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Neurology Clerkship Information/Study Guide

This document provides information for medical students on their neurology clerkship, including expectations and guidelines. It discusses the format for chairman's rounds, which involves presenting a complete history and exam of a patient. Students are expected to know their patients daily status, any tests ordered, and how their clinical diagnosis correlates with test results. The document also includes an appendix on aphasias and guidelines for performing and documenting the history and physical exam, including formulating the clinical problem, diagnostic impressions, differential diagnosis, and treatment plan.

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0% found this document useful (0 votes)
184 views58 pages

Neurology Clerkship Information/Study Guide

This document provides information for medical students on their neurology clerkship, including expectations and guidelines. It discusses the format for chairman's rounds, which involves presenting a complete history and exam of a patient. Students are expected to know their patients daily status, any tests ordered, and how their clinical diagnosis correlates with test results. The document also includes an appendix on aphasias and guidelines for performing and documenting the history and physical exam, including formulating the clinical problem, diagnostic impressions, differential diagnosis, and treatment plan.

Uploaded by

olivukovic
Copyright
© © All Rights Reserved
We take content rights seriously. If you suspect this is your content, claim it here.
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Neurology Clerkship Information/Study Guide

JUNIOR/SENIOR NEUROSENSORY CLINICAL ROTATION


INDIANA UNIVERSITY SCHOOL OF MEDICINE

WELCOME
TO
NEUROLOGY

I swear by Apollo Physician, by Asclepius, by Health, by Panacea, and by all the gods and
goddesses, making them my witnesses, that I will carry out, according to my ability and
judgment, this oath and this indenture .... I will use treatment to help the sick according to my
ability and judgment, but never with a view to injury and wrongdoing. I will keep pure and holy
both my life and my art. In whatsoever houses I enter, I will enter to help the sick, and I will
abstain from all intentional wrongdoing and harm .... Now if I carry out this oath, and break it
not, may I gain forever reputation among all men for my life and for my art-, but if I transgress it
and forswear myself, may the opposite befall me.

Oath of Hippocrates

TO: JUNIOR and SENIOR MEDICAL STUDENTS

FROM: JOSÉ BILLER, M.D.

NEUROLOGY TEXTS
:

*An Introduction to Clinical Neurology, Pathophysiology, Diagnosis and Treatment. A.


Guberman. Little, Brown and Company, 1994.

*Neurology Section in Cecil's Textbook of Medicine, 18th Edition, Saunders, 1988.

*Principles of Neurology. Companion Handbook. R.D. Adams and M. Victor, 4th Edition,
McGraw Hill Book Company.

*Techniques of the Neurologic Examination, A Programmed Text. William E. DeMyer. McGraw


Hill, Inc., 1994.

*Brazis PW, Masdeu JC, Biller J. Localization in Clinical Neurology (3rd Edition). Little, Brown
and Company, 1996.

*Choose one or more out of these five starred references.


CHAIRMAN'S ROUNDS

INTRODUCTION
Unless otherwise specified, "Chairman's Rounds', are held once weekly on each service. In spite
of the whispered stories you may have heard, it is not a punishment but rather a teaching exercise.
Remember this is not a graded exercise. Your grade is determined by your attending physician
and your test, not by chairman's rounds. Nevertheless, we recognize that presentations in front of
groups can be disconcerting, and some nervousness is natural.

THE FORMAT

The presentation will be a complete history and neurologic examination of a patient. The
chairman is at his liberty to interrupt and ask you to elaborate upon a historical issue or clinical
finding. To ensure the rounds go smoothly one should have the pertinent radiological folders
handy (CT, MRI, angiogram ... ), but do not give lab tests or radiologic tests as part of the history
or objective findings. This is a clinical exercise. The studies will be looked at the end and see
how your clinical diagnosis correlates with the paraclinical investigations.

Appendix 2

APHASIAS
SENSORY MOTOR MIXED
BROCA WERNICKE CONDUCTION GLOBAL TRANS- TRANS- TRANS-
CORTICAL CORTICAL CORTICAL
NON- NON- NON- NON-
SPONTANEOUS SPEECH FLUENT FLUENT FLUENT
FLUENT FLUENT FLUENT FLUENT
AUDITORY GOOD- SEVERELY GOOD- VERY
GOOD POOR POOR
COMPREHENSION NORMAL IMPAIRED NORMAL POOR
READING GOOD-
COMPREHENSION
GOOD POOR
NORMAL ? POOR GOOD POOR

READING ALOUD POOR POOR POOR ? POOR POOR POOR

WRITING POOR POOR POOR ? POOR POOR POOR

VERY
NAMING POOR POOR POOR POOR POOR POOR
POOR
GOOD- GOOD-
REPETITION POOR POOR POOR IMPAIRED GOOD
NORMAL NORMAL

PARAPHASIA - + + ? + - +

Form of Examination
History

1. Please record the name and relationship of the person from whom the history is obtained if
other than the patient.

2. Record verbatim the patient's chief complaint. If there are many, ask them to tell you what their
chief problem is.

3. Pursue individual symptoms as if you were a reporter, i.e., where, what, why, when, details
are important, For example, if the patient is having episodes of confusion, ask about the first
spell, how long it lasted, how it evolved (fast onset, gradual, fast defervescence, etc.), associated
symptoms, time of day, what was being done at the time, how like all other spells was the first,
etc. 80-90% of the diagnosis is history and you are likely to be out of luck if you don't know
where you are going by the end of the history.
4. Next, past medical history and surgical history, habits, medications, family history, and review
of systems.

Physical Symptoms

1. Complete physical examination:

 a. This includes rectal on all patients, breast exam, genital exams - pelvic examination for
women and testicular examination for men.
 b. Please remember that the eyes and ears are sensory organs. Record the examination of
the auricle, external auditory meatus, TM, cornea and conjunctiva, in the general exam
and save Rinne, Weber, visual acuity, visual fields, fundus, pupils and ocular motility for
the neurologic exam.
 c. In the general examination, examine the skull, neck and back, paying particular
attention to structural defects, bruits and painful sites

2. Do the neurological examination in this order:

Mental status
Cranial nerves
Motor system strength (proximal versus distal - major groups)
tone
reflexes
pathologic reflexes
Cerebellar
Sensory system
Station and gait

Recording the History and Physical-Examination

1. Organizing the history and physical findings

Present your written record of the patient contact in the same compulsively organized fashion
with which you obtained the information. Remember, if you stray from your organization, you
will forget important items and the record will be a morass to the next reader.

2. Formulation

At the end of the history and physical examination, formulate the clinical problem in a capsule
paragraph which summarized the pertinent findings.

3. Diagnostic impression

The impression should consist of:

 a. An anatomical localization of the lesion(s). Note whether the condition is unifocal,


multifocal or diffuse.
 b. A diagnosis based on all you know using basic categories of disease: neoplastic,
traumatic, infectious, autoimmune/inflammatory, vascular, degenerative/demyelinating,
nutritional, toxic/metabolic, congenital/developmental/inherited, or psychologic.

4. Differential diagnosis

Please read about the disease you have diagnosed and be prepared to give basic information about
the disease process and the differential diagnosis.

5. Plan

Discuss how you will evaluate each of the unknowns in your differential diagnosis and how you
will treat each of your knowns.

6. Caution

Whenever you write a note in a patient's chart, you are contributing to a legal document. Under
no circumstances should such an entry contain argumentative issues or demeaning statements
about the patient or other members of the health care team. Therefore, make only those
statements behind which you stand and on which you are going to act. For instance, if you do not
intend to study the patient in any way to prove or disprove that he has a remotely possible
diagnosis, don't say "rule out" that diagnosis in the chart.

Aims of the Rotation

1. You should learn how to perform and record a neurological examination.

2. You should know the major groups of neurologic diseases and be familiar with the texts to
which you can turn for more information.

3. You should be able to formulate a neurologic problem in terms of the basic anatomy and the
basic kinds of disease which affect that part of the anatomy.

4. You should have a good direct or indirect exposure to a variety of neurologic disease.

5. You should have a knowledge of what laboratory or radiological investigations should be


made.

Expectations

Some students are upset at the number of physical examinations they are required to do, the
length of rounds, and the amount of "scut" work there is to do. You are an integral part of a busy
service. Without your assistance and insights, everything runs less efficiently and is done less
well. This is not unique to neurology, nor to this school, nor to medicine. There is no simple way
for us to do pre-digest and deposit neurology as a discipline into the minds of students. We will
be happy to give you readings to do about your patients. There will be many mini-lectures and
discussions during rounds. You will be expected to participate by knowing-.
1. how your patients are every day
2. what tests they are to be having
3. how the examination has changed from admission
4. at least the bare minimum of reading on each case.

If you expect to be given honors on the rotation, you must exceed those minimum requirements
and demonstrate that you are doing more than the bare minimum. The excuse that there is "no
time to study" is unacceptable.

Presentations

You will be presenting your patients to the assembled groups. Be prepared to present the history
and physical concisely, covering the pertinent negatives as well as the positive findings. For
example, when giving a history on a patient with episodic loss of consciousness, ask about "deja-
vu", "jamais-vu", disorientation, unusual smells and tastes. Report these as present or absent
because they are germane to this symptoms.

Please do not continually say "the patient denies" since this connotes disbelief or incredulity.
Simply state what the patient's response was - e.g., "The patient does not smoke and drinks
socially." If you do not believe the patient, you should have evidence such as "but has cigarette-
stained hands" or "but smelled of alcohol."

Be prepared to present your patient. Do not drift into this presentation.

2. Formal Lectures

The faculty believes that the didactic lectures in Neurology are important. These will be given
daily during your rotation. The lectures are a supplement to your independent study and your
ward experience. The lectures also give you the opportunity to ask questions. We expect your
attendance at these lectures. We do not consider the availability of "canned lecture notes" as an
alternative to attendance to the lectures.

3. Independent Study

After much discussion and review of several neurological texts, the faculty recommends:

1. Neurology Section in Cecil's Textbook of Medicine, 1988, 18th Edition, Saunders.

2. Principles of Neurology, Companion Handbook. R.D. Adams and M. Victor, 4th Edition,
McGraw Hill Book Company.

3. An Introduction to Clinical Neurology, Pathophysiology, Diagnosis, and Treatment. A.


Guberman, Little, Brown and Company, 1994.

4. Technique of the Neurologic Examination, A Programmed Text. William E. DeMyer, McGraw


Hill, Inc., 1994.

The Final Examination in Neurology


At the end of your rotation, there will be an examination in Neurology. If you have not
completed your rotation, you will not be permitted to take the examination. The examination
will be multiple choice format. Material covered in the formal lectures and the recommended
texts will be tested.

Evaluation by Faculty/Residents

Your performance on your clerkship will be evaluated by the faculty and residents. They will
evaluate your ability to obtain a neurologic history, to perform a neurologic examination, to
formulate a diagnosis and to devise a plan for further investigation.

Your evaluation will also include the faculty and resident's assessments of your fund of
knowledge in Neurology. Your rapport with patients, colleagues and other medical personnel will
also be judged.

Your Grade in Neurology


Your final grade in Neurology will be based on the results of your examination and your
performance during the rotation.
HISTORY TAKING AND NEUROLOGIC EXAMINATION
"The Basis of the Clinical Diagnosis Rests Upon
a Careful History-Taking"

Name _________________________________ Date of Birth ______________


mo day year

Age ____________

Race c-caucasian b-black o-other

Sex w-woman m-man

A. HISTORY OF PRESENT ILLNESS - "Avoid leading questions."

1. Headaches (see classification of headaches; Appendix 1)

"Most headaches seen by physicians are vascular (migraine, cluster), scalp muscle contraction
(tension), or combined vascular and scalp muscle contraction headache."

- Onset
· Location-
Intensity-
Duration-
Pattern (i.e.: continuous, periodic, etc.)-
Associated symptoms (i.e.: photophobia, sonophobia, nausea, vomiting. visual complaints)

II. Vertigo (see Clinical Evaluation of the Dizzy Patient)

May be peripheral (i.e.: Labyrintine) or central (i.e.: Vestibular connections)


- Intensity-
Evolution-
Associated symptoms (i.e.: auditory, visual, gastrointestinal, sensory, others)

III. Visual Complaints.

Amaurosis Fugax
Diplopia

IV. Auditory Complaints

- Deafness -
Tinnitus

V. Deglutition/Phonation

- Dysphagia -
Dysphonia

VI. Speech-

Dysarthria -
Aphasia (see classification of aphasias; Appendix 2)

VII. Disturbances of Alertness-

Syncope-
Seizure-
Coma

VIII. Sleep Disturbances

- Insomnia-
Excessive daytime sleepiness
- Narcoleptic Syndrome-
Sleep Apnea Syndrome

IX. Motor Complaints


- Weakness-
Clumsiness-
Abnormal movements

X. Sensory Complaints

- Pain (i.e.: neuritic, radicular, central)


onset
intensity
location
radiation-
Paresthesia
XI. Disturbances of Sphincter Control

- Incontinence-
Urinary retention-
Constipation

XII. Sexual Disturbances

- Impotence-
Impaired erection-
Impaired ejaculation

B. PAST HISTORY

Hypertension
Cardiac Disease - ischemic
Cardiac Disease - valvular
Cardiac Arrhythmia
Diabetes
Hyperlipidemia
Cigarette smoking
Alcohol consumption
Migraine
Oral contraceptives
Exposure to neurotoxins
Drug abuse
Sexual behavior
Head trauma
Previous seizures
Childhood illness
Syphilis
Obstetric trauma
Perinatal history

C. FAMILY HISTORY (parents & siblings)

"Family clustering is common in many forms of neurological disease."

Hypertension
Cardiac disease
Diabetes
Stroke
Stroke - under age 50
Neurological/Mental disorders
D. NEUROLOGICAL EXAMINATION

Mental Status (see Mini-Mental State Examination; Appendix 3)

a. Level of Alertness
b. Orientation
- person-
place-
time
C. Attention
d. Memory Tests
- recent events-
three names-
number sets

e. Calculation and Abstraction


- serial 7's-
simple addition-
proverb interpretation-
similarities and differences-
reversals

f. Language (see classification of aphasias; Appendix 2) - spontaneous speech


- comprehension-
repetition
- naming
- reading-
writing
9. Visuo-spatial
h. Right-Left
i. Affect
i. Hallucinations, delusions, ideations (suicidal)
k. Executive functions

2. Symbolic Functions
a. See language
b. Praxis
c. Gnosis

3. Skull
a. Head circumference
b. Palpation
c. Auscultation

4. Neck
a. Meningeal Signs
- neck stiffness
- Kernig
- Brudzinski
b. Range of Motion
c. Bruits (Grade I-VI)

5 Cranial Nerve Tests

I- Olfactory (Don't use irritative substances)

II- Visual Acuity


Visual Fields to Confrontation
Ocular Fundus
Color vision

III-IV-VI -Pupillary size, shape, reactivity, RAPD


Extraocular movements

V - Facial sensation to pain, temperature and light touch Corneal reflex


Strength of masticatory muscles
Jaw jerk

VII - Smiling - emotional and voluntary


Taste - anterior two-thirds of tongue
Sensation - external auditory canal
Salivary secretion (sublingual, submandibular)

VIII VIII - Hearing, with tuning fork (128 cps)


Cochlear - Weber
- Rinne
Vestibular - Nystagmus
- Past-pointing
- Ataxia

IX-X - Gag reflex


Motility of vocal cords
Voluntary palatal movements
Taste posterior 1/3 of the tongue

XI - Strength of SCM and Trapezius

XII - Tongue protrusion


Atrophy
Tremor
Fibrillations

6. Upper Limbs

a. Bulk

b. Tone
C. Strength
0. no trace of movement
1. flicker of muscle contraction C5 (Sh Abd, Elb Flx)
2. some movement around a joint C6 (Wr Ext)
3. movement against gravity C7 (Elb Ext, Wr Flx. Fing, Flx)
4. movement against some resistance C8 (Fing Flx.- intrinsics)
5. full strength TI (Fing Abd, Fing Add)

d. Coordination
Finger-Finger
Finger-Nose
Rapid alternating movements Check-response (Stewart-Holmes)

e. Sensory (Appendix 4)
Pain
Light Touch
Temperature
Position
Vibration (128 Hz tuning fork)
Cortical Sensory Modalities
stereognosis
graphesthesia
two-point discrimination

f. Reflexes
0. Absent
1. Hypoactive
2. Normal
3. Increased
4. Increased often with clonus

1. Biceps (C5-C6)
2. Brachioradialis (C5-C6)
3. Triceps (C7-8)
4. Finger Flexion (C8-TI)

7. Trunk

a. Strength of anterior abdominal wall muscles

b. Superficial abdominal reflexes (T8-n2)

c. Sensory (Appendix 4)
Pain
Light touch
Temperature
Vibration

d. Spine
Inspection
Palpation
Auscultation

8. Lower Extremities
a. Bulk L3 (Knee Ext)
b. Tone L4 (Ank- dorsiflex, inversion)
c. Strength L5 (EHL, Toe Ext)
d. Coordination SI (Ft Ev, Ft Plnt Flx, Glt Max)
Heel-Knee-Shin S2 (Ft intrinsics)
e. Sensory (Appendix 4)
Pain
Light touch
Temperature
Position
Vibration (I 28 Hz tuning fork)
Cortical sensory modalities (see 6e)

f. Reflexes
Cremasteric (LI -L2)
Patellar (L2-L4)
Achilles (SI-S2)
Plantar Response

9. Gait-Station
Arm Swing
Width of Gait
? Limp
Toe Walking
Heel Walking
Tandem Walking
Romberg Test

10. Summary
a. Anatomical Diagnosis (Where is the problem?)

Cerebral hemispheres (F,P,T,O)


CNS Brainstem (midbrain, pons, medulla)
Cerebellum (vermis, hemispheres)
Spinal cord (C,T,L,S)

Anterior horn cell


Roots
PNS Plexus Nerves
Neuromuscular junction (pre-postsynaptic)
Muscle

b. Etiological diagnosis (What is the problem?)


- congenital-
genetic-
traumatic-
metabolic-
toxic-
nutritional-
infectious (viral, bacterial, fungal, protozoal, helminths, etc.)-
immunological-
demyelinating-
vascular (ischemic-hemorrhage)-
neoplastic (primary-metastatic)-
degenerative-
idiopathic

c. Pathogenesis (Why?)

d. Evaluation

e. Therapeutic/Management (What can be done?)

The Mini-Mental State Examination

I What is the year, season, date, day of the week, month? (5 points)

2. Where are we: country, state, city or town, hospital, floor of building? (5 points)

3. The examiner names three objects, taking 1 second to say each. The patient is asked to repeat
the names of all three objects after the examiner has said them. (3 points)

4. Serial sevens. One point for each correct answer. Stop after five answers. Or spell the word
"world" backwards. (5 points)

5. Recall the three objects named in #3. (3 points)

6. The patient is shown a pencil and a watch and asked to name them. (2 points)

7. The patient is asked to repeat: "No ifs, ands, or buts." (1 point)

8. The patient is handed a sheet of paper and asked to carry out a three-stage command: "Take
this paper in your night hand, fold it in half, and put it on the floor." (3 points)

9. The patient is shown a sign that reads "Close your eyes" and is asked to obey the sign. (1 point)

10. The patient is asked to write a sentence. (1 point)

11. The patient is asked to copy a drawing of intersecting pentagons. (1 point)

Interpretation of Results:

Scores of 12 or less out of 30 indicate a high probability of organic illness.


NEUROLOGY - I & II

José Biller, MD
Indiana University School of Medicine
Indianapolis, Indiana

CEREBROVASCULAR DISEASE (ISCHEMIC)

A. Importance of Cerebrovascular Disease:


Third cause of death in industrialized societies
500,000 persons/year have strokes in U.S.A.
Most common neurologic reason for hospital admission
Stroke related cases are nearly $14 million in the U.S.A. each year.

B. Types of Cerebrovascular Disease:


Ischemic Stroke - 80-85% of cases
Atherothrombotic large artery occlusion
Atheroembolic large artery occlusion
Cardioembolic stroke
Small artery occlusion (Lacune)
Ischemic stroke of other, demonstrated etiology (e.g.: vasculitis, dissection,
fibromuscular dysplasia, etc.)
Ischemic stroke of undetermined etiology
Intracerebral hemorrhage - 10% of cases
Subarachnoid hemorrhage - 6-8% of cases

C. Ischemic Cerebrovascular Disease Major Risk Factors

Arterial Hypertension 6x
Cardiac Disease 2-6x*
Transient Ischemic Attacks
(TIA's)10x
Prior Strokes 10x
Asymptomatic Carotid Bruits 3x
Diabetes Mellitus 2-4x
Cigarette Smoking 2x *Rheumatic Afib, relative
risk=17x

D. Spectrum of Ischemic Cerebrovascular Disease:

Asymptomatic Carotid Bruit/Stenosis


TIA
Reversible Ischemic Neurological deficit (RIND)
Completed (established) Infarction
Progressive Infarction ("Stroke in Evolution").

E. Asymptomatic Carotid Bruit:


The presence of a bruit alone has limitation as a screening tool. Correlative studies using
angiography or ultrasound show only about 60% agreement with auscultation in predicting the
presence of stenosis.
Found in about 4% of people over age 45
Marker for atherosclerosis, poor correlation with hemodynamically
consequential carotid stenosis Overall risk of stroke is about 2%/year; subsequent strokes not
always ipsilateral to bruit
Overall risk of death is about 4%/year

F. Asymptomatic Carotid Stenosis:


Found in 10-25% of patients with symptomatic atherosclerosis in other vascular beds, and in 25-
40% of those identified after a contralateral carotid endarterectomy.
Annual ipsilateral neurologic event rate is about 5%, majority of initial events are
TIA's
Coronary artery disease is their major cause of death
High risk subgroups >60% stenosis
Major ulceration (?)
Intraplaque hemorrhage (?)

G. Asymptomatic Carotid Bruits/Stenosis and Major Non-Carotid Surgery:


Neither carotid bruits or stenosis demonstrated by non-invasive techniques identify subgroup of
patients at increased risk of perioperative stroke
Current data do not appear to substantiate the need for prophylactic carotid endarterectomy in
patients with symptomatic carotid stenosis undergoing other surgical procedures (e.g.: CABG,
AAA repair, etc.)

H. Asymptomatic Carotid Stenosis Management:


ACAS data supports prophylactic CEA in patients with > 60% stenosis, provided that < 2%
operative stroke/death rate is achieved, but controversy remains.
CASANOVA Study
Mayo Clinic Study
VAH Study
ACAS

I. Transient Ischemic Attacks:


10% of patients with ischemic stroke have prior TIA's
One-third of patients with TIA's have infarctions within the first few years after the TIA.

J. Transient Ischemic Attacks Symptoms:

Carotid Artery Vertebrobasilar Arterial Distribution


Distribution Partial or complete (bilateral) blindness
Amaurosis Fugax Homonymous hemianopia
(ipsilateral) Vertigo
Contralateral paresis, Ataxia or disequilibrium not associated
sensory loss, with vertigo
Clumsiness Sensory loss, paresis, clumsiness
Aphasia Bilateral or unilateral
Dysarthria Crossed or alternating between attacks
Contralateral homonymous Dysarthria
hemianopia (rarely) Diplopia
Combination of the above Dysphagia
Combination of the above

Transient isolated vertigo, diplopia or dysphagia are not specific for the diagnosis of
vertebrobasilar TIA.

K. Causes of Transient Ischemic Attacks:

Thromboembolism Non-Atherosclerotic
Cardioembolism Vasculopathies
Impairment of Distal Flow Small Vessel Disease (Lacunes)
Hematological/Rheological Mechanical Interference with
Disorders Blood Flow
Steal Syndromes

L. Transient Ischemic Attacks Differential Diagnosis:

Space Occupying Lesions Labyrinthine Disorders


Focal Seizures Unruptured Aneurysms
Migraines Local Eye Pathology
Metabolic Disorders Others

M. Investigations of Transient Ischemic Attacks:


CBC, PT, PTT, ESR, VDRL, 6/60, 12/60, Urinalysis 12 lead ECG
Chest roentgenogram
CT scan
Non-invasive Carotid Studies (Duplex), Holter ECG, Echocardiography, Cerebral Arteriography,
MRI of the brain, MRA (optional studies)

N. Treatment of Transient Ischemic Attacks:


The first priority in managing patients with TIA's or small strokes is to establish a firm diagnosis.
The best management is not well defined. Prevention of cerebral infarction followed by treatment
of associated disease states and the amelioration of risk factors, should be the major aim for the
TIA patient. Current data supports prophylactic CEA in symptomatic patients with carotid TIA's
and/or minor strokes when linear stenosis on angiography is 70-99%. Specific therapeutic options
include the use of platelet antiaggregating agents, (aspirin or ticlopidine), anticoagulants, and
CEA.

Treatment of TIA (Cont)


Medical Therapy
Management of risk factors (hypertension, diabetes, cigarette smoking, etc.)
Platelet antiaggregating agents
Aspirin 325 mg - 1.3 grams per day
Ticlopidine 500 mg per day
Anticoagulants*
Oral anticoagulants have been used for decades in the prophylaxis of cerebral infarction in
patients who have experienced TIA's. Results of controlled studies failed to demonstrate a
statistical significant difference in stroke incidence and mortality between the treated and
untreated groups. Further studies are in progress.

Oral anticoagulants remain an important therapy to reduce the incidence of embolization


from the heart in patients with cardioembolic cerebral ischemia, and as primary prevention
in patients with non valvular atrial fibrillation.

The use of anticoagulants has also been recommended by some authorities for patients who
sustain recurrent episodes of focal cerebral ischemia despite platelet antiaggregants.
However, recent studies comparing prophylactic oral anticoagulants with platelet
antiaggregants, suggest that although oral anticoagulants reduce the risk of stroke in
patients with threatened stroke, neither study showed a significant difference between the
two groups.

O. Cerebral Infarction - Pathophysiology:


Normal CBF (50-55 ml/100g/min)
Threshold for synaptic transmission failure (18 ml/100g/min)
Threshold for membrane pump failure (8 mg/100g/min)
Ischemic penumbra
CBF = 8 - 18 ml/100g/min
Loss of EEG
Flat evoked potentials
Normal ATP
Normal extracellular K+

P. Cerebral Infarction of Cardiac Origin - Common Sources:

Myocardial Infarction Prosthetic heart valves


Mural thrombus Calcific heart valves
Ventricular aneurysms Nonbacterial thrombotic "marantic"
Hypokinetic regions endocarditis
Cardiomyopathies Infective endocarditis
Cardiac Arrhythmias Intracardiac Tumors
Atrial fibrillation Atrial myxoma
Sick-sinus syndrome Intracardiac Defects with
Valvular Heart Disease Paradoxical
Congenital valvular heart disease Embolism
Rheumatic Patent foramen ovale
Mitral valve prolapse Atrial septal defect

Q. Cerebral Infarction Syndromes

Syndromes in the carotid arterial Alexia without agraphia (dominant


circulation hemisphere)
Middle cerebral artery syndrome Contralateral hemiparesis.
Contralateral Contralateral
hemiparesis/hemianesthesia hemianesthesia
Homonymous hemianopia Contralateral choreoathetoid
Aphasia (dominant hemisphere) movements
Hemineglect (nondominant hemisphere) Impaired ocular movements
Apraxia (nondominant hemisphere) Depressed mental status
Alexia Ipsilateral oculomotor nerve palsy
Finger agnosia with
Acalculia contralateral cerebellar ataxia,
Right-left disorientation choreoathetosis or hemiplegia
Agraphia Basilar trunk syndrome
Anterior cerebral artery syndrome Altered consciousness
Contralateral Quadriplegia
hemiparesis/hemianesthesia Impaired horizontal gaze
Leg involved more than arm Preserved eyelid and vertical eye
Abulia movements
Akinetic mutism Posterior inferior cerebellar or
Paratonia vertebral
Left arm apraxia artery (Wallenberg Syndrome)
Sphincter incontinence Ipsilateral facial
Syndromes in the vertebrobasilar hypalgesia/thermoanesthesia
arterial Ipsilateral palatal, pharyngeal or
circulation vocal cord
Posterior cerebral artery paresis
Contralateral homonymous hemianopia Ipsilateral Horner syndrome
Cortical blindness Ipsilateral nystagmus
Agnosia for familiar faces Ipsilateral cerebellar ataxia
Achromatopsia Contralateral body
hypalgesia/thermoanesthesia

R. Cardioembolic Stroke - Evaluation:

Diagnosis of embolic strokes of cardiac origin remains inferential.


History and General Physical Examination
Neurological Examination
Blood Screen
Blood Cultures
CT or MRI Brain Scans
Cerebral Angiography
Two-dimensional Echocardiogarphy
Doppler Echocardiography
Contrast Echocardiography
Transesophageal Echocardiography
Radionuclide Ventriculography
Indium - 111 Platelet Scintigraphy
Cardiac Computed Tomography
Ultrafast Cardiac CT
MRI of the Heart
Cardiac Catheterization

S. CEREBRAL ISCHEMIA - MANAGEMENT:


Management - General Aspects: Thrombolytic Agents:
Early Diagnosis and Management Streptokinase
Cardiac, Neurological, Neurovascular Urokinase
Examinations Acylated Streptokinase-
CT Plasminogen
Activator
Supportive/Ancillary Treatment: Tissue-Type Plasminogen
Airway Activator
Blood Pressure r-Pro-urokinase
Fluids-Electrolytes
Prevention of Complications Hemorheological Treatment:
Hemodilution
Treatment of Cerebral Edema: Isovolemic Paradigms
Medical Management Hypovolemic Paradigms
Surgical Options Hypervolemic Paradigms
Ancrod
Pharmacological Protection: Pentoxifylline
Calcium Channel Blockers Low-Molecular Weight Dextran
Opiate Receptor Antagonists Perfluorocarbons
Barbiturates
Excitatory Neurotransmitter Other Medical Therapies:
Antagonists Aminophylline
Anti-intercellular adhesion molecules Cerebral Vasodilators
Beta-Blockers
Antithrombotic Agents: GM1 Gangliosides
Heparin Vasopressors
Low Molecular Weight Heparinoids
Prostacyclin
Platelet Anti-Aggregating Drugs

Conclusions:

Ischemic stroke is a major cause of death and disability. Despite its high incidence, acute
management remains controversial. Most current forms of therapy are designed to reduce
complications of a recent stroke or prevent recurrences. Experimental data suggest that the
optimal time for intervention should be the immediate hours following brain ischemia.

CEREBROVASCULAR DISEASE - HEMORRHAGIC

A. HEMORRHAGIC CEREBROVASCULAR DISEASE:

Parenchymal Hemorrhage (ICH)


Subarachnoid Hemorrhage (SAH)
Hemorrhage into the pituitary (Pituitary Apoplexy)
Subdural/Epidural Hemorrhage

B. CAUSES OF PARENCHYMAL HEMORRHAGE


Causes of Spontaneous Intracerebral Hemorrhage
a. Hypertension g. Vasculitis/Vasculopathies
Collagen vascular disease
b. Arterial Aneurysms Temporal arteritis
saccular Isolated central nervous system angiitis
infective Moyamoya
neoplastic
traumatic h. Drug Related
Amphetamines
c. Vascular Malformations Phenylpropanolamine
arteriovenous Talwin-pyribenzamine (T's and Blues)
telangiectasias Ephedrine
cavernous angiomas Pseudoephedrine
venous angiomas Cocaine
varices Phencyclidine (PCP)
others
i. Cerebral Venous Occlusive Disease
d. Bleeding Diathesis
Leukemias j. Following Surgery
Thrombocytopenia carotid endarterectomy
Disseminated Intravascular Coagulation cardiac surgery
Polycythemia vera neurosurgery
Hyperviscosity Syndromes
Hemophilia k. Miscellaneous
Hypoprothrombinemia pregnancy
Afibrinogenemia pheochromocytoma
Sickle Cell Anemia lightning stroke
Anticoagulant Therapy
Thrombolytic Therapy
Others

e. Cerebral Amyloid Angiopathy

f. Brain Tumors
1. Primary
a) malignant
b) benign
2. Metastatic
a) choriocarcinoma
b) melanoma
c) lung
d) renal

C. CLINICAL PRESENTATION:

P General manifestations
P Manifestations according to location
Putamen
Lobar
Thalamus
Pons
Cerebellar
Others

D. EVALUATION:

History
Physical examination
Neurological examination
Laboratory screen
CBC, Platelet, PT, PTT, ESR
Blood chemistries, electrolytes
Urinalysis
CT of brain
Chest roentgenogram
12 lead ECG
In Selected Cases:

MRI of brain, MRA


Cerebral arteriography
CSF
Screen for systemic vasculitis
Bleeding time, fibrinogen, fibrin degradation products,
clotting factors
Sickle cell screen
Blood/urine screens for drugs
Brain/meningeal biopsy

E. MANAGEMENT:

Airway adequacy
Raised intracranial pressure Rx
ICP monitoring (?)
Blood pressure Rx
Anticonvulsants (?)
Surgery

F. ANEURYSMAL SUBARACHNOID HEMORRHAGE:

85% of cases of SAH


11/100,000 population
Peak age 55-60 years
High mortality

G. ANEURYSMAL SUBARACHNOID HEMORRHAGE - EVALUATION:

Early diagnosis
CT
LP if CT is negative
Cerebral angiography (4 vessel)
Clinical grading

H. ANEURYSMAL SUBARACHNOID HEMORRHAGE - LOCATION OF


ANEURYSMS:

Anterior communicating artery


Posterior communicating artery
Middle cerebral artery
Internal carotid artery
Anterior cerebral artery
Vertebrobasilar system

I. ANEURYSMAL SUBARACHNOID HEMORRHAGE - MANAGEMENT:

Stroke or Intensive Care Unit


Airway/ventilation
Cardiac monitoring
Bed rest
Skin protection
DVT prophylaxis
Sphincters
Nutritional requirements
Analgesics
Antiemetic
H2 blockers
Sedatives
Anticonvulsants
Nimodipine (calcium channel blocker)
Fluid/electrolytes
Blood pressure Rx
Raised intracranial pressure Rx
Surgery

early (<72 hrs)


late (< 10 days)

Vasospasm Rx
Prevention of rebleeding

SEIZURES

A. DEFINITION - SEIZURES:
Transient disturbance of cerebral function due to abnormal neuronal discharges.
u Epileptic seizures
u Non-epileptic seizure
(Syncope, metabolic derangements, parasomnias, movement disorders)
Psychogenic
B. DEFINITION - EPILEPSY:
Disorders characterized by a predisposition to recurrent seizures.
Active cases on therapy: 45-100 million worldwide; 1.5-3.5 million in USA.

C. CLASSIFICATION OF EPILEPTIC SEIZURES;

I. Partial seizures (seizures begin locally)


II. Generalized seizures (bilaterally symmetrical and without local onset)
III. Unclassified epileptic seizures
IV. Status epilepticus

D. CLASSIFICATION OF PARTIAL SEIZURES:


Simple partial seizures (without impaired consciousness)
Complex partial seizures (with impaired consciousness)
Partial seizures with secondary generalization (simple or complex seizures
spreading to bilateral
involvement)

E. CLASSIFICATION OF SIMPLE PARTIAL SEIZURES:

focal motor with or without march


focal motor with inhibition of movement
postural seizures
adversive seizures
vocalization or ictal aphasia
somatosensory
visual
auditory
vertiginous
automatic

F. CLASSIFICATION OF COMPLEX PARTIAL SEIZURES:

with cognitive symptomatology


with affective symptomatology
with psychosensory symptomatology
with psychomotor symptomatology
compound forms

G. FEATURES OF COMPLEX PARTIAL SEIZURES:

often accompanied by "aura"


EEG shows abnormality starting locally
altered or complete loss of consciousness
may have prominent emotional or thought disorder during
seizure
post-ictal confusion lasting minutes or hours

H. CLASSIFICATION OF PARTIAL SEIZURES WITH SECONDARY


GENERALIZATION
simple partial "generalized tonic clonic seizure
complex partial "generalized tonic clonic seizure
simple partial "complex partial" generalized tonic clonic
seizure

I. CLASSIFICATION OF GENERALIZED SEIZURES:

Absence
Tonic-clonic
Clonic-tonic-clonic
Clonic
Myoclonic
Atonic (drop attacks)
Tonic

J. CLASSIFICATION OF ABSENCES SEIZURES:

simple absence
clonic components (myoclonic absences)
increased tone (retropulsive absences)
decreased tone (atonic absences)
automatism (automatic absences)
autonomic phenomena

K. FEATURES OF ABSENCE SEIZURES:

abrupt onset, no warning


EEG - 3 per second spike-slow wave pattern
loss of consciousness
no bladder or bowel incontinence
no post-ictal confusion

L. FEATURES OF GENERALIZED TONIC-CLONIC


SEIZURES:

little or no warning
EEG definitely abnormal at start
loss of posture with high risk of self injury
loss of consciousness
bladder or bowel incontinence likely
violent contraction of limb and trunk muscles
post-ictal confusion lasting minutes to hours

M. CLASSIFICATION OF STATUS EPILEPTICUS:

Convulsive

tonic-clonic status
myoclonic status
clonic-tonic-clonic status
Non-convulsive

absence status or "petit mal" status


complex partial status
simple partial status
partial motor status (e.g. epilepsia partialis continua)

CLASSIFICATION OF STATUS EPILEPTICUS (CONT)

partial sensory status


partial status with vegetative or autonomic symptoms
partial status with cognitive symptoms
partial status with affective symptoms
Non-epileptic psychogenic seizures

N. PSYCHOGENIC SEIZURES - DEFINITION:


Sudden change in behavior or mentation not associated with any physiologic etiology or
abnormal paroxysmal discharge of electrical activity from the brain.

O. EPILEPTIC VS NON-EPILEPTIC SEIZURES:


Distinguishing Features

Epileptic Seizures Psychogenic Seizures


In-Phase Clonic Activity Out of Phase Clonic Activity
No Pelvic Thrusting Pelvic Thrusting
No Side to Side Movements Side to Side Movements P. ETIOLOGY OF SEIZURES:

idiopathic
symptomatic
trauma
congenital malformations
genetic disease
infections (e.g. meningitis, encephalitis)
metabolic derangements (e.g. hypoglycemia, hypocalcemia, hypo/hypernatremia)
drug overdose (e.g. tricyclics, theophylline, lidocaine)
drug withdrawal (e.g. ethanol, sedative-hypnotics)
tumors
cerebrovascular disorders

Q. EVALUATION:

history
general physical examination
neurological examination
EEG
blood screen (glucose, BUN, creatinine, lytes, CBC, ESR, LFTs, ABGs, drug
screen)
CT or MRI
If CNS infection suspected - CSF

R. ANTICONVULSANT THERAPY - GUIDELINES

establish diagnosis of epilepsy


use right drug for seizure type
use monotherapy
treat the patient and not the serum levels

Drug Indication Maint. Dose Half-Life Optimal Rx Minimum # of


(mg/kg/d) (hr) (µg/ml) daily doses

Phenytoin GTC;P 3-5(4-8) 18-24 10-20 1


Phenobarbital GTC;P 2-3(2-5) 48-120 15-45(10-40) 1
Primidone GTC;P 10-25(5-20) 6-12 5-12(5-15) 3
Carbamazepine GTC;P 10-20(5-25) 12-18 4-8(4-12) 2
Valproic Acid GTC;A;M 20-60(10-60) 6-18 40-100(50-100) 3
Ethosuximide A 20-35 24-36 40-100 2
Clonazepam A;M 0.05-0.2 20-40 20-80(ng/ml) 2

GTC = generalized tonic clonic; P = simple or complex partial


A = absence; M = myoclonic

S. STATUS EPILEPTICUS DEFINITION: "A condition characterized by an epileptic seizure


which is so frequently repeated or so prolonged as to create fixed and lasting condition."

T. STATUS EPILEPTICUS - ETIOLOGIES:

antiepileptic drug withdrawal


brain trauma
stroke
meningitis
encephalitis
anoxic encephalopathy
metabolic derangement
toxin exposure
drug overdose

U. STATUS EPILEPTICUS (TONIC-CLONIC) MANAGEMENT:

medical emergency - life threatening condition


mortality: 6.6%-20%
prognosis depends on underlying cause
risks of neurologic sequelae increase with duration of status
Assess airway, ventilation, hemodynamics
draw blood for: glucose, BUN, creatinine, lytes, CBC, LFTs, calcium,
phosphorus, toxicology, ABGs
infuse 50 ml of D 50% plus thiamine 100 mg IV
begin Diazepam 2 mg/min IV (max 20 mg) or Lorazepam (4-8 mg)
start phenytoin 18-20 mg/kg IV (50 mg min)
if seizures persist start phenobarbital 10 mg/kg IV (100 mg/min)
if seizures continue proceed with barbiturate coma (Pentobarbital) or general
anesthesia (Halothane and neuromuscular junction blockade)

DEMENTIA

A. DEFINITION: Dementia is an acquired organic syndrome characterized by


widespread deterioration of intellect, behavior and personality, associated with a
normal level of consciousness.

B. EPIDEMIOLOGY:
4-5% of persons over age 65 have severe dementia
10% of persons over age 65 have mild to moderate dementia
First most common type - Alzheimer's Disease
Second most common type - Vascular Dementia

C. CLASSIFICATION:
I. Degenerative

Alzheimer's Disease Progressive Supranuclear Palsy


Pick's Disease Striato-Nigral Degeneration
Parkinson's Disease Olivo-Ponto-Cerebellar Atrophy
Parkinson's - Dementia - ALS complex of Hallevorden - Spatz Disease
Guam Other Multisystem Atrophies
Huntington's Disease Gerstmann - Straussler

II. Vascular
Multi-Infarct Dementia
Binswanger's Disease
Vasculitides

III. Neoplasia
Primary and metastatic tumors (e.g. frontal lobe, non-dominant temporal lobe,
diencephalon,corpus callosum)
Remote effect of malignancy

IV.Trauma
Non-penetrating head injuries (e.g. dementia pugilistica)
Subdural hematoma

V. Infectious/Inflammatory

Neurosyphilis Jakob-Creutzfeld Disease


Chronic Meningitis (e.g. fungal, TBC, Whipple's Disease
others) Behcet's Disease
Encephalitis Vogt - Koyanangi - Harada
AIDS Disease
Progressive Multifocal Systemic Lupus Erythematosus
Leukoencephalopathy (PML) Cogan's Syndrome
Subacute Sclerosing Panencephalitis (SSPE) Temporal Arteritis
Subacute Rubella Encephalitis Sarcoidosis
Multiple Sclerosis

VI . Metabolic/Endocrine

Chronic Renal Failure Hypothyroidism


Dialysis Dementia Cushing's Disease
Portosystemic Encephalopathy Addison's Disease
Chronic Cerebral Hypoxia Panhypopituitarism
Wilson's Disease Hyper and Hyponatremia
B12 deficiency Hyper and Hypocalcemia
Pellagra Hypoglycemia
Porphyria

VII. Toxic
Alcohol related (e.g. Korsakoff's, Marchiafava-Bignami, multivitamin deficiency, etc.)
Drugs (e.g. anticholinergic, sedatives, hypnotics, anticonvulsants, antihypertensives,
psychotropics, etc.)
Heavy metals
Solvents
poisons

VIII. Hydrocephalus
Communicating
Non-Communicating

IX. Storage Disorders


Adult metachromatic leukodystrophy
Ceroid Lipofuscinosis (Kuf's Disease)
Adrenoleukodystrophy
Cerebrotendinous Xanthomatosis

X. Pseudo-Dementia

D. COMMONLY REPORTED DIAGNOSES


(AM J MED 83:101, 1987) (ANN INT MED 97:231, 1982)
Diagnosis % Diagnosis %
Alzheimer's 39 Alzheimer's 48.5
Pseudo-dementia 18 Alcohol-related 10.6
Multi-infarct 13 Multi-infarct 9.6
Miscellaneous 8 Others 7.4
Alcohol-related 7 Normal pressure hydrocephalus 5.4
Metabolic 4 Mass lesions 3.7
Tumor 3 Huntington's 3.7
Hydrocephalus 3 Drug toxicity 2.0
Huntington's 2 Others (reversible) 2.0
Infections 1
Parkinson's 1
Toxic (drug) reactions 1

E. EVALUATION:
History, Physical/neurological examination (Hachinski ischemic score - see below)
Mini-mental state examination (screening test - see table below)
Mattis dementia rating scale
Alzheimer's disease assessment scale
Specialized neuropsychological examination
Routine tests
CBC with differential, ESR
Urea, creatinine, calcium, phosphorus, electrolytes, glucose
Liver function tests
Serum B12, Serum Folate
TSH
VDRL
Urinalysis
Chest roentgenogram
ECG
CT scan
Selective Tests
CSF
EEG
MRI
radionuclide cisternography (?)
lumbar infusion testing (?)
HIV
ANA
serum copper, ceruloplasmin, 24-hour urine copper
urine for porphobilinogen, Watson-Schwartz test
serum, peripheral blood leukocytes cultured fibroblasts for enzymatic deficiencies
(arylsulfatases, ceroid lipofuscin, etc.)
Cerebral angiogram
Jejunal biopsy
Brain biopsy

ÝISCHEMIC SCORE* (Hachinski et al: Arch Neurol 32:632, 1975)


Abrupt onset 2
Step wise deterioration 1
Fluctuating course 2
Nocturnal confusion 1
Relative preservation of personality 1
Depression 1
Somatic complaints 1
Emotional incontinence 1
Hx of hypertension 1
Hx of stroke 2
Focal neurological symptoms 2
Focal neurological signs 2
Other evidence of arteriosclerosis 1

* Scores of greater than 4 indicate a higher probability of Alzheimer's Disease and scores of
7 and above indicate a high probability of multi-infarct dementia.

ÝThe Mini-Mental Examination* (Folstein et al. J Psych Res 12:189, 1975)g


1. What is the year, season, date, day of the week, month? (5 points)
2. Where are we: country, state, city or town, hospital, floor of building? (5 points)
3. The examiner names three objects, taking 1 second to say each. The patient is asked to
repeat the
names of all three objects after the examiner has said them. (3 points)
4. Serial sevens. One point for each correct answer. Stop after five answers. Or spell the
word "world"
backwards. (5 points)
5. Recall the three objects named in #3. (3 points)
6. The patient is shown a pencil and a watch and asked to name them. (2 points)
7. The patient is asked to repeat: "No ifs, and, or buts." (1 point)
8. The patient is handed a sheet of paper and asked to carry out a three-stage command:
"take this paper
in your right hand, fold it in half, and put it on the floor." (3 points)
9. The patient is shown a sign that reads "Close your eyes" and is asked to obey the sign. (1
point)
10. The patient is asked to write a sentence. (1 point)
11. The patient is asked to copy a drawing of intersecting pentagons. (1 point)

* Scores of 12 points or less out of 30 indicate a high probability of organic illness.

F. Management:
Team approach (physician, visiting nurse, social worker)
Treat specific causes
Adequate food and fluid intake
Treat intercurrent illness and associated conditions
Environmental therapy (avoid unfamiliar surroundings, challenging situations, frequent
relocations)
Counseling (spouse, caretaker, etc.)
Pharmacotherapy
Antidepressants
Avoid sedatives
Avoid unproven therapies (e.g. cerebral vasodilators, etc.)
Tacrine
£ POLYMYOSITIS AND DERMATOMYOSITIS

II. A. DEFINITION- Polymyositis - Autoimmune condition characterized by inflammation


and degeneration
of muscle fibers.
Dermatomyositis - Autoimmune condition characterized by inflammatory changes in
muscle and skin.

B. CLINICAL CLASSIFICATION:
I. Polymyositis of the adult
II. Dermatomyositis of the adult
III. Dermatomyositis of childhood and the young adult
IV. Dermatomyositis associated with connective tissue disorder (scleroderma, SLE, RA,
MCTD, Sjögren)
V. Polymyositis associated with connective tissue disorder (Scleroderma, SLE, RA,
MCTD, Sjögren)
VI. Dermatomyositis associated with malignancy (e.g.: ovary, stomach)
VII. Polymyositis associated with malignancy (e.g.: ovary, stomach)

C. SYMPTOMS AND SIGNS: Onset of the disease is insidious


Weakness of girdle and proximal limb muscles
Muscle pain and tenderness
Weakness of flexor muscles of the neck
Dysphagia
Respiratory muscle weakness
Cardiac involvement (ECG changes, atrial arrhythmias, AV conduction defects, BBB,
complete heart block)
Interstitial pneumonitis
Raynaud's phenomenon
Skin changes (eyelids, malar region, knuckles, periungal, elbows, knees, upper chest)
Calcification of interstitial tissues

D. DIAGNOSIS:
Clinical
Enzymes
- CK (MM), Aldolase
- EMG (myopathic changes, increase muscle irritability)
- Muscle biopsy - degeneration, regeneration, inflammatory changes (PM),
perifascicular atrophy, inflammatory changes (DM)
E. TREATMENT
Corticosteroids
Azathioprine
Methotrexate
Plasma exchange
Total Body irradiation
Treatment of underlying malignancy or connective tissue disease

£ MYASTHENIA GRAVIS

A. DEFINITION: Autoimmune disease characterized clinically by fluctuating muscle


weakness and
abnormal fatigability associated with acetylcholine receptor (AChR) deficiency at the
neuromuscular
junction (NMJ). Neuropathologically, the motor end plate contains fewer AChR sites.

B. EPIDEMIOLOGY:
Incidence - 2-5/yr/million population
Prevalence - 43-64/million
F>M among younger patients
M>F among patients older than 50 yrs.
HLA-A1, HLA-B8, DRW3

C. SIGNS AND SYMPTOMS: Onset is often insidious but may be abrupt. Course is
unpredictable, but
most often is fluctuating.
Muscle Weakness
- Ptosis (unilateral, bilateral or alternating)
- Diplopia (variable and made worse with fatigue)
- Facial weakness (myasthenic snarl)
- Palatal/laryngeal weakness
- Dysphagia, inability to clear secretions
- Weak cough
- Proximal limb muscle weakness
- Myasthenic crisis (incidence 12%-20%/mortality 3%)
- Fatigability
- End of day worsening

D. ADULT CLINICAL VARIANTS:


Ocular Form (15-20%)
Mild Generalized (30%)
Moderately Severe Generalized (20%)
Acute fulminating (11%)
Late severe (9%)

E. ASSOCIATED DISEASES
SLE, RA, Sjögren's, Polymyositis, Eaton-Lambert
Ulcerative colitis, pemphigus, pernicious anemia
Hyper/hypothyroidism
Thymic hyperplasia (70%)
Thymomas (15%)

F. DIAGNOSTIC TESTS:
Edrophonium (Tensilon)
Prostigmine
Acetylcholine receptor antibodies
EMG studies
- decremental response at 3Hz > 10%

DIAGNOSTIC TESTS (CONT)

- single fiber EMG (increase jitter)


Tensilon tomography
CT of chest
T4, TSH, RF, ANA
VC, TV, PE max, PI max

G. SYMPTOMATIC TREATMENT
Anticholinesterase drugs
Corticosteroids
Azathioprine
Cyclosporine
Cyclophosphamide
Thymectomy
Avoid Drugs which may exacerbate MG

H. TREATMENT OF MYASTHENIC CRISIS


Hospital admission
FVC measurements
Intubation if FVC < 15 ml/kg
d/c anticholinesterase drugs
Rx underlying infection
d/c hypnotics, sedatives, or potentially aggravating drugs
Plasma exchange (daily or qod X 5 exchanges)
Adjust dose of corticosteroids

£ ACUTE INFLAMMATORY-POSTINFECTIOUS POLYNEUROPATHY (Gullain-


Barré)

A. DEFINITION: Acute, monophasic, immunologically mediated, demyelinative


polyneuropathy associated
with lymphocytic infiltrates scattered throughout the spinal nerve roots and peripheral
nerves. Axonal
damage and Wallerian degeneration may occur.

B. EPIDEMIOLOGY: Most common cause of acute neuromuscular paralysis.


Incidence: 1.7 per 100,000 persons per year
M>F
No predilection for gender or age
No geographical, seasonal, or yearly variation
Mortality 1%-5%

C. CRITERIA FOR DIAGNOSIS: (From Asbury AK, Ann Neurol (Suppl) 1-5, 1981)
I. Features Required for Diagnosis
Ý Progressive motor weakness of more than one limb. The degree ranges from minimal
weakness of the legs, with or without mild ataxia, to total paralysis of the muscles of all four
extremities and the trunk, bulbar and facial paralysis, and external ophthalmoplegia.
Ý Areflexia - Universal areflexia is the rule, though distal areflexia with definite
hyporeflexia of the biceps and knee jerks will suffice if other features are consistent.

II. Features Strongly Supportive of the Diagnosis


Progression
Relative symmetry
Mild sensory symptoms and signs
Cranial nerve involvement
Recovery
Autonomic dysfunction
Absence of fever at onset of neuritic symptoms

D. COMMON PRECEDING EVENTS:


Viral infections (usually respiratory)
Infections mononucleosis
Mycoplasma pneumonia
Viral exanthems
Campylobacter
Post-surgery
Pregnancy
Systemic Lupus Erythematosus
Hodgkin's disease
Non-Hodgkin's lymphoma

E. DIFFERENTIAL DIAGNOSIS:
Myasthenia gravis
Botulism
Periodic paralysis
Poliomyelitis
Epidural abscess
Acute intermittent porphyria
Diphtheritic polyneuropathy
Lyme disease
Toxic polyneuropathies
Organophosphate poisoning
Tick paralysis
Critical illness polyneuropathy
Hypophosphatemia
Basilar artery thrombosis

F. DIAGNOSTIC EVALUATION:
EMG, NCS, F-waves (slowing of conduction velocities, prolonged distal latencies, abnormal
late responses)
Blink reflexes (prolonged or absent)
SSEP
CSF (! protein without pleocytosis)
Vital capacity (VC), maximum pulmonary expiration (PEmax), maximum pulmonary
inspiration (Plmax)

G. TREATMENT:
Supportive
Prevention of complications (monitor heart rate, BP, ECG, VC, PE max, Pl max)
Proper positioning
DVT prophylaxis
Fluid and electrolyte balance
Nutritional support
Analgesia
Psychological support
Early recognition and management of respiratory failure
- inability to clear secretions
- VC < 2-3 times predicted tidal volume (VC < 25ml/kg early intubation is associated with
risk of pulmonary complications)
- PEmax < 40 cmH2O
- Plmax < 20 cmH2O
Plasma exchange (shortens the duration and severity of illness if begun within 2 weeks of
the illness)
IvIg

£ MOTOR NEURON DISEASE IN ADULTS

A. DEFINITION - Progressive degenerative disorder of the motor neurons of the spinal


cord, medulla, pons
and motor cortex, characterized clinically by variable degrees of muscle wasting and upper
motor neuron
signs.

B. EPIDEMIOLOGY:
Incidence - 0.4-1.8/100,000 population
M>F
Clusters in Guam, and Kii Peninsula (Japan)

C. CLINICAL FORMS:
Amyotrophic lateral sclerosis
Progressive muscular atrophy
Progressive bulbar palsy
Primary Lateral Sclerosis (?)
Pseudobulbar palsy
D. CLINICAL COURSE: The usual clinical course is one of steady progression, leading to
death within 3
yrs in approximately 50% of patients. Rare patients may live up to 30 years.
50% die by 3 years
20% die by 5 years
10% die by 10 years
few survive 20 yrs or longer

E. SIGNS AND SYMPTOMS


Muscle weakness
- small hand muscles, tongue, feet
Muscle cramps (particularly nocturnal)

SIGNS AND SYMPTOMS (CONT)

Muscle atrophy
Fasciculations
Spasticity, hyperactive reflexes, extensor plantar responses
Preserved eye movements (in general)
Preserved intellect (in general)
Preserved bladder function
Preserved autonomic functions
Absent sensory signs (in general)

F. DIAGNOSIS: The diagnosis is made on the basis of the clinical features. There are no
specific paraclinical markers.
EMG/NCS (Widespread denervation)
Muscle biopsy (seldom needed)
CK (may be slightly elevated)
CSF (protein may be elevated)
Endoscopy, barium swallow, ENT evaluation
Vital capacity

ÝOther investigations are obtained to rule out "treatable" causes of motor neuron disease:
ÝMRI or Myelogram of cranio-cervical junction/spinal cord.
- R/O foramen magnum tumors, basilar invagination, narrowed spinal canal,
intra/extramedullary tumors, syringomyelia, cervical spondylosis
ÝUrine/blood for heavy metals
- lead, mercury, tri-ortho-cresyl phosphate, mercury (?)
ÝT4, TSH, Glucose, Calcium, Phosphorus
- r/o hyperthyroidism (proximal weakness and fasciculations)
- r/o hyperinsulinism (pancreatic adenoma)
- r/o hyperparathyroidism
ÝSearch for occult malignancy, dysproteinemia
- ALS and Waldenstrom's macroglobulinemia
- ALS and renal carcinoma
- ALS and lymphoma
ÝTensilon test, AChR antibodies
-r/o myasthenia gravis
ÝNCV's
- r/o inflammatory polyradiculoneuropathy
ÝCK, Muscle bx, EMG
- R/O inflammatory myopathy

G. OTHER DISORDERS ASSOCIATED WITH MOTOR NEURON FINDINGS:


Dementia, Jakob-Creutzfeld
Parkinsonism, Shy-Drager syndrome
Spino-cerebellar degenerations
Poliomyelitis
Post-radiation motor neuron finding
Post-electrical injury motor-neuron findings

H. TREATMENT: In the absence of specific therapy, treatment is symptomatic


Spasticity: Baclofen, Diazepam
Cramps: Phenytoin, Quinine sulfate
Sialorrhea: Amitriptyline, Clonidine
Dysphagia: Anticholinesterase, N-G tube, Surgery
Respiratory infections: Prophylactic vaccines, Rx of underlying respirator infection
Respiratory failure: Long-term mechanical ventilation (individual basis)
Future prospects: Ciliary neurotrophic factor (CNTF), other neurotrophic factors

£ PERIPHERAL NEUROPATHIES

A. Classification: Adequate categorization can be accomplished in 75% of cases.


Mononeuropathies
Entrapment (e.g.: carpal tunnel syndrome, Saturday night palsy (radial), tardy ulnar palsy,
meralgia paresthetica)
Mononeuritis Multiplex
Diabetes
Vasculitis (e.g.: PAN, SLE, RA)
Dysproteinemias
Leprosy
Lyme
Endocarditis
AIDS
Sarcoidosis
Multifocal variant of chronic inflammatory demyelinating polyradiculoneuropathy (CIDP)
Familial pressure sensitive neuropathy
Symmetrical Polyneuropathies
Acute
Guillain Barre' syndrome
Acute intermittent porphyria
Diphtheria
Toxins
Subacute/Chronic
Metabolic Disorders (e.g.: diabetes, uremia, hepatic failure, hypothyroidism)
Toxins (e.g.: alcohol, heavy metals, industrial toxins, herbicides, pesticides)
Drugs (e.g.: antimicrobials, psychotropics, cardiovascular drugs,
antineoplastic agents, B6)
Dysproteinemias
Amyloidosis
Osteosclerotic Myeloma
Carcinomatous neuropathy
CIDP
Inherited neuropathies (e.g.: HMN, HSN, HMSN, Refsum, Bassen-Kornsweig, Tangier,
Metachromatic Leukodystrophy)

B. Investigations
History
General Physical Examination
Neurological Examination
Biochemical Tests
EMG/NCS
Nerve Biopsy (selective cases: e.g.: vasculitis, sarcoidosis, leprosy, CIDP)

£ MULTIPLE SCLEROSIS

A. DEFINITION: Disease of unknown etiology characterized pathologically by widespread


occurrence in the white matter of the central nervous system of patches of demyelination,
followed by gliosis.

B. EPIDEMIOLOGY: More common in temperate than in tropical climates


Prevalence in northern climates: 60-70/100,000
Prevalence in southern climates: 6-15/100,000

C. ETIOLOGY:
1. Autoimmune vs. viral (both are not exclusive)
2. Inherited predisposition
a. 5-20% show familial aggregation
b. Association with DW2 and DRW2 in populations with HLA-A3 and HLA-B7
c. HLA-A3 and HLA-B7 much higher in northern caucasians

D. PATHOLOGY:
Gross
1. Foci of demyelination scattered throughout the cortex, brainstem and spinal cord. Optic
nerves and chiasm are often involved, as are the pons and cerebellar white matter.

2. Distribution of plaques - Most conspicuous in the periventricular white matter, about the
angles of the lateral ventricles and beneath the floor of the fourth ventricle. Optic pathways
and spinal cord frequently involved.

Micro
1. Loss of myelin, reduction in number, or even absence of oligodendrocytes. Astrocytosis
may be pronounced. Lymphocytes and plasma cells can be found. Relative preservation
of axons.

E. CLINICAL FEATURES:
Peak ages of onset
women - 20-35 years old
men - 35-45 years old
overall - 30 years old

Symptoms and signs


Optic neuritis (25-30% of patients with ON later develop MS)

CLINICAL FEATURES (CONT)

Pyramidal signs (30% of patients)


Genito-urinary symptoms (30% of patients)
Sensory symptoms (paresthesias, Lhermitte's sign)
Cerebellar symptoms and signs (dysarthria, ataxia, intention tremor)
Brainstem signs (nystagmus, internuclear ophthalmoplegia, ocular motility disturbances,
Trigeminal neuralgia, facial anesthesia, facial myokymia, vertigo, deafness (less frequent)
Mental symptoms (eutonia, euphoria, depression, dementia)
Seizures (tonic, focal, generalized) - in 5% at some time
Other symptoms

Clinical Course
remissions and exacerbations
progressive without remissions
acute MS
neuromyelitis optica (Devic's syndrome)
benign
malignant

Disease Severity
"benign disease" - 30%
"malignant course" - 10%
"intermediate course" - 60%
F. DIAGNOSTIC CRITERIA (Shumacher et al. - 1965)
1. Objective abnormalities attributable to CNS dysfunction.
2. Involvement of two or more separate parts of the CNS, either by history or by neurologic
examination.
3. Neurologic examination must reflect predominantly white matter involvement.
4. The involvement must have occurred in two or more episodes separated by a period of
one month, or must have occurred in a step-wise fashion over a period of at least
six months.
5. The manifestations must not be better attributed to some other disease (by a physician
competent in clinical neurology)

CLINICALLY DEFINITE MULTIPLE SCLEROSIS

CLINICALLY PROBABLE MULTIPLE SCLEROSIS

CLINICALLY POSSIBLE MULTIPLE SCLEROSIS

G. LABORATORY EVALUATION:
CT - Hypodense lesions in periventricular white matter
- Acute lesions may enhance
- Chronic disease may result in enlarged ventricles

MRI - Increased signal intensity on T2WI in white matter


- Chronic plaque, # signal on T1WI, ! signal on T2WI
- More sensitive than CT
- Disease activity correlates with Gadolinium MRI

LABORATORY EVALUATION (CONT)

EVOKED POTENTIALS
VEP - 85% abnormal - definite MS
- 58% abnormal - probable MS
- 37% abnormal - possible MS
BAEP - 37% abnormal with BS symptoms/signs
- 21% abnormal without BS symptoms/signs
SSEP - 77% abnormal - definite MS
- 67% abnormal - probable MS
- 49% abnormal - possible MS
CSF ANALYSIS: Lumbar puncture has not been shown to have any adverse effect on the
course of the disease, and it should be performed diagnostically in all suspected cases.
- WBC >5/mm3 in 30%
> 5/mm3 in 5%
>20/mm3 in 1%
>90% of cells are mononuclear
- Protein <55mg/dL in 75%
>100mg/dL unusual
- lgG elevated in 50% of patients
- lgG index increased in 80-90% of patients
- Oligoclonal bands in 70-90% of patients with definite MS
- Oligoclonal bands may still be seen, even when the CSF total IgG is not elevated
- Myelin basic protein elevated in 50% of patients with definite MS
- Free Kappa chains in 85% of patients with definite MS
- Gamma globulin elevated in 75% of patients

H. THERAPY:
1. Symptomatic
Spasticity: Physical Therapy, Baclofen, Diazepam, Dantrolene Sodium, Surgery
Dystonic: Carbamazepine
Spasms: Phenytoin, Baclofen
Episodic Pain: Amitriptyline, Non-Steroidal Anti-Inflammatory Drugs
Trigeminal Neuralgia: Carbamazepine
Seizures: Carbamazepine, Phenytoin
Bladder Dysfunction: Propantheline, Straight Catheter
Cerebellar Tremor; Isoniazid
Depression: Amitriptyline, Desipramine, Imipramine, Supportive Therapy
Emotional: Amitriptyline
Incontinence: L-Dopa, Bromocriptine
Anxiety: Alprazolam, Diazepam

2. Immunomodulators
ACTH Methylprednisolone
Cyclophosphamide Azathioprine
Cyclosporine A Beta Interferon
Poly ICLC Transfer Factor
Copolymer 1 Methisoprinol
Plasmapheresis Lymphoctyopheresis
Antilymphocyte Globulin Total Lymphoid Irradiation

£ CHOREATIC DYSKINESIAS

A. DEFINITION - CHOREA: Involuntary movement disorder characterized by sudden,


brief,
spontaneous, irregular and unpredictable jerks of the appendicular, facial or turncal
musculature. The movements may be unilateral (hemichorea) or bilateral, occur at rest or
during volitional acts, cease during sleep, intensify during stress, and often are camouflaged

by superimposition on a purposeful act.

B. CLASSIFICATION:
Huntington's disease Sydenham's
Chorea gravidarum Hereditary chorea with Acanthocytosis
Familial Paroxysmal Choreoathetosis Benign Hereditary Chorea
Senile Chorea Drug Induced Chorea
Systemic lupus erythematosus - oral contraceptives
Polycythemia Vera - neuroleptics
Stroke (basal ganglia infarcts) - phenytoin
Trauma - levodopa
Hyperthyroidism
Hyponatremia
Subdural hematoma
Post-thalamotomy

C. HUNTINGTON'S DISEASE
autosomal dominance, complete penetrance
defect localized to short arm of chromosome 4
prevalence - 5-10 cases per 100,000 population
age of onset 35-42 years
Onset before age 15 (Westphal variant)
- akinetic rigid presentation
- seizures
- intellectual decline
Mean duration of illness 10-25 years
Clinical/Paraclinical Studies
- chorea (chorea initially, followed by dystonia)
- dementia
- altered behavior
- increase risk of suicide
- CT/MRI: caudate atrophy, hydrocephalus "ex-vacuo"
- PET: decreased striatal glucose metabolism

D. MANAGEMENT:
Anti-dopaminergic agents
- phenothiazines, butyrophenones, thioxanthenes
- reserpine, tetrabenazine
Psychological Support
Antidepressants (e.g.: tricyclics)
Genetic counseling

£ PARKINSONISM AND OTHER MOVEMENT DISORDERS

A. DEFINITION - PARKINSONISM: A striatal dopamine deficiency syndrome resulting


from
degeneration of pigmented nigral neurons that terminate in the striatum.

B. EPIDEMIOLOGY:
Common
Prevalence 1 per 1000 population
Incidence 20 cases per 100,000 individuals per year
Middle age and elderly

C. CLASSIFICATION:
Primary (Parkinson's Disease)
Secondary
- Drug induced (phenothiazines, butyrophenones, thioxanthines, metoclopramide,
reserpine, alpha-methyldopa)
- Infectious (post-encephalitic, lues, Jakob-Creutzfeld)
- Toxin (MPTP, carbon monoxide, carbon disulfide, manganese, cyanide)
- Metabolic (Wilson's disease, Hallevorden-Spatz disease, parathyroid dysfunction)
- Structural (basal ganglia tumors, repeated head injury)
- Vascular (?)
- Parkinsonism Plus (Progressive supranuclear palsy, Shy-Drager, olivo-ponto-cerebellar
degeneration, striato-nigral degeneration, corticospinal degeneration with neuronal
achromasia, Parkinson-dementia complex of Guam, Parkinsonism with amyotrophy)

D. SYMPTOMS AND SIGNS: Early manifestations are non-specific


Tremor
Bradykinesia/Akinesia
Rigidity
Loss of normal postural reflexes

E. SEVERITY OF DISEASE (Hoehn and Yahr Scale)


No visible Disease STAGE 0
Mild Disease STAGE I - Disease involves only one side of the body
STAGE II - Disease involves both sides of the body, but does not
impair balance
Moderate Disease STAGE III - Disease impairs balance or walking
Advanced Disease STAGE IV - Disease markedly impairs balance or walking
STAGE V - Disease results in complete immobility

F. MANAGEMENT:
Anticholinergic Drugs, Amantadine, Levodopa + Peripheral Dopa Decarboxylase Inhibitor
(Sinemet 10:100, Sinemet 25:100, Sinemet 25:250), Sinemet CR (Levodopa,
200mg/carbidopa 50mg), Bromocriptine, Other Dopamine Agonists (e.g.: Pergolide,
Lisuride), MAO-B Inhibitors (Deprenyl), Antioxidants (Alpha Tocopherol),
Antidepressants
(Amitriptyline, Trazodone, Fluoxetine), Beta Blockers (for action tremor if present), Brain
Grafts (?), Physical Therapy

£ TREMOR

A. Definition: The most common of the dyskinesia, is characterized by involuntary,


rhythmic,
oscillatory movements about a fixed point resulting from alternating contractions of
antagonists muscles.

B. Classification
Resting (3.5 - 7 Hz)
- Parkinsonism
Postural (6 -11 Hz)
-Physiological tremor
- Anxiety
- Hyperthyroidism
- Alcohol
-Hypoglycemia
-Sympathomimetic
- Lithium Carbonate
- Tricyclics (imipramine, amitriptyline)
- Benign (essential) Tremor (may be familial)
Intention (3 - 7 Hz)
- Brainstem/Cerebellar Disease (e.g.: multiple sclerosis, spino-cerebellar degeneration)

C. Management
Resting Tremor
- D/C offending drugs (e.g.: neuroleptics)
- Rx for Parkinson's disease
Postural Tremor
- Rx underlying cause
- D/C offending drug (e.g.: lithium, imipramine)
- Beta blockers (essential tremor)
- Primidone (essential tremor)
Intention Tremor
- Rx underlying cause

£ MYOCLONUS

A. Definition: Myoclonus is a disorder characterized by unexpected, shock-like,


involuntary,
repetitive, synchronous or asynchronous contraction of a muscle or group of axial or
appendicular muscles. Myoclonus may be focal or generalized.

B. Classification
Generalized
Symptomatic
a. Myoclonus in idiopathic epilepsy
b. Progressive myoclonic epilepsy
Familial myoclonic epilepsy (Unverricht-Lundberg disease)
Myoclonus associated with spinocerebellar degeneration

Classification (Cont)

(Ramsay-Hunt syndrome)
Lafora body disease
GM2 gangliosidosis (Tay-Sach's disease)
Ceroid lipofuscinosis (Batten's disease)
Sialidosis (cherry red spot myoclonus syndrome)
C. Others
Encephalitis lethargica
Jakob-Creutzfeld disease
Alzheimer's disease
Subacute sclerosing panencephalitis
Infantile myoclonic encephalopathy
Post cerebral anoxia (Lance-Adams syndrome)
Hepatic, renal respiratory failure
Hyponatremia, hypocalcemia
Withdrawal of addictive drugs (e.g.: alcohol)
Benign essential (familial) myoclonus

Focal (segmental)
Symptomatic
Subacute myoclonic spinal neuronitis
Spinal cord tumors, infarcts, trauma
Others
Palatal myoclonus
Hemifacial spasm
Cortical reflex myoclonus
Epilepsia partialis continua

£ DYSTONIA

A. Definition: Disorder characterized by slow, long-sustained, contorting, involuntary


movements and postures involving proximal appendicular and axial muscles. Dystonic
movements are typically slow and "wrapping", although sporadically patients may
demonstrate superimposed, rapid, involuntary jerks termed dystonic spasms.

B. Classification
Generalized Symptomatic
Encephalitis lethargica Wilson's disease
Lesch-Nyham disease Juvenile Huntington's disease
Hallevorden-Spatz disease Athetoid cerebral palsy
Ataxia telangiectasia Mitochondrial encephalopathies
Drug related (e.g.: neuroleptics) Idiopathic
Dystonia musculorum deformans Autosomal recessive
Sex-linked recessive Autosomal dominant
Sporadic Paroxysmal
Paroxysmal kinesogenic choreoathetosis Paroxysmal dystonic choreoathetosis
Dystonia with diurnal fluctuations Focal (segmental)
Symptomatic Post-hemiplegic dystonia

Classification (CONT)

Post-thalamotomy dystonia Idiopathic


Spasmodic torticollis Writer's cramps (occupation cramps)
Blepharospasm and oromandibular dystonia Orofacial dyskinesia

C. Management
Levodopa, Carbamazepine, Benzodiazepines, Anticholinergics, Tetrabenazine,
Phenothiazines (?), Butirophenones (?), Sterotaxic surgery.

£ TICS

A. Definition: Sudden, rapid, usually stereotyped (may have a component of suggestibility),


and predominantly clonic hyperkinesias.

B. Classification
Simple Tics
transient tic of childhood
chronic simple tic
Complex Multiple Tics
Gilles de la Tourette syndrome
ages 5 - 15 years
mode of transmission - major semidominant gene
waxing waning course
duration greater than 1 year
multiple or single tics
vocalizations
copropraxia
echopraxia
echolalia
coprolalia
Rx: haloperidol, pimozide, clonidine, tetrabenazine
Chronic multiple tics
Symptomatic Tics
Encephalitis lethargica
Drug induced tics
Posttraumatic
Neuro-acanthocytosis
£ NEUROLOGICAL COMPLICATIONS OF ALCOHOLISM

1. ALCOHOLIC INTOXICATION
< 50 mg/dl - mild incoordination
400-700 - coma, respiratory depression, death (Rx of ethanol induced coma is supportive)
- R/O ethanol induced hypoglycemia, alcoholic ketoacidosis, or ethylene glycol,
methanol or isopropanol intoxication

2. WITHDRAWAL SYNDROMES
A. Minor Syndrome
Stage I
a) onset 6-24 hours after reduction of intake
b) adrenergic overdrive
c) 25% progress to Stage II; 10% progress to Stage III
Stage II
a) Stage I symptoms, plus visual, auditory and tactile hallucinations
Stage III (withdrawal seizures or rum fits)
a) onset 7-48 hours after cessation of drinking (50% occur 13-24 hours after drinking has
ceased)
b) generalized tonic-clonic seizures
c) single in 40% of cases
d) status epilepticus in 4% of cases
e) normal interictal EEG. Heightened photoconvulsive response
B. Major Syndrome (Delirium Tremens)
Stage IV (early presentation (24 hrs), or late presentation (12 days)
a) marked adrenergic overdrive
b) frank hallucinations
c) 5-15% mortality
C. Management
Stages I-II Thiamine
Multivitamins
Folate
Chlordiazepoxide, Clorazepate, Oxazepam, Diazepam
Propranolol, Atenolol
Clonidine
Stage III Most alcohol withdrawal seizures do not require pharmacologic
intervention
Stage IV Intensive care
Treatment as in Stages I-II-III
Support vital signs and volume status
Restrain patient

3. NUTRITIONAL DISEASES OF NERVOUS SYSTEM SECONDARY TO ALCOHOL


A. Wernicke's Encephalopathy
confusional state
ataxia
ocular abnormalities
NUTRITIONAL DISEASES OF NERVOUS SYSTEM SECONDARY TO ALCOHOL
(CONT)

hypothermia
Management: Thiamine, bed rest, nutritional supplements
B. Korsakoff Amnestic Syndrome
anterograde amnesia
retrograde amnesia
intact immediate recall
confabulation (not essential for dx)
loss of insight
C. Alcoholic Amblyopia
D. Pellagra
Dementia
Dermatitis
Diarrhea
Neuropathy
E. Peripheral Neuropathy
axonal damage
segmental demyelination

4. DISEASES OF UNCERTAIN PATHOGENESIS ASSOCIATED WITH ALCOHOLISM


A. Selective Form of Cerebellar Degeneration
ataxia of gait and trunk
little involvement of the arms
absent nystagmus or dysarthria
B. Marchiafava - Bignami Disease
C. Central Pontine Myelinolysis
D. Cerebral Cortical Atrophy
E. Alcoholic Dementia
alcohol dependence
persistence for at least 3 months after cessation of drinking
other potential causes of dementia ruled out
F. Myelopathy
G. Myopathy

5. NEUROLOGICAL DISORDERS CONSEQUENT UPON CHRONIC LIVER DISEASE


AND
PORTO-SYSTEMIC SHUNT
A. Hepatic Encephalopathy and Coma
Intellectual deterioration, delirium, hyperventilation, metabolic alkalosis
Ocular abnormalities
Asterexis, myoclonus, seizures
Paratonia, decerebrate rigidity
Management - Treat precipitating factor; protein free diet, empty bowel of nitrogen
-containing materials. Neomycin, Lactulose, Bromocriptine, L-Dopa
B. Acquired Chronic Hepato-Cerebral Regeneration
C. Spastic Paraplegia
6. INCREASED INCIDENCE OF TRAUMA
A. Head Trauma
Subdural Hematomas
Traumatic Encephalopathy

INCREASED INCIDENCE OF TRAUMA (CONT)

B. Post-Traumatic Seizure Disorder


C. Entrapment Neuropathies

7. CONSEQUENCES UPON THE FETUS


A. Fetal Alcohol Syndrome

8. OTHER ASSOCIATIONS
A. Vitamin B-12 Deficiency
B. Hypoglycemia
C. Stroke
D. Movement Disorders

£ TUMORS OF THE NERVOUS SYSTEM

A. Classification:
I Tumors of Glial Origin
Astrocytoma (Grades I-IV)
Oligodendroglioma
Ependymoma

II Tumors of Neuronal Cells and Primitive Bipotential Precursors


Medulloblastoma
Ganglioneuroma and Ganglioglioma

III Tumors of Mesenchymal Origin


Meningioma

IV Tumors of the Cranial and Spinal Nerve Roots


Schwannoma
Neurofibroma

V Tumors of the Lymphoreticular System


Primary CNS Lymphoma

VI Tumors of the Choroid Plexus


Papilloma of the Choroid Plexus

VII Tumors of Blood Vessels


Hemangioblastomas
VIII Tumors of the Pineal Gland
Pineocytoma
Pineoblastoma
Germ Cell Tumors
Glial Cell Tumors

XI Tumors Derived from Ectopic Tissues


Craniopharyngioma
Teratomas
Dermoid Cyst
Cholesteatoma
Lipoma
Chordoma

X Tumors Derived from Embryonic Structures


Colloid Cyst of the Third Ventricle

XI Tumors Invading the CNS by Direct Extension


Pituitary Adenoma
prolactinoma, growth hormone secreting, ACTH secreting, non-secreting adenoma
(chromophobe)
Glomus Jugulare Tumor

XII Metastatic Tumors


lung, breast, kidney, malignant melanoma (most common)

B. Symptoms and Signs:


Focal Neurological Deficits
Increased Intracranial Pressure
Seizures
Endocrine Dysfunction

C. Evaluation:
History
General Physical Examination
Neurological Examination
Neuro-Ophthalmology Evaluation
CT without and with intravenous contrast
MRI without and with gadolinium
EEG
Cerebral angiography (seldom needed)
Endocrine evaluation of pituitary and hypothalamic activity (if indicated)
Blood count, biochemical profile, urinalysis
Chest roentgenogram
Bone scan, IVP, GI series, bone marrow, CT of chest/abdomen (if indicated)

D. Management:
Anticonvulsants
Corticosteroids
Surgery (conventional, stereotactic)
Radiation therapy
Chemotherapy
Dopamine agonists (e.g.: bromocriptine " prolactinomas)

£ THE COMATOSE PATIENT

A. DEFINITION - A state of altered consciousness characterized by unarousability and


unresponsiveness

B. PATHOPHYSIOLOGY:
1. Diffuse, bilateral cerebral hemispheric lesions
2. Dysfunction of brainstem reticular activating mechanism

C. TYPES OF PATHOLOGIC PROCESS THAT CAUSE COMA:


Supratentorial mass lesions
Infratentorial mass lesions
Metabolic encephalopathies
Psychogenic "coma"

D. EXAMINATION OF THE COMATOSE PATIENT:


"The vital functions should be attended before any diagnostic steps are taken"

a. Respiratory Pattern Possible Cause


Hyperventilation Central Neurogenic Hyperventilation
Pulmonary edema
Primary respiratory alkalosis
Metabolic acidosis

Hypoventilation Central alveolar hypoventilation


"Ondine's" curse
Pulmonary insufficiency

Irregular breathing
Cheyne-Stokes Bilateral dysfunction
(hemispheres, diencephalon)
Central Neurogenic Low midbrain, upper pontine
Hyperventilation lesion
Apneustic Breathing Mid-caudal pontine lesion
Ataxic Breathing Medullary lesion
b. Blood Pressure
Arterial Hypertension Reflex response to increase intracranial pressure
Chronic hypertension
Arterial Hypotension Hypovolemia
Hemorrhagic shock
Myocardial depression

c. Temperature
Hyperthermia Meningitis
Encephalitis
Sepsis
Disruption of autonomic pathways

EXAMINATION OF THE COMATOSE PATIENT (CONT)

Hypothermia Hypoglycemia
Hypothyroidism
Wernicke's encephalopathy
Sedative overdose
Environmental exposure
d. Meningismus Meningitis
Subarachnoid hemorrhage
Tonsillar herniation

e. Pupils: The pupillary pathway is relatively resistant to metabolic insults. The presence
or absence of the pupillary light reflex is the single most important physical sign
distinguishing structural from metabolic coma (e.g.: metabolic cause of coma - small and
reactive
pupils).
Diencephalic - small, reactive
Tectal - large "fixed", hippus
Midbrain - midposition fixed
III Nerve (Uncal Herniation) - fixed and dilated
Pontine - pinpoint with preserved light reflex (use magnifying glass)

f. Ocular Motility: Most comatose patients have their eyes closed by tonic contractions of
orbicularis oculi
Oculocephalic reflex (Doll's headeye phenomenon) - Vestibular portion of CN VIII
Oculovestibular reflex (Caloric response) - Connection of brainstem pathways with CN III,
IV and VI
Spontaneous eye movements
- Periodic alternating gaze
- repetitive divergence
- Ocular bobbing and varieties
- Nystagmoid jerking of a single eye
- Vertical ocular myoclonus
E. HERNIATION SYNDROMES
« Cyngulate herniation syndrome
« Uncal herniation syndrome
« Central herniation syndrome
« Downward cerebellar tonsillar herniation syndrome
« Upward cerebellar herniation syndrome

F. GLASGOW COMA SCALE:

Eyes Open Spontaneously 4


To verbal command 3
To pain
No response 1

Best Motor Response To verbal command Obeys 6


To painful stimulus* Localizes pain 5

Flexion - withdrawal 4
Flexion - abnormal 3
(decorticate rigidity)
Extension 2
(decerebrate rigidity)
No response 1

Best Verbal Oriented and 5


Responses** converses
Disoriented and 4
converses
Inappropriate words 3
Incomprehensible 2
sounds
No response 1
Total 3-15

The Glasgow Coma Scale, based upon eye opening, verbal and motor responses, is a
practical means of monitoring changes in level of consciousness. If response on the scale
is given a number, the responsiveness of the patient can be expressed by summation of the
figures. Lowest score is 3; highest is 15.

* Apply knuckles to sternum; observe arms.


** Arouse patient with painful stimulus if necessary.

G. GENERAL MEASURES
Airway__________clear airway
Breathing__________intubation?
Circulation__________Vasopressors?
CBC with diff, glucose, lytes, liver enzymes, metabolic/toxicologic screen

Dextrose 50% W 50 ml I.V.


Thiamine 100 mg I.V.
Naloxone 0.4-1.2 mg I.V.
seizures apparently or likely

GENERAL MEASURES (CONT)

Diazepam (max 20 mg) 2 mg/min I.V., or


Lorazepam (max 4-8 mg) 2 mg/min I.V.
plus, either
Phenytoin 18-20 mg/kg I.V. (50 mg/min)
or
Phenobarbital 10 mg/kg I.V. (100 mg/min)

if persistent seizures
Barbiturate Coma
General Anesthesia
Fluid balance and alimentation
Control of body temperature

H. SPECIAL BRAIN THERAPY


Osmotherapy
Steroids
Hypothermia
Barbiturate loading

£ BRAIN EDEMA AND HERNIATION SYNDROMES

A. Definition - Brain Edema: Abnormal accumulation of fluid associated with volumetric


expansion of brain tissue.
B. Classification of Brain Edema
Vasogenic Cytotoxic Ischemic Interstitial
Location
Gray Matter - + + -
White Matter + + + +
Focal + - + +
Diffuse - + - -

Representative Disorders
Tumors, Anoxia, Infarcts Obstructive
Abscess, Brain Death hydrocephalus
Hematoma, Water intoxication
Infarcts
Lead Encephalopathy,
Purulent Meningitis

Therapeutic Effects
Corticosteroids + - - -
Ventricular Shunt - - - +

C. Intracranial Pressure - (ICP): The cranial cavity contains three constituents: brain
substance (including interstitial fluid), cerebrospinal fluid (CSF), and blood volume
(arterial
and venous blood).

Brain = 1400 grams; CSF = 75 ml; Blood volume = 75 ml


ICP - pressure within the intracranial space; normal ICP = 3 -15 mm Hg
Cerebral Perfusion Pressure (CPP) - pressure available to perfuse the brain
CPP = MABP - ICP (normal = 80 - 90 mm Hg), minimum needed = 50-60 mm Hg.
ICP wave forms - A, B, C waves
A waves ("plateau" waves) - 50 - 100 mm Hg
last 5 - 20 minutes, can reflect clinical deterioration
B waves - 20 - 50 mm Hg
rate of 1 to 2 per minute
C waves - related to the Traube-Herring plot of blood pressure

D. Herniation Syndromes: Cingulate, Uncal, Central, Downward cerebellar tonsillar


herniation,
and Upward cerebellar herniation

E. Management: Therapy must be prompt to prevent secondary cerebral damage. Optimize

CPP (MABP-ICP).
Remediable factors likely to increase ICP (e.g.: straining and coughing, obstruction to
venous drainage, hypoxia, hypercapnia, hyperthermia, seizures, arterial hypertension,
hyponatremia, etc) should be corrected. Differentiate tissue shifts from jeobally increased
ICP.
Optimal Head Positioning
15 - 30 degree head up
neutral position
elevation of torso may decrease CPP
Hyperventilation
PaCo225 torr (some favor moderate hypocapnia: 35-38 torr).
minimize noxious stimuli of intubation; maintain mormoxia (SpO2>95%)
(e.g.: xylocaine, pentothal)
Fluid Restriction
2/3 maintenance
avoid hypotonic solutions
Osmotic Agents - Mannitol (20% solution), Glycerol (10% solution)
Mannitol 0.75 - 1 g/Kg IV over 15 minutes (bolus)
0.25 g/Kg q 4 hours
dosage according to clinical response, serum osmolality, ICP
Serum osmolality should not exceed 320m Osm because of risks of dehydration, renal
failure,
acidosis. Avoid hypernatremia.
replace fluid lost by diuresis (crystalloids)
maintain circulatory normovolemia
adequate glucose control (150 - 250 mg/100 ml)
Non Osmotic Diuretics
Furosemide (0.3 - 0.7 mg/Kg)
Ethacrynic Acid
Acetazolamide
Others
Corticosteroids (see B for indications)
Barbiturates
CSF Drainage
Surgery (e.g.: hemicraniectomy; skull vault removal).

£ SPINAL CORD COMPRESSION

A. Introduction: It is essential that spinal cord compression is recognized promptly. Failure


to do so, may condemn the patient to permanent paraplegia or quadriplegia. Tumors,
spondylosis, trauma, pyogenic epidural infections, epidural and subdural hematomas
provide
the major causes of spinal cord compression (Table 1).

Causes of Spinal Cord Compression


Lesions of the Spine
Trauma Disk Herniation
Reticuloses (e.g.: multiple myeloma) Metastatic Tumors
Cervical Spondylosis Rheumatoid Arthritis
Paget's Disease of Bone Congenital Malformations (e.g.:
achondroplasia, spinal stenosis,
(diastematomyelia).

Extramedullary Lesions
Primary Tumors (e.g.: meningioma, neurofibroma)
Metastatic Tumors (e.g.: metastatic carcinoma, lymphoma, sarcoma, neuroblastoma)
Pyogenic Epidural Infections

Intramedullary Lesions
Tumors (e.g.: astrocytoma, ependymoma, metastasis)
Intramedullary Abscess
Vascular (e.g.: hematomyelia, angioma)

The most common tumors to metastasize to the spine are breast, lung and prostate,
although unknown primary tumors occur in up to 10% in some series (Table 2).

Primary Tumors Causing Epidural Spinal Compression


Primary Tumor Posner Gilbert & Posner Greenberg & Posner
Breast 20 28 21
Lung 9 21 11
Prostate 7 14 12
Kidney 5 12 3
Lymphoma 18 8 2
Myeloma 1 8 1
Melanoma 1 7 5
Sarcoma 16 6 -
Head & Neck 8 6 -
GI 4 5 -
Embryonal - 5 -
Female 4 1 -
Reproductive
Neuroblastoma 5 - -
Other 7 5 24
Unknown - 4 4
TOTAL 105 130 83

B. Clinical Presentation: Depending on the cause, the array of symptoms and signs may
vary,
but the development of extrinsic spinal cord compression usually follows a sequential
pattern.
1. Spinal Pain
2. Radicular Pain
3. Weakness
4. Sensory Loss
5. Reflex Changes
6. Disorders of Sphincters

C. Diagnostic Evaluation: Once the diagnosis of spinal cord compression is suspected, the
following should be obtained. The diagnostic procedure of choice nowadays is without
question MRI of the spine. MRI allows one not only to find the extent of the lesion but also
allows one to examine for multiple lesions.
Roentgenogram of the spine
Myelography
CT scan of the spine
MRI of the spinal cord

D. Treatment
High dose steroids (reduce spinal cord edema, oncolytic effect)
Radiation Therapy
Surgical Decompression
resectable lesion
unknown primary
already undergone maximum RT
deterioration while on RT
Chemotherapy

Diagnostic and Therapeutic Algorithm for Patients with Spinal Cord Compression

Suspect Spinal Cord Compression


i
MRI of Spine and/or Myelogram with CT

Dexamethasone g

Known Tumor Unknown Tumor

Radiation Previous Radioresistant


Therapy Radiation Tumor
Therapy

Improvement Neurological Tissue Diagnosis


or Deterioration (Decompression)
Stabilization

Surgical Decompression Radiation Therapy

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