, mass adjacent to dura. In general, isointense on T1
depending on tumor grade. and T2, with intense contrast enhancement and as-
sociated “dural tail” of enhancement (Fig. 19-3).
MENINGIOMA • Calcification seen on CT. Angiography can show
rich vascularization. Also noted on CT or plain x-
• Origin: arises from meningothelial (mesodermal) rays is “hyperostosis” (osteoblastic reaction) which
cells of the dura mater. Almost always benign. Can may represent tumor invasion of the bone.
Figure 19-3 • Axial and sagittal MRI scans of the brain showing a brightly enhancing meningioma (arrows). On the sagittal view,
the arrow tip is also pointing to the dural tail at the margin of the tumor.
(Reproduced with permission from Patel P. Lecture Notes: Radiology. Oxford: Blackwell Publishing, 2005:269.)
12887_CH19.qxd 10/4/08 3:29 PM Page 136
• Treatment: surgical removal, often preceded by • Presentation: fast growing tumor that infiltrates
endovascular embolization of the feeding vessels, surrounding tissue and extends toward the
but many lesions ⬍4 cm are treated with radio- fourth ventricle, producing hydrocephalus (with
surgery, with good control rates. Stereotactic ra- headache, unsteadiness, and vomiting); may
diosurgery such as gamma knife radiosurgery is spread via the CSF intracranially, and to the spinal
an option when resection or other radiation is dif- cord. Can also spread extracranially to bone and
ficult or dangerous. Recurrent meningiomas are bone marrow.
difficult to treat. • Imaging: MRI of the brain and the spinal cord,
• Prognosis: 5-year survival 70% to 95%; malignant with contrast, to evaluate subarachnoid metastasis.
transformation very rare. CSF studies for malignancy (if no contraindica-
tion). Bone scan and bone marrow aspiration are
MEDULLOBLASTOMA indicated due to the possible extracranial exten-
sion of the tumor.
• Origin: primarily at the medullary velum of the • Treatment: surgery plus radiation and chemother-
fourth ventricle (Fig. 19-4); up to 30% from the apy. Children ⬍3 years old are more susceptible to
cerebellar hemispheres. Among the primitive neu- adverse effect of radiation on brain development.
roectodermal tumors (PNET). In those cases, chemotherapy may allow the delay
• Epidemiology: almost 8% of PBT, and 30% of pedi- of radiation treatment. High recurrence rate.
atric brain tumors. • Prognosis: poor in children ⬍3 years, or with
• Pathology: small round cells with a high mitotic metastatic disease or subtotal resection. Good
index. prognostic factors include radical resection and ra-
diation dose above 50 Gy to the entire neuroaxis.
Under these conditions, recurrence-free survival is
about 50% at 5 years.
SCHWANNOMA
Figure 19-5 • Sagittal and coronal postcontrast MRI scans of the brain demonstrating a pituitary adenoma (arrows). Note that the
tumor is anterior to the brainstem and extends upward, compressing the optic chiasm.
(Reproduced with permission from Armstrong P, Wastie M, Rockall A. Diagnostic Imaging, 5th ed. Oxford: Blackwell Publishing, 2004:406.)
12887_CH19.qxd 10/4/08 3:29 PM Page 138
become large enough, they can compress neighbor- SECONDARY (METASTATIC) BRAIN
ing structures (optic chiasm, cavernous sinus, etc.),
producing focal symptoms. In general, diagnosis is
TUMORS
by imaging studies and laboratory evaluation of hor-
Metastases are the most common brain tumors and
monal status. Surgical removal may be through a
originate from malignant neoplasms outside the
trans-sphenoidal approach.
CNS. The most frequent metastatic brain tumors
Suprasellar craniopharyngioma is a slow-growing
originate in the lung, skin (melanoma), kidney (renal
tumor characterized by the benign nature of its cells
cell carcinoma), breast, and colon. Malignant cells
but malignant behavior of its growth. It accounts for
reach the brain via the bloodstream (crossing the
1% to 3% of intracranial tumors and 13% of
blood-brain barrier) or through Batson’s plexus
suprasellar tumors in adults and 50% in children. It
(pelvic and GI tumors). In general, metastatic lesions
tends to invade neighboring structures, complicat-
are located at the junction of white and gray matter
ing treatment. Tumors present with headache, vi-
and tend to be solitary, but multiple metastases are
sual disturbance, and endocrine dysfunction. The
not unusual. MRI with contrast is the preferred diag-
radiologic hallmark is the appearance of a suprasel-
nostic study (see Fig. 19-6). Treatment depends on
lar calcified cyst. Treatment can entail full surgical
the number of metastases, the immediate mass effect
resection, or minimal resection with radiation or
of the lesion, and the general status of the patient.
radiosurgery.
Single lesions can be resected, followed by whole
brain radiation or radiosurgery. Radiosurgery is used
more often for three or fewer lesions, especially if the
systemic disease is under good control—to prevent
the long-term side effects of whole brain radiation,
chemotherapy, or both. The prognosis is poor be-
cause metastases usually represent a more advanced
stage and extension of the primary cancer.
KEY POINTS
• “Drop metastases” are intradural extramedullary
spinal metastases that arise from intracranial le-
sions. The most frequent source is ependymomas
and medulloblastomas, but they can also be seen
with choroid plexus papilloma and other PBT.
• Medulloblastoma: avoid lumbar puncture unless CT
shows no obstructive lesion—to prevent cerebellar
tonsillar herniation due to increased intracranial
pressure.
• NF (neurofibromatosis)-2–associated tumors: bilat-
eral vestibular schwannomas, meningiomas, and
intramedullary ependymomas.
• In primary CNS lymphoma remember to evaluate
Figure 19-6 • Contrast-enhanced CT scan of the brain showing the patient’s immune status.
several metastatic lesions characterized by rounded areas of
hyperdensity. • Metastases that bleed easily include melanoma,
(Reproduced with permission from Armstrong P, Wastie M, Rockall A. renal carcinoma, and choriocarcinoma.
Diagnostic Imaging, 5th ed. Oxford: Blackwell Publishing, 2004:402.)
12887_CH20.qxd 10/4/08 3:30 PM Page 139
Chapter Demyelinating
Diseases of the
20 Central Nervous
System
down the spine when the patient flexes the neck, (a)
and a worsening of symptoms and signs in the heat,
termed Uhthoff’s phenomenon.
KEY POINTS
• MS is characterized by multiple lesions separated in
(b) Secondary progressive phase (with or without further
space and time. superimposed relapses)
• Almost any neurologic symptom can occur, de-
pending on the location and burden of lesions.
• Features characteristic of MS include ON, transverse
myelitis, INO, Lhermitte’s sign, and a worsening of
symptoms in the heat.
(c)
Figure 20-2 • MRI images of multiple sclerosis lesions, demonstrated on FLAIR sequences.
(Reproduced with permission from Ginsberg L. Lecture Notes: Neurology, 8th ed. Oxford: Blackwell Publishing, 2005:133.)
exam, as well, evidence of old optic nerve or other demyelination spreading upward from the corpus cal-
neurologic lesions should be sought. losum, termed Dawson’s fingers.
The two most useful laboratory studies are MRI and The characteristic CSF finding is oligoclonal
CSF analysis. On MRI, new MS lesions appear as dis- bands, found in more than 90% of MS patients at
crete T2-hyperintense areas in the white matter of the some point during their illness. These reflect in-
brain or spinal cord. Ovoid lesions are classic. Fluid- trathecal production of IgG antibodies by plasma cell
attenuated inversion recovery (FLAIR) sequences also clones. Although highly suggestive of MS, they can
show these lesions particularly well (Fig. 20-2). Acute also be found in other neurologic disorders. CSF
lesions may not be evident on T1-weighted images but studies during an acute relapse may show a moderate
may enhance with gadolinium. Old, chronic MS le- pleocytosis and elevated protein. Calculation of the
sions may become T1-hypointense, with a “black hole” IgG index, based on relative levels of IgG and albu-
appearance. MS lesions have a predilection for partic- min in the CSF and serum, can also suggest intrathe-
ular areas, including the periventricular white matter, cal antibody production.
juxtacortical regions, corpus callosum, and cerebellar Finally, visual evoked potentials can be used in
peduncles. Sagittal images may demonstrate foci of suspected MS to document evidence of old optic
12887_CH20.qxd 10/4/08 3:30 PM Page 143
neuritis. There is often an increased latency of the a common protocol. Although the effect of steroids
P100 wave on the affected side. on the long-term outcome is unclear, the duration of
acute relapses is often shortened. A well-publicized
trial demonstrated that intravenous steroids used to
KEY POINTS treat optic neuritis delayed but did not prevent the
subsequent development of MS.
• The diagnosis of MS begins with a thorough history The therapies used in the chronic treatment of MS
and examination, particularly directed toward iden- are immune-modulating agents (Table 20-2). These
tifying past episodes of neurologic dysfunction. include beta-1a interferon and beta-1b interferon,
• MRI is the best imaging modality to detect both which are available in injection form and have been
new and old MS lesions. shown to decrease the rate of relapses, the burden of
• The characteristic CSF abnormality is the presence lesions seen on MRI, and the rate of accumulated dis-
of oligoclonal bands. ability. Both are currently used in relapsing-remitting
• Visual evoked potentials may provide evidence of and some secondary progressive patients. Side effects
old optic neuritis. can include flu-like symptoms, depression, and injec-
tion-site reactions. It is important to check a CBC
and liver function test routinely; interferons may
cause leukopenia and reversible transaminitis.
PATHOLOGY Patients who are doing poorly on interferons may
have developed neutralizing antibodies to the inter-
The histologic appearance of an acute MS lesion is a ferons that reduce their effectiveness.
sharply defined area of myelin loss with relative Glatiramer acetate is a polypeptide formulation
preservation of axons and associated signs of perivas- injected subcutaneously that is also used in relapsing-
cular inflammation, including the presence of remitting patients. Mitoxantrone, a chemotherapeu-
macrophages, lymphocytes, and plasma cells. Reactive tic agent that may be useful in patients with
astrocytes may be present. Chronic MS lesions are worsening MS, has dose-limiting cardiotoxicity as a
hypocellular and have extensive glial proliferation. potential drawback.
In patients who no longer respond to the above
TREATMENT therapies, other immunosuppressive agents may be
used, including azathioprine, cyclophosphamide, and
Treatment for MS falls into three categories: acute methotrexate. Some use periodic pulses of cortico-
therapies for relapses, chronic therapies that treat the steroids. Of course these agents have a wide range of
underlying disease process, and symptomatic therapies accompanying toxicities.
that address the various complications of the disease. Several of the symptomatic complications that
Acute relapses of MS are most commonly treated accompany MS have specific treatments. Spasticity
with corticosteroids. A course of intravenous methyl- can be managed with baclofen, diazepam, or tizani-
prednisolone followed by an oral prednisone taper is dine. Bladder dysfunction can be managed with
anticholinergic agents (for urinary urgency) as well as CSF typically will show a lymphocytic pleocytosis
intermittent self-catheterization. It is particularly im- (usually with more cells than seen in MS) and an el-
portant to address urinary problems so as to prevent evated protein. Oligoclonal bands are rarely present.
recurrent infections, which can trigger MS relapses When the illness is indistinguishable clinically or ra-
and lead to chronic renal disease. Unfortunately there diologically from the initial episode of MS, defini-
are no effective treatments for tremor and ataxia, tive diagnosis of MS may not be possible unless or
which are common disabling symptoms. until a second episode of neurologic dysfunction
occurs.
Chapter
Infections of the
21 Nervous System
It is important for physicians to be familiar with the attempted passive extension at the knee when the
common types and manifestations of nervous system hip is flexed) and Brudzinski’s sign (an involuntary
infections for several reasons. First, this category of flexion at the hip[s] when the neck is flexed).
neurologic illness can be quite acute in presentation.
Additionally, nervous system infections can have Etiology
devastating and potentially life-threatening conse-
quences in some cases. Finally, for many of them, The most common organisms causing bacterial
specific therapies are tailored to the identified etio- meningitis vary depending on age of presentation.
logic organism. The introduction of vaccines against Streptococcus
pneumoniae (“pneumococcus”), Neisseria meningitides
(“meningococcus”), and Haemophilus influenzae has
BACTERIAL INFECTIONS successfully reduced the incidence of acute bacterial
meningitis among children in the United States. In
Three common and important forms of bacterial most cases, bacteria reach the subarachnoid space
nervous system infection are acute bacterial meningi- through hematogenous spread from the respiratory
tis, brain abscess, and spinal epidural abscess. tract, although bacterial meningitis may also be a di-
rect sequela of traumatic or mechanical invasion into
ACUTE BACTERIAL MENINGITIS the subarachnoid space, such as after neurosurgical
procedures or open head injury. It is also possible to
Clinical Findings have direct infiltration of the subarachnoid space
from parameningeal foci, such as the sinuses.
Acute bacterial meningitis is a medical emergency. It
is critical for all physicians to know its presentation,
its initial diagnostic evaluation, and the urgency with
Diagnostic Workup
which a potential case of bacterial meningitis needs The critical test in the diagnosis of acute bacterial
to be addressed. The cardinal findings include meningitis is cerebrospinal fluid (CSF) analysis from
headache, fever, and neck stiffness. Patients can also lumbar puncture (LP). Because of the concern that LP
be confused or have a depressed level of conscious- may precipitate brain herniation in the presence of a
ness, develop seizures, or have other focal neurologic focal intracranial mass with increased intracranial pres-
symptoms or signs, depending on the extent to which sure, it is generally accepted that head imaging (usually
the meningeal infectious or inflammatory process with CT, because it is available more readily) should be
also affects the brain parenchyma (causing menin- performed before LP when papilledema is present on
goencephalitis). Two classically described physical fundoscopic examination or if there are any focal signs
signs associated with meningitis, though not specific on neurologic examination suggesting the possibility of
to the bacterial form, are Kernig’s sign (pain upon an intracranial lesion. Some physicians advocate head
145
12887_CH21.qxd 10/4/08 3:31 PM Page 146
Treatment
Figure 21-1 • Parasagittal MRI showing a multilocular brain ab- Prolonged courses of intravenous antibiotics are the
scess. The MRI was performed with a gadolinium and shows
mainstay of treatment for spinal epidural abscesses,
ring enhancement of the lesion with surrounding edema.
(Reproduced with permission from Ginsberg L. Lecture Notes: Neurology. although in some cases neurosurgical drainage is
8th ed, Oxford: Blackwell Publishing, 2005:113.) necessary. When a clinical syndrome of acute cord
compression or cauda equina involvement is present,
surgical decompression may be required urgently.
SPINAL EPIDURAL ABSCESS
Clinical Findings
KEY POINTS
Spinal epidural abscesses typically present with the
combination of neck or back pain and focal neurologic • Abscesses affecting the central nervous system are
signs consistent with spinal cord compression or mass lesions that are often ring-enhancing on radio-
cauda equina involvement, depending on the level of logic studies with contrast.
the abscess. For thoracic or lumbar abscesses, these • They present with focal neurologic signs that
signs may include lower extremity weakness, sensory are dependent on their intracranial or spinal
loss with a detectable sensory “level” on examination, location.
and urinary and sexual dysfunction, while for cervical • Prolonged courses of intravenous antibiotics are
abscesses the upper extremities may be involved as the mainstay of treatment, but surgical drainage is
well. Fever is not necessarily present. Symptoms may necessary sometimes.
come on acutely or more insidiously; an acute presen-
tation often suggests associated spinal cord infarction.
TUBERCULOUS INFECTION
Etiology
Spinal epidural abscesses can be sequelae of spinal Tuberculosis, though less common in the United
instrumentation, including epidural or spinal anes- States, is a prevalent infection throughout much of
thetic introduction and spine surgery. In these cases the world. Mycobacterium tuberculosis affects the
the responsible organisms are often skin pathogens nervous system in a number of recognized ways: tu-
such as staphylococcal species. Abscesses can also be berculous meningitis, intracranial tuberculomas, and
the result of spread from more anterior infections, Pott disease (tuberculoma of the spine).
including vertebral body osteomyelitis or diskitis.
Tuberculous Meningitis
Diagnostic Workup Tuberculous meningitis arises from hematogenous
Spine imaging is generally indicated when there is clin- dissemination of mycobacteria from a pulmonary
ical suspicion based on history and physical examina- source. A number of features distinguish tuberculous
tion of an intraspinal lesion such as an epidural abscess. meningitis from acute pyogenic bacterial meningitis
In general, the administration of contrast (with either (described previously). First, meninigitis caused by
12887_CH21.qxd 10/4/08 3:31 PM Page 148
Mycobacterium tuberculosis has a predilection for vertebral bodies often suggests this diagnosis rather
affecting the basal meninges (those at the base of the than metastatic cancer. Treatment includes antituber-
brain) and thus can present with cranial nerve palsies culous drugs and spine stabilization procedures if
in addition to the usual features of acute bacterial necessary.
meningitis. Also, a basal meningitis more commonly
leads to hydrocephalus or brain infarcts from inflam-
mation affecting cerebral vessels. Second, tubercu-
lous meningitis tends to have a more subacute or
KEY POINTS
chronic, insidious presentation than acute bacterial • Tuberculosis affects the nervous system in several
meningitis, so a prolonged prodrome of malaise and different ways, including meningitis, focal brain
fairly nonspecific constitutional symptoms may pre- lesions, or focal spine lesions.
cede the appearance of frank neck pain or stiffness. • Tuberculous meningitis has a predilection for the
Finally, the cerebrospinal fluid profile in tuberculous basal meninges, is typically insidious, can present
meningitis typically demonstrates a leukocytosis with with cranial nerve palsies, and has a different CSF
lymphocytic predominance, rather than polymor- profile from bacterial meningitis.
phonuclear predominance (except initially), and the
• Pott’s disease, or tuberculosis of the spine, affects
CSF glucose is often very low. Acid-fast bacilli stain- the nervous system when there is direct invasion
ing of the CSF can identify mycobacterial infection, into the epidural space.
but cultures of this organism can take weeks to grow
and may never actually become positive. Polymerase
chain reaction (PCR) testing of mycobacterial
antigens is available, however. Treatment of tubercu- LYME DISEASE
lous meningitis requires a regimen of multiple antitu-
berculous drugs that penetrate the intrathecal space Lyme disease, caused by the spirochete Borrelia
effectively. burgdorferi and transmitted by the deer tick, is a com-
mon infection in the northern United States and in
Intracranial Tuberculoma Europe. Lyme disease affects the nervous system in
several recognizable ways, including Lyme-associated
Tuberculomas are mass lesions caused by M. tuber- meningitis, cranial nerve palsies, and a syndrome of
culosis infection. Although uncommon in the United polyradiculopathy.
States, tuberculomas are one of the most common
focal brain lesions in the developing world.
Typically, they present with features that would be Clinical Findings
expected for any inflammatory mass lesion within While the typical rash of erythema chronicum migrans
the brain, including headache, focal neurologic can occur within the first week after a bite from an
symptoms and signs, and seizures. They can calcify, infected tick, neurologic manifestations typically do
be variably enhancing on radiologic studies with con- not appear until the more disseminated stage of
trast, and are sometimes associated with hydro- Lyme disease, several weeks after the bite. Headache,
cephalus. Radiologic differential diagnosis typically neck stiffness, and myalgias may develop into more
includes brain tumor, bacterial abscess, or cysticer- frank signs of meningismus along with cranial nerve
cosis (see below). Appropriate treatment includes palsies (most commonly affecting the facial nerve,
prolonged courses of antituberculous therapy and either unilaterally or bilaterally). In the persistent
neurosurgical intervention if needed. stage of systemic disease, several months after the ini-
tial bite, polyradiculopathy (often with significant
Pott’s Disease pain), polyneuropathy, and/or encephalopathy (with
signs of white matter signal change) may occur.
Pott’s disease, or tuberculosis of the spine, typically
presents with neurologic symptoms and signs when
Diagnostic Workup
vertebral body infection extends into the epidural
space, leading to subacute spinal cord or cauda equina Serologic tests of the blood or CSF can be diagnostic,
compression, depending on the level of involvement. but sometimes not until late in the course of the dis-
Fever and back pain are common. Spread to adjacent ease. The routine CSF profile typically demonstrates
12887_CH21.qxd 10/4/08 3:31 PM Page 149
a lymphocytic pleocytosis with elevated protein and course, are unrevealing. Testing the blood and CSF for
normal glucose. A PCR assay of the CSF is available virus-specific serologies and PCR assays can be useful
for spirochetal antigen. In cases of encephalopathy, in identifying the responsible virus. Treatment gener-
MRI of the brain can sometimes show patchy foci of ally involves just supportive care, unless HSV1 is
signal change in the white matter, while in cases of suspected (see below).
peripheral nervous system involvement EMG/nerve
conduction studies may be useful. ENCEPHALITIS
Chapter
Disorders of the
22 Spinal Cord
The central nervous system (CNS) comprises the ating joint position sense. They remain ipsilateral to
brain and spinal cord. The spinal cord extends from their origin for the length of the spinal cord, crossing
the medulla, through the foramen magnum, down in the brainstem. Fibers of the anterolateral spinothal-
the spinal canal, about 45 cm (in adults) to the filum amic tracts begin in the peripheral nerves subtending
terminale, a connective tissue band anchoring the pain and temperature sensation, enter the cord and
cord to the end of the canal. The brain and spinal synapse within two levels, and then cross the cord and
cord are protected from external forces by the sur- ascend contralateral to the limbs from which they
rounding bones (the skull and vertebrae), and by the convey sensation.
meninges, particularly the tough, resilient connective The spinal cord gives off motor nerve roots ante-
tissue of the dura mater. They are also protected riorly and sensory roots posteriorly at each level.
chemically by the blood-brain (or blood-CNS) bar- Seven cervical nerves exit the canal just above the
rier. The spinal cord is the classic example of the ap- corresponding vertebrae, but there is no C8 verte-
plicability of neuroanatomy to clinical localization in bra; the C8 nerve root exits just above the first tho-
Neurology and thus to determining diagnosis and racic vertebra. C1 has no sensory fibers. Below this,
treatment plans. So it is crucial to review the basic nerves exit below the corresponding vertebral bod-
anatomy. ies, from T (thoracic) 1 to T12, L (lumbar) 1 to L5,
and S (sacral) 1 to S5. The corresponding level of the
cord itself is typically a few bony levels above the
ANATOMY roots—e.g., the T10 level of the cord itself may lie
adjacent to the T8 vertebra. The spinal cord ends at
In cross section, the center of the spinal cord con- about the L1 vertebral level. (Thus, it makes no
tains the gray matter and neuron cell bodies sense to scan the lumbar spine to visualize a spinal
(Fig. 22-1). The anterior horn of the grey matter cord lesion!)
contains primarily the alpha motor neurons and
motor fibers innervating skeletal muscles.
Surrounding the gray matter are white matter tracts.
The most important descending motor tract is the KEY POINTS
corticospinal tract (CST) in the lateral portion of
the cord. The CST descends from the cortex and • The corticospinal tract is the primary descending
crosses the midline in the medulla to become con- motor tract. It crosses in the medulla.
tralateral to its cortical origins and thus ipsilateral to • Ascending dorsal column fibers carry position
the limbs it controls once below the brainstem (Fig. sense; they cross in the brainstem.
22-2). The CST synapses on alpha motor neurons in • The spinothalamic tract carries information on pain
the anterior horn. and temperature; it crosses the cord near the level
Among several ascending sensory tracts are the of entry.
heavily myelinated posterior (dorsal) columns, medi-
152
12887_CH22.qxd 10/4/08 3:31 PM Page 153
local (e.g., root) signs, the level of the lesion cannot spinal levels and be missed easily on radiologic studies,
be determined exactly, and the examination must appearing very similar to a sheath or other lining of the
focus carefully on all higher levels. spinal canal. Clinical suspicion must remain high for
epidural abscesses because they are so dangerous, diffi-
cult to detect (even with good radiologic technology),
SPINAL CORD SYNDROMES and generally quite treatable with surgical drainage and
antibiotics. (See also Chapter 21 on infections.)
TRANSECTION Compressive lesions within the dura but outside of
the spinal cord itself (“intradural, extramedullary”),
Severe trauma may cause complete transection of the include meningiomas and neurofibroma masses.
spinal cord. Localization proceeds according to the Other lesions such as multiple sclerosis plaques and
principles above. If transection occurs above the level CNS gliomas can occur within the cord itself
of the C3–C5 nerve roots (which control the (“intramedullary”). Primary spinal cord tumors are
diaphragm), respiratory insufficiency may result. rare.
Though apparently above the level of the lesion, a
Horner’s syndrome may result from cervical cord dis-
ease due to the transit of sympathetic fibers through HEMICORD SYNDROMES
the upper cervical spinal cord. Abdominal reflexes
are lost with lesions above T6. Bowel and bladder When one side of the spinal cord is affected by an
dysfunction may follow lesions above the sacral cord injury or other lesion, this can be manifested as a
level. A transverse myelitis may produce a similar “hemicord” or Brown-Sequard syndrome. Classic
clinical picture and may mimic a transection, but it localization in Neurology diagnoses these lesions
usually develops over a longer period and eventually readily. There is weakness (and usually hyperreflexia)
with evidence of inflammation, such as a spinal fluid ipsilateral to and below the lesion due to dysfunction
pleocytosis. of the corticospinal tract, as well as impaired position
sense below the lesion from involvement of posterior
column fibers ascending on the same side. Loss of
SPINAL CORD COMPRESSION pain and temperature perception below the level of
the lesion, however, is contralateral to the lesion
Spinal cord compression is a neurologic emergency because nerve fibers subtending pain and tempera-
although it may evolve over hours to days. ture sensation begin contralaterally and cross below
Lesions causing spinal cord compression can be the level of the lesion. A Brown-Sequard syndrome
extradural, intradural but extramedullary, or can be caused by trauma or by cord compression, and
intramedullary. Extradural (outside of the dural lin- occasionally by multiple sclerosis or other illnesses.
ing) lesions are relatively common causes of cord
compression. The lesions are often in the bones or are
in the intervertebral disks. Bony lesions from metasta- CENTRAL CORD LESIONS
tic cancer (especially from breast and prostate cancer)
are relatively common causes of cord compression. A structural abnormality in the center of the spinal
Usually, they are associated with significant pain due cord particularly affects spinothalamic tract fibers
to the bony disease; compression of the cord itself crossing at the level of the lesion. Deficits in pain and
does not hurt. Pressing or percussing on all levels of temperature sensation are usually bilateral and over
the vertebral column is important in looking for bony several segments. Thus, there can be a “cape-like” loss
lesions. Other masses such as epidural abscesses and of these sensations over the shoulders and arms, with
hematomas can produce acute and threatening cord preservation of the same sensations above and below
compression. the lesion (Fig. 22-3). The sensory loss is described as
Epidural abscesses can follow skin infections or “dissociated” because pain and temperature sensation
tuberculosis or many other infections and may spread is affected, but touch and position sense is not. In ad-
from a local osteomyelitis. They are often associated dition, a variety of motor and sensory functions can
with radicular and other local pain. They can produce be impaired below the lesion.
cord compression with loss of motor and sensory func- The classic central cord lesion is syringomyelia, an
tion below the lesion. They can extend over several expansion of the (potential) fluid space in the center
12887_CH22.qxd 10/4/08 3:32 PM Page 155
LMN signs
Spastic paraparesis
of the spinal cord, usually over several levels. Sensory Figure 22-4 • Sagittal MRI scan of the spinal cord showing a
deficits are most common, as the crossing spinotha- hypointense region in the middle of the cord that represents a
fluid-filled syrinx cavity (large black arrow). This syrinx is associ-
lamic tracts are affected with enlargement of the cav- ated with a type I Chiari malformation characterized by the
ity. Numbness may begin in the hands; loss of alpha downward displacement of the cerebellar tonsils through the
motor neurons in the same area may lead to wasting foramen magnum (small black arrow).
and weakness, often developing over months or years. (Reproduced with permission from Ginsberg L. Lecture Notes: Neurology.
Spasticity is usually a later sign. Loss of pain and tem- 8th ed, Oxford: Blackwell Publishing, 2005:123.)
MULTIFOCAL AND DIFFUSE CORD cephalad portion of the ASA arises from branches of
DYSFUNCTION the two vertebral arteries, joining at the top of the
cord. Caudally, the largest single artery supplying the
Some illnesses affect the cord more diffusely. ASA is the artery of Adamkiewicz, originating from
Radiation therapy and paraneoplastic syndromes perforating arteries from the aorta (of which there
affect the cord broadly. Radiation myelopathy are several), entering the spinal canal at about the
develops 6 months to years after radiotherapy. L2 level. This large artery supplies blood superiorly
Syphilis can affect posterior columns preferentially through much of the thoracic cord. The anterior
(tabes dorsalis), although this is rare now. Vitamin horns and corticospinal tracts are perfused primarily
B12 deficiency can cause posterior column dysfunc- from the ASA. Supplying the dorsal columns posteri-
tion. Demyelinating and vascular lesions may be orly is a plexus of many arteries rather than one large
multifocal. vessel, in turn fed by segmental arteries that arise
from the aorta and course along the ribs, giving off
radicular arteries next to the nerve roots near
the cord.
CAUDA EQUINA AND CONUS The spinal cord, like the brain, can incur a stroke
LESIONS when the blood supply is compromised, usually by
atherosclerotic disease and occasionally by vasculi-
Cauda equina lesions are those affecting the spinal tis. Strokes can occur following systemic or local
nerve roots within the spinal canal in the lumbar hypotension, or by occlusion of a vessel, sometimes
and sacral regions, without affecting the spinal cord when injured during aortic surgery or by dissection.
itself. Cauda equina lesions produce wasting, weak- The most common form of cord stroke is the ante-
ness, and fasciculations in the appropriately inner- rior spinal artery syndrome. This causes weakness
vated muscles, often with substantial pain. Sacral below the lesion, and there may be intense radicular
root dysfunction can cause bowel, bladder, and sex- pain or back pain and sphincter dysfunction.
ual dysfunction. Cauda equina syndromes can be Sensory loss is prominent, but usually not involving
produced by narrowing or obstruction of the spinal position sense because posterior column function is
canal in the lumbosacral region, by infections, and unaffected in this syndrome—a major neurologic
by central disks below the level of the spinal cord. examination clue to the diagnosis. The thoracic cord
At the tip of the spinal cord, there are lesions of is the least well perfused and most vulnerable area.
the conus medullaris, which includes centers con- The border between the vascular supply from the
trolling bowel, bladder, and sexual function. Causes vertebral arteries above and the inferior blood sup-
include compressive lesions and intramedullary ply may reach up to about T4, and that can be
abnormalities such as tumors. Lesions here can pro- the clinical level of cord dysfunction. Systemic
duce a mixture of upper motor neuron findings such hypotension can lead to a watershed infarct affect-
as hyperreflexia, Babinski signs, and particularly ing this area.
prominent sphincter dysfunction, as well as radicu- Strokes are diagnosed clinically; MRI can show the
lar pain. If they remain below the lumbar cord, lesion in many cases. Angiography of the spinal cord
conus lesions may leave leg strength and reflexes vessels is very difficult and may lead to complica-
intact while severely affecting bowel, bladder, and tions. With the sudden deficit, investigations are usu-
sexual function. ally too late to help. There are no good treatments for
spinal cord infarction. The prognosis is uncertain but
often poor.
VASCULAR DISEASE OF THE SPINAL Strokes also include hemorrhages, and hematomas
CORD AND THE ANTERIOR SPINAL can cause serious cord deficits. Venous infarctions
ARTERY SYNDROME occur very rarely; some result from coagulopathies.
Emboli to the cord are rare. Spinal AVMs are often
The blood supply for the anterior two-thirds of the very difficult to diagnose and may present in a stut-
spinal cord comes primarily from the large solitary tering fashion over months or years. Dural arteriove-
longitudinal anterior spinal artery (ASA) running nous malformations may cause slowly progressive
along most of the ventral surface of the cord. The spinal cord deficits.
12887_CH22.qxd 10/4/08 3:32 PM Page 157
different in presentation at different ages, and often abnormalities. Some are evident on inspection of the
clearly genetic in origin. SMAs present (usually in lower back; most can be diagnosed with MRI as
childhood) with weakness and atrophy from anterior prompted by clinical suspicion, and many produce se-
horn cell degeneration. Werdnig-Hoffmann disease is vere neurologic deficits.
an SMA presenting in infancy. Evaluation is most Herniated disks may compress the spinal cord in
appropriately done by pediatric neuromuscular spe- the cervical (or rarely thoracic) region. Herniated
cialists with command of the neurophysiology and lumbar disks may compress lumbar nerve roots, often
genetic testing. causing significant pain and eventually, wasting and
weakness of innervated muscles. Bowel and bladder
dysfunction may occur with compression of sacral
KEY POINTS roots. With severe pain and with motor deficits, sur-
gical removal of the herniated disc can be curative,
• ALS is a relentlessly progressive degenerative but some extruded disks are reversible on their own
disease leading to loss of anterior horn cell and with time.
peripheral nerve function, with weakness and signs
of denervation.
• It also affects the corticospinal tracts, causing SPINAL CORD DIAGNOSTIC TESTS
spasticity and additional loss of motor control.
Many different radiologic techniques can help in eval-
• Patients with ALS often die within a few years of
uating spinal cord problems. Plain x-rays can show
diagnosis, often from respiratory failure.
bony abnormalities, such as dislocation of the verte-
• When considering a diagnosis of ALS, it is important bral bodies. Lateral views can show one vertebra
to look for other (treatable) diagnoses such as displaced significantly enough on another (spondy-
extensive spine disease. lolisthesis) to produce spinal cord or root dysfunction.
Plain x-rays may show lytic lesions of the vertebrae
from metastases, leading to spinal cord compression.
CT scanning is also very helpful with bony abnormal-
CONGENITAL AND DEGENERATIVE ities, especially when the clinical examination indi-
ILLNESSES OF THE SPINE cates the axial level to be scanned. MRI can produce
excellent longitudinal (sagittal) views of the entire
Many congenital abnormalities affect the spinal cord. length of the spinal cord. T2 and FLAIR sequences
A syrinx in the cervical cord, or even extending ros- can help to show intrinsic lesions of the spinal cord,
trally into the brainstem, can be associated with a such as tumors (sometimes with expansion of the
Chiari malformation (a downward protrusion of the cord itself), multiple sclerosis, and other inflamma-
medulla, with or without the cerebellum, through the tory tissue changes, including those of a transverse
foramen magnum). At the caudal end of the canal, myelitis. Vascular lesions such as strokes and hemor-
failure of proper closure of the neural tube can result rhages are often demonstrated well. CT and MRI axial
in midline structural deficits referred to as “dys- images can show root compression from disks or other
raphisms,” some as mild as pilonidal cysts in the lum- structural abnormalities. The sagittal MRI is often
bar midline. Spina bifida is an incomplete closure of particularly helpful in the diagnosis of a central cord
the posterior parts of the vertebrae; it may be asymp- lesion such as a syrinx and may help to show an
tomatic. More severe deficits include larger openings epidural abscess or other lesions. Myelograms (with
of the spinal canal such as a meningocele (protrusion contrast material in the spinal fluid) are performed
of the meninges into the tissues of the back beyond infrequently now, but occasionally they can demon-
the spinal canal) or even myelomeningocele—with strate vascular abnormalities around the spinal cord or
protrusion of spinal cord tissue itself. The more severe other structural problems, especially in cauda equina
lesions are associated with paraplegia and maldevel- roots, that are not seen well on other tests. Evoked
opment of the legs. There are many related congeni- potentials can demonstrate poor conduction in the
tal abnormalities. Hypertrophy of the filum terminale sensory tracts of the spinal cord, but they are used sel-
can produce a “tethered cord syndrome,” with pain dom since the development of MRI. Cerebrospinal
and dysfunction of the spinal cord, especially at lower fluid from a lumbar puncture can provide evidence of
levels. This is often associated with other structural infection, inflammation, or malignancy.
12887_CH23.qxd 10/4/08 3:33 PM Page 159
Chapter
The Peripheral
23 Nervous System
The peripheral nervous system (PNS) consists of The next step is to recognize a pattern of PN that
cranial nerves, spinal roots, peripheral nerves, neu- will help to determine the etiology of the disease
romuscular junction, muscles, and autonomic gan- (Table 23-1). Finally, characterize the primary
glia. Afferent fibers connect the sensory receptors to pathologic process by using electrodiagnostic
the CNS, and efferent fibers connect the CNS to studies, including nerve conduction studies and
the effector (motor) apparatus. Three classically de- EMG.
scribed pathologic changes affect peripheral nerve
axons:
• Wallerian degeneration: After injury to axons and KEY POINTS
myelin, a distal disintegration of axon and myelin
occurs. • The symptoms associated with involvement of small
nerve fibers are neuropathic pain (described as
• Neuronal (or axonal) degeneration: This develops
aching, shooting, throbbing, or burning); tempera-
after damage to the cell body of the neuron, re-
ture sensations; and autonomic dysfunction (cardiac
sulting in the distal dying of the axon and subse-
arrhythmias, orthostatic hypotension, impotence,
quent loss of myelin.
incontinence, and constipation).
• Demyelination: The myelin sheath is lost as a
result of this process. • The symptoms and signs associated with involve-
ment of large fibers are loss of vibration and joint
position sense, weakness, fasciculations, and loss of
APPROACH TO PERIPHERAL deep tendon reflexes.
NEUROPATHY
The goals in the evaluation of peripheral neuropathy
(PN) are to localize the site of disease to the axon, INVESTIGATION OF THE
myelin sheath, cell body, or vascular structures; iden- PERIPHERAL NERVOUS SYSTEM
tify the cause; and prescribe treatment when avail-
able. A logical and rational approach to the diagnosis of
Start by determining the types of symptoms peripheral nervous system (PNS) disorders is funda-
(motor, sensory, autonomic, or mixed); the distribu- mental. Tests are ordered sequentially, guided by
tion of weakness (proximal or distal, symmetric or the history, and clinical and electrodiagnostic find-
asymmetric); the nature and distribution of sensory ings. In general, first-line tests include CBC, ESR,
involvement (small fiber, large fiber, or mixed); and and rheumatoid profiles (for collagen disease,
the evolution of the condition (acute, subacute, or leukemia, vasculitis); renal and liver function tests
chronic) (Box 23-1). (for uremic and hepatic disease); glucose and Hb-
159
12887_CH23.qxd 10/4/08 3:33 PM Page 160
䊏 BOX 23-1 Approach to the Classification of protein (Guillain-Barré syndrome, chronic inflam-
matory demyelinating polyneuropathy); CSF pleo-
Peripheral Neuropathy
cytosis (Lyme disease, AIDS, paraneoplastic);
Functional involvement serum HIV test (AIDS neuropathy); Lyme titers;
Motor anti-Hu Ab (paraneoplastic); anti-GM1, MAG Ab
(autoimmune neuropathy); and genetic testing for
Sensory
hereditary neuropathy.
Small fiber Electrodiagnostic studies include nerve conduc-
Large fiber tion studies and EMG. A nerve biopsy should be
Small and large fiber performed when indicated.
Autonomic
Anatomic distribution EPIDEMIOLOGY
Asymmetric
Symmetric The prevalence of PN among patients with no rec-
ognized exposure to diseases or neurotoxic agents is
Upper extremity
2%. Diabetes mellitus is the most common risk
Lower extremity factor, followed by alcoholism, nonalcoholic liver
Temporal course disease, and malignancy. Among patients with one or
Acute: GBS, porphyria, diphtheria, polio, toxins two risk factors, the prevalence is 12% and 17%,
(thallium, lead, arsenic, Adriamycin), respectively.
paraneoplastic, uremia, vasculitis The most common causes of PN in the United
Subacute: deficiency states (vitamins B1 and B12),
States are hereditary (30%), followed by cryptogenic
toxins, uremia, diabetes, sarcoidosis, (23%), diabetes mellitus (15%), multifocal motor
paraneoplastic, vasculitis, toxins, drugs neuropathy (MMN), vitamin B12 deficiency, and
drugs (Box 23-2).
Chronic: CIDP, diabetes, uremia
Relapsing: CIDP
Pathologic mechanism
Axonal
Demyelination KEY POINTS
Combined neuropathy • A mnemonic for the most common causes of pe-
CIDP, chronic inflammatory demyelinating polyneuropathy; GBS,
ripheral neuropathies is DANG THE RAPIST: dia-
Guillain-Barré syndrome. betes, alcohol, nutritional, Guillain-Barré, trauma,
hereditary, environmental (toxins and drugs), rheu-
matic (vascular), amyloid, paraneoplastic, infec-
tions, systemic disease, and tumors.
A1C levels (diabetes); vitamin B12 and folate levels • Polyneuropathy refers to symmetric involvement
(neuropathy with macrocytosis); thyroid function of the peripheral nerves, usually of the legs more
than the arms and distal more than proximal seg-
tests (hypothyroid neuropathy); and serum protein
ments—the “stocking-glove” pattern.
electrophoresis and urine protein electrophoresis
(dysproteinemias, monoclonal gammopathy, lym- • Mononeuropathy refers to involvement of a
phoma, amyloidosis). single nerve—for example, median neuropathy
Second-line tests include urine porphobilinogen at the wrist, also known as carpal tunnel syn-
(acute intermittent porphyria); urine heavy metals drome.
such as lead, arsenic, and mercury; arsenic in hair • Mononeuropathy multiplex refers to involvement
and nails (arsenic neuropathy); hepatitis B antigen of individual nerves in a multifocal distribution.
(Ag), antineutrophil cytoplasmic antibodies (Abs) • Radiculopathy refers to involvement of nerve
(Wegener’s granulomatosis); CT scan of the chest roots (Table 23-4).
(cancer survey, carcinomatous neuropathy); CSF
12887_CH23.qxd 10/4/08 3:33 PM Page 161
disappear after 3 days. Over 50% of patients develop and possible conduction block. Early EMG changes
facial weakness, and 10% have extraocular muscle include decreased motor unit recruitment. Routine
paralysis. Pain is common. Autonomic dysfunction laboratory evaluation should include CBC, ESR, liver
may be present, with orthostatic hypotension, tran- function tests, and HIV test. The differential diagno-
sient hypertension, and cardiac arrhythmias. sis includes spinal cord disease such as transverse
The Miller-Fisher variant is characterized by gait myelitis and acute neuromuscular junction problems
ataxia, areflexia, and external ophthalmoplegia, usu- (myasthenia) or myopathy.
ally without limb weakness. Nerve conduction
studies are normal, and anti-GQ1b Abs are positive in
90% of cases. Treatment
Patients should be hospitalized. Monitoring should
include frequent measurement of the forced vital ca-
Diagnostic Evaluation pacity (FVC) and negative inspiratory pressure. An
Albuminocytologic dissociation in the CSF (elevated FVC below 15 mL/kg warrants transfer to the inten-
protein but few or no cells) is characteristic. Usually sive care unit and likely intubation. Medical treat-
the CSF protein rises after the first few days. Early ment includes intravenous immunoglobulin (IVIg) or
electrodiagnostic findings may include prolonged dis- plasmapheresis (equally effective). Intravenous
tal latencies, variably prolonged or absent F waves, steroids are not proven to be beneficial.
12887_CH23.qxd 10/4/08 3:33 PM Page 163
progressive sensory loss in the lower extremities intensive care unit for more than 2 weeks. The etiol-
(stocking distribution, beginning with toes and feet ogy is unclear; often it may be related to an infection.
before hands). Autonomic insufficiency can be an Electrodiagnostic studies show an axonal neuropathy.
important feature. Weakness is a late feature.
HEREDITARY NEUROPATHIES
Diagnostic Evaluation
Diagnosis is straightforward in established diabetes Hereditary neuropathies are the most prevalent in-
with typical clinical findings. It is an axonal polyneu- herited neurologic disease and also the most common
ropathy, usually involving small and large fibers. cause of polyneuropathy in patients referred to neu-
rologic clinics in Western countries.
Charcot-Marie-Tooth disease (CMT) is the most
Treatment
common inherited PN, with an estimated prevalence
Glucose control is the best treatment. Symptomatic of 40 per 100,000 adults and 19 per 100,000 chil-
management of neuropathic pain includes the use of dren. CMT typically presents in adolescence with
NSAIDs, tricyclic antidepressants, duloxetine, or an- symmetric, slowly progressive distal muscular atro-
ticonvulsants such as gabapentin, pregabalin, lamot- phy of the legs and feet; in most cases, it eventually
rigine, and others. involves the hands. Hammer toes and pes cavus are
common. The age of onset, severity, and rate of pro-
gression can vary, even within the same family.
KEY POINTS
• Diabetic polyneuropathy is the most common and
important of the diabetic neuropathies.
KEY POINTS
• It usually involves small and large fibers. • CMT-2 is the only axonal motor neuropathy of the
• The neuropathy is distal and symmetric, with a CMT family; the others are primarily demyelinating.
stocking-glove distribution. • Hereditary sensory and autonomic neuropathy
• Neuropathic pain may respond to anticonvulsants (HSAN) is a hereditary neuropathy that affects auto-
such as gabapentin. nomic sensory or motor nerves.
• There is no specific drug or gene therapy for hered-
itary neuropathies.
DIAGNOSTIC EVALUATION
ENTRAPMENT NEUROPATHIES
Investigations include recording cardiovascular, sudo-
Entrapment neuropathies are a common group of motor, gastrointestinal, genitourinary, respiratory,
mononeuropathies produced by nerve entrapment and pupillary autonomic functions. These include
(pressure, stretch, friction, and so forth). They are re- heart rate (R to R) variability with different maneu-
viewed in Table 23-3. vers (deep breath, Valsalva, etc.), tilt-table testing,
sudomotor responses (quantitative sudomotor axon
reflex test [QSART]), and plasma and urinary cate-
KEY POINTS cholamines. The evaluation aims to assess the degree
of autonomic system dysfunction with emphasis on
• Leprosy is among the most common causes of neu-
localizing the site of the lesion. Additional testing
ropathy in the world.
will help to determine the cause of the dysfunction
• HIV neuropathies are common. (primary or secondary).
• Tips to remember about peripheral neuropathies
are found in Table 23-5.
TREATMENT
Myasthenia gravis (MG) and the Lambert-Eaton sodium channels that line the troughs of the endplate
myasthenic syndrome (LEMS) are the two most com- membrane folds, resulting in muscle contraction. The
mon diseases of the neuromuscular junction (NMJ) action of acetylcholine is terminated when it is metab-
(Table 24-1). Fatigable muscle weakness is the defin- olized by acetylcholinesterase in the synaptic cleft.
ing clinical feature of these disorders. In order to un-
derstand the clinical manifestations, pathophysiology,
and approach to the treatment of these diseases, it is MYASTHENIA GRAVIS
necessary to have some understanding of the anatomy
and physiology of the NMJ. Nerve and muscle have Acquired MG is an immunologic disorder in which
both undergone structural and functional special- antibodies are directed against the postsynaptic
ization at the NMJ, their point of contact. At the (muscle) nicotinic acetylcholine receptor (nAChR).
presynaptic bouton, secretory vesicles containing Blockade and downregulation of these nAChRs re-
acetylcholine are concentrated at active zones formed duce the probability that a nerve impulse will gen-
by clusters of P/Q-type voltage-gated calcium chan- erate a muscle action potential.
nels. Across the synaptic cleft, the muscle membrane
is thrown into folds at what is known as the muscle EPIDEMIOLOGY
endplate. Acetylcholine receptors are clustered at the
peaks of these folds. Depolarization of the nerve ter- Acquired MG is the most common disorder of NMJ
minal, mediated by a sodium-dependent action poten- transmission. Its incidence is bimodal, with a peak in
tial, leads to activation of the voltage-gated calcium the second and third decades of life (during which
channels, which in turns leads to calcium influx into women are more commonly affected) and a peak in
the presynaptic bouton. The rise in intracellular cal- the seventh and eighth decades (when it is more
cium triggers the release of acetylcholine via a process common in men). Earlier-onset MG is often associ-
known as exocytosis, whereby the synaptic vesicles ated with thymic hyperplasia, whereas thymoma is
dock at the active zones and then fuse with the seen more commonly in the patients with later-onset
presynaptic membrane to release their contents into disease.
the synaptic cleft. The acetylcholine molecules dif-
fuse across the cleft to bind to the acetylcholine re-
ceptors. This generates an inward sodium current PATHOGENESIS
through the acetylcholine-receptor ion pore, which
leads to depolarization of the muscle endplate. This, In acquired MG, antibodies are directed against the
in turn, triggers activation of the voltage-dependent postsynaptic nAChR. These antibodies directly
169
12887_CH24.qxd 10/4/08 3:35 PM Page 170
block the binding of acetylcholine and lead to a toward demonstrating weakness and fatigability. The
complement-mediated attack and internalization of patient should be asked to sustain a gaze or limb pos-
receptors. The result is distortion of the endplate ture for a few minutes as well as following a brief
with loss of the normal postjunctional folds and a re- period of exercise or repetitive muscle activity. DTRs
duction in the concentration of the receptors. Thus, are usually preserved or, if reduced, are in proportion
even though acetylcholine is released normally from to the degree of muscle weakness.
the presynaptic bouton, its effect at the endplate is Most patients with MG have generalized disease,
reduced, with the result that the nerve impulse is but as many as 15% may have involvement restricted
less likely to generate a muscle action potential. This to the ocular muscles. The sensitivity of the ancillary
failure of neuromuscular transmission is what ac- diagnostic tests depends on whether the disease is
counts for the weakness in patients with MG. generalized or restricted.
Fatigability occurs because of depletion of presynap- Presentation with respiratory muscle weakness,
tic vesicles with sustained activity. termed myasthenic crisis, constitutes a medical emer-
gency. Respiratory muscle weakness may be present
even in patients who do not appear short of breath,
CLINICAL MANIFESTATIONS underscoring the importance of obtaining formal
measures of pulmonary function—forced expiratory
Fatigable muscle weakness is characteristic. The spe- volume in 1 second (FEV1) and negative inspiratory
cific symptoms depend on the distribution of this force (NIF)—in every patient with active disease.
weakness. Ocular involvement is most common, Myasthenic crisis should be distinguished from
manifesting as ptosis and diplopia. The pupils are cholinergic crisis (a state of increased cholinergic drive
never involved. Bulbar muscle weakness is next most due to overmedication with cholinesterase inhibitors).
frequent and manifests as dysarthria or dysphagia. Apart from respiratory muscle weakness, cholinergic
Limb weakness is usually proximal and symmetric. crisis is also characterized by the presence of increased
Symptoms are typically worse with sustained activity bronchial secretions, salivation, diarrhea, nausea,
or toward the end of the day. Examination is directed vomiting, and diaphoresis.
12887_CH24.qxd 10/4/08 3:35 PM Page 171
DIAGNOSTIC EVALUATION
KEY POINTS
The diagnosis of MG is primarily clinical, but support • MG is mediated by antibodies directed against the
for the diagnosis may be obtained from various tests. muscle nAChR.
Edrophonium chloride (Tensilon) is an antiacetyl- • It presents with fatigable muscle weakness.
cholinesterase agent. It is administered intravenously
• MG is treated with acetylcholinesterase inhibitors,
and the patient observed for improvement in muscle
steroids, and immunosuppressive therapy.
strength. Antibodies against the nAChR may be de-
tected in about 80% of patients with generalized MG
and 55% of patients with ocular MG. Elevated titers
confirm the diagnosis but negative titers do not ex-
clude it. Seronegative MG is clinically indistinguish- LAMBERT-EATON MYASTHENIC
able from seropositive disease. Antibodies directed SYNDROME
against MuSK (muscle-specific kinase) may be present
in some patients with generalized seronegative disease. EPIDEMIOLOGY
Repetitive nerve stimulation reveals a decremental
response that is seen more commonly in proximal LEMS is an uncommon condition that is usually as-
muscles. Single-fiber electromyography is the most sociated with an underlying small cell lung carci-
sensitive clinical test of neuromuscular transmission. noma. It is caused by antibodies directed against the
The characteristic finding in MG is increased jitter. presynaptic P/Q-type voltage-gated calcium channel.
By reducing presynaptic calcium entry, these anti-
TREATMENT bodies reduce the release of acetylcholine, leading to
weakness.
Antiacetylcholinesterase drugs such as pyridostigmine
inhibit the synaptic degradation of acetylcholine and CLINICAL MANIFESTATIONS
thus prolong its effect. Although pyridostigmine pro-
vides adequate symptomatic therapy for many pa- Patients present with fatigable proximal weakness.
tients with MG, it does not affect the underlying im- DTRs are reduced or absent. In contrast to MG, bul-
munopathology. Immune-modulating therapy thus bar and ocular symptoms are rare, but autonomic
serves as the mainstay for most patients with MG. complaints (dry eyes, dry mouth, and impotence) are
There are few controlled trials of immunosuppressive common. The characteristic finding is that of muscle
therapy, but steroids, steroid-sparing agents such as facilitation: with brief intense exercise, muscle
azathioprine and cyclosporine, plasmapheresis, and in- strength increases, and reflexes may appear tran-
travenous immunoglobulin (IVIg) have all been used siently. Fatigue develops with sustained activity.
with some success. Plasmapheresis and IVIg provide
rapid (but relatively short-lived) immunosuppression
for patients with severe disease. Steroids and steroid- DIAGNOSTIC EVALUATION
sparing agents are the mainstay for long-term immune
therapy. The place and timing of thymectomy are not The presence of elevated anti–voltage-gated calcium
clear, but most would agree that it facilitates easier im- channel antibody titers together with an incremental
munosuppression in young patients. response on repetitive nerve conduction studies helps
Patients who present with respiratory muscle to establish the diagnosis.
weakness (myasthenic crisis) warrant admission to an
intensive care unit, careful monitoring of respiratory TREATMENT
function with intubation, and mechanical ventilation
if necessary. Plasmapheresis or IVIg as well as high- The diagnosis of LEMS should prompt a thorough
dose steroids are appropriate under such circum- search for an underlying malignancy, even though a
stances, given their relatively rapid onset of action. tumor is not always found. Initial therapy is directed
Cholinesterase inhibitors are typically ineffective in at the underlying malignancy; in many patients, no
patients with myasthenic crisis and should be discon- further therapy is required. Steroids, azathioprine,
tinued (a practical measure that obviates the need to IVIg, and plasmapheresis have all been used, but
distinguish myasthenic from cholinergic crisis). with less success than in MG. 3,4-diaminopyridine is
12887_CH24.qxd 10/4/08 3:35 PM Page 172
the most effective medication for improving muscle ence of a family history, the nature of the symptoms
strength in patients with LEMS, but it is not FDA- and pattern of weakness as well as the tempo of the
approved in the United States. disease should allow a reasonable preliminary diagno-
sis to be made. Investigations like serum CK, EMG,
and muscle biopsy should then lead to a definitive
KEY POINTS diagnosis in most cases.
The symptoms of muscle disease may be negative
• LEMS is mediated by anti–voltage-gated calcium (weakness and fatigue) or positive (muscle pain,
channel antibodies. cramps, or stiffness). Weakness is the most common
• It has a strong association with underlying small cell and important symptom; a detailed history of the sorts
lung cancer. of activities with which the patient has difficulty pro-
vides a good indication of the pattern of weakness.
Generalized fatigue or tiredness does not indicate a
muscle disease, particularly when this is an isolated
SKELETAL MUSCLE DISORDERS symptom. Muscle pain (myalgia) is a common symp-
tom and also does not usually imply primary disease of
Disorders of skeletal muscle are a diverse group of muscle, particularly when it is an isolated symptom.
conditions that do not lend themselves to easy classi- Myalgias may be a feature of the inflammatory and
fication. Discussion of these diseases is further com- metabolic myopathies. Patients with myotonia may
plicated by the array of terminology used commonly. complain of difficulty releasing a handgrip or of open-
A few words of clarification may help. Myopathy is a ing their eyes after squeezing them shut tightly.
nonspecific term used to refer to disorders of skeletal The tempo of the symptoms is of major diagnos-
muscle. Muscular dystrophy refers to a group of tic importance. For example, acute or subacute onset
hereditary conditions in which muscle biopsy of progressive weakness is a feature of some of the
demonstrates dystrophic changes (fiber splitting, in- inflammatory myopathies, whereas chronic, slowly
creased connective tissues). Myotonia is a state of progressive (over years) weakness is most often en-
increased, sustained muscle contraction or impaired countered in the muscular dystrophies. Episodic weak-
relaxation. The term congenital indicates onset of ness suggests one of the channelopathies or metabolic
clinical disease in the early infantile period. Myositis myopathies. The age of onset may also help point to a
implies an inflammatory process. particular disease process. For example, among the
Broadly speaking, it is still useful to think of these dystrophies, the onset of Duchenne muscular dystro-
disorders as inherited or acquired. The inherited disor- phy (DMD) is usually around the age of 3, while many
ders encompass the muscular dystrophies, the congen- of the limb-girdle dystrophies begin only during ado-
ital myopathies, and the channelopathies as well as the lescence. Of the inflammatory myopathies, dermato-
metabolic and mitochondrial myopathies. The ac- myositis (DM) may occur at any age, but polymyositis
quired disorders include the inflammatory my- is rare in children, and inclusion body myositis (IBM)
opathies, endocrine and drug- or toxin-induced usually affects the elderly. Finally, the family history
myopathies, and a group of myopathies associated may be very helpful, and the specific pattern of inher-
with other systemic illnesses. With recent advances in itance should be determined.
molecular genetics, there has been a shift toward
thinking about and classifying at least the hereditary
disorders on the basis of the underlying molecular DYSTROPHINOPATHIES
defect. The approach adopted here is an attempt to
synthesize clinical classification with newly acquired DMD and Becker muscular dystrophy (BMD) result
knowledge of the genetic basis of many of the inher- from different mutations of the same gene, dys-
ited skeletal muscle disorders. trophin, and are thus said to be allelic.
There is no single defining clinical feature of dis-
orders of skeletal muscle. However, the selective in- CLINICAL MANIFESTATIONS
volvement of particular groups of muscles (i.e., focal
patterned weakness) is highly suggestive of a myo- DMD and BMD should be thought of as a single dis-
pathic process. A detailed history and examination order representing a spectrum of severity, with DMD
with particular attention to the age of onset, the pres- more severe than BMD. Inheritance is X-linked, and
12887_CH24.qxd 10/4/08 3:35 PM Page 173
onset is usually in childhood. The child may use an most frequent causes are mutations in calpain-3,
arm to push down on his or her thighs when arising dysferlin, one of the sarcoglycans, or FKRP (Fukudin
from the floor (Gowers sign), and there may be related protein). Some are due to mutations in pro-
pseudohypertrophy of the calf muscles. Proximal mus- teins known as the sarcoglycans, which form part of
cle weakness, including neck flexors, predominates; the multimolecular dystrophin-associated glycopro-
there is usually sparing of ocular and bulbar muscles. tein complex.
DMD is relentlessly progressive, with the child be-
coming wheelchair-bound by the age of 10 or 12. DIAGNOSTIC EVALUATION
Although primarily a disorder of skeletal muscle, car-
diac and gastrointestinal smooth muscle involvement CK level is usually elevated. The EMG is myopathic,
as well as CNS involvement are common. In DMD, and biopsy demonstrates nonspecific dystrophic
death usually occurs around age 20 because of respira- changes. Immunohistochemistry and Western blot
tory insufficiency and aspiration. Life expectancy is analysis on muscle biopsy, as well as DNA analysis on
also reduced in BMD, but usually not so severely. whole blood may help to distinguish the diffferent
limb-girdle muscular dystrophies.
DIAGNOSTIC EVALUATION
A number of characteristic syndromes have been PM and DM are characterized by proximal (usually
identified. These include myoclonic epilepsy with symmetric) muscle weakness. Weakness in IBM is
ragged red fibers (MERRF); mitochondrial myopathy, often asymmetric and may affect both proximal and
encephalopathy, lactoacidosis, and stroke (MELAS); distal muscles. Early selective involvement of fore-
progressive external ophthalmoplegia (PEO); and the arm and finger flexors, as well as of knee extensors
Kearns-Sayre syndrome. (quadriceps) and ankle extensors, should arouse sus-
picion of this diagnosis. Pharyngeal and neck flexor
muscles may be affected, but facial and respiratory
DIAGNOSTIC EVALUATION muscles are usually spared. IBM is often diagnosed
only when patients thought to have PM fail to
There are no characteristic clinical or electrophysio- respond to steroids. DM is distinguishable by the as-
logic findings in the mitochondrial myopathies, but a sociated purplish discoloration of the eyelids (he-
common finding is the co-occurrence of a myopathy liotrope) and papular erythematous scaly lesions over
and a peripheral neuropathy. Serum or CSF lactate the knuckles (Gottron patches).
and pyruvate are often increased. The histopatho- Extramuscular manifestations are frequent in DM.
logic changes are also nonspecific and include the Cardiac manifestations include conduction defects,
presence of ragged red fibers and variability of cy- tachyarrhythmias, myocarditis, and congestive cardiac
tochrome oxidase staining. failure. Interstitial lung disease associated with the
presence of anti-Jo-1 antibodies occurs in approxi-
mately 10% of patients. DM may occur in the context
KEY POINTS
of systemic sclerosis or other mixed connective tissue
• The mitochondrial myopathies are clinically and disease, and there is an increased incidence of malig-
genetically heterogeneous. nancy in patients with DM. In contrast to DM and
• The myopathy is frequently accompanied by other IBM, PM is more often associated with other autoim-
systemic manifestations (e.g., seizure, stroke, mi- mune diseases, including Crohn’s disease, vasculitis,
graine, diabetes). sarcoidosis, MG, and others.
• Serum lactate and pyruvate are often increased.
• Muscle biopsy may show ragged red fibers. PATHOGENESIS
DM is a microangiopathic disorder in which antibod-
ies and complement are directed primarily against
DISTAL MYOPATHIES intramuscular blood vessels. Inflammation is due to
muscle ischemia. PM is mediated by CD8⫹ T lym-
The distal myopathies are a group of largely heredi- phocytes, while IBM is likely both an inflammatory
tary conditions in which muscle weakness at onset is and neurodegenerative disorder.
12887_CH24.qxd 10/4/08 3:35 PM Page 176
Chapter
Pediatric
25 Neurology
178
12887_CH25.qxd 10/4/08 3:35 PM Page 179
movements, or seizures. In older children, spasticity, but the presence of a static (not worsening) disorder
dystonia, developmental delay, and drooling are com- is suggestive. One must rule out other entities that
mon presentations. may present with dystonia, ataxia, or spasticity but
which progress with time (e.g., metabolic disorders,
DIAGNOSTIC EVALUATION metachromatic leukodystrophy, and movement dis-
orders such as levodopa-responsive dystonia). MRI is
The diagnosis of CP is based on the clinical symp- indicated only to exclude other structural causes such
toms and signs. The cause may not be determined, as tumor, stroke, or AVMs.
12887_CH25.qxd 10/4/08 3:35 PM Page 180
TREATMENT • Severe: 25 to 40
• Profound: less than 25
In general, a multidisciplinary approach is necessary,
with early infant stimulation, physical and occupa- There are many causes of mental retardation.
tional therapy, orthopedic and psychological evalua- Among them are prenatal and postnatal trauma (e.g.,
tion, and speech therapy. intracerebral hemorrhage and hypoxic-anoxic en-
cephalopathy); congenital and postnatal infection
(e.g., congenital rubella, syphilis, cytomegalovirus,
KEY POINTS toxoplasmosis, and HIV infection); chromosomal
abnormalities (e.g., Down syndrome, fragile X syn-
• Cerebral palsy (CP) is a static disease; if the disease drome, Angelman syndrome, Prader-Willi syn-
is progressing, it is not CP. drome); chromosomal translocations (e.g., cri du chat
• It occurs in almost 3 per 1,000 births. syndrome); inherited metabolic disorders (e.g., hy-
• The most common abnormality is spasticity. pothyroidism, galactosemia, Tay-Sachs disease); and
toxic, nutritional, and environmental causes. Table
25-3 summarizes some chromosomal abnormalities
MENTAL RETARDATION AND associated with mental retardation.
Developmental delay is the failure to acquire age-
DEVELOPMENTAL DELAY appropriate cognitive, language, fine or gross motor
skills, or social skills. The Denver Developmental
Mental retardation is the failure to develop normal
Assessment is a standard test that can help establish
mental capacities. It can be classified by the results of
the diagnosis. Many of the etiologies of developmen-
standard intelligence tests such as the Stanford-Binet
tal delay are similar to those responsible for mental
IQ and the Wechsler Preschool and Primary Scale of
retardation and include intrauterine toxins and infec-
Intelligence–Revised. Normal IQ is 100 with a stan-
tions, genetic abnormalities, migrational disorders,
dard deviation of 15. Mental retardation is classified
hypoxic-ischemic encephalopathy, and inborn errors
as follows:
of metabolism. Most often, though, no cause for de-
• Mild: IQ between 55 and 70 velopmental delay is found, in which case it is labeled
• Moderate: IQ between 40 and 55 idiopathic.
12887_CH25.qxd 10/4/08 3:35 PM Page 181
DIAGNOSTIC EVALUATION
AUTISTIC SPECTRUM DISORDERS
The diagnosis is clinical. Differential diagnosis in-
Autism is a developmental disorder of brain function. cludes other causes of speech and language prob-
Usually, the etiology is unknown. Autism is the most lems, such as deafness, mental retardation, and
common of the disorders that fall under the banner seizures (Landau-Kleffner syndrome). Asperger
of pervasive developmental disorder. syndrome can be considered a variant of autism
12887_CH25.qxd 10/4/08 3:35 PM Page 182
• Neurodegenerative diseases involving the white • Infants with severe hypotonia but only marginal
matter include metachromatic leukodystrophy, weakness usually do not have a disorder of the
Krabbe disease, adrenoleukodystrophy, Pelizaeus- lower motor unit.
Merzbacher disease, Canavan disease, and Alexander
disease.
• Peripheral nerve involvement is found in metachro-
matic leukodystrophy, Krabbe disease, Canavan ATTENTION DEFICIT–
disease, and adrenoleukodystrophy. HYPERACTIVITY DISORDER
• Congenital macular cherry-red spots (red color of
the macula compared with a pale retina) are found CLINICAL MANIFESTATIONS
in Tay-Sachs disease, Sandhoff disease, Niemann-
Pick disease, Gaucher disease, metachromatic The essential features of attention deficit–hyperactiv-
leukodystrophy, and sialidoses. ity disorder (ADHD) are inappropriate inattention,
impulsivity, and hyperactivity for age. Children with
12887_CH25.qxd 10/4/08 3:35 PM Page 184
KEY POINTS
DIAGNOSTIC EVALUATION
• Children with ADHD usually have a positive family
A diagnosis is made by clinical history and neuropsy- history for the disorder.
chological screening tests. Children usually have nor- • Stimulants like methylphenidate and dextroam-
mal IQs but low scores on tests of sustained atten- phetamine are often effective treatments for
tion. Imaging and laboratory tests are generally not ADHD.
helpful.
12887_BM_Questions.qxd 10/4/08 3:13 PM Page 186
Q Questions
1. A 78-year-old woman with dementia and rigidity is hospi- agnostic study indicates that this is likely a sensory neu-
talized with dehydration. During her hospitalization, she ronopathy. Which one of the following tests will help to
becomes agitated and has prominent visual hallucina- find the possible etiology?
tions. After a dose of haloperidol, she becomes very rigid a. Anti-GM1 antibodies
and mute. The most likely type of dementia in this patient b. Anti-DNA antibodies
is: c. Anti-Hu antibodies
a. Alzheimer disease (AD) d. MRI of the spine
b. Parkinson disease (PD) e. CT myelogram
c. Dementia with Lewy bodies
d. Pick disease 5. A 40-year-old woman is evaluated in the ER after a
e. Vascular dementia motor vehicle accident resulting in left facial injuries.
Examination after she recovers acutely demonstrates that
2. A 32-year-old woman presents to the ER complaining of her left seventh and eighth cranial nerves remain dys-
blurred vision and pain in the right eye. Your evaluation functional. Which of the following skull structures may
shows decreased visual acuity in the right eye that does have been affected by her injury?
not correct with pinhole testing. There is a relative afferent a. Cribriform plate
pupillary defect (RAPD) on the right, and testing of the b. Optic canal
right visual field shows a small central scotoma. The most c. Superior orbital fissure
likely localization of the lesion is the: d. Internal auditory meatus
a. Optic chiasm e. Jugular foramen
b. Optic nerve
c. Optic tract 6. A 54-year-old woman was seen in the ER complaining of
d. Occipital cortex a severe headache. Head CT was normal, and an LP was
e. Optic radiations performed. The opening pressure was 14 cm H2O, and CSF
analysis showed the following: 150 red blood cells, xan-
3. In the course of evaluating an infant with developmental thochromic fluid, protein 55 (slightly increased), 15 white
regression, a pediatric neurologist notes a cherry-red spot blood cells (90% lymphocytes), and normal glucose. Which
on funduscopic examination. Which of the following diag- of the following statements is true?
noses is consistent with that finding? a. The xanthochromia may have been caused by a trau-
a. Alexander disease matic tap.
b. Hurler syndrome b. The lymphocytic pleocytosis indicates an active infec-
b. Krabbe disease tious process.
d. Niemann-Pick disease c. Viral meningitis is unlikely because of the normal CSF
e. Canavan disease glucose.
d. The lymphocytic pleocytosis is likely reactive to the
4. A 62-year-old woman presents with progressive distal presence of blood within the CSF.
symmetric paresthesias and dysesthesias, with preserved e. The opening pressure is elevated and reflects pseudo-
muscle strength. She smokes cigarettes. Your electrodi- tumor cerebri.
186
186
12887_BM_Questions.qxd 10/4/08 3:13 PM Page 187
Questions • 187
7. A 29-year-old woman is brought into the ER in an unre- family indicates that, over the previous year, he has made
sponsive state. Her temperature is 37°C, heart rate 84 per unusual movements with his hands, and he seems to have
minute, respirations 10, and blood pressure 152/84. On ex- some memory difficulties. His father died in his 50s with a
amination, she withdraws to noxious stimulation only. Her similar clinical syndrome, including prominent chorea and
right pupil is 10 mm and does not constrict to light. Her left dementia. The most likely genetic abnormality will be lo-
pupil is 5 mm and reacts normally. Which of the following calized on chromosome:
is clinically contraindicated? a. 19
a. Raising the head of the bed b. 6
b. Intravenous administration of mannitol c. 4
c. Hyperventilation d. 11
d. LP e. 21
e. Neurosurgical consultation
12. A 55-year-old woman with a history of ovarian cancer and
8. A patient presents with gradually worsening weakness of moderate alcohol consumption is seen in the Neurology
the proximal arm and leg muscles symmetrically over sev- ambulatory clinic with a 1-month history of progressive
eral months. On examination, neck flexors and extensors unsteadiness of gait and dysarthria. Examination confirms
are found to be weak also. There is no muscle pain or ten- the presence of both gait and limb ataxia as well as nys-
QUESTIONS
derness. What is the most likely site of dysfunction in the tagmus. These symptoms were fairly abrupt in onset, pro-
nervous system? gressed over a period of a few weeks, and now appear to
a. Peripheral nerve have stabilized, but there has been no sign of spontaneous
b. Brachial plexus improvement. Which of the following statements is cor-
c. Spinal nerve root rect?
d. Internal capsule a. The findings of gait ataxia, dysarthria, and nystagmus in-
e. Muscle dicate diffuse involvement of the cerebellum and
suggest that alcohol consumption is the likely cause.
9. An 8-year-old boy is brought to a child psychiatrist for b. The constellation of symptoms and their temporal
evaluation of potential attention deficit–hyperactivity evolution are most consistent with paraneoplastic cere-
disorder. His mother states that his teachers have been bellar degeneration, a disorder associated with
concerned about his attention because they frequently underlying gynecologic malignancy.
have to repeat instructions to him. At home his brother has c. The constellation of symptoms and their temporal
noticed that he will stare for several seconds at a time, dur- evolution are most consistent with paraneoplastic cere-
ing which he does not respond to questions. An EEG bellar degeneration (PCD), but ovarian cancer is an un-
demonstrates a 3-Hz spike-and-wave pattern. Which of the usual cause of this syndrome.
following is the most appropriate treatment? d. The symptoms and signs indicate cerebellar hemi-
a. Methylphenidate (Ritalin) spheric dysfunction and are most suggestive of a
b. Ethosuximide (Zarontin) metastasis from the underlying ovarian cancer.
c. Clonidine (Catapres) e. The sudden onset of symptoms and diffuse cerebellar
d. Fluoxetine (Prozac) involvement suggest midline cerebellar hemorrhage as
e. Carbamazepine (Tegretol) the cause.
10. A 28-year-old woman comes to the ER with a severe uni- 13. A 45-year-old man with multiple sclerosis (MS) comes to
lateral throbbing headache accompanied by photophobia the Neurology clinic complaining of urinary incontinence.
and phonophobia. These headaches started in her teens He indicates that he experiences increased urgency and
and she has one every month. Which of the following med- frequency of urination. The most likely urodynamic finding
ications is effective as abortive treatment? in this patient is:
a. Propranolol a. An atonic bladder
b. Sumatriptan b. A spastic bladder
c. Verapamil c. Stress incontinence
d. Amitriptyline d. Absence of abnormalities
e. Valproic acid e. Overflow incontinence
11. A 42-year-old man is brought to the neurologist for evalu- 14. A 65-year-old man complains of a 3-month history of
ation of a few months’ history of personality changes. His intermittent urinary incontinence. Urodynamic studies
12887_BM_Questions.qxd 10/4/08 3:13 PM Page 188
show an atonic bladder. Which of the following is most with left carpal tunnel syndrome and right sciatic neu-
likely responsible for his problem? ropathy. What is the most likely diagnosis?
a. Diabetes a. Mononeuropathy multiplex
b. Old stroke b. Axonal polyneuropathy
c. Multiple sclerosis c. Demyelinating polyneuropathy
d. Right parietal tumor d. Neuromuscular junction disease
e. Pineal tumor e. Polyradiculopathy
15. A 35-year-old man is seen in the Neurology outpatient 18. A 70-year-old man develops the acute onset of an inabil-
clinic with the complaint that his fingers occasionally “get ity to speak. Examination reveals that he struggles to pro-
stuck” when he tries to open jars. On examination you nounce a complete word and cannot string words
find subtle weakness of the fingers and toes as well as together. He is unable to repeat a sentence but can fol-
percussion myotonia. You suspect the diagnosis of my- low simple and multistep commands. What is the most
otonic dystrophy. Which of the following statements is likely diagnosis?
true? a. Global aphasia
a. Myotonic dystrophy is a systemic disorder that may b. Conduction aphasia
also cause cataracts, diabetes, mental retardation, and c. Broca aphasia
cardiac arrhythmias. d. Wernicke aphasia
b. Myotonic dystrophy is primarily a disorder of skeletal e. Transcortical motor aphasia
muscle.
c. Myotonic dystrophy should not be considered in the 19. A 28-year-old woman is brought to the ER by her husband.
differential diagnosis because it is an inherited disorder In addition to having neck stiffness, she has had a fever for
that typically manifests itself either at birth or early in several days, has been somewhat confused, and has not
life. been “acting like herself.” LP shows 9 white blood cells
d. Myotonic dystrophy is an autosomal recessive with a lymphocytic predominance, 32 red blood cells, pro-
disorder caused by a triplet expansion in the DMPK tein ⫽ 63, and glucose ⫽ 65. Gram stain is negative. What
gene. is the most likely diagnosis?
e. Electromyography is usually normal in myotonic dys- a. Bacterial meningitis
trophy and genetic testing is essential to confirm the b. Viral meningitis
diagnosis. c. Fungal meningitis
d. Meningitis from tuberculosis
16. An 18-year-old woman is brought to the Neurology e. Subarachnoid hemorrhage
clinic by her mother, who explains that her daughter
has been behaving strangely recently and appears to have 20. A healthy 32-year-old man is brought to the ER after he
paranoid delusions. She has a slight tremor of both hands stopped speaking suddenly, fell to the ground, lost con-
and the examiner notes that there is a brownish discol- sciousness, and shook for 2 minutes. After the event, he
oration of the cornea in the vicinity of the limbus. was noted to have a tongue laceration and urinary incon-
Laboratory studies show a mild transaminitis. Which of the tinence. He has no history of similar events. His physical
following test results are most likely? exam shows a mild right hemiparesis. Routine labs and a
a. Increased serum copper and ceruloplasmin with head CT are normal. An EEG performed the next day is nor-
decreased 24-hour urinary copper mal. The normal EEG suggests that this man:
b. Increased serum copper with decreased serum cerulo- a. Had a pseudoseizure and does not require anticon-
plasmin and increased 24-hour urinary copper vulsants.
c. Decreased serum copper and ceruloplasmin and b. Needs admission for long-term video-EEG monitoring.
increased 24-hour urinary copper c. Probably had a seizure, and the normal EEG result is not
d. Increased 24-hour urinary copper but decreased cop- surprising.
per staining on liver biopsy d. Requires hyperventilation to elicit an absence seizure
e. Increased serum copper and 24-hour urinary copper on EEG.
with decreased serum ceruloplasmin e. Has actually had an ischemic stroke rather than a seizure.
17. A 40-year-old woman with SLE develops weakness of her 21. Two days after coronary artery bypass surgery, a 62-year-
right finger and wrist extensors and pain on the right old man with hypertension complains that “there is an-
dorsum of her hand several months after being diagnosed other man’s arm in bed” with him. When asked to hold up
12887_BM_Questions.qxd 10/4/08 3:13 PM Page 189
Questions • 189
his arms, the patient raises his right arm only. When asked 26. A 55-year-old man with a history of tick bite and erythema
about his left arm, he claims it is the examiner’s or another chronicum migrans is diagnosed with Lyme disease. He
patient’s. What is the most likely diagnosis? asks his primary care physician about neurologic symp-
a. Right hemispheric stroke with neglect toms he should watch for. Which of the following is an
b. Left hemispheric stroke with neglect early neurologic manifestation of Lyme disease?
c. Conversion disorder a. Facial nerve palsy
d. Adjustment disorder b. Painful polyradiculopathy
e. Alien-limb phenomenon c. Spinal cord compression
d. Leukoencephalopathy
22. A 35-year-old man with no known history of seizures is e. Generalized epilepsy
brought in by paramedics in status epilepticus. Which of
the following medications is used as initial therapy for this 27. A 34-year-old man is seen in the Neurology outpatient
condition? clinic with symptoms of headache and bilateral lower
a. Benzodiazepines motor neuron (LMN) facial weakness. There is no history of
b. Barbiturates a skin rash. Neurologic examination discloses a relative
c. Propofol afferent papillary defect in the right eye as well as the bi-
d. Carbamazepine lateral facial weakness.
QUESTIONS
e. Lamotrigine a. Guillain-Barré syndrome (GBS) is the most likely diag-
nosis, and he should have an LP to help confirm the
23. Subfalcine herniation most often results in which of the diagnosis.
following? b. Lyme disease is the most likely diagnosis, and Borrelia
a. Ipsilateral third nerve palsy serology should be sent to confirm the diagnosis.
b. Contralateral third nerve palsy c. Sarcoidosis is likely the correct diagnosis, and appropri-
c. Ipsilateral hemiparesis ate investigations include MRI of the brain, LP, and
d. Contralateral hemiparesis chest x-ray.
e. Bilateral leg weakness d. Multiple sclerosis (MS) is most likely the correct diagno-
sis, as bilateral facial weakness and optic neuropathy
24. A 23-year-old woman presents with loss of vision in the right are both common manifestations of this disease.
eye accompanied by slight pain in that eye over a period of e. Vasculitis, causing mononeuritis multiplex, is the most
3 days. She has 20/200 acuity, red desaturation, and an af- likely diagnosis, and so the patient should be referred
ferent pupillary defect in the right eye. The remainder of her for rheumatologic evaluation.
examination and MRI are normal. A diagnosis of optic neuri-
tis is made. Which of the following is true about treatment? 28. A 64-year-old man with a history of hypertension presents
a. Interferon beta-1b will hasten recovery from this to the ER with the sudden onset of numbness of his left
episode. leg, arm, and face. His motor examination is normal. What
b. Mitoxantrone is the most effective treatment. is the most likely site of his lesion?
c. Medical treatment is not likely to help optic neuritis. a. Right thalamus
d. Oral corticosteroids are preferred for the treatment of b. Left thalamus
optic neuritis. c. Left postcentral gyrus
e. Corticosteroids may delay the development of multiple d. Right precentral gyrus
sclerosis. e. Right corona radiata
25. A 22-year-old right-handed woman develops horizontal 29. While playing baseball with some friends, a 15-year-old boy,
diplopia acutely. Your evaluation shows normal right lat- who was not wearing a helmet, was hit accidentally on the
eral gaze but difficulty with adduction of the right eye side of the head with a ball. He was knocked unconscious
while looking to the left and nystagmus in the abducting briefly but recovered fully. Two hours later he became in-
left eye. What is the most likely anatomic localization? creasingly lethargic, so his parents brought him to the ER.
a. Left paramedian pontine reticular formation (PPRF) When you evaluate the patient, he is barely arousable to
producing a right internuclear ophthalmoplegia (INO) your voice. He has mild weakness on the left side of his
b. Right PPRF producing a right one-and-a-half syndrome body, and his right pupil is slightly larger than the left pupil;
c. Right medial longitudinal fascicle (MLF) producing a the right pupil does not appear to react to light. What is the
right INO most likely cause of the patient’s symptoms and signs?
d. Left medial longitudinal fascicle producing a right INO a. Concussion
e. Lateral geniculate nuclei b. Epidural hematoma
12887_BM_Questions.qxd 10/4/08 3:13 PM Page 190
c. Diffuse axonal injury left 5 mm, both reactive to light. What other findings will
d. Ischemic infarct help to localize the lesion?
e. Drug intoxication a. Look at the pupils in the dark and check tongue deviation.
b. Look for evidence of ptosis in the left eye and anhidro-
30. Which of the following syndromes or diseases could cause sis on the left face.
bilateral weakness and loss of pain and temperature sensa- c. Look for evidence of ptosis in the right eye and an-
tion with preservation of joint position sense in both legs? hidrosis in the right face.
a. Amyotrophic lateral sclerosis (ALS) d. Look for evidence of horizontal diplopia and a cut in
b. Vitamin B12 deficiency the right visual field.
c. Brown-Séquard syndrome e. Look for evidence of dysarthria and hemiparesis.
d. Anterior spinal artery syndrome
e. Tabes dorsalis 35. A 35-year-old woman presents to the ER reporting a few
days of progressive ascending muscle weakness. She had a
31. A 2-year-old child presents with new seizures. Her viral infection a few weeks earlier. On examination, you
mother tells you that the child is not walking yet. He has find diffuse weakness and areflexia. The most likely finding
a 5-year-old brother with a seizure disorder and mental in the CSF is:
retardation. On examination, using the Wood’s lamp, you a. High protein–high cell count
find hypomelanotic lesions. The most appropriate next b. High protein–low cell count
test is: c. Low protein–high cell count
a. Skeletal surveillance d. Low protein–low cell count
b. Skin biopsy e. Normal CSF
c. Head CT or MRI
d. No need for further tests 36. A 33-year-old man is seen in the ER for difficulty walking. He
e. LP has paresthesias in his feet and a left footdrop. Initial physi-
cal exam shows mild distal weakness in both legs, with ab-
32. A 3-year-old boy is brought to his pediatrician for evalua- sent ankle jerks and reduced reflexes throughout. While the
tion of repetitive behaviors, delay of language develop- patient is waiting in the ER, his weakness worsens, involving
ment, and social isolation. He otherwise has normal motor the arms, but he has no difficulty breathing. You want to
development. Which of the following is a required feature admit the patient to the intensive care unit. What will be
of autism but not of Asperger syndrome? your best argument to convince your ER attending to do so?
a. Abnormal language development a. Absence of upper extremity reflexes
b. Social isolation b. Decreased gag reflex
c. Onset after age 3 c. A forced vital capacity FVC below 25 mL/kg
d. Failure to meet milestones for gross motor develop- d. The patient’s weakness is worsening very quickly, and
ment you fear that he may need mechanical ventilation
e. Failure to meet milestones for fine motor development e. You don’t have an argument in this case
33. A 62-year-old woman with a history of small cell lung 37. A 35-year-old man who is HIV-positive presents with radic-
carcinoma presents to the Neurology clinic complaining of ular pain in the legs and associated bladder distention. The
bilateral paresthesias of the lower extremities. She has no most likely agent responsible for these symptoms is:
history of diabetes or family history of polyneuropathy. a. Cytomegalovirus
She describes severe pain in the soles of her feet when b. Clostridium
standing and has difficulty walking. On examination, there c. Toxoplasma
is severe pain to light touch over both soles. On your sen- d. Cryptococcus
sory examination description, you will state that this pa- e. Pneumocystis carinii
tient has:
a. Hyperesthesia 38. A 45-year-old woman presents to the ER with “dizziness,”
b. Paresthesia by which she means that she feels a spinning sensation.
c. Allodynia The sensation is intermittent and seems to be exacerbated
d. Sensory loss by head movement. She has some nausea with the
e. Hypesthesia episodes but otherwise has no other symptoms, such as
double vision, weakness, hearing loss, tinnitus, or difficulty
34. A 38-year-old man presents to the ER complaining of mild swallowing. What diagnosis is most likely?
headache. He had neck trauma a week earlier. The exam a. Vestibular neuronitis
shows anisocoria, with the right pupil being 3 mm and the b. Ménière disease
12887_BM_Questions.qxd 10/4/08 3:13 PM Page 191
Questions • 191
QUESTIONS
c. It is an autoimmune disorder caused by antibodies
e. Prednisone
directed against presynaptic voltage-gated calcium
channels. 44. A 35-year-old man presents with his spouse to your office
d. It is an autoimmune disorder caused by antibodies for difficulty concentrating. Further history also reveals
directed against postsynaptic nicotinic acetylcholine that he has fallen asleep while driving as well as in the mid-
receptors. dle of important business meetings, despite sleeping at
e. It is an autoimmune disorder caused by antibodies least 8 hours each night. He denies hallucinations or a his-
directed against the synaptic enzyme acetyl- tory of his knees buckling while laughing. His wife reports
cholinesterase. that he snores loudly while sleeping. His examination is
normal with the exception of moderate obesity. Which of
40. A patient complains of difficulty chewing. On examination the following tests would be most helpful in diagnosing
he is found to have decreased strength of his muscles of this patient’s disorder?
mastication. Which of the following cranial nerves is re- a. Multiple sleep latency test (MSLT)
sponsible for this motor function? b. EEG
a. Trigeminal c. MRI of the brain
b. Facial d. LP
c. Oculomotor e. Polysomnography
d. Glossopharyngeal
e. Hypoglossal 45. A previously healthy 21-year-old presents to the ER after
being involved in a high-speed motor vehicle accident.
You note that the patient is unresponsive, makes no spon-
41. The following patients are being evaluated in a neurologic
taneous movement, and has a dilated pupil on the right
intensive care unit. For which one would the Glasgow
that is nonreactive to light. What is the best explanation
Coma Scale (GCS) be used most commonly to follow his or
for these signs?
her clinical status?
a. Infarction of the left occipital lobe
a. A 75-year-old man in coma after cardiac arrest
b. Concussion from the motor vehicle accident
b. A 29-year-old woman with delirium after medication
c. Uncal herniation
overdose d. Cervical neck fracture
c. A 69-year-old woman with a thromboembolic stroke e. Diffuse axonal injury
and Broca aphasia
d. A 20-year-old man who is unresponsive after head 46. An 84-year-old man is transferred from another hospital
trauma with a reported hypertensive hemorrhage. The films from
e. A 59-year-old man with subarachnoid hemorrhage that hospital are not available, and there are no further
after aneurysm rupture details. Which of the following is the most likely location of
his hemorrhage?
42. A 68-year-old man taking warfarin falls while in the hospi- a. Pons
tal, is found on the floor, and is difficult to rouse. He has a b. Midbrain
new right hemiparesis and an intracranial hemorrhage is c. Internal capsule
12887_BM_Questions.qxd 10/4/08 3:13 PM Page 192
Questions • 193
55. A 9-year-old boy presents with difficulty walking. arrives he is feeling fine and is able to give a clear account
Neurologic examination demonstrates, among other of what happened. He recalls walking to the bathroom to
things, that he performs rapid alternating movements urinate. Shortly thereafter he became light-headed and
poorly, with a lack of proper rhythm and coordination. This felt as if his vision were graying out. These symptoms
finding, called dysdiadochokinesis, is most typically associ- lasted for about 30 seconds. The next thing he recalls is
ated with dysfunction of which of the following brain awakening on his bathroom floor. His wife notes that he
structures? was unconscious only briefly. Which of the following
a. Basal ganglia descriptions pertinent to this clinical scenario is correct?
b. Medulla a. The symptoms of light-headedness and graying out of
c. Cerebellum vision are atypical symptoms described by patients
d. Parietal lobe with syncope.
e. Thalamus b. He has micturition syncope.
c. Orthostatic hypotension is the likely explanation for his
56. An ischemic stroke involving the right side of the pons could syncopal episode.
lead to which of the following patterns of weakness? d. Vasovagal syncope is the likely explanation for his syn-
a. Left facial weakness and right body weakness copal episode.
b. Right facial weakness and left body weakness e. Vestibular neuronitis is the likely explanation for his
QUESTIONS
c. Right facial weakness and right body weakness symptoms.
d. Left arm weakness and right leg weakness
e. Right arm weakness and left leg weakness 61. A 36-year-old man comes to the ER with a 4-day history
of fever and a generalized unwitnessed seizure 2 hours ear-
57. A 27-year-old woman with complex partial seizures is well lier. MRI of the brain with gadolinium shows contrast en-
controlled on carbamazepine. Which of the following is a hancement of both temporal lobes and, in a nontraumatic
characteristic side effect of this medication? tap, 10,000 RBCs and 15 white blood cells. What is the most
a. Thrombocytopenia likely organism responsible for this clinical picture?
b. Agitation a. Enterovirus
c. Diabetes insipidus b. Streptococcus species
d. Nephrolithiasis c. Cryptococcus neoformans
e. Hyponatremia d. Herpes simplex virus (HSV-1)
e. Meningococcus
58. A 53-year-old construction worker is brought to the ER
with a severe, sudden-onset headache accompanied by 62. A 55-year-old woman comes to the Neurology clinic com-
vomiting. A CT scan of his head demonstrates a subarach- plaining of numbness in the last two fingers of her right
noid hemorrhage. Which of the following is a common hand; it tends to worsen at night. On examination, you find
cause of subarachnoid hemorrhage? a positive Tinel sign at the right elbow (percussion of the
a. Tearing of bridging veins ulnar nerve at the right elbow produces a tingling sensa-
b. Laceration of the middle meningeal artery tion in the last two fingers of the right hand). You are con-
c. Aneurysmal rupture vinced that this is an ulnar neuropathy at the right elbow
d. Amyloid angiopathy and perform electrodiagnostic studies. Why do you think
e. Arteriovenous malformation rupture that this is a peripheral nerve problem?
a. The acuteness of presentation
59. A 45-year-old woman has an MRI scan of the brain for eval- b. The physical examination findings
uation of progressive headaches. The MRI scan shows a le- c. The symptoms described by the patient
sion that enhances in a homogeneous manner with con- d. You don’t think this is a peripheral nerve problem.
trast administration. Which of the following lesions is most e. There is no CNS complaint.
likely to account for the appearance of the MRI scan?
a. Glioblastoma multiforme 63. A 25-year-old man is now comatose after suffering blunt-
b. Meningioma force trauma to the head. On the basis of the clinical his-
c. Brain abscess tory, neurologic exam, and head CT scan, he is diagnosed
d. Toxoplasmosis with an epidural hematoma. Of the following choices,
e. Granuloma which is the best treatment option?
a. Neurosurgical decompression
60. A 75-year-old man is brought to the ER after having lost b. Hyperventilation
consciousness briefly in his bathroom. By the time he c. Administration of mannitol
12887_BM_Questions.qxd 10/4/08 3:13 PM Page 194
d. Conservative management with close monitoring of 68. A 65-year-old obese woman is referred to the Neurology
vital signs and neurologic status clinic with complaints of burning pain in both feet, which
e. Administration of tissue plasminogen activator has been present for several months. You suspect that she
may have a small fiber peripheral neuropathy. The most
64. A 19-year-old man is admitted to a Neurology service with likely findings on examination are:
an episode of transverse myelitis. Workup includes an MRI a. Symmetric weakness and atrophy of intrinsic muscles
of his head and LP. Which of the following distinguishes of the feet with loss of ankle reflexes
acute disseminated encephalomyelitis (ADEM) from multi- b. Symmetric stocking pattern diminution of pinprick and
ple sclerosis (MS)? temperature sensation
a. Presence of oligoclonal bands in the CSF c. Symmetric stocking pattern diminution of vibration
b. Pleocytosis with neutrophilic predominance and joint position sense with absent ankle reflexes
c. Monophasic course d. Symmetric stocking pattern diminution of all sensory
d. Multiple lesions on MRI modalities with absent DTRs in the arms and legs
e. A positive family history of ADEM e. Symmetric stocking pattern diminution of vibration
and joint position sense with retained ankle reflexes
65. A 55-year-old man with type 2 diabetes presents with a
5-week history of pain in his right knee, followed by weak- 69. A 45-year-old man presents with a several-month history
ness and atrophy of his right quadriceps. Exam shows of weakness in his lower and upper extremities. On exami-
weakness of the right quadriceps and iliopsoas muscles nation, in addition to weakness in multiple muscle groups,
and an absent right knee jerk. This presentation is most he demonstrates atrophy, hyperreflexia, spasticity of the
characteristic of what? legs, and bilateral Babinski signs. Fasciculations in multiple
a. Diabetic distal symmetric polyneuropathy muscles are also noted. His sensation to pain, temperature,
b. Proximal diabetic neuropathy or diabetic amyotrophy and joint position sense appear intact. What is his most
c. Mononeuropathy multiplex likely diagnosis?
d. Stroke a. Amyotrophic lateral sclerosis (ALS)
e. These conditions are not seen in diabetics. b. Vitamin B12 deficiency
c. Anterior spinal artery syndrome
66. A 19-year-old man is accidentally hit on the left side of the d. Central cord syndrome
head with a baseball bat while playing a game with some e. Brown-Séquard syndrome
friends. He loses consciousness and is taken to an emer-
gency room. A head CT scan showed a lenticular shaped 70. A 25-year-old man presents to your office with excessive
hyperdensity in the epidural space over the left temporal daytime sleepiness, visual hallucinations while falling
region that is exerting some mild mass effect on the brain. asleep, and a history of transiently losing tone in his ex-
Which of the following mechanisms best explains the pa- tremities and falling to the ground when he is angry or
tient’s head CT scan results? laughing. Of the following choices, what would be his sin-
a. Tearing of bridging veins gle best treatment option?
b. Laceration of the middle meningeal artery a. Pemoline
c. Impact of the brain over bony prominences of the skull b. Venlafaxine
d. Rotational acceleration and deceleration of the head c. Clomipramine
e. Rupture of a cerebral aneurysm d. CPAP
e. Methylphenidate
67. A 56-year-old woman is referred to the Neurology clinic
by her optometrist, who noted that she had limited 71. A 54-year-old man is seen in the Neurology clinic with com-
movement of her eyes. The patient herself notes only plaints of resting tremor of the left hand and a general feel-
that she has fallen a few times in recent months. ing of slowing down. As an example, he explains that it takes
Examination confirms that there is marked limitation of him at least 20 minutes to get dressed in the morning. You
vertical eye movements (both up and down gaze). There suspect that he has idiopathic Parkinson disease (PD). If you
is mild rigidity in both arms and legs but no tremor. Her are correct, examination would be most likely to show
postural reflexes are poor. Which of the following is the which of the following combinations of physical signs?
most likely diagnosis? a. Asymmetric rest tremor, asymmetric rigidity, and poor
a. Parkinson disease (PD) postural reflexes
b. Progressive supranuclear palsy (PSP) b. Symmetric rest tremor, asymmetric rigidity, and poor
c. Corticobasal ganglionic degeneration postural reflexes
d. Miller-Fisher syndrome (MFS) c. Asymmetric rest tremor, symmetric rigidity, and poor
e. Chronic progressive external ophthalmoplegia (PEO) postural reflexes
12887_BM_Questions.qxd 10/4/08 3:13 PM Page 195
Questions • 195
d. Symmetric rest tremor and rigidity and poor postural b. He likely has a form of apraxia due to a lesion in the
reflexes right frontal lobe.
e. Asymmetric rest tremor, symmetric rigidity, and impair- c. He likely has a form of Wernicke aphasia due to a lesion
ment of vertical gaze in the left inferior frontal lobe.
d. He likely has a form of apraxia due to a lesion in the
72. A 55-year-old man with a history of hypertension is seen in right parietal lobe.
the ER with complaints of clumsiness and incoordination; e. He likely has a form of apraxia due to a lesion in the left
these began 2 days earlier and have increased in severity. He parietal lobe.
also reports double vision on lateral gaze, which resolves
when one eye is covered. He is awake, alert, and oriented. 76. The most reliable method for distinguishing between a
Examination shows restricted eye movements in all direc- “traumatic” spinal tap (lumbar puncture) and a subarach-
tions, with eye abduction in both directions most limited. noid hemorrhage is the presence of:
DTRs are absent, and there is impaired joint position sense. a. Increased opening pressure
The most likely diagnosis is: b. Increased red cell count
a. Brainstem stroke c. Increased white cell count
b. Cerebellar infarction with compression of the brainstem d. Xanthochromia
c. Miller-Fisher syndrome (MFS) e. Pain upon needle insertion
QUESTIONS
d. Myasthenia gravis (MG)
e. Alcoholic cerebellar degeneration
77. The magnetic resonance imaging sequence that is most
sensitive for the presence of blood breakdown products
73. A 44-year-old woman presents to the ER complaining of
(e.g., after a hemorrhage) is:
urinary incontinence and lower back pain. What will be the
a. T1
most useful next diagnostic procedure to try in the effort
b. T2
to find the etiology of her problem?
c. Contrast-enhanced T1
a. Urodynamic studies
d. FLAIR
b. Blood testing including glucose level
e. Susceptibility
c. MRI of the spine
d. Post-void residual
e. LP 78. Which of the following disorders is most closely associated
with REM sleep behavior disorder?
74. A 48-year-old woman reports recurrent episodes of stab- a. Alzheimer disease
bing unilateral pain associated with tearing and conjuncti- b. Multiple sclerosis
val injection. Which of the following is characteristic of c. Multiple system atrophy
chronic paroxysmal hemicrania as opposed to cluster d. Myasthenia gravis
headache? e. Primary lateral sclerosis
a. Unilateral pain
b. Conjunctival injection 79. Which of the following vascular malformations is the most
c. Male predominance likely to result in an intracranial hemorrhage?
d. Indomethacin responsivity a. Arteriovenous malformation
e. Headache duration of hours b. Capillary telangiectasia
c. Cavernous hemangioma
75. A 75-year-old right-handed man with hypertension, dia- d. Developmental venous anomaly
betes, and hypercholesterolemia is seen in the ER. His e. Vein of Galen
family explains that he has had difficulty doing things
around the house for the last few days. The patient him- 80. An 81-year-old right-handed man with hypertension and
self admits that he has found it difficult to get dressed hypercholesterolemia presents with the sudden onset of a
and to prepare his breakfast, but he feels healthy other- dense right hemiplegia. His language is normal, and he has
wise. On examination his speech is fluent, and he is able normal eye movements and pupillary reactions. He has no
to name objects and repeat short phrases without diffi- sensory deficits. What is the most likely localization of his
culty. He is, however, unable to mimic certain activities stroke?
described by the examiner, although he seems to have a. Left motor cortex
no difficulty understanding what it is that he is supposed b. Left internal capsule
to do. c. Left thalamus
a. He likely has a form of Wernicke aphasia due to a lesion d. Left midbrain
in the left superior temporal lobe. e. Left lateral medulla
12887_BM_Questions.qxd 10/4/08 3:13 PM Page 196
81. In which of the following disorders would the highest ele- 86. A 71-year-old with a clinical diagnosis of Alzheimer disease
vation of creatine kinase (CK) be expected? comes to autopsy after a fatal motor vehicle accident.
a. Becker muscular dystrophy Which of the following is a neuropathological hallmark of
b. Duchenne muscular dystrophy Alzheimer disease?
c. Lambert-Eaton myasthenic syndrome a. Lewy bodies in the substantia nigra
d. Limb-girdle muscular dystrophy b. Lewy bodies in cortical neurons
e. Myotonic dystrophy c. Prominent atrophy of caudate
d. Spongiform changes in cortex
82. A 68-year-old man with no major medical problems attends e. Neurofibrillary tangles
his annual visit with his primary care physician. The doctor
wishes to perform a brief screening neurologic examination. 87. A 34-year-old man comes for neurologic consultation be-
Which of the following parts of the neurologic exam would cause of paroxysmal episodes of speech difficulty that
be the most sensitive for the detection of potential abnor- have occurred recently. The best way to distinguish
malities in multiple different parts of the nervous system? whether these are seizures or other types of events is:
a. Deep tendon (muscle stretch) reflexes a. History
b. Gait evaluation b. Neurologic examination
c. Visual field examination c. Brain MRI
d. Joint position sense testing d. Routine EEG
e. Total weight-lifting capacity e. Empiric anticonvulsant trial
83. A 78-year-old woman with a history of coronary artery dis- 88. A 16-year-old college student is seen in the emergency
ease and hypercholesterolemia develops the sudden room for fever, confusion, and headache. Lumbar puncture
onset of paralysis of all four extremities. On examination is performed. Which of the following cerebrospinal fluid
her eyes are open, she appears alert, and she can consis- profiles is most consistent with acute bacterial meningitis?
tently respond to complex questions and commands by a. Normal white blood cell count, high protein, low
blinking her eyes but otherwise has minimal facial move- glucose
ment and no movement of the extremities. This condition b. Normal white blood cell count, high protein, high
is best described as: glucose
a. Locked-in syndrome c. Elevated white blood cell count, high protein, low
b. Persistent vegetative state glucose
c. Brain death d. Elevated white blood cell count, high protein, high
d. Coma glucose
e. Stupor e. Decreased white blood cell count, high protein, high
glucose
84. A 30-year-old man is found to have increased intracranial
pressure after a head injury. Which of the following treat- 89. A 55-year-old man presents with headache and right hand
ments can serve to lower intracranial pressure? weakness. On examination you find bilateral papilledema
a. Lowering the head of the bed and upper motor neuron weakness in the right arm and leg.
b. Intravenous fluid load MRI with contrast shows an enhancing mass in the left frontal
c. Depression of respiratory rate region, crossing the corpus callosum in a “butterfly” pattern
d. Mannitol with surrounding edema. Prior to requesting a biopsy, you
e. Basilar artery stent discuss with your resident that this is most likely a:
a. Meningioma
85. An 80-year-old man has developed gradually worsening b. Astrocytoma
memory over the past several years. His wife also reports c. Glioblastoma
that he appears to have vivid visual hallucinations at times, d. Ependymoma
and his alertness has been fluctuating on a day-to-day e. Schwannoma
basis. Examination demonstrates bradykinesia and rigidity
in the extremities, without any dyskinesias. What is the 90. You evaluate a 22-year-old woman complaining of visual
most likely diagnosis? problems. Your examination shows bitemporal visual field
a. Alzheimer disease defects. Where is the lesion?
b. Dementia with Lewy bodies a. Right optic nerve
c. Vascular dementia b. Right occipital lobe
d. Huntington disease c. Left optic radiation
e. Progressive supranuclear palsy d. Optic chiasm
12887_BM_Questions.qxd 10/4/08 3:13 PM Page 197
Questions • 197
e. This visual field defect is nonphysiologic, suggesting a the emergency room, she is found to have rotatory and
psychiatric explanation. downbeating nystagmus during the Dix-Hallpike maneuver
with the head tilted one way but not the other. The neuro-
91. You are asked to evaluate a 33-year-old construction logic examination is otherwise entirely normal. Which of the
worker who is complaining of paresthesias in the first and following is the most likely diagnosis?
second digits of his right hand. Your physical examination a. Meniere disease
shows no weakness but a mild decrease in light touch over b. Cerebellar stroke
the thumb. You request a nerve conduction study to rule c. Benign positional paroxysmal vertigo (BPPV)
out carpal tunnel syndrome, and it turns out to be normal. d. Perilymph fistula
On repeated history, the patient indicates that on occa- e. Vestibular neuronitis
sion, he gets a sharp, “electric” pain travelling from his
neck to the right hand. What are you missing? 95. A 77-year-old woman with a history of migraine in her 20s
a. A median neuropathy at the wrist and 30s is seen by her primary care physician with the
b. A neuromuscular junction disorder affecting distal complaint that she has experienced headaches again for
hand muscles the first time in many years. Upon further enquiry she
c. A C8–T1 radiculopathy reports a sense of generalized fatigue and notes that there
d. A lower trunk brachial plexopathy is discomfort over her right temple when she brushes her
QUESTIONS
e. A C6-7 radiculopathy hair. The neurologic examination is normal. Which of the
following would be the most appropriate clinical course?
92. A 75-year-old man underwent surgery to correct a large a. Reassurance that her headaches likely represent recur-
abdominal aortic aneurysm. The procedure appeared to rence of her old migraines. No further investigations
go well, but you are called a few hours later to evaluate are needed
the patient who states that he cannot move or feel his b. MRI of the brain to rule out an intracranial mass lesion,
legs. On the way to the ICU, you consider the pos- as new-onset headaches in the elderly are commonly
sible causes of his symptoms and plan your physical exa- caused by raised intracranial pressure
mination. What is the most important test to help localize c. Lumbar puncture to rule out high or low pressure
the lesion? headaches
a. MRI of the spine d. ESR, CRP, and temporal artery biopsy, as giant cell ar-
b. Sensory level teritis is the most likely diagnosis
c. Reflexes in lower extremities e. Explanation that she likely has trigeminal neuralgia,
d. Plantar flexion reflex given the distribution of her symptoms over the right
e. Toe position sense temporal region
93. A 19-year-old man presents to the emergency depart- 96. A 63-year-old man with poorly controlled hypertension
ment with 2 days of ascending weakness. He had diarrhea is brought to the emergency room after being found by his
3 weeks earlier. He looks comfortable. On examination, wife in a confused state. He had been fine when she left to
you find moderate weakness in all limbs, with normal go shopping, but when she returned several hours later,
strength in facial muscles. You suspect Guillain-Barré syn- she found that he wasn’t making any sense when talking.
drome and recommend admission to Neurology. What When you examine him you find that his naming is im-
should be done first? paired and his verbal fluency is reduced, but other lan-
a. Spinal tap to look for albuminocytologic dissociation guage functions are intact. You note that his speech is soft.
b. Call for an emergency EMG to verify diagnosis Which of the following conclusions is most accurate?
c. Send the patient for a whole spine MRI to rule out cord a. The reduced verbal fluency, together with an anomia, is
compression most suggestive of a posterior (Broca) aphasia.
d. Obtain pulmonary function tests, including FVC b. The hypophonia, together with the evidence for a lan-
e. Start high-dose steroids and then move to the floor guage impairment, is most suggestive of a subcortical
aphasia.
94. A 55-year-old woman is seen in the emergency room with c. He does not have an aphasia given that his language
the complaint that when she rolled over in bed in the morn- functions other than verbal fluency and naming are
ing she felt acutely vertiginous for about 30 seconds, with intact.
associated nausea and vomiting. Over the course of the day, d. The impaired ability to name objects (anomia) is most
the vertigo has recurred, each time precipitated by turning suggestive of a conduction aphasia.
her head. She has no other symptoms and feels well in be- e. The soft speech, together with the anomia and reduced
tween the episodes of vertigo. She is known to have poorly verbal fluency, suggests that he has a transcortical
controlled diabetes and hypertension. When examined in motor aphasia.
12887_BM_Questions.qxd 10/4/08 3:13 PM Page 198
97. A 27-year-old African-American woman with diabetes 99. Which of the following are the cardinal features of idio-
presents to the outpatient Neurology clinic with suba- pathic Parkinson disease?
cute onset of bilateral facial weakness. She explains that a. Tremor, bradykinesia, rigidity, and postural instability
the symptoms have developed over the course of the last b. Bradykinesia, dementia, tremor, and rigidity
few days. She also reports having a slightly raised and c. Rigidity, hallucinations, tremor, and postural instability
tender rash over the anterior aspects of both shins. d. Tremor, rigidity, bradykinesia, and gaze palsy
On examination you find bilateral lower motor neuron fa- e. Tremor, autonomic dysfunction, bradykinesia, and
cial palsy as well as tender erythematous nodules over rigidity
both shins. Which of the following is the most likely
diagnosis? 100. Which of the following statements regarding higher
a. Guillain-Barré syndrome cortical function is true?
b. Lyme disease a. Aphasia is characterized by a problem with articulation
c. Neurosarcoidosis of words.
d. Diabetes b. Apraxia is defined by the inability to carry out an auto-
e. Tuberculosis matic or unlearned motor task.
c. Agnosia is an inability to recognize objects through a
98. Ataxia may be a manifestation of which vitamin deficiency? sensory modality even when the primary sensory
a. Vitamin A modality is unimpaired.
b. Vitamin B d. Neglect is a form of apraxia in which there is insuffi-
c. Vitamin C cient attention paid to one hemispace.
d. Vitamin D e. Agraphia is a disorder in which affected individuals are
e. Vitamin E unable to draw pictures.
12887_BM_Answers.qxd 10/4/08 3:11 PM Page 199
A
Answers • 199
Answers
1. c (Chapter 12) generally associated with positive anti-Hu antibodies (anti-
The presence of visual hallucinations is an early symptom neuronal antibodies) and can also be associated with parane-
of dementia with Lewy bodies (DLB). Other characteristics oplastic encephalomyelitis, ataxia, and autonomic neuropa-
include cognitive decline, fluctuations of alertness, extrapyra- thy. Anti-GM1 has been associated with multifocal motor neu-
midal symptoms, and an extraordinary sensitivity to neu- ropathy with conduction block. MRI of the spine would not
roleptics. Visual hallucinations and sensitivity to neuroleptics help at this stage. Other causes of sensory neuronopathy in-
are not early signs of AD, PD, Pick disease, or vascular clude Sjögren syndrome, pyridoxine intoxication, and
dementia. chemotherapy (cisplatin). Chest CT to search for occult malig-
nancy is also recommended.
2. b (Chapter 4)
5. d (Chapter 1)
Decreased visual acuity that does not correct with pinhole
testing, an RAPD, and a central scotoma is characteristic of Each cranial nerve courses through a particular foramen, or
optic nerve disease. A lesion affecting the optic chiasm will opening, in the skull. Skull base fractures and other such in-
produce a bitemporal heteronymous hemianopia. If a lesion juries can result in damage to these structures and injury to
affects the optic tract, the optic radiations (in both temporal the associated cranial nerves. The seventh (facial) and eighth
and parietal areas) or the occipital cortex (unilaterally), it will (vestibulocochlear) nerves both course through the internal
produce a homonymous hemianopia; that in the occipital cor- auditory meatus, which may have been damaged in this
tex may be “macular sparing.” woman’s case.
199
12887_BM_Answers.qxd 10/4/08 3:11 PM Page 200
The “blown” right pupil suggests that herniation of the right 13. b (Chapter 9)
hemisphere has compressed the right oculomotor nerve. MS characteristically produces an upper motor neuron blad-
Choices A through C are all measures that acutely decrease der or spastic bladder with increased frequency and urgency.
ICP, while neurosurgery may be needed as a more definitive Stress incontinence is an involuntary loss of urine during
intervention. Performing an LP in this situation could be dan- coughing, sneezing, laughing, or other physical activities that
gerous and could actually precipitate worsening herniation. increase intra-abdominal pressure. An atonic bladder is char-
acterized by overflow incontinence and increased capacity
8. e (Chapter 5) and compliance.
Symmetric proximal weakness usually suggests a primary
muscle problem, as does weakness of neck flexors and ex- 14. a (Chapter 9)
tensors. The absence of muscle pain and tenderness does Atonic bladder implies an LMN lesion at the level of the conus
not argue against a primary muscle pathology. The other medullaris, cauda equina, sacral plexus, or peripheral nerves.
listed choices would not usually result in this pattern of It is characterized by overflow incontinence and increased ca-
weakness. pacity and compliance. Diabetes is the only one in the group
able to produce that type of lesion.
9. b (Chapter 15)
This child likely has absence seizures, which are frequently 15. a (Chapter 24)
diagnosed after a teacher or parent notices inattention, “day- Myotonic dystrophy is a multisystem disorder that may also
dreaming,” or staring episodes. Absence seizures last a few cause frontal balding, diabetes, and gastrointestinal symp-
seconds each, can occur many times a day, and have a classic toms. It is the most common adult-onset muscular dystrophy.
EEG appearance. Ethosuximide and valproic acid are typical It is inherited in an autosomal dominant fashion and is caused
drugs of choice. by a triplet repeat expansion in the DMPK gene. EMG typically
shows myotonic discharges.
10. b (Chapter 10)
This woman is suffering from a migraine headache. 16. b (Chapter 16)
Sumatriptan is effective as abortive treatment. The other She likely has Wilson disease, an autosomal dominant disor-
medications are effective in decreasing the severity and fre- der of copper metabolism that presents with neuropsychiatric
quency of attacks and are used as preventive therapy. symptoms as well as a movement disorder. The pigment
changes in the cornea are Kayser-Fleischer rings and are char-
11. c (Chapter 12) acteristic of Wilson disease.
This case represents an early onset of dementia with associ-
ated personality changes and movement disorder (chorea)— 17. a (Chapter 5)
the classic triad of HD. HD is linked to chromosome 4p16.3, The patient’s current symptoms are suggestive of a right radial
also known as the HD gene, encoding for a protein called hun- neuropathy. Multiple sequential mononeuropathies, each af-
tingtin. The mutation produces an unstable CAG repeat fecting a single peripheral nerve, are known as mononeuropa-
sequence with more than 40 repeats. HD is not linked to the thy multiplex. Pain is a typical feature. Patients with rheumato-
other chromosomes listed. logic conditions are susceptible; vasculitis may be involved.
Answers • 201
pleocytosis. Fungal meningitis is usually associated with hypo- lateral gaze plus nystagmus of the abducting left eye.
glycorrhacia (defined as a CSF-serum glucose ratio below 0.4). Adduction during convergence is maintained because this ac-
Subarachnoid hemorrhage characteristically produces a large tion does not depend on the MLF. “One-and-a-half syndrome”
number of RBCs (thousands). occurs as a consequence of a lesion involving the PPRF or
sixth-nerve nucleus and the adjacent ipsilateral MLF. This pro-
20. c (Chapter 2) duces an ipsilateral gaze palsy and INO on the contralateral
side; the only eye movement present in the lateral plane is ab-
About 50% of patients with epilepsy have normal routine
duction of the contralateral eye.
EEGs. A seizure is a clinical diagnosis, and this patient’s con-
vincing story supersedes the negative EEG. Long-term video-
EEG monitoring is not required to prove the diagnosis of 26. a (Chapter 21)
seizure. While hyperventilation can help to elicit absence Aseptic meningitis and cranial nerve palsies (such as facial
seizure activity on EEG, his history and age make an absence nerve palsy) are among the early manifestations when the
seizure unlikely. Although an ischemic stroke can precipitate nervous system becomes involved in Lyme disease. Painful
a seizure, this man’s history is most suggestive of seizure. The polyradiculopathy or leukoencephalopathy are two (typically
right hemiparesis is more likely a Todd paralysis rather than an later) nervous system complications of Lyme. Spinal cord
ischemic stroke. compression and generalized epilepsy would not be ex-
pected to occur as a direct consequence of this disorder.
21. a (Chapter 11)
This patient exhibits a form of neglect, in which he does not 27. c (Chapter 18)
recognize his left arm as his. Right frontal or parietal lesions Sarcoidosis is one of the most common causes of bilateral LMN
are the most common etiology. In the alien-limb phenome- facial weakness. It is also an important cause of a lymphocytic
non, patients retain awareness of the limb but feel that it is meningitis (hence the headache) and may cause a variety of
not under their control. other cranial neuropathies, including optic neuropathy (hence
the relative afferent papillary defect). MS is another important
22. a (Chapter 15) cause of optic neuritis, but bilateral facial weakness would be
unusual. GBS may cause bilateral facial weakness but typically
Benzodiazepines are the first agents used in the treatment al-
in the context of areflexia and generalized weakness; the rela-
gorithm for status epilepticus. Typically, phenytoin and then
tive afferent papillary defect would be unusual. Lyme disease
phenobarbital are used subsequently. Propofol is used if sta-
may cause bilateral facial weakness similarly (although unilat-
tus epilepticus becomes refractory, while carbamazepine and
eral facial weakness would be more common); the afferent pap-
lamotrigine are anti-epileptic drugs that are not available in
illary defect would not be expected. Vasculitis is an extremely
parenteral form.
unusual cause of bilateral facial weakness.
ANSWERS
cerebral artery with leg weakness as the result. Ipsilateral third
tient’s stroke risk factors, he most probably has had a pure
nerve palsy is the first sign of uncal (not subfalcine) herniation.
sensory stroke. The most likely lesion is in the contralateral
Continued uncal herniation may result in compression of the
thalamus, because the sensory pathways cross prior to
contralateral cerebral peduncle against the free edge of the
synapsing in the thalamus. The left postcentral gyrus is on the
tentorium, leading to ipsilateral hemiparesis (the “Kernohan’s
wrong side to explain the patient’s deficit. Also, it is unusual to
notch” phenomenon). Contralateral third nerve palsy and con-
have sensory loss of the face, arm, and leg equally from a
tralateral hemiparesis are not features of subfalcine herniation.
stroke affecting the postcentral gyrus. This is because the
middle cerebral artery provides blood to the face and arm re-
24. e (Chapter 20) gions of the cortex, while the anterior cerebral artery supplies
Intravenous corticosteroids may delay but not prevent the de- blood to the leg region. The precentral gyrus is predominantly
velopment of MS in a patient with optic neuritis. They are pre- involved in motor pathways and not the sensory system. A le-
ferred to oral corticosteroids. Inteferon beta-1b and mito- sion of the right corona radiata would be expected to cause a
xantrone are used for MS but not in the treatment of isolated left hemiparesis rather than left hemisensory loss.
optic neuritis.
29. b (Chapter 17)
25. c (Chapter 4) The middle meningeal artery travels between the skull and
Lesions of the MLF produce an INO. The clinical characteristics the dura. When this vessel is damaged (typically due to
of a right INO include inability to adduct the right eye in left trauma resulting in a skull fracture that lacerates that artery),
12887_BM_Answers.qxd 10/4/08 3:11 PM Page 202
Answers • 203
Answers • 203
39. d (Chapter 24) middle cranial fossa from head trauma. If large enough, the
The primary antigenic target in autoimmune MG is the post- mass lesion causes displacement of the medial portion of the
synaptic acetylcholine receptor. Presynaptic voltage-gated temporal lobe (uncus) downward over the tentorium cere-
calcium channels are the target of the Lambert-Eaton myas- belli. This typically results in compression of the brainstem
thenic syndrome. and entrapment of the third cranial nerve. This compression
can cause coma due to disruption of the ascending arousal
system from the brainstem. It causes an ipsilateral dilated
40. a (Chapter 1)
pupil due to compression of the parasympathetic nerve fibers
The trigeminal nerve is responsible for the muscles of masti- (traveling with the third cranial nerve) that normally cause
cation. The facial nerve innervates the muscles of facial pupillary constriction. Diffuse axonal injury can result in coma
expression, the oculomotor nerve subserves eye movements, but would not be expected to be responsible for a unilateral
the glossopharyngeal nerve innervates some pharyngeal dilated pupil that is nonreactive to light.
muscles, and the hypoglossal nerve moves the tongue.
46. a (Chapter 14)
41. d (Chapter 3)
Intracerebral hemorrhages caused by hypertension are most
The GCS—which provides a composite assessment of unre- often found in the basal ganglia, thalamus, pons, and cerebel-
sponsive patients based on their eye movements, motor func- lum, in order of decreasing frequency.
tion, and language ability—is typically used for patients after
head trauma. It has prognostic value for head-injured patients 47. c (Chapter 13)
and is easy for nonphysicians to use.
Pemoline and methylphenidate are stimulants used for the
treatment of narcolepsy. Clomipramine is a tricyclic antide-
42. b (Chapter 3)
pressant used for the treatment of cataplexy. Because ob-
A noncontrast head CT is the imaging study of choice in sus- structive sleep apnea is characterized by repetitive episodes
pected intracranial hemorrhage. This allows for the easiest de- of upper airway obstruction during sleep, treatment is often
lineation of acute blood, which should appear hyperdense with CPAP, which helps maintain airway patency during sleep.
(bright) on this study. Head CT with contrast, skull x-ray, and Alcohol and sedating drugs such as benzodiazepines can de-
brain perfusion scan do not help to identify acute blood. crease upper airway tone, resulting in worsened symptoms.
Cerebral angiography would be indicated only if a ruptured Last, obesity is a risk factor for obstructive sleep apnea, so
aneurysm or other vascular anomaly were suspected as the weight loss may prove beneficial in obese patients.
cause of an intracranial hemorrhage.
48. a (Chapter 19)
43. e (Chapter 10) A headache that is either different from the normal pattern or
The patient’s clinical presentation is typical for temporal progressive deserves to be investigated further with a brain
arteritis: age over 50, pain over the temporal arteries, jaw clau- imaging study. Slowly progressive brain tumors can be asso-
dication, and an elevated ESR. Definitive diagnosis is made by ciated with a normal neurologic exam or minor abnormalities.
ANSWERS
temporal artery biopsy. Treatment with prednisone for sev- Nausea and vomiting need not be present, especially in the
eral months must be initiated early, because involvement of early stages of a tumor. Administration of pure oxygen is an
the ophthalmic artery can lead to blindness if diagnosis and effective treatment for cluster headaches, but the patient’s
treatment are delayed. description is not consistent with this diagnosis.
response (Babinski sign). Signs of lower motor neuron (LMN) 56. b (Chapter 5)
dysfunction include hypotonia, decreased or absent reflexes, “Crossed signs” can occur with unilateral lesions in the pons
and a flexor plantar response (downgoing toe). Weakness may if descending motor fibers heading for the ipsilateral facial
be present with either UMN or LMN dysfunction. nucleus are affected, with the descending fibers heading for
the contralateral spinal cord. With right pontine lesions, the
51. a (Chapter 2) right face and left body could be weak.
CT is the imaging modality of choice for demonstrating acute
intracranial bleeding. While it is true that MRI provides better 57. e (Chapter 15)
visualization of the contents of the posterior fossa, a cerebel- Characteristic side effects of carbamazepine include hypona-
lar hemorrhage usually will be visible on CT. Patients with tremia, agranulocytosis, and the risk for Stevens-Johnson
pacemakers and other implanted metal objects cannot un- syndrome. Except for the hyponatremia, these side effects
dergo MRI. Although MRI with diffusion-weighted imaging is are rare.
the most sensitive modality for ischemic stroke, a susceptibil-
ity-weighted MRI sequence is preferred for detecting intracra- 58. c (Chapters 14 and 17)
nial blood.
Tearing of bridging veins produces a subdural hematoma.
Laceration of the middle meningeal artery causes an epidural
52. b (Chapter 21)
hematoma. Amyloid angiopathy is a cause of lobar hemor-
In the presence of severe Lyme disease with CNS involvement, rhage in the elderly. Although arteriovenous malformation
as in this case, intravenous antibiotics followed by oral ther- (AVM) rupture is a cause of subarachnoid hemorrhage,
apy comprise the first choice. Here, intravenous ceftriaxone is aneurysmal rupture is a more common cause.
the first choice. The combination of oral amoxicillin and doxy-
cycline is the most common treatment for uncomplicated 59. b (Chapter 19)
Lyme disease. Fluconazole is an antifungal and has no value in
the treatment of Borrelia burgdorferi infection. Meningiomas enhance in a bright and mainly homogeneous
manner. Certain tumors (particularly glioblastoma multiforme
and metastatic lesions), brain abscesses, toxoplasmosis, gran-
53. c (Chapter 12) ulomas, and active demyelinating lesions typically show ring
Pathologically, PD is characterized by progressive death of enhancement after contrast administration. While lym-
dopaminergic neurons of the substantia nigra pars compacta. phomas can enhance in a homogeneous manner, they can
Most cases of PD are sporadic, but there are reports of familial also be ring-enhancing.
cases in which mutations in the parkin and ␣-synuclein genes
have been described. Impairment of vertical gaze is a common 60. b (Chapter 7)
feature of progressive supranuclear palsy (PSP), a neurodegen-
Micturition syncope is a form of reflex or neurogenic syn-
erative disorder that is also characterized by parkinsonian fea-
cope that involves the triggering of cardioinhibitory and/or
tures. Despite the gait manifestations of PD, early falls are
vasodepressor responses. The symptoms of light-headed-
actually uncommon (but are common in PSP).
ness and graying of vision are typically reported by patients
with syncope. Other symptoms might include a heavy feel-
54. d (Chapter 24) ing at the base of the neck, buckling at the knees, and tinni-
DMD and BMD are allelic disorders due to mutations in the tus. Although orthostatic hypotension is a common cause of
dystrophin gene, located on the X chromosome. The inheri- syncope, the occurrence of syncope after micturition, rather
tance pattern is X-linked. The limb-girdle muscular dystrophies than upon standing, suggests that this is not the cause in
are a heterogeneous group of disorders, some with autosomal this case. Vasovagal syncope is another common cause of
dominant and some with autosomal recessive inheritance. syncope but typically occurs in the setting of acute pain or
Mutations in a wide variety of genes have been reported in pa- with a strong emotional response. Vestibular neuronitis is
tients with limb-girdle muscular dystrophy, including the characterized by vertigo, and there is no associated loss of
sarcoglycan genes. consciousness.
Answers • 205
HSV infection is suspected, however, treatment should begin in the epidural or subdural spaces. Diffuse axonal injury results
promptly with intravenous acyclovir even while tests are from rotational acceleration and deceleration of the head and
pending, because mortality is close to 70% in untreated cases. can be associated with either a normal head CT scan or hem-
orrhages within the deep white matter of the brain. Lastly, rup-
62. b (Chapter 23) ture of a cerebral aneurysm results in subarachnoid hemor-
rhage and not an epidural hematoma.
Physical examination is the most important information to de-
fine symptoms as belonging to the peripheral nervous system
(PNS). Sensory symptoms can have a central or peripheral ori- 67. b (Chapter 16)
gin. The acuteness of the presentation does not help localiza- Progressive supranuclear palsy is a disorder characterized by
tion in this case. Paresthesias may be seen in both PNS and parkinsonism, supranuclear impairment of eye movements
CNS dysfunction. (vertical gaze typically affected more prominently than hori-
zontal gaze), and impaired postural reflexes. Corticobasal
63. a (Chapter 17) ganglionic degeneration and PD may also cause rigidity and
poor postural reflexes, but are not typically associated with
Neurosurgical decompression is the treatment of choice for
eye movement abnormalities. The MFS and chronic PEO
an epidural hematoma that has resulted in uncal herniation.
are both associated with eye movement abnormalities,
This is a neurosurgical emergency, so conservative manage-
but these disorders affect the external ocular muscles rather
ment would only result in further neurologic decline. While
than the supranuclear gaze centers and are not associated
hyperventilation and administration of mannitol may help to
with extrapyramidal features.
decrease intracranial pressure, these are temporizing mea-
sures; neurosurgical decompression is necessary to remove
68. b (Chapter 18)
the accumulating blood. Because the patient has a hemor-
rhage, tissue plasminogen activator, which is used in acute Small-fiber neuropathy typically produces symptoms of
ischemic strokes, would be contraindicated. neuropathic pain, and examination discloses impaired tem-
perature and pinprick sensation. Other sensory modalities are
mediated by large fibers. Weakness and atrophy reflect
64. c (Chapter 20)
involvement of motor fibers rather than small-fiber sensory
ADEM is a monophasic demyelinating illness. MS is character- function.
ized by multiple white matter lesions separated in space and
time and is therefore not monophasic. Oligoclonal bands in 69. a (Chapter 22)
the CSF are more common in MS than in ADEM. The pleocy-
tosis of ADEM is lymphocytic. Both MS and ADEM can produce The patient exhibits both upper motor neuron signs (hyper-
multiple lesions on MRI. ADEM is acquired and commonly reflexia, spasticity, and Babinski signs) and lower motor neu-
occurs after viral infections or vaccinations. A positive family ron signs (atrophy and fasciculations), which are the hallmark
history is more likely to be relevant for a patient with MS. of ALS. Weakness can occur with either lower motor neuron
(LMN) or upper motor neuron (UMN) dysfunction. None of the
other options listed would cause widespread findings in both.
65. b (Chapter 23)
ANSWERS
Vitamin B12 deficiency classically results in degeneration of
This is a common presentation of proximal diabetic neuropa- the dorsal columns (loss of joint position sense) and corti-
thy, also known as diabetic amyotrophy. It represents a form cospinal tracts (UMN signs). Anterior spinal artery syndrome
of polyradiculoneuropathy that has a predilection for the lum- usually results from infarction of the anterior spinal artery,
bosacral plexus and in general tends to recover sponta- causing ischemia to the anterior two-thirds of the spinal cord.
neously over months to years. The etiology is likely different Therefore dorsal columns are spared, but weakness and loss
from the more common distal symmetric polyneuropathy of pain and temperature sensation result because of involve-
seen in diabetes. ment of the ventral horns and spinothalamic tracts. Central
cord syndrome is most common in the cervical cord and typi-
66. b (Chapter 17) cally results in loss of pain and temperature sensation in a
The patient’s symptoms and head CT findings are consistent cape-like distribution. Brown-Séquard syndrome results from
with an epidural hematoma, which results from laceration of hemisection of the spinal cord. The classic features are ipsilat-
the middle meningeal artery. The classic head CT finding of an eral weakness and loss of joint position sense with contralat-
epidural hematoma is a hyperdense region with a biconvex or eral loss of pain and temperature sensation below the lesion.
lenticular shape. Tearing of bridging veins results in a subdural
hematoma. Impact of the brain over the bony prominences of 70. e (Chapter 13)
the skull results in cerebral contusions. On head CT, these areas The patient’s history of excessive daytime sleepiness, visual
appear as hyperdensities within the brain parenchyma and not hallucinations while falling asleep (hypnagogic hallucinations),
12887_BM_Answers.qxd 10/4/08 3:11 PM Page 206
and transient loss of tone triggered by emotional states (cata- with inability to perform certain actions described by the ex-
plexy) is characteristic of narcolepsy. Of the choices listed, aminer. “Apraxia” refers to the inability to perform a learned
methylphenidate is the best option, as it will treat the exces- motor task and it is typically caused by lesions in either the
sive daytime sleepiness and cataplexy. Clomipramine and ven- frontal or parietal lobe of the dominant hemisphere.
lafaxine are primarily effective for treating the cataplexy but
will not improve the patient’s daytime sleepiness. CPAP is a 76. d (Chapter 2)
treatment for obstructive sleep apnea. Pemoline is an effective
Xanthochromia is the yellow discoloration of the supernatant
medication, but due to possible hepatic toxicity, it is usually re-
(if blood has been present for a few hours) in a spun sample of
served for use when other medications have failed.
CSF that characterizes the presence of blood due to a sub-
arachnoid hemorrhage. In a traumatic tap, the red cells pre-
71. a (Chapter 16) cipitate, and the supernatant is colorless. Increased opening
The extrapyramidal features of idiopathic PD are typically pressure, increased white cell count, and pain upon needle in-
asymmetric. Postural reflexes may be impaired in a number of sertion may or may not be present in either condition.
extrapyramidal disorders including idiopathic PD. Impaired Increased red cell count is seen in both subarachnoid hemor-
vertical gaze is more typical of progressive supranuclear palsy rhage and a traumatic tap.
than of idiopathic PD.
77. e (Chapter 2)
72. c (Chapter 8) While T1 and T2 images may detect blood breakdown prod-
MFS is a disorder characterized by ataxia, ophthalmoplegia, ucts, susceptibility imaging or gradient-echo imaging is the
and areflexia. It is considered a variant of the Guillain-Barré most sensitive technique for determining the presence of in-
syndrome and is associated with the finding of anti-GQ1b an- tracranial hemorrhage. Contrast-enhanced T1 is more useful
tibodies in the serum. Stroke (involving either the brainstem for detecting the presence of a brain tumor. FLAIR imaging is
or cerebellum) should be sudden in onset and typically would the single best MRI technique for screening for most types of
not be expected to progress over a period of several days. intracranial lesions.
Ophthalmoplegia may be seen in both MG and the MFS, but
areflexia is not a feature of MG. Alcoholic cerebellar degener- 78. c (Chapter 13)
ation may be associated with a peripheral neuropathy and
Synucleinopathies are associated with REM sleep behavior
loss of joint position sense and deep tendon reflexes but
disorder. Examples of synucleinopathies are Parkinson dis-
should not produce ophthalmoplegia (unless associated with
ease, Lewy body dementia, and multiple system atrophy.
Wernicke encephalopathy, in which case confusion should
Alzheimer disease, multiple sclerosis, myasthenia gravis, and
also be present).
primary lateral sclerosis are not synucleinopathies and are not
associated with REM sleep behavior disorder.
73. c (Chapter 9)
Acute urinary incontinence is an emergency. MRI of the spine 79. a (Chapter 14)
will help to determine whether an acute lesion is responsible
Of the vascular malformations, arteriovenous malformations
for the incontinence (cauda equina or conus medullaris syn-
are at the greatest risk to bleed, with a rate of bleeding of
drome, spinal cord compression, etc.). Determination of the
approximately 2% to 3% per year. Capillary telangiectasias,
PVR would not help in this situation, and urodynamic studies
cavernous hemangiomas, and developmental venous anom-
are not indicated in the acute setting. Lumbar puncture is not
alies are vascular malformations which rupture much less
indicated in this situation.
frequently, and are thus less likely to result in an intracra-
nial hemorrhage. The vein of Galen is a normal anatomic
74. d (Chapter 10) structure.
Both chronic paroxysmal hemicrania and cluster headache
are unilateral and can produce conjunctival injection. Chronic 80. b (Chapter 14)
paroxysmal headache is more common in women, whereas
The patient has a pure motor stroke involving the right side.
cluster headache is more common in men. Response to in-
Possible localization for this syndrome includes the left corona
domethacin is seen in chronic paroxysmal hemicrania but not
radiata, left internal capsule, and the left side of the base of the
in cluster headache. Episodes of chronic paroxysmal hemicra-
pons. Infarction of the motor cortex capable of producing a
nia typically last for 20 minutes rather than hours.
right hemiplegia would also likely cause an aphasia. Thalamic
strokes produce more prominent sensory than motor deficits.
75. e (Chapter 11) Infarction of the midbrain sufficient to produce a hemiplegia
Although the patient’s symptoms are somewhat nonspecific, would also be associated with eye movement abnormalities.
examination shows that he has normal language function but The lateral medullary (Wallenberg) syndrome is associated
12887_BM_Answers.qxd 10/4/08 3:11 PM Page 207
Answers • 207
with ipsilateral ataxia, ipsilateral Horner syndrome, and ipsilat- of Lewy bodies in the substantia nigra suggests Parkinson dis-
eral facial sensory loss, with contralateral impairment of pain ease, and in cortical neurons suggests dementia with Lewy
and temperature in the arm and leg, nystagmus, and vertigo. bodies. Prominent atrophy of the caudate is seen in
Weakness is absent in a Wallenberg syndrome because motor Huntington disease. Spongiform changes in cortex suggest
fibers travel more anteriorly within the medulla. the possibility of Creutzfeldt-Jakob disease.
82. c (Chapter 1)
88. c (Chapter 21)
The ability to walk in a steady, coordinated manner requires
A CSF leukocytosis, elevated protein, and depressed glucose
the concerted functioning of multiple parts of the nervous
level form the characteristic profile in acute bacterial menin-
system, including motor pathways, sensory tracts, and the
gitis. Viral meningitides typically do not depress the CSF
cerebellum, among other things. Testing for gait abnormali-
glucose. Fungal and tuberculous meningitides can share a
ties is thus a sensitive way to detect abnormalities in many dif-
common profile with bacterial meningitis except that the
ferent nervous system functions.
leukocytosis predominantly involves lymphocytes rather
than neutrophils (except initially).
83. a (Chapter 3)
Locked-in syndrome, which generally occurs with large le-
89. c (Chapter 19)
sions in the base of the pons, such as infarcts from cardiac em-
bolism or basilar artery stenosis, is characterized by loss of all The typical “butterfly” pattern is characteristics of glioblas-
significant motor function except eye blinking or perhaps ver- toma multiforme. There are other tumors that can cross white
tical eye movements, with preservation of awareness and matter tracts, like lymphoma. The other options are very un-
cognitive function. A large pontine lesion will typically affect likely to produce this radiologic pattern. Moreover, the usual
corticobulbar and corticospinal fibers bilaterally, but blinking location of meningiomas, ependymomas, and schwannomas
and vertical eye movements are preserved because of intact is not those found on this MRI.
midbrain function.
90. d (Chapter 4)
ANSWERS
84. d (Chapter 3) Bitemporal visual field defects are seen in conditions affecting
Mannitol is an osmotic diuretic which can be used to lower in- the optic chiasm, such as suprasellar tumors. Lesions in the
creased intracranial pressure, although the benefit may be left optic radiation produce a right homonymous hemianopia,
transient. Lowering the head of the bed, loading intravenous and lesions of the right occipital lobe a left homonymous
fluids, or a decrease in respiratory rate would all have the effect hemianopia. Optic nerve lesions produce unilateral visual
of raising intracranial pressure. Basilar artery stenting is not an field defects.
appropriate intervention for increased intracranial pressure.
91. e (Chapter 6)
85. b (Chapter 12)
Sensory symptoms in the thumb can be related to median
Dementia with Lewy bodies may be the second most com- neuropathies (as in a carpal tunnel syndrome) but also to
mon type of dementing illness after Alzheimer disease. It is higher lesions such as those seen in a C6 radiculopathy. Lower
characterized by a parkinsonian motor syndrome, visual hal- trunk brachial plexopathy or C8 or T1 radiculopathies could
lucinations, and marked fluctuations in alertness, as well as an involve the 4th and 5th digits and intrinsic muscles of the
exquisite sensitivity to neuroleptic medications. hand (including those innervated by the median nerve). The
fact that the EMG did not show median neuropathy at the
86. e (Chapter 12) wrist, plus the history of radicular pain, makes a C6 or C7
The two neuropathological hallmarks of Alzheimer disease radiculopathy the most likely cause. Neuromuscular junction
are amyloid plaques and neurofibrillary tangles. The presence disorders do not present with pain or sensory symptoms.
12887_BM_Answers.qxd 10/4/08 3:11 PM Page 208
92. e (Chapter 22) the ESR and CRP and proceeding to temporal artery biopsy are
The patient appears to have an anterior spinal artery syn- critical if the feared complication of blindness from an anterior
drome (ASAS), a well-recognized complication of abdominal ischemic optic neuropathy is to be avoided. Migraine is very un-
aortic surgery. It usually includes a dissociated sensory loss as likely; it would be a mistake to assume that a new headache in
the anterior two-thirds of the spinal cord is perfused by the a 77-year-old woman represents recurrence of an old problem.
ASA, while the posterior third (posterior columns) is perfused MRI and LP are of no value in suspected GCA.
by posterior spinal arteries. Therefore, the corticospinal and
spinothalamic tracts are affected in ASAS, but the posterior 96. b (Chapter 11)
columns remain intact, with preservation of joint position The anomia (impaired naming) and reduced verbal fluency
sense. A sensory level should be present but may not help to indicate the presence of an aphasia (language disorder). The
define the location of the lesion (nor will reflexes). MRI of the reduced verbal fluency does suggest an anterior location, but
spine can help corroborate your clinical diagnosis but not the hypophonia is most suggestive of a subcortical (usually
show much quickly. thalamic) syndrome.
208
208
12887_BM_Appendix.qxd 10/4/08 3:12 PM Page 209
Appendix: Evidence-
Based Resources
Chapter 2 Chapter 6
Hasbun R, Abrahams J, Jekel J, et al. Computed tomography of Cervero F. Spinal cord mechanisms of hyperalgesia and allo-
the head before lumbar puncture in adults with suspected dynia: role of peripheral input from nociceptors. Prog Brain
meningitis. N Engl J Med 2001;345:1727–1733. Res 1996;113:413–422.
Kidwell CS, Chalela JA, Saver JL, et al. Comparison of MRI and Landy S, Rice K, Lobo B. Central sensitisation and cutaneous
CT for detection of acute intracerebral hemorrhage. JAMA allodynia in migraine: implications for treatment. CNS Drugs
2004;292:1823–1830. 2004;18:337–342.
Newman NJ. Neuro-ophthalmology and systemic disease— Delancey JO, Ashton-Miller JA. Pathophysiology of adult uri-
Part I. An annual review (1994). J Neuroophthalmol 1995; nary incontinence. Gastroenterology 2004;126(suppl 1):
15:109–121. S23–S32.
Newman NJ. Neuro-ophthalmology and systemic disease— Payne CK. Epidemiology, pathophysiology, and evaluation of
Part II. An annual review (1994). J Neuroophthalmol 1995; urinary incontinence and overactive bladder. Urology 1998;
15:241–253. 51(suppl 2A):3–10.
209
12887_BM_Appendix.qxd 10/4/08 3:12 PM Page 210
Thomas DR. Pharmacologic management of urinary inconti- Mohr JP, Thompson JL, Lazar RM, et al. A comparison of war-
nence. Clin Geriatr Med 2004;20:vii–viii, 511–523. farin and aspirin for the prevention of recurrent ischemic
stroke. N Engl J Med 2001;345:1444–1451.
Chapter 10
Edlow JA, Caplan LR. Avoiding pitfalls in the diagnosis of sub- Sacco RL. Risk factors for TIA and TIA as a risk factor for stroke.
arachnoid hemorrhage. N Engl J Med 2000;342:29–36. Neurology 2004;62(suppl 6):S7–S11.
Headache Classification Subcommittee of the International Tissue plasminogen activator for acute ischemic stroke.
Headache Society. The International Classification of Headache The National Institute of Neurological Disorders and Stroke
Disorders: 2nd edition. Cephalalgia 2004;24(suppl 1):9–160. rt-PA Stroke Study Group. N Engl J Med 1995;333:1581–1587.
Lipton RB, Bigal ME, Goadsby PJ. Double-blind clinical trials of Chapter 15
oral triptans vs. other classes of acute migraine medication— Chang BS, Lowenstein DH. Mechanisms of disease: epilepsy. N
a review. Cephalalgia 2004;24:321–332. Engl J Med 2003;349:1257–1266.
Purdy RA, Kirby S. Headaches and brain tumors. Neurol Clin Nguyen DK, Spencer SS. Recent advances in the treatment of
2004;22:39–53. epilepsy. Arch Neurol 2003;60:929–935.
Watkins PJ, Thomas PK. Diabetes mellitus and the nervous sys- Lacomblez L, Bensimon G, Leigh PN, et al. A confirmatory
tem. J Neurol Neurosurg Psychiatry 1998;65:620–632. dose-ranging study of riluzole in ALS. ALS/Riluzole Study
Group II. Neurology 1996;47(suppl 4):S242–S250.
Chapter 19
Hentschel SJ, Lang FF. Current surgical management of Chapter 23
glioblastoma. Cancer J 2003;9:113–125. Koller HB, Kieseier C, Jander S, et al. Chronic inflammatory de-
myelinating polyneuropathy. N Engl J Med 2005;352:
Soffietti R, Ruda R, Mutani R. Management of brain metas- 1343–1356.
tases. J Neurol 2002;249:1357–1369.
Kornberg AJ, Pestronk A. Antibody-associated polyneuropa-
Chapter 20 thy syndromes: principles and treatment. Semin Neurol
Beck RW, Cleary PA, Anderson MM, et al. A randomized 2003;23:181–190.
controlled trial of corticosteroids in the treatment of optic
neuritis. The Optic Neuritis Study Group. N Engl J Med Verma S, Estanislao L, Simpson D. HIV-associated neuropathic
1992;326:584–588. pain: epidemiology, pathophysiology, and management. CNS
Drugs 2005;19:325–334.
Bergamaschi R, Ghezzi A. Devic’s neuromyelitis optica: clinical
Chapter 24
features and prognostic factors. Neurol Sci 2004;25(suppl 4):
Dalakas MC, Hohlfeld R. Polymyositis and dermatomyositis.
S364–S367.
Lancet 2003;362:971–982.
Calabresi PA. Diagnosis and management of multiple sclero- Emery AE. The muscular dystrophies. Lancet 2002;359:
sis. Am Fam Physician 2004;70:1935–1944. 687–695.
Filippini G, Munari L, Incorvaia B, et al. Interferons in relapsing Newsom-Davis J. Therapy in myasthenia gravis and
remitting multiple sclerosis: a systematic review. Lancet 2003; Lambert-Eaton myasthenic syndrome. Semin Neurol 2003;
361:545–552. 23:191–198.
Frohman EM. Multiple sclerosis. Med Clin North Am 2003; Sanders DB. Lambert-Eaton myasthenic syndrome: diagnosis
87:867–897. and treatment. Ann N Y Acad Sci 2003;998:500–508.
Garg RK. Posterior leukoencephalopathy syndrome. Postgrad Vincent A, Palace J, Hilton-Jones D. Myasthenia gravis. Lancet
Med J 2001;77:24–28. 2001;357:2122–2128.
Chapter 21 Chapter 25
Hussein AS, Shafran SD. Acute bacterial meningitis in adults. A Online: Mendelian inheritance in man: http://www.ncbi.
12-year review. Medicine 2000;79:360–368. nlm.nih.gov/entrez/query.fcgi?db5OMIM
Schmutzhard E. Viral infections of the CNS with special em- Nissenkorn A, Michelson M, Ben-Zeev B, et al. Inborn errors of
phasis on herpes simplex infections. J Neurol 2001;248: metabolism: a cause of abnormal brain development.
469–477. Neurology 2001;56:1265–1272.
Lacomblez L, Bensimon G, Leigh PN, et al. Dose-ranging study Wenger DA, Coppola S, Liu SL. Insights into the diagnosis and
of riluzole in amyotrophic lateral sclerosis. ALS/Riluzole Study treatment of lysosomal storage diseases. Arch Neurol
Group II. Lancet 1996;347(9013):1425–1431. 2003;60:322–328.
12887_BM_Index.qxd 10/4/08 3:13 PM Page 212
Index
Page numbers followed by t refer to tables; page numbers followed by f refer to figures.
Abducens, 35, 36f Aneurysm, in circle of Willis, 101, 102f Ataxia, 9, 58–62, 59b, 60t –61t
Abnormal optic disc, 33–34, 34t Angiography, 14, 14f Ataxic hemiparesis, 100
Abscess, 146–147, 147f, 154 Angular gyrus, 78f, 81 Atherosclerosis, 98
Absence seizure, 104, 104f Anisocoria, 32 Atonic bladder, 65, 65t, 67t
Acetylcholinesterase inhibitors, 87, 169 Anomia, 77 Atonic seizure, 104
Acrylamide, 166 Anosognosia, 83 Attention, assessment of, 5, 27
Acute bacterial meningitis, 145–146 Anterior circulation, 96–97, 97f, 99 Attention deficit-hyperactivity disorder
Acute confusional state, 27–28, 84 Anterior ischemic optic neuropathy (ADHD), 183–185
Acute disseminated encephalomyelitis (AION), 33–34, 34t Autistic spectrum disorders, 181–182
(ADEM), 144 Anterior spinal artery syndrome, 156 Autonomic failure, syncope with, 56–57
Acute inflammatory demyelinating Anterolateral system. See Autonomic neuropathies, 166
polyneuropathy (AIDP), 161–162, 166 Spinothalamic tract Autosomal dominant spinocerebellar
Acyclovir, 74, 149 Antiacetylcholinesterase drugs, 171 degenerations, 60
AD. See Alzheimer disease Antibiotics, 146–149 AVMs. See Arteriovenous malformations
ADEM. See Acute disseminated Anticholinergics, 67t, 68, 112, 114t, Azathioprine, 126, 143, 171, 176
encephalomyelitis 143–144 AZT. See Zidovudine
ADHD. See Attention deficit- Anticoagulation, 120
hyperactivity disorder Baclofen, 114, 143
Anticonvulsants, 71, 93, 121,
Adie’s pupil, 33 149–150, 165 Bacterial infections, 145–149, 147f
AEDs. See Antiepileptic drugs Antidepressants, 56, 67t, 68, 92, 94 Ballism, 116
Agnosia, 81 Antiemetics, 71 Barbiturates, 26, 123
AIDP. See Acute inflammatory Antiepileptic drugs (AEDs), 107–108, Becker muscular dystrophy (BMD),
demyelinating polyneuropathy 108f, 108t, 110, 121 170t, 172–173
AION. See Anterior ischemic optic Antihypertensives, 56, 68, 87t Benign positional paroxysmal vertigo
neuropathy (BPPV), 55, 56f
Antiphospholipid syndrome (APS), 129
Akathisia, 112 Benzodiazepines, 92–93, 114
Antiplatelet drugs, 101
Akinetic-rigid gait, 61, 61t Benztropine, 113t
Antipsychotics, 114t, 117, 177
Albendazole, 150 Beta agonists, 115b
Antipyretics, 112
Alcohol disorders, 58, 127–128, 127t Beta blockers, 56, 71, 112, 176
Antiretroviral therapy, 151, 162b
Alexia without agraphia, 80 Bethanechol, 67t
Antithrombotic agents, 101
Allodynia, 52 Bilateral pontine base stroke, 99
Aphasia, 27, 77–80, 78f, 78t –79t
Alpha-adrenergic agonists, 67t Bladder incontinence, 63–68, 64f,
Apraxia, 9, 37, 80–81
65t, 67t
Alprostadil, 68 APS. See Antiphospholipid syndrome
Bleeding, in brain, 100f –102f, 101–102
ALS. See Amyotrophic lateral sclerosis Arcuate fasciculus, 78f, 79
BMD. See Becker muscular dystrophy
Altered consciousness, 21–28, 22f, 23t, Argyll Robertson pupil, 33
Botulinum toxin, 116
24b –25b, 24f Arousal disorders, 94
BPPV. See Benign positional paroxysmal
Alzheimer disease (AD), 84–87, 87t Arteriovenous malformations
vertigo
Amantadine, 112, 113t –114t (AVMs), 102
Brachial plexus, 44, 45f
Amiodarone, 166 Asperger syndrome, 181–182
Bradykinesia, 111
Amphetamines, 94 Aspirin, 87t, 101
Brain
Amphotericin, 150 Astasia-abasia, 62
abscess of, 146, 147f
Amyotrophic lateral sclerosis (ALS), Asterixis, 124 bleeding in, 100f –102f, 101–102
157–158 Astrocytoma, 133–134, 134f herniation of, 121–122
212
12887_BM_Index.qxd 10/4/08 3:13 PM Page 213
Index • 213
infarction of, 54–55, 58, 99 Chronic inflammatory demyelinating Corticosteroids, 26, 129, 143–144, 146,
ischemia of, 98–99 polyradiculoneuropathy (CIDP), 163 176, 177t
tumors of, 131–138, 132t, CIDP. See Chronic inflammatory CP. See Cerebral palsy
134f –138f, 151 demyelinating polyradiculoneuropathy CPAP. See Continuous positive airway
Brain death, 27 Cilostazol, 101 pressure
Brain hemorrhage. See Hemorrhage Cimetidine, 177t CPP. See Cerebral perfusion pressure
Brainstem, 22–24, 23t, 47, 47f, 52t, Circadian rhythms, 92–93 Cranial nerves, 4t, 5–7, 6t, 23, 35–36
53–55 Critical illness neuropathies, 165
Circle of Willis, 97, 98f, 101, 102f
Broca’s aphasia, 78, 78t Cryptococcal meningitis, 150
Circulation, 96–97, 97f –98f, 99
Bromocriptine, 112, 113t CSD. See Cortical spreading depression
Cisplatin, 162b, 166
Brown-Sequard syndrome, 154 CSF. See Cerebrospinal fluid
Clinical manifestations. See specific
Brudzinski’s sign, 145 disorders and diseases, e.g., Acute CT. See Computed tomography
Calcium-channel blockers, 102 bacterial meningitis, Alzheimer disease Cyclophosphamide, 129, 143, 163
Carbamazepine, 74, 108t, 118, 174 Clomipramine, 94 Cyclosporine, 144, 171, 177t
Carbidopa, 111, 113t Clonazepam, 94, 116
Clonidine, 117 Dantrolene, 112
Carotid circulation. See Anterior
circulation Clopidogrel, 87t, 101 Decarboxylase inhibitor, 111, 114t
Cataplexy, 93–94 Clozapine, 89, 177 Decerebrate posturing, 24, 24f
Catechol-O-methyl transferase Cluster headache, 71 Decorticate posturing, 24, 24f
inhibitors, 112, 114t CNS. See Central nervous system Deep tendon reflexes. See Muscle stretch
Cauda equina, lesions of, 156 Cocaine eyedrops, 32 reflexes
Cavernous angiomas, 102 Coma, 21–28, 22f, 23t, 24b –25b, 24f Degenerative spinal illnesses, 158
CDH. See Chronic daily headache Communication disorders, 5, 77–83, 78f, Delirium, 27, 84
Central cord lesions, 154–155, 155f 78t –79t, 81f Dementia, 84–91, 85b
Complex partial seizures, 27, 103 Alzheimer disease, 84–87, 87t
Central (transtentorial) herniation, 122
with extrapyramidal features, 88–90
Central nervous system (CNS), 131–138 Compression, of spinal cord, 153–154
HIV-associated, 151
demyelinating diseases of, 139–144, Computed tomography (CT), 12–14 with idiopathic Parkinson
140t, 141f –142f, 143t of brain abscess, 146 disease, 111
primary brain tumors, 131–138, of central nervous system tumors, infectious causes of, 90–91
132t, 134f –137f, 151 133–135, 134f, 138f metabolic causes of, 91
secondary (metastatic) brain of coma and altered consciousness, vascular, 84, 87t, 88, 100f –102f,
tumors, 138, 138f 25–26 101–102
Central pontine myelinolysis, 130 of diffuse axonal injury, 120, 121f
Dementia with Lewy bodies, 88–89
Central sensory loss, 52t, 53 of epidural hematoma, 119, 120f
for meningitis, 11, 145 Demyelinating diseases
Cerebellum, 10–11, 54–55, 58–62, 59b, of central nervous system, 139–144,
of spinal cord disorders, 158
60t, 99 140t, 141f –142f, 143t
of subdural hematoma, 119, 120f
Cerebral hemisphere disorders, 47, 47f, 99 of vascular disease, 100, of peripheral nervous system,
Cerebral herniation, 10–11 100f, 102f 159–164
Cerebral hypotonia, 183 Concussion, 54, 120–121 Depressed consciousness, 24, 24b –25b
Cerebral palsy (CP), 178–180 Conduction aphasia, 78t, 79 Dermatomes, sensory loss in, 51f, 53
Cerebral perfusion pressure (CPP), 123 Confusion, 27. See also Acute Dermatomyositis, 172, 175–176
Cerebrospinal fluid (CSF), analysis of, confusional state Desmopressin, 67t
10–12, 11t, 142, 145–146, 149–150 Congenital spinal illnesses, 158 Development, 178, 179t–180t
Cerebrovascular disease. See Vascular Consciousness, 5, 120. See also Altered Developmental delay, 180–181, 181t
disease consciousness Developmental regression, 182–183,
Channelopathies, 172, 174 Continuous positive airway pressure 182t, 184t
Charcot-Marie-Tooth disease, 165 (CPAP), 95 Developmental venous anomalies
Children. See Pediatric neurology Conus, lesions of, 156 (DVAs), 102
Chlorpromazine, 177 Coordination, examination of, 4t, 9 Dexamethasone, 176
Chorea, 115, 115b Copper metabolism, Wilson disease and, Dextroamphetamine, 94, 185
Chronic daily headache (CDH), 73 117–118 Dextrose, 22, 22f
Chronic GBS. See Chronic inflammatory Cortical spreading depression (CSD), 70 Diabetes mellitus, neuropathies of, 45,
demyelinating polyradiculoneuropathy Corticospinal tract, 152, 153f, 156–157 126–127, 126b, 164–165, 164t
12887_BM_Index.qxd 10/4/08 3:13 PM Page 214
214 • Index
Diabetic amyotrophy, 45, 126–127 EMG. See Electromyography Generalized seizure, 103
Diabetic polyneuropathy, 164–165, 164t Encephalitis, 149 Generalized tonic-clonic (GTC) seizure,
Diagnostic evaluation. See specific disorders Encephalomyelitis, 144 104, 109, 121
and diseases, e.g., Acute bacterial Encephalopathy, 27, 182t Gerstmann’s syndrome, 81
meningitis, Alzheimer disease Encephalopathy of fulminant failure, 124 Giant cell arteritis (GCA), 73
3,4-Diaminopyridine, 171–172 Endocrine myopathies, 176–177 Gille de la Tourette syndrome, 117
Diazepam, 143 Entacapone, 113t Glasgow Coma Scale, 21, 122, 122t
Diffuse axonal injury, 120, 121f Entrapment neuropathies, of peripheral Glatiramer acetate, 143, 143t
Diffuse cord dysfunction, 156 nervous system, 166, 167t Glioblastoma multiforme, 133, 134f
Diplopia, 35–37, 35t, 36f Ependymoma, 134–135 Gliomas, 133. See also Low grade gliomas
Dipyridamole, 87t, 101 Epidural abscess, 154 Global aphasia, 78t, 80
Dissociated sensory loss, 52 Epidural hematoma, 119, 120f Glucocorticoids, 176, 177t
Distal myopathies, 175 Epilepsy, 15–16 Grand mal seizure. See Generalized
Distal sensory polyneuropathy, 165 seizures and, 103–110, 104f –105f, tonic-clonic seizure
Distal symmetric sensory polyneuropathy, 106t, 108t, 109f Granulomatous disorders, neuropathy of,
of diabetes mellitus, 126 status epilepticus, 109, 109f 125–126
Diuretics, 26, 56, 73, 123 Episodic ataxia (EA), 59–60 GTC seizure. See Generalized
Dizziness, 54–57, 55b, 56f, 56t Erectile dysfunction (ED), 68 tonic-clonic seizure
DMD. See Duchenne muscular Erythema chronicum migrans, 148 Guillain-Barré syndrome, 161–162
dystrophy Essential myoclonus, 116
Donepezil, 87, 87t Essential tremor (ET), 115 HAART. See Highly active antiretroviral
therapy
Dopaminergic agonists, 93, 111, 114t Estrogen therapy, 67t, 87, 87t
Haloperidol, 115, 117, 177
Dopaminergic antagonists, 89, 117 ET. See Essential tremor
HD. See Huntington disease
Double vision. See Diplopia Ethosuximide, 108t
Head trauma. See Trauma
D-penicillamine, 118, 177t Examination. See Neurologic examination
Headache, 69–74
Driving, seizures and, 109 Extracranial Doppler sonography, 14
central nervous system tumors
Drowsiness, 21 Extrapyramidal features, dementias and, 131
Drug-induced movement disorders, 112 associated with, 88–90 with meningitis, 145
Drug-induced myopathies, 176–177, 177t Eye misalignment, 35–37, 35t, 36f primary headache disorders,
Duchenne muscular dystrophy (DMD), Eye movements, 35, 36f 69–72, 106t
170t, 172–173 secondary headache disorders, 11,
Facial pain, 73–74 69, 72–73
Duloxetine, 165
Fatigable muscle weakness. See Weakness Hemangioblastoma, 137
DVAs. See Developmental venous
anomalies Febrile seizure, 105 Hematoma, 119–120, 120f
Dysarthria-clumsy hand syndrome, 100 First aid, for seizures, 109 Hematomyelia, 155
Dysdiadochokinesis, 9 Fludrocortisone, 56, 166 Hemiballismus, 116
Dysequilibrium, 54 Fluphenazine, 177 Hemicord syndromes, 154
Dysesthesias, 51 Focal peripheral neuropathy, of diabetes Hemiparetic gait, 61, 61t
mellitus, 126 Hemispheric lesions, ataxia with, 58
Dysraphisms, 158
Folic acid, 110 Hemorrhage, 58, 72, 100f –102f, 101–102
Dyssomnias, 94–95
Foster-Kennedy syndrome, 34 Heparin, 101
Dystonia, 116
Fourth nerve. See Trochlear nerve Hepatic encephalopathy, 124–125
Dystrophinopathies, 172–173
Friedreich ataxia, 59 Hereditary neuropathies, of peripheral
EA. See Episodic ataxia Frontal gait, 61, 61t nervous system, 165
ED. See Erectile dysfunction Frontal lesions, 81, 82 Hereditary spastic paraparesis, 157
Edrophonium chloride, 171 Frontotemporal dementia, 90 Herniated disks, 158
EEG. See Electroencephalography Fungal infections, 150 Herniation syndromes, 121–122
Electroencephalography (EEG), 15–16, Herpes simplex virus 1 (HSV1)
15f, 26, 104, 104f, 107 Gabapentin, 74, 93, 108t, 115, 165 encephalitis, 149
Electromyography (EMG), 16–17, 16t Gadolinium, 12–13, 142–144 Higher cortical function, disorders of, 5,
Embolism, 98 Gait disorders, 4t, 9, 58–62, 59b, 60t – 61t 77–83, 78f, 78t –79t, 81f
Emery-Dreifuss muscular dystrophy, Ganglioglioma, 137 Highly active antiretroviral therapy
170t, 174 GCA. See Giant cell arteritis (HAART), 151
12887_BM_Index.qxd 10/4/08 3:13 PM Page 215
Index • 215
HIV. See Human immunodeficiency virus of nervous system, 145–151, 147f Lithium, 71
Horner’s syndrome, 32, 33b, 154 peripheral neuropathies associated Liver failure, hepatic encephalopathy
HSV1 encephalitis. See Herpes simplex with, 165–166 with, 124–125
virus 1 encephalitis Inflammatory myopathies, 175–176 LMN. See Lower motor neuron
Human immunodeficiency virus (HIV), Inherited episodic ataxia, 59 Locked-in syndrome, 27
91, 151, 165–166 Inherited mitochondrial myopathies, 175 Lomustine, 134
Huntington disease (HD), 89 Inherited neurodegenerative disorders, Lou Gehrig disease. See Amyotrophic
Hydroxyamphetamine eyedrops, 32 182–183, 182t, 184t lateral sclerosis
Hyperesthesia, 52 INO. See Internuclear ophthalmoplegia Low grade gliomas, 133–134, 134f
Hyperglycemia, neuropathy of, 127, 164 Interferon beta-1a, 143, 143t Lower motor neuron (LMN), 46f
Hyperkalemic periodic dystrophy, Interferon beta-1b, 143, 143t Low-pressure headache, 11, 72
170t, 174 Internuclear ophthalmoplegia (INO), Lumbar puncture, 10 –11, 11t, 25–26,
Hypertension, hemorrhage with, 102 35, 140 72, 145–147
Hypertensive leukoencephalopathy, 144 Intracerebral hemorrhage (ICH), 102 Lumbosacral plexus, weakness of, 44
Hyperthyroidism, 129–130 Intracranial hemorrhage, 100f –102f, Lumbosacral polyradiculoneuropathy, 166
Hypesthesia, 52 101–102 Lyme disease, 148–149
Hypoglycemia, neuropathy of, 127 Intracranial pressure (ICP), 26, 123 Lymphoma, of CNS, 137, 151
Hypokalemic periodic dystrophy, Intracranial tuberculoma, 148 Lysosomal disorders, 183
170t, 174 Intravenous immunoglobulin, 162, 166,
171, 176 Magnetic resonance angiography (MRA),
Hypoperfusion, systemic, 99
Investigations, neurologic. See Neurologic 14, 14f
Hypothyroid myopathy, 176
investigation Magnetic resonance imaging (MRI),
Hypothyroidism, 129–130, 130b 12–14, 12f –13f
Ischemia, brain, 98–99
Hypotonic infant, 183 of brain abscess, 146, 147f
Ischemic stroke syndromes, 99–100
of central cord lesions, 155f
IBM. See Inclusion body myositis of central nervous system tumors,
Joint position sense. See Proprioception
Ibuprofen, 87t 133–138, 134f –137f
ICH. See Intracerebral hemorrhage Kayser-Fleischer ring, 118 of coma and altered conscious-
ICP. See Intracranial pressure Kernig’s sign, 145 ness, 25
of leukoencephalopathies, 144
Idiopathic intracranial hypertension Kernohan notch phenomenon, 122
of multiple sclerosis, 142, 142f
(IIH), 72–73 Korsakoff’s syndrome, 128 of spinal cord disorders, 158
Idiopathic Parkinson disease. See Parkinson of vascular disease, 100, 101f
disease Labyrinth, infraction of, 54–55
Magnetic resonance venography
Idiopathic torsion dystonia, 116 Labyrinthine concussion, 54
(MRV), 14
IIH. See Idiopathic intracranial Lactulose, 125
Mannitol, 26, 123
hypertension Lacunar syndromes, 100
Marcus-Gunn pupil. See Relative afferent
Imipramine, 67t Lambert-Eaton myasthenic syndrome pupillary defect
Immune-mediated neuropathies, of (LEMS), 169, 170t, 171–172
Maturation, 178, 179t –180t
peripheral nervous system, 161–164 Lamotrigine, 108t, 165, 177t Medial lemniscal system, 48, 50f
Immune-modulating agents, 143, 143t Language. See Communication disorders Medial longitudinal fasciculus, 35, 36f
Immunosuppressants, 127, 129, Lateral medulla stroke, 99 Medial tegmentum stroke, 99
144, 163 L-dopa therapy, 111, 114t, 177, 177t Medulloblastoma, 136, 136f
Inclusion body myositis (IBM), 172, LEMS. See Lambert-Eaton myasthenic Memantine, 87, 91
175–176 syndrome
Memory, assessment of, 5
Incontinence, bladder, 63–68, 64f, 65t, 67t Leprosy, neuropathy of, 166
Ménière disease, 55
Indomethacin, 72 Lethargy, 21
Meningioma, 135–136, 135f
Infant, hypotonic, 183 Leukoencephalopathies, 144
Meningitis, 11, 22, 145–150
Infarction. See also Stroke Levetiracetam, 108t Meningocele, 158
of brain, 54–55, 58, 99 Levodopa, 93, 113t –114t
of labyrinth, 54–55 Meningoencephalitis, 145
Lewy bodies, 88–89, 111 Mental retardation, 180–181, 181t
of spinal cord, 156
Lhermitte’s sign, 140–141 Mental status, 4t, 5, 5f, 23, 27, 131–133
Infection
dementia with, 90–91 Light-headedness, 54 Metabolic disorders, 124–130, 125t
Guillain-Barré syndrome with, Limb-girdle muscular dystrophy, 170t, alcohol and nutritional disorders,
161–162 172–173 127–128, 127t
12887_BM_Index.qxd 10/4/08 3:13 PM Page 216
216 • Index
Metabolic disorders (cont.) Muscular dystrophy, 172–173 nerve conduction studies and
antiphospholipid syndrome, 129 Myalgia, 172 electromyography, 16–17,
central pontine myelinolysis, 130 Myasthenia gravis (MG), 169–171, 170t 16t –17t, 48
dementia associated with, 91 of peripheral nervous system,
Myasthenic crisis, 170 –171
diabetes mellitus, 45, 126–127, 159–160, 162b
Mydriatic agents, 33 positron emission tomography, 14
126b, 164–165, 164t
hepatic encephalopathy, 124–125 Myelin. See Demyelinating diseases single-photon emission computed
neurosarcoidosis, 125–126 Myeloma, neuropathies associated tomography, 14
peripheral neuropathies associated with, 164 vascular imaging studies, 14, 14f
with, 164–165, 164t Myelomeningocele, 158 Neuromuscular junction (NMJ) disorders,
systemic lupus erythematosus, Myoclonic seizure, 104 16, 42, 169–177, 170t
128–129 Neuronal degeneration, 159
Myoclonus, 116, 117b
thyroid disease, 129–130, 130b Neuronitis, 54–55
Myopathy, 172
Metastatic brain tumors, 138, 138f Neurons, 48
Myositis, 172
Methotrexate, 126, 137, 143, 176 Neuro-ophthalmology, 29–39, 30f
Myotonia, 172
Methylphenidate, 94, 185 abnormal optic disc, 33–34, 34t
Myotonic dystrophy, 170t, 173–174
Methylprednisolone, 143 diplopia, 35–37, 35t, 36f
Metoclopramide, 71, 177 Naloxone, 22, 22f nystagmus, 38t, 39
MFS. See Miller Fisher syndrome pupil disorders, 31–33, 33b
Narcolepsy, 93–94
supranuclear eye movements, 37
MG. See Myasthenia gravis Narcotics, 68 symptoms approach to neuro-
Midodrine, 56, 166 NCS. See Nerve conduction studies ophthalmologic disturbances,
Miller Fisher syndrome (MFS), 60, 162 Neglect, 5, 82, 82f 29–31, 31b, 31t
Misalignment, of eyes, 35–37, 35t, 36f Nerve conduction studies (NCS), 16–17, Neurosarcoidosis, 125–126
Mitochondrial myopathies, 175 17t, 48 N-methyl-D-aspartate receptor
Mitoxantrone, 143 Nerve roots, 43t – 44t, 44, 52t, 53, antagonists, 87
Mixed incontinence, 65 156, 168t NMJ disorders. See Neuromuscular
MMN. See Multifocal motor neuropathy Nervous system. See also Central nervous junction disorders
Modafinil, 94 system; Peripheral nervous system NMS. See Neuroleptic malignant
infections of, 145–151, 147f syndrome
Monoclonal gammopathies, neuropathies
associated with, 164 Neurocutaneous disorders, 183, 185t Nondominant hemisphere syndromes,
Neurocysticercosis, 150 82–83, 82f
Mononeuropathies, 42– 43, 165–166
Neurogenic syncope, 56, 56t NSAIDs, 87, 165
Mononeuropathy multiplex, 43
Neuroleptic malignant syndrome (NMS), Nutritional disorders, 127–128, 127t
Motor function, examination of, 4t,
7– 8, 7f, 8t, 23 112, 177 Nystagmus, 38t, 39, 54–55, 56f
Movement disorders, 111–118, Neuroleptics, 89
Obstructive sleep apnea (OSA), 95
112t –114t, 115b, 117b Neurologic disorders. See also specific
Oculomotor apraxia, 37
MRA. See Magnetic resonance disorders, e.g., Aphasia, Dementia
CSF findings in, 11t Oculomotor nerve, 33–37
angiography
incontinence with, 66 ODS. See Optic disc swelling
MRI. See Magnetic resonance imaging
Neurologic examination, 3–9, 4t, 5f, 6t, Olanzapine, 177
MRV. See Magnetic resonance
7f – 8f, 8t Oligodendroglioma, 134
venography
of coma and altered consciousness, ON. See Optic neuritis
MS. See Multiple sclerosis 21–24, 22f, 23t, 24f, 27
Multifocal cord dysfunction, 156 One-and-a-half syndrome, 35–36, 36f
of headache, 70
Multifocal motor neuropathy of language function, 79t Ophthalmology. See Neuro-
(MMN), 163 of reflexes, 4t, 8, 8f, 23–24, 23t, ophthalmology
Multi-infarct dementia. See Vascular 44, 44t Opioids, 93
disease of seizure, 107 Optic disc, abnormalities of, 33–34,
of sensory system, 48–52, 51f, 52t 34t
Multiple mononeuropathies, 165–166
Neurologic investigation, 10–17 Optic disc swelling (ODS), 33
Multiple sclerosis (MS), 66, 139–144,
computed tomography, 12–14 Optic nerve, 5 – 6, 6t
140t, 141f –142f, 143t
CSF analysis, 10–12, 11t
Muscle disorders, primary, 41–42 Optic neuritis (ON), 33, 34t, 140–143
electroencephalography, 15–16,
Muscle stretch reflexes, 8, 8f, 23, 15f Orthostatic hypotension, 57
44, 44t magnetic resonance imaging, 12–14, OSA. See Obstructive sleep apnea
Muscle weakness. See Weakness 12f –13f Overflow incontinence, 65, 67t
12887_BM_Index.qxd 10/4/08 3:13 PM Page 217
Index • 217
218 • Index
Index • 219