M3 NEUROLOGY NOTES

Anatomy notes

Disease in:
● Cerebellum → strong, but trouble with movement timing and accuracy
● Basal ganglia → strong and accurate movements, but problems initiating and maintaining. Often have
superimposed, involuntary movements.
● Prefrontal cortex → problems with executive function (impulsivity, impersistence, apathy). Normal strength,
coordination, sensation, language function, memory, calculation skills.

● Angular gyrus - can’t name things. It’s the brain’s dictionary. PCA infarct disconnects occipital lobe from angular
gyrus → alexia without agraphia

● Language dominant hemisphere → apraxia

● Non-dominant hemisphere → neglect or extinction. Attends to both sides of the world, so knocking it out leaves a

void.

Imaging Notes

1. Cerebral angiography - 0.5% chance of stroke!

a. Good for acute bleeds, MRI FLAIR is best for subacute (days to weeks) bleeds
b. Good for bone abnormalities
c. Areas of increased density enhance (denser = brighter) - bone, blood, contrast, bullets (foreign bodies)
d. Inferior to MRI for most pathology - resolution isn’t as good

2. Perfusion CT - use contrast to see areas of perfusion

3. CT angiography - like cath angiogram but no risk of stroke, detail isn’t as good, requires contrast

4. MRI T1 - fluid is black. Best for anatomy. Contrast will enhance some pathology. No radiation, better resolution
than CT.

5. MRI T2 - fluid is white. Better for pathology

6. MRI FLAIR - abnormal fluid is white (e.g., CSF is dark). Best for pathology, subacute bleeds (days to weeks).
Good for intrinsic bone abnormalities (bone marrow)

7. MR angiography- no dye, no radiation

8. MR diffusion - can identify strokes within minutes and determine if any prenumbra remains → signals whether to

use aggressive treatment to save the tissue. Shows cytotoxic edema as Na+, Ca++, and lactic acid enter cells. The
intracellular water moves less than extracellular because of cell membrane confines.

9. MR perfusion - inject contrast to see perfusion, just like with CT perfusion.

a. Compare diffusion to perfusion to see if there is any penumbra left. If everything matches, only dead and
alive tissue, none at risk.

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10. MR spectroscopy - can distinguish brain tumors from MS (e.g., myelin breakdown products). Tumor - increased
creatinine, increased lactic acid

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Outline of Introduction to Clinical Neurology, by Dr. Douglas Gelb

Chapter 4: Stroke

Ischemic stroke
Two causes of ischemic stroke
1. Local obstruction - can be from emboli or local disease in the artery. For local disease, atherosclerosis is most
common; other causes = fibromuscular dysplasia, arteritis, dissection of the arterial wall, migraine, coagulopathy,
and lipohyalinosis (affects small penetrating arteries, seen in HTN).
2. Obstruction of venous drainage - clot in cerebral sinus or brain. Most often in coagulopathy or severe
dehydration. Patients report headache from increased ICP.

Can transform into hemorrhagic stroke -> deterioration in condition or asymptomatic (small petechial hemorrhages).

Imaging: Ischemia is not detectable on CT for hours to days. Can see impeded diffusion on MRI for two weeks.

Treatment for clotted arteries:

1. tpA for 4.5 hours
2. Intra arterial tpA for up to 6 hours
3. Removal with intra arterial device for up to 8 hours - not known if this improves outcomes

Treatment for venous clots

1. Maybe IV heparin. Sometimes thrombolytic agent into the clot, but no controlled trials

Hemorrhagic stroke

1. Primary parenchymal hemorrhage

a. Suspect if the deficit gets worse over several hours or if the patient looks like a stroke but is unusually
SLEEPY or OBTUNDED early in the course. Headache is another clue - in 50%. But 25% of ischemic
strokes have headache.
b. Usually due to rupture of small penetrating arteries because of chronic HTN = lipohyalinosis (smooth
muscle expansion, lumen narrows). Often cerebellum, BG, brainstem, thalamus, internal capsule.
c. Amyloid angiopathy - atrophy of smooth muscle cells, weakens walls. Usually lobar hemorrhages.
d. Treatment - only resect the hematoma if it’s in the CEREBELLUM - prevents brainstem compression
2. SAH - can be caused by other types of vascular problems (venous angiomas), but often rupture of berry
aneurysm on circle of Willis (risk in HTN, PKD, systemic collagen-vascular disease - ED, fibromuscular
dysplasia).
a. Sx: worst headache of their lives, n/v, stiff neck, photophobia. May have low grade fever. Can have focal
or diffuse symptoms, signs.
b. Diagnosis: CT scan. If negative, do lumbar puncture to look for blood and rule out meningitis. Then
cerebral angiogram to look for the source of the bleed.
c. Treatment:
i. Clip or coil the aneurysm within 3 days, if impossible, wait 10-14 days. Coiling requires annual
angiograms to check placement.
ii. Permissive HTN - only treat if SBP > 160.
iii. nimodipine - ⅓ get vasospasm 4-10 days after the initial hemorrhage. Diffuse, progressive. Treat
with fluid, vasopressors, endovascular balloon dilation.
3. Vascular aneurysm rupture can cause SAH or parenchymal hemorrhage
a. AV malformation - artery and vein with no intervening capillary bed. < 3 cm → surgery, or radiation if
surgery not possible. > 3 cm → endovascular embolization (= glue), then resection.

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 b. Cavernous angiomas - distended blood vessels of varying thickness without any intervening
parenchyma. Low pressure system, usually asymptomatic. Resect if symptoms, intractable epilepsy, or
recurrent hemorrhage
c. Venous angiomas - one or more dilated veins. Low pressure system, usually asymptomatic, no
treatment.
d. Capillary telangiectases - multiple small caliber, very thin-walled vessels within normal brain, almost

never hemorrhagic → no treatment needed.

Notes on types of strokes

PCA blockage in dominant hemisphere → alexia without agraphia

Lateral medulla stroke = Wallenberg’s syndrome

1. Usually minimal weakness
2. Sensory loss in the ipsilateral face and contralateral arm, leg, trunk
3. Ipsilateral Horner’s syndrome
4. Ispilateral ataxia
5. Dysarthria/dysphagia
6. Nystagmus and vertigo

Medial medulla
1. Weakness and loss of sensation (esp proprioception) in contralateral arm, leg.
2. Ipsilateral tongue weakness (CN 9, 10 are in the medulla)

Pons
1. Weakness and loss of sensation in the ipsilateral face, contralateral arm and leg
2. Impaired gaze in ipsilateral direction (CN 6?)
3. Nystagmus
4. Horner’s syndrome
5. Ataxia - ipsilateral or contralateral

Midbrain
1. Weakness in contralateral face, arm, leg
2. Ipsilateral CN3 palsy (in midbrain)
3. Contralateral ataxia - affects cerebral peduncle

Lacunar strokes - note these syndromes can also be caused by other mechanisms
1. Pure motor
2. Pure sensory
3. Ataxic hemiparesis (mild weakness)
4. Clumsy hand dysarthria

SAH - usually doesn’t involve brain parenchyma → no focal sx

Transcortical aphasia (sensory, motor, mixed) = watershed area affected

Complications of stroke

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 1. Most important is increased ICP - consider hemicraniotomy, moderate hypothermia, mannitol, etc. Especially
likely with parenchymal hemorrhage, also bad for SAH because high risk of rebleeding.
2. Seizures - give anti-epileptic drugs fast because seizures → rise in ICP
3. Hyponatremia - from SIADH or cerebral salt wasting
4. Depression - but no indication for prophylactic meds
5. Impaired swallowing → aspiration. Might need intubation

Exacerbating factors - hypoxia, hyperthermia, hypotension, hyperglycemia.

→ Allow permissive HTN, espcially in patients who previously had HTN

Primary prevention

1. Manage HTN - ACE inhibitors (esp ramipril) and losartan may have extra benefits
2. Quit smoking! It doubles stroke risk
3. Diabetes - reduce stroke risk by managing HTN, taking a statin. Tight glycemic control might not make a
difference, but still good to do.
4. Dyslipidemia - reduced risk of hemorrhage, but increased risk of ischemic stroke. Use statins.
5. Afib → warfarin, unless < 70 yrs and no other risk factors. Then aspirin is okay.

Secondary prevention

TIA or stroke plus:

1. Cardioembolic source or dissection → warfarin. True for afib, mural thrombus after MI, mechanical valves, etc.
Continue as long as the clot source remains. Goal is INR of 2-3, higher for mechanical valves. Do not anticoagulate
if bacterial endocarditis → risk of cerebral hemorrhage
2. Aortic arch stenosis → asprin or warfarin
3. Stenosis of intracranial arteries, penetrating artery disease, PFO → aspirin

4. Coagulopathy → treat as appropriate. E.g, antithrombin 3 deficiency → warfarin. Polycythemia vera, phlebotomy
and hemodilution
5. TIA or stroke in the distribution of the internal carotid artery with high grade stenosis → CEA.
a. Symptomatic and stenosis > 70% → definitely CEA. If only 50-69%, consider CEA - no benefit for < 50%

Do surgery within 2 weeks of event.

i. Risk of stroke is 6x greater for symptomatic stenosis than asymptomatic.
ii. Consider stenting in younger patients or if not surgical candidate.
b. Asymptomatic and stenosis > 80% → CEA generally.
6. Not taking warfarin → take aspirin, clopidigrel, or Aggrenox = aspirin + dipyridamole.
7. LDL > 100 → statin
8. Primary prevention principles still apply

Stroke or TIA in anyone:

1. Admit to hospital for cardiac rhythm monitoring. Strokes can cause arrhythmias and need to evaluate for a-fib. If
don’t catch a-fib, arrange short term event monitoring.
2. Echo - TEE is more sensitive and more specific than TTE, but it is more invasive.
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 Determining mechanism of stroke

1. Clinical features can narrow the possibilities:

a. Arterial distributions? Size of the infarct? Penetrating arteries won’t produce stroke > 2 cm in diameter.
b. Multiple cortical infarcts in different vascular territories → embolism, diffuse atherosclerosis, coagulopathy,
vasculitis
c. Shape: wedge → embolism. Irregular/patchy in watershed area → hypoperfusion, either global or from
stenotic artery
2. Imaging:
a. Generally must image carotids and heart (TEE or TTE). Can skip heart imaging if the patient already has
an indication for anticoagulation and imaging wouldn’t change anything.
b. Intracranial/extracranial vessel imaging.
i. Intraarterial angiography is the gold standard, but MRA and CTA aren’t invasive and offer good
results. Must be careful with these three tests in renal disease because of the dye

Chapter 5: Seizures

Region of onset: focal OR generalized. Focal is also known as partial.

Focal seizures
Focal can be simple (no impaired consciousness) or complex (impaired consciousness). Can have secondary
generalization.
● Simple focal seizures - no loss of consciousness.
● Complex focal seizures - lose consciousness. Often have motionless stare when the patient doesn’t respond,
with involuntary, automatic behavior (automatisms). Smack lips, chew, wring hands, pick at clothes, rearrange
objects, walk in circles, say short stereotyped phrases. May have forced movement of the head on in one
direction. Usually can’t remember.

Focal seizure location of onset affects symptoms!

● Primary motor cortex → rhythmic jerking of the affected body part, rigid posturing of the body part, alternating

tonic/clonic movements
● Prefrontal cortex → more complex patterns of motor activity
● Primary sensory cortex → local paresthesias or numbness
● Occipital lobe → visual illusions/hallucinations.

● Medial temporal lobes → rising sense of epigastric discomfort or nausea. Other manifestations - fear, olfactory

symptoms, auditory illusions or hallucinations, and distortions of memory - deja vu or jamais vu

Persistent focal deficits are more common with focal seizures than general.

Generalized seizures
● Usually impaired consciousness, but sometimes might be so brief (especially myoclonic seizures) that can’t tell
consciousness was lost.

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 ● Generalized tonic clonic most common - upward eye deviation, pupils dilate, lose consciousness. May contract
respiratory muscles and larynx → cyanosis. Entire thing usually lasts 90-120 seconds, usually unresponsive for
minutes to hours.
● Tonic seizures, clonic seizures less common
● Atonic seizure - sudden decrease in muscle tone which can be local or generalized. Can fall, usually without loss
of consciousness (drop attacks) - last 1-2 seconds.
● Infantile spasms → intellectual delay/disability
● Myoclonic seizures - nonrhythmic, rapid, jerking movements. Can be local or widespread. Can also have
nonepileptic myoclonus, like leg jerk when falling asleep
● Absence seizures - last 10 seconds, can be brought on with hyperventilation. Eyelids can flutter. Spike and wave
pattern on EEG. Differential dx = complex partial seizures (motionless staring, less easily brought on with
hyperventilation), ADD, other behavioral disturbance.

Inducers of seizure:
● hyper/hypoglycemia
● hypoNa, hypoCa, hypoMg,
● uremia, hepatic failure,
● prescription drugs - antidepressants, antipsychotics, aminophylline and other methyl xanthines, lidocaine,
penicllins, narcotic pain meds
● recreational drugs - cocaine, heroin, PCP, MDMA
● fever in kids (2-4% of kids). Usually generalized, < 15 mins. Increased risk of epilepsy, but still < 5%. Risk
increases with seizure > 15 mins, recurrence w/in 24 hours, focal features, abnormal neuro dev, FH of epilepsy. If
none of these features, epilepsy risk is < 1%.
○ treat only with anti-fever meds and sponge baths!
● sleep deprivation! Can be useful for EEG testing.

Epilepsy

One seizure → 50% chance of second. Does not necessarily have epilepsy - consider family history, EEG, structural brain

abnormalities in deciding whether dx is appropriate.

Two seizures → 70% chance of more. Probably have epilepsy → need treatment.

Symptomatic epilepsy - epilepsy is a symptom of underlying injury (structural, metabolic), either ongoing or in the past
Idiopathic epilepsy - known or likely to be genetic, fits within a syndrome

EEG: ictal EEG is diagnostic. Interictal can reveal tendency toward epilepsy. One interictal EEG will be abnormal in 50-
70% of people with epilepsy, 10-20% will have normal EEG even with repeat testing. Of people in general with abnormal
EEG, 2-3% never have seizure symptoms.
● Can try to induce seizure with hyperventilation or sleep deprivation.

Focal epilepsy
1. Genetic/idiopathic = benign rolandic epilepsy or benign childhood epilepsy with centrotemporal spikes.
Usually simple seizures (no LOC, can talk, maybe unilateral facial twitches) but can generalize. Should resolve
but can use AEDs to decrease frequency
a. EEG = epileptiform activity in the Sylvian fissure area.
2. Symptomatic
a. Mesial temporal sclerosis manifests in teens. Simple or complex seizures.
b. Often stroke induced in older patients

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General epilepsy
1. Idiopathic: childhood absence, juvenile myoclonic seizures
2. Lennox Gastaut syndrome - severe condition that manifests between 2-8 years. Mental retardation + diffuse
slow spike and wave EEG + multiple types of general seizures

Diagnosis of seizure
● Get the full story - what was first abnormal, how it spread, how long each stage lasted, any loss of consciousness,
incontinence, injury, etc.
● Try to identify prior spells
● Work up:
○ Labs: electrolytes including Ca and Mg, glucose, BUN, creatinine, liver enzymes, blood counts
○ LP to look for infection
○ 1st seizure → imaging. Best is MRI w/ and w/out contrast, but often only CT without contrast can be done
in the ER. If so, can do MRI later as an outpatient
○ Outpatient EEG (interictal)

Spells that aren’t seizures:

1. Spells with loss of consciousness
a. Syncope - often vasovagal, excessive parasympathetic tone in response to increase in sympathetic
activity
i. Premonitory onset (or not)
ii. Brief confusion after, no post-ictal period
iii. Incontinence less common than with seizures, but can happen
2. Spells without loss of consciousness
a. Migraine
i. Some people with migraine don’t have headache! Some people with seizure have severe
headache after!
ii. Slower onset than seizure
b. TIA
i. Faster onset than seizure. Negative symptoms.
c. Cataplexy = sudden loss of muscle tone with narcolepsy
3. Psuedoseizures = psychological in nature
a. Long period of motionless unresponsiveness, asychnronous limb movements, side to side head shaking,
dramatic bilateral limb movements while talking, and crying after
b. Variation between spells (e.g. different symptoms)
c. Happen more/only during stressful times

Seizure meds
Dilantin = phenytoin
Lyrica = pregabalin
Depakote = valproic acid
Keppra = levitiracetam
klonapin = clonazepam

1. Focal seizures can all be lumped together

a. Use carbamazepine, phenytoin, oxcarbazepine, topiramate, and valproic acid
b. The only agent that should NOT be used is ethosuximide. Only for absence seizures, which are general
seizures
2. Absence
a. Ethosuximide (best) and valproic acid. If the patient has multiple kinds of seizures, gotta use valproic
acid.
3. Myoclonic seizures
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 a. Valproic acid
4. Generalized tonic-clonic
a. Phenytoin (FDA approved), valproic acid, lamotrigine, levetiracetam, topiramate (FDA approved)
5. Infantile spasms
a. Vigabatrin - but ⅓ develop irreversible visual field narrowing. Must do regular vision checks. Can also
give ACTH as corticotropin

Treatment principles:
1. Begin at low dose and increase slowly - increase until seizures are controlled or side effects are too much. Don’t
rely on therapeutic drug levels! Drug levels are mainly useful to track which dose is effective for a particular
patient.
2. Use one drug at a time. If that doesn’t work, ADD A SECOND and gradually increase the dose of the second. If
that doesn’t work, gradually withdraw the drug that doesn’t seem to be working and replace with a new drug.
3. Levitiracetam/keppra, gabapetin, and pregabalin/lyrica do not affect the drug levels of other drugs! Easiest to
add on as an adjunct.

Non-drug options:
1. Surgical resection of the seizure focus - can fix seizures in 80% who fail medical therapy
2. Other ablative surgeries
3. Vagus nerve stimulation - about as effective as meds!
4. Ketogenic diet in kids, maybe also adults - high fat, adequate protein, low carb

Status epilepticus = a state of continuous or frequent seizures with failure to return to a baseline level of alertness
between seizures.
● Treat seizures once outside of the window for normal length for the patient. If that isn’t known, treat after 5-10
mins
● ABCs then meds
● Give lorazepam first, but it has a short half life - add fosphenytoin after. Then can add midazolam and
phenobarbitol.
● Generalized convulsive status epilepticus has the worst prognosis.

Pregnancy
● Teratogenicity occurs during first trimester - so if took the drug through 1st trimester, not really any need to stop
(except maybe valproic acid)
● If the woman has been seizure free for a few years, it may be possible to withdraw AEDs. If not, the goal should be
to use one drug (higher risks with multiple drugs), use the lowest dose possible, and to avoid valproic acid if
possible. Also avoid phenytoin and phenobarbital if you can. Risk of neural tube defects → reduce with 0.4 mg per

day of folic acid.

● Best to avoid withdrawing the drug during periods of sleep deprivation, like several months after delivery.

Chapter 6: NEUROMUSCULAR DISORDERS

Motor neuron disease: Affects anterior horn cells. Look for motor signs/symptoms without sensory involvement and a
patchy distribution, often assymetric, without obvious proximal vs distal muscle involvement.
1. ALS:
○ UMN + LMN affected, no sensory. 50% motor neurons are lost before weakness is detected. Usually starts
in one arm → contralateral arm → ipsilateral leg → contralateral leg → bulbar muscles. But any pattern is

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 possible. If starts in bulbar → distal arms → thorax → legs. Doesn’t affect extraoccular muscles, no
bowel or bladder incontinence!
○ Also emotional incontinence - crying/laughing at weird times, excessive forced yawning. 20-40% have
cognitive involvement, big overlap with frontal-temporal dementia.
○ Usually sporadic, can be familial (mutation in superoxide dismutase - might be gain of function)
2. Progressive muscular atrophy (PMA) - 10% of adults with motor neuron disease. Only LMN
3. Spinal muscular atrophy (SMA) - genetic disorders affecting LMNs, usually present in infancy or childhood but
can hit adults.
4. Viral infections - poliovirus, other enteroviruses: flu-like illness → fulminant focal or multifocal weakness with LMN
characteristics. Also West Nile Virus.

Radiculopathies: Affect dorsal or ventral roots. Can be asymptomatic or painful. Usually motor + sensory symptoms, but
one or the other may be worse. Affected region will be consistent with a nerve root or roots. Affects proximal and distal
regions - e.g., proximal AND distal muscle weakness (contrast polyneuropathy).
● Often degenerative diseases of the spinal column - can affect vertebral bodies, facet joints, or discs. Can be
tumors or abcesses, vasculitis, infection, metabolic issues, inflammatory demyelination
● Diabetes - prone to radiculopathy in the thoracic nerve roots
● Herpes zoster → shingles, usually pain and rash

● Lyme disease and CMV → polyradiculopathy

Plexopathy: Signs/symptoms suggest polyradiculopathy but the pattern doesn’t conform to the distribution of any
individual nerve root or combo of roots, or to the distribution of any individual peripheral nerve or combo of nerves.
● Cancer, radiation, trauma, metabolic disorders (diabetes), autoimmune
● Diabetes hits lumbosacral plexus most often, autoimmune goes for brachial plexus more often

Neuropathy: involvement of a nerve or nerves (polyneuropathy or mononeuropathy).

1. Polyneuropathy: Usually affect the longest nerves first → hit the feet first and move up. Then at the knees, the

hands get involved (stocking/glove). Usually symmetric. But other patterns are possible!
a. Bell’s Palsy - caused mostly by herpes simplex or varicella zoster. Have LMN facial weakness, often
pain (esp ear), maybe changes in hearing or taste, maybe sensory problems. Usually recover within 3
months, most have full recovery.
i. Bad signs if completely weak at the peak, non-ear pain, old.
ii. Tx = prednisolone and acyclovir.
b. Many causes of polyneuropathy
i. D - diabetes. Can have painless loss of sensation w/ weakness OR painful loss of sensation.
ii. A - alcohol. Probably mostly due to malnutrition
iii. N - nutrition, including B1/thiamine, B6, B12, E
iv. G - Guillain Barre = acute demyelinating polyradiculopathy. Weakness peaks in 4 wks.
Usually CSF with elevated protein and normal cell count. PLEX and Iv Ig. Get EEG because of
risk of autonomic insufficiency.
v. T - toxic (lead, heavy metals, arsenic, too much B6, medications)
vi. HE - hereditary. Most common is Charcot Marie Tooth disease, many mutations involved.
vii. R - recurrent - chronic inflammatory demyelinating polyradiculopathy. Progresses over 2
months. CSF with elevated protein and normal cell count. PLEX and Iv Ig. Prednisone is effective,
not true for AIDP.
viii. A - amyloid
ix. P - porphyria
x. I - infectious - lyme disease, HIV, leprosy, diphtheria, mono
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 xi. S - systemic - uremia, hypothyroid, lupus, Sjogren’s, Wegener’s. Generally produce axonal
neuropathy, not demyelinating.
xii. T - tumors = paraneoplastic, CIDP associated w/ multiple myeloma
2. Mononeuropathy - most often from compression. Good to stabilize the joint, can try steroids. Then surgery.
3. Mononeuropathy multiplex - hits one nerve and then another and another, but can’t see a pattern that would
indicate a polyneuropathy. When compression/trauma can’t explain, most often caused by vasculitis.

Neuromuscular junction: Motor signs/symptoms only, hits the proximal muscles first. Fatigue is most prominent in the
most common NMJ disease, myasthenia gravis. Dyplopia, dysphagia, dysarthria are common. Antibody levels do not
correlate with disease severity.
1. Myasthenia gravis - usually starts with ptosis, diplopia, or both. Early problems with speech, swallowing, or
chewing. 25% only have problems with lid, eye, and bulbar muscles. In limbs, usually proximal >> distal. Maximal
weakness in 2-5 years. Course is often fluctuating (not true of primary muscle disease)
a. Tx = Ach esterase inhibitor (pyridostigmine, edrophonium/tensilon test), immune supression,
thymectomy if symptoms begin < 60 yrs or have a thymoma (15%)
2. Lambert Eaton Myasthenic Syndrome - affects autonomic ganglia → dry mouth, impotence. Ach esterase

inhibitor (pyridostigmine), PLEX, Iv Ig

3. Botulism - affects autonomic ganglia.

Muscle disease: Motor signs/symptoms, usually but not always hits the proximal muscles first. With some exceptions,
usually spare the muscles innervated by cranial nerves! Diplopia, dysarthria, dysphagia are rare.
1. Muscular dystrophies: hereditary diseases w/ mutations in structural proteins that maintain membrane stability
2. Biochemical defects
a. McArdle’s disease - myophosphorylase deficiency → can’t breakdown glycogen to glucose quickly.
Asymptomatic at rest, but pain/fatigue/cramping with exercise

b. Carnitine palmitoyl transferase deficiency - defective utilization of fatty acids → pain/fatigue/cramping

after prolonged exercise, okay for short bursts

3. Endocrine causes: hypo/hyperthyroid, hyperPTH, Cushing’s, etc
4. Systemic illness: Sarcoidosis, cysticercosis, trichinosis
5. Intrinsic muscle inflammation - best diagnostic test is muscle biopsy. May have muscle pain, often mild.
a. Dermatomyositis - most common in kids and early adult life. Progresses over weeks.
Humorally/antibody mediated. Give prednisone.
b. Polymyositis - progresses over months. T cell mediated. Give prednisone.
c. Inclusion body myositis - Accumulate beta amyloid and tau protein in muscle. Maybe T cell mediated.
Weak forearm flexors and knee extensors, asymmetric, dysphagia, more facial involvement that DM or
PM. Progresses over years. No treatment.

Diagnostic tests
1. Nerve conduction studies: stimulate a peripheral nerve, measure amplitude of response (= # of fibers present)
and velocity of response (assess myelin sheath). Evaluate several sensory and motor nerves to see if one group
is more affected. Can tell if problem is axonal loss or demyelination. Best for large fiber somatic nerves.
2. Neuromuscular junction transmission: Test by repeatedly stimulating the motor nerve - should continue to
cause action potentials in the muscle fiber. But won’t in MG or lambert eaton.
3. Needle electromyogram: Records the electrical activity of muscle fibers preceding contraction. Can tell if the
muscle has been denervated or not → can tell whether the problem is neuropathic or myopathic.
4. Nerve biopsy - can see primary axon damage, primary demyelination, and vasculitis affecting the small arterioles
supplying the nerve. Most often sural nerve at the ankle

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 5. Skin biopsy - can assess small fiber nerves (nerve conduction studies not good for that) by looking for changes
in intraepidermal nerve fiber density and morphology on skin biopsy. Small fiber neuropathies (e.g., diabetes) are
often very painful.
6. Muscle biopsy - can see dystrophies, congenital myopathies, metabolic myopathies, and inflammatory
myopathies.
7. Serum creatine kinase - elevation can signal muscle damage
8. Antibody assays
9. Genetic tests
10. Imaging - when a focal process is suspected (mononeuropathy, plexopathy, radiculopathy)

CHAPTER 7: DEMENTING ILLNESSES

People with dementia typically have trouble providing specific examples of their deficits - even if they acknowledge having
memory problems. If they can recall exactly when and what they forgot, they probably don’t have dementia.

Dementia: acquired, persistent decline of intellectual function that causes impaired performance of daily activities, without
clouding of the sensorium or underlying psych disease

Delirium: Acute, transient, fluctuating confusional state w/ impairment in maintaining and shifting attention, often w/
sensory misperception and disorganized thinking.
● Suspect with intermittent sleepiness, disorientation, and poor processing of new material, with intact higher
cognitive functions.

Psuedodementia: related to depression. Suspect if the person has vegetative signs (eating, sleeping changes), or the
decline began after a sad event

Mild cognitive impairment: acquired, persistent impairment in one or more cognitive domains that’s more severe than
would be expected for normal aging, but not so severe that it interferes with with social or occupational functions.
Consciousness is preferred. Can be amnestic (memory - most common) or non-amnestic (memory is fine). No convincing
evidence that treating does any good.

Primary Dementing Illnesses

1. Alzheimer’s
a. 1% of 60 y/o, doubles every 5 years after. 10% familial with AD inheritance
b. Hits temporal and parietal lobes most. Lose cholinergic neurons in the nucleus basalis of Meynert. Problem
with alpha secretase → normally cleaves the AB peptide in half.
c. All three genes involved in familial forms increase AB peptide production - presenilin 1 and 2, gene for
APP (amyloid precursor protein).
d. Severity correlates with severity of tau
e. Memory loss is the first symptom and most prominent - others vary a lot. Later - can even have
movement issues like bradykinesia, rigidity, spasticity, psych symptoms (delusions, agitation, depression)
f. CSF - has lower levels of AB peptide and higher levels of total tau and phosphorylated tau
g. Tmt: donepezil, rivastigmine, galantamine, memantine (NMDA antagonist). Set the clock back by 6
months. Start one of the 3 cholinesterase inhibitors early, then memantine later when disease becomes
more severe.

2. Dementia with Lewy Bodies

a. Lewy bodies throughout the cortex. Loss of substantia nigra dopamine neurons AND loss of cholinergic
neurons in the nucleus basalis of Meynert. Distinguish from Alzheimer’s based on:
i. early Parkinson’s features (esp. rigidity and bradykinesia),

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 ii. early visual hallucinations,
iii. marked fluctuations in cognition/alertness
iv. Also: REM sleep behavior disorder, very sensitive to antipsychotics (antidopamine), episodes of
falling/LOC, systematized delusions, other types of hallucinations - tactile, olfactory; prominent
depression
b. Also, compared to Alzheimer’s have less severe memory problems and more severe impairment of
visuospatial and executive function.
c. Tmt: Same as Alzheimer’s. Levodopa and dopamine agonists are less effective than in Parkinson’s, but
can still try. If need antipsychotics, use one of the drugs with fewer extrapyramidal side effects:
clozapine/clozaril, quetiapine/seroquel, olanzapine/zyprexa

3. Frontotemporal dementia (5-15%)

a. Younger age of onset than Alzheimer’s. 10% autosomal dominant.
b. Present with progressive behavioral disturbances or progressive language disturbances. Initially speares
memory and other cognitive function
i. Personality/behavior = both frontal lobes hit. Apathy, blunt affect, attn problems, poor planning,
impaired reasoning, changed eating habits, disinhibition, inappropriate sexual behavior, neglect
hygeine
ii. Language -
1. progressive nonfluent aphasia (comprehension relatively intact) if hits around the
sylvian fissure/lateral sulcus
2. Semantic dementia - fluent but empty speech, loss of comprehension, anomia. Hits
anterior temporal lobe.
c. Most have TDP-43 inclusions (ALS overlap) or Tau inclusions, most of the rest have FUS inclusions
d. Progresses faster than Alzheimer’s, esp. if also have ALS. No treatment, just behavior management.

Primary Progressive Aphasia

1. Progressive nonfluent aphasia - most often CBD or PSP, but can be FTD
2. Semantic aphasia - most often FTD
3. Logopenic progressive aphasia - more in Alzheimer’s. Slow, hesitant speech, word finding trouble, can’t repeat,
can’t understand

4. Vascular Dementia
a. Suspect if hx of strokes, hx of stroke risk factors, focal abnormalities, abrupt onset of dementia, stepwise
progression, brain imaging suggests ischemic lesions
b. Alzheimer’s is 5x as common!
c. Patients who have penetrating artery disease are still considered asymptomatic for carotid stenosis
d. Cholinesterase inhibitors

5. Normal Pressure Hydrocephalus

a. Ventricular enlargement without increase in ICP. Improves in response to shunting. Wacky, wobbly, wet.
No structural obstruction - might have had previous meningeal irritation (meningitis, SAH)
b. Shunting is often worth a try - risks are infection and subdural hematoma.

6. Creutzfeldt Jakob Disease

a. Usually > 50 y/o. Death in months to one year. 5-15% familial.
b. Suspect when very rapid progression of dimentia, with prominent myoclonus or ataxia early in the course.
c. Discrete neurologic or psych symptoms → declining cognitive function, myoclonic jerks. Also can see
ataxia, dysarthria, psychosis, etc. → akinetic mutism
d. Different variants - can have cerebellar signs early, early visual signs, or mimic motor neuron disease

13
 e. Most have CSF with elevated 14-3-3 (neuron chaperone protein), tau, and neuron specific enolase. Also
have characteristic EEG - periodic complexes once per second.

CHAPTER 8: MOVEMENT DISORDERS

Festination: involuntary tendency for movement to decreased amplitude and increased frequency
Intention tremor: worst when approaching the target of a goal directed movement (terminal kinetic tremor)
Kinetic tremor - can be initial, transition (during movement), or terminal/intentional

Movement disorders are either hypokinetic, hyperkinetic, or ataxic.

Essential tremor
● Postural and terminal tremor, worse in upper extremities, usually bilateral, can be assymetric (esp at onset). Often
head tremor, may also have voice tremor.
● No rigidity, postural problem, or bradykinesia
● Can be drug induced - SSRIs, TCAs, many others
● Test for hyperthyroid!
● Beta blockers and primidone. If that doesn’t work, then deep brain stimulator in the contralateral ventral
intermediate nucleus

Parkinson’s
● Often begins in a single limb, progresses to the other limb on the same side, then goes to the other side of the
body
○ Often have pain, olfactory dysfunction, sleep disorders, and autonomic dysfunction.
○ REM sleep behavior disorder and constipation often precede the dx by many years
○ Later: get dyskinesia/involuntary movements
● Genetic transmission is rare. Synthetic drug MPTP induced parkinsonian syndrome in IV drug users.
● Drug induced: antipsychotic meds, anti-emetics (reglan/metoclopromide, others), reserpine, calcium channel
blockers, amiodarone, some immunosuppressants, manganese or CO poisoning
● Treatment:
○ L-dopa crosses the BB barrier and is converted to dopamine in neurons by dopa decarboxylase
■ Carbidopa blocks peripheral dopa decarboxylase. L-dopa + carbidopa = Sinemet
■ Entacapone blocks peripheral breakdown of L-dopa by COMT. Tolcapone also enters CNS, but
lots of hepatotoxicity.
○ Dopamine receptor agonists are good because don’t require processing by pre-synaptic cells which
decrease with disease progression, but lots of side effects (daytime sleepiness, others). Good to use after
dyskinesias start.
■ Currently used: bromocriptine, pramipexole, and ropinirole
■ Cabergoline is another one with a long half life, but only approved for hyperprolactinemia
■ Patients on dopamine agonists + l-dopa have fewer dyskinesias and motor fluctuations than L-
dopa alone, but Parkinson’s not as well controlled.
○ Anticholinergics for rest tremor
○ MAO-B inhibitors - selegiline and rasagiline improve symptoms, may slow disease progression. START
WITH THESE - ADD L-DOPA LATER
○ Surgery: deep brain stimulation of the basal ganglia helps, but only if the patient is still responding to L-
dopa. Tremor may respond even when meds no longer help. Not an option in patients with dementia.
● Treatment for non-motor symptoms
○ Hallucinations - quetiapine and clozapine antipsychotics. These are least likely to worsen Parkinsonian
symptoms.

Other Parkinsonian Syndromes

1. Dementia with Lewy Bodies - alpha synuclein

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 2. Progressive Supranuclear Palsy - Tau
a. Resembles Parkinson’s early, but then see characteristic eye movements - gaze palsies with intact VOR,
b. Prominent gait disturbances/falls, tremor is less common.
c. Neck dystonia, axial rigidity. Early dysphagia, dysarthria.
d. Subtle cognitive deficit, mainly in executive function.
e. 50% need help walking in 4 years, wheelchair by 8 years.
f. Can try L-dopa, but usually doesn’t help

3. Corticobasal Degeneration - Tau

a. Alien limb. Spreads to ipsilateral limb before hitting the other half of the body. Sometimes progressive
aphasia or sensory neglect on one side.
b. Parkinsonian symptoms = rigidity and bradykinesia, often myoclonic jerks
c. Impaired exec function, but global deficits are mild to moderate
d. Dysarthria and dysphagia are common later
e. Dopaminergic treatment helps some

4. Multiple System Atrophy

a. Parkinsonianism, cerebellar dysfunction, autonomic impairment = orthostatic hypotension, urinary
retention or incontinence, impotence, constipation, or thermoregulatory abnormalities. May also have
spasticity, CN abnormalities, anterior horn dysfunction, or peripheral neuropathy
b. ⅔ have REM sleep behavior disorder
c. Some respond to dopaminergic meds

Hereditary Ataxias

1. Friedrich’s Ataxia
a. AR inheritance - the most common inherited ataxia. GAA trinucleotide repeats in mito protein frataxin -
too much iron builds up
b. Comes on in teen years with gait difficulty. LE’s - loss of position and vibration, absent reflexes, positive
babinski. Also ataxic speech, can affect upper extremities.
c. 50% have skeletal deformities (scoloiosis, pez cavus)
d. 60% have hypertrophic cardiomyopathy
e. Disability within 15 years, life expectancy after onset is 30-40 years

2. Ataxia telangectasia
a. Comes before < 10 y/o. Ataxic gait → UE ataxia → ataxic speech. Choreoathetosis or dystonia, difficulty
with saccadic eye movements - have to THRUST HEAD in the direction of gaze
b. Telangectasias appear AFTER ataxia (think of the name - ataxia-telangectasia)
c. 60% have immune deficiency - lots of sinus/lung infections. Increased risk of cancer, esp. lymphoma
d. Wheelchair bound by 12 years old.

3. Spinocerebellar ataxias
a. > 30 different kinds. All autosomal dominant inheritance!
b. Symptoms usually begin in adolescence or later. Ataxic gait → limb movements → speech. Slow
progression

4. Fragile X Associated Tremor/Ataxia Syndrome (FXTAS)

a. Maternal grandfathers of boys with fragile X - begins after 55, slowly progressive ataxia, kinetic tremor,
parkinsonianism, and polyneuropathy

15
 b. Have intermediate length frataxin genes

5. Huntington’s Disease
a. 10% have onset before 20 years - will have Parkinsonianism > chorea
b. Tetrabenazine is a catecholamine depleter can lessen chorea, but can worsen or cause depression. Can
also use phenothiazines and atypical antipsychotic agents.

6. Tardive Dyskinesia
a. 20% of patients taking antipsychotics or anti-emetics → hyperkinetic movements, especially dystonia or
dyskinetic movements. Risk increases with age and duration of therapy
b. Reducing dose can be the initial precipitating or exacerbating therapy, and resuming/increasing can give
short term relief, but only makes things worse long term
7. Dystonias
a. Can be isolated problem or part of a larger condition.
b. Dystonia that begins in adulthood is usually focal or segmental. Most common are torticollis,
blepharospasm (involuntary bilateral eye closure), and writer’s cramp.
c. Dystonia that begins in childhood is usually generalized
i. Most common form is DYT1 dystonia. Autosomal dominant with low penetrance. Begins before
10 y/o in 50% of patients. Starts in one limb, spreads to the rest of the body over 1-10 years.
Disabling. Can do deep brain stimulation.
ii. Dopa-responsive dystonia - rare, dramatic response to L-Dopa indefinitely. Marked diurnal
variation - almost normal in the morning, but then increasing dystonia, parkinsonianism, and
hyperreflexia.
d. Tx in general: botulism toxin for focal dystonias, baclofen

8. Wilson’s Disease
a. Autosomal recessive disorder of copper metabolism
b. Progressive - but often reversible - dysarthria, dystonia (focal, segmental, multifocal, general), gait
disturbance, tremor (rest, postural, or kinetic), parkinsonism, choreoathetosis, dysphagia, psych
symptoms, and cognitive deterioration. Can happen in any combo and any sequence.
c. Present with liver problems between 8 and 16, with neurologic symptoms after puberty. Get copper in
liver and brain.
d. Dx: slit lamp for kayser fleischer rings (in 98% with neuro sx, 50% with hepatic sx), increased copper in
urine collection, low ceruloplasmin (but low end of normal in 15% with the disease and low in 10-20% of
asymptomatic carriers), free serum copper
e. Tx: zinc to block intestinal absorption, trientine (chelating agent)

9. Tourette’s
a. Autosomal dominant, incomplete penetrance, boys > girls. Usually comes on between 3 and 8 y/o, almost
always by adolescence.
b. OCD and ADHD in 50%
c. Tx: haloperidol, fluphenazine, pimozide, atypical antipsychotics.
d. Tx for OCD: SSRIs and CBT

CHAPTER 9: SLEEP DISORDERS

Main questions - is the problem with staying awake during the day, falling asleep or staying asleep at night, or are there
abnormal sensations/behavior during sleep? Parasomia = abnormal movement or behavior during sleep.

Sleep physiology

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Three stages of NREM sleep: N1, N2, and N3/delta (= slow wave). Go from N1 → N2 → N3/delta → N2 → REM → N2 →
N3/delta and so on. Cycle 4-6 times per night. At the beginning of the night, N3 periods are longer than REM, and the
reverse is true later in the night.

1. Ascending Reticular Activating System (ARAS) keeps us awake with norepi, ACh, serotonin, and histamine.
2. GABA-ergic “hypnogenic neurons” put us to sleep.
3. REM-on cells = cholinergic cells that initiate REM
4. REM-off cells use serotonin, norepi, and histamine to stop REM

Hypocretin/orexin is an NT in some hypothalamic neurons - inhibits REM sleep, promotes wakefulness, and stimulates
feeding and motor activity. Involved in balancing motor excitation and inhibition during emotionally charged activities.

Trouble staying awake

1. Insufficient sleep
2. Sleep apnea - OSA is most common cause of excessive daytime sleepiness. Central sleep apnea is possible,
too. CPAP is best, if still tired can also do modafinil and armodafinil (narcolepsy meds)
3. Narcolepsy -
a. four symptoms, but only 50% have all four:
i. Chronic excessive daytime sleepiness, regardless of the amount of sleep at night. *Universal
symptom*
ii. Cataplexy - loss of postural tone that occurs while awake, like REM atonia. Can be very subtle,
involve only one muscle group, or be generalized. May have just a subjective feeling of
weakness, ptosis, buckling of legs, etc. Consciousness and hearing are preserved. Often
provoked by sudden strong emotions (e.g., laughter), usually lasts several minutes. *Most specific
for narcolepsy* - basically doesn’t happen outside of narcolepsy
1. 90% of pts with cataplexy have low hypocretin levels in CSF!
iii. Sleep paralysis - at onset of sleep or awakening, like REM atonia.
iv. Hypnagogic/hypnapompic hallucinations - vivid auditory or visual dream-like experiences
b. Dx: mean sleep latency < 8 mins plus 2+ sleep onset REM periods (< 15 minutes of sleep onset)
c. Tmt: Stimulants, usually modafinil, armodafinil, or dextroamphetamine, or methylphenidate.
Nighttime gaba hydroxybutyrate can improve cataplexy and daytime sleepiness.

Trouble sleeping
1. Sleep onset delay
a. Can be psychophysiologic insomnia (basically conditioned association between bed and unsuccessful
sleep).
i. Tx: benzodiazepenes, but risk of dependence. Can try nonbenzo’s that still bind to GABA
complex: zaleplon (sonata), zolpidem (ambien), and eszopiclone (lunesta)
ii. Restless leg syndrome exacerbates psychophysiologic insomnia.
1. Worse in the evening and at night than during the day, occur mostly when lying down or
sitting.
2. Can be associated w/ iron-deficiency anemia - sometimes resolves with iron
replacement, so check iron and ferritin levels. Also associated with uremia.
3. Often responds to dopamine agonists.
b. Delayed sleep phase syndrome
2. Early morning awakening
a. Depression - most common cause of early AM wakening in older patients. Also assoc’ed with shortened
REM latency, reduced NREM sleep, and variable disturbance of sleep onset.
b. Alcohol
c. Advanced sleep phase syndrome - go to bed early, wake up early
3. Others: sleep fragmentation, sleep state misperception
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Abnormal Behavior during sleep

1. NREM sleep parasomnias:

a. Night terrors: wake from slow wave sleep, screaming, intense anxiety and autonomic activation (dilated
pupils, sweating, tachycardia, tachypnea, piloerection). Kid can’t be awakened or consoled, but calms
after several minutes. No story/plot, usually don’t remember much other than vague scary image or
thought.
b. Sleep talking and sleep walking
c. Confusional arousals = confusion, slow responses, inappropriate behavior, and poor coordination
following arousal from slow-wave sleep. Usually lasts a few minutes
d. Enuresis = bed wetting. Can treat with behavioral techniques, TCAs, oxybutynin, others.
e. Periodic limb movements of sleep - might also have restless leg syndrome (most with RLS have
PLMS)
f. Hypnic jerks, bruxism, sleep related rhythmic movement disorder

2. REM sleep parasomnias

a. REM sleep behavior disorder - REM atonia breaks down and patients act out dreams. Usually elderly
and idiopathic, but ⅓ may have underlying neuro disorder
i. Suggestive feature of dementia with lewy bodies. ⅔ of patients with Multiple System Atrophy,
25% Parkinson’s
b. Nightmares - hardly any automatic arousal, easily wake up, can remember the dream, usually a story.
PTSD is a common cause, some meds can, too (L-Dopa, beta adrenergic blockers, antidepressants).
Also abrupt drug withdrawal. Do CBT. SSRI or TCA is sometimes used to suppress REM.
c. Cluster headaches often occur during REM

CHAPTER 10: MULTIFOCAL CNS DISORDERS

Two broad categories: (1) focal diseases with multifocal progression, and (2) intrinsically multifocal

Focal with Multifocal Progression

1. Metastatic Cancer -
a. Can hit the brain, the spinal cord directly, or the bone of the spine. Lung cancer, breast cancer,
melanoma, and testicular cancer are common primaries.
b. Dx: MRI of the brain, biopsy if possible
c. Can cause increased ICP via edema - dexamethasone first, then hyperventilation and osmotic diuresis
d. 5-10% of patients with systemic cancer have spread to the meninges - esp. if breast, leukemia,
lymphoma, lung cancer, and melanoma. Life expectancy < 6 months.
i. Can cause meningeal irritation → meningitis-like symptoms
ii. Hydrocephalus from blockage of CSF
iii. Compression of cranial or spinal nerves as they exit meningeal spaces → multiple cranial
neuropathies or polyradiculopathies
iv. Dx:
1. Examine cytology of CSF - may require 3+ LPs. Flow cytometry can identify monoclonal
B and T cells. Do assays for tumor markers.
2. Spinal MRI - more sensitive than 1 LP. Do before LP because LP will cause
enhancement
e. Cancers can spread to brachial and sacral plexus - more often than going to individual peripheral nerves
or muscles

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 f. Paraneoplastic syndromes - LEMS, cerebellar degeneration, polyneuropathies (esp pure sensory),
dermatomyositis, encephalopathy

2. CNS infections - can be focal (abscess, focal myelitis), multifocal (multiple abscesses or sites of involvement),
diffuse (meningitis or encephalitis)

a. Abscess: Can look like a tumor on imaging (contrast enhancing lesion, surrounding edema, often ringed).
But abscess is usually subacute (days to weeks), while tumor is chronic (months) Can look at CSF -
culture vs. cytology
i. Tx: excision or aspirate with CT or MRI, systemic antibiotics

b. Infective endocarditis
i. Cerebral embolism in 20-40% - can be sterile or infectious. Sterile → stroke, infectious →

strokes, meningitis, abscesses, arterial infection → aneuysmal dilation, aka mycotic aneurysm.

1. Rupture of mycotic aneurysm can cause SAH, intraparenchymal hemorrhage, or

intraventricular hemorrhage. Unruptured MA’s can embolize → stroke.
ii. Diagnosis:
1. At least 3 separate venous blood culturs
2. Echo - but negative result doesn’t rule out endocarditis
3. MRI of the brain
4. If a patient has a stroke, do an MRA as soon as it’s safe to look for MA.
a. If see MA, then repeat MRA at the end of abx. If it’s smaller, continue abx. If it’s
unchanged or bigger, probably resect or coil.
b. If MRA doesn’t show MA, do catheter angiography if the stroke was hemorrhagic.
If it was ischemic, probably don’t need further testing unless considering long-
term anticoagulation.
iii. Treatment
1. Empiric broad spectrum antibiotics to cover staph aureus, many strep species, and gram
negative rods - e.g., nafcillin, ampicillin, and gentamicin.
a. Can substitute vancomycin for nafcillin if worried about S aureus resistance
2. Generally avoid anticoagulation with infective endocarditis - doesn’t prevent growth
of vegetation, just increases risk of hemorrhagic transformation and/or rupture of MA. But
can anticoagulate if the endocarditis is on an artificial valve (except staph aureus - do 2
wks of abx first)
3. Delay valve replacement for 2 weeks after stroke.

c. Specific Infective Bugs

i. HIV
1. Opportunistic infections and cancer
a. Toxo, CMV, syphilis, tuberculosis, herpes, lymphoma, PML/JC virus,
cryptococcus, nocardia, atypical TB, other fungal infections (candida, histo,
mucormycosis, etc).
i. Treat toxo with sulfadiazine and pyrimethamine
ii. Treat cryptococcus with amphotericin with or without flucytosine
iii. Brain imaging and LP. If see multiple lesions and + for toxo IgG, can
treat for toxo and then biopsy if no improvement in 10-14 days. But if
single lesion only, go straight to biopsy - less likely to be toxo.
b. Cancers - CNS lymphoma, Kaposi’s sarcoma,
i. CNS lymphoma - treat with antiviral meds!
c. Immune Reconstitution Inflammatory Syndrome (IRIS) - begin HAART, and
then a few weeks later deteriorate, even though viral loads are decreasing and
19
 CD4 counts are increasing. Can see progression of appropriately treated
infection or new opportunistic condition. Some patients respond to steroids.
2. Direct effect on CNS and PNS.
a. CNS - HIV associated dementia = nonspecific mood changes, psychomotor
slowing, concentration problems. Can seem like depression. Then generalized
cognitive decline, tremor, myoclonus, incontinence, gait trouble, babinski, etc.
Responds to zidovudine.
b. PNS - polymyositis, dermatomyositis, IBM, distal symmetric peripheral
polyneuropathy, AIDP, CIDP, mononeuropathy multiplex, progressive
polyradiculopathy
3. Inflammatory reaction
4. Neurotoxic effects of meds
5. Increased risk of strokes

ii. Syphillis
1. Disease course:
a. Primary syphillis: chancre at site of infection - heals over 3-6 weeks
b. 2ndary syphilis: Flu-like symptoms, rash, lymphadenopathy, mucosal lesions.
Only 5% have neurologic symptoms (meningitis). Resolves over weeks to
months, virus goes latent
c. Tertiary syphilis in 10-30%: Skin, osseous, cardiovascular, neuro manifestations
2. Only 4-6% ever develop neurosyphilis
a. 1st 1-2 years: aseptic meningitis
b. 1-10 years, typically 5-7 years: meningovascular syphilis
c. 10-30 years: general paresis and tabes dorsalis. Have small irregular pupils that
constrict to accommodate but don’t react to light
i. General paresis: diffuse cortical dysfunction
ii. Tabes dorsalis: destruction of posterior nerve roots → loss of

proprioception, ataxia, lightning-like pain, urinary incontinence

3. Testing:
a. VDRL and RPR are present in 2ndary syphilis, but disappear in tertiary
b. Specific antibodies (FTA and MHA-TP) are present always, but don’t indicate
active infection.
c. Method: Test for FTA or MHA-TP. If positive, then do an LP to look for signs of
active syphilis - elevated WBC, increased protein, positive VDRL.

iii. Lyme disease - another spirochete!

1. Tick bite/initial rash is like the syphilis chancre.
2. Few weeks/months later - subacute or chronic meningitis, usually mild and resolve
without treatment. Can have cranial nerve palsies (esp facial nerve) and radicular pain.
Parenchymal infection of brain or spinal cord is rare, but can cause focal deficits or
encephalitis. Can also get peripheral neuropathy.
3. Borrelia burgdorferi is tough to culture and CSF PCR has 50% false negative rate!
Diagnose based on serum antibodies and clinical characteristics.
4. Tx: IV ceftriaxone, cefotaxime, or penicillin. Also doxycycline or chloramphenicol.

iv. Tuberculosis - another spirochete!

1. Can remain dormant in CNS for months or years. Then tuberculous foci rupture or grow
into the subarachnoid or intraventricular space → meningitis. Especially likes the base of
the brain

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 2. Tough to diagnose - may not have any other areas of active TB infection, might have
false negatives for all TB tests - even CSF cultures. PCR of CSF has 100% specificity but
only 75% sensitivity.

v. Herpes virus
1. Herpes encephalitis
a. HSV1 → herpes encephalitis in adults

b. HSV2 → herpes encephalitis in neonates, adult aseptic meningitis.

c. PCR of CSF. Treat with acyclovir if suspect
2. Shingles
a. famciclovir and valacyclovir reduce the duration of postherpetic neuralgia
b. Vaccine reduce incidence of shingles by 61% and postherpetic neuralgia by 67%
c. Spread to anterior root → focal weakness (usually in distribution of the nerve root
that corresponds to the affected dermatome), myelitis, encephalitis, aseptic

meningitis
3. Ramsay Hunt syndrome (zoster oticus, zoster auricularis, zoster cephalicus)
a. Vesicular eruption in the external auditory meatus, with ipsilateral facial
weakness, often with hearing loss, tinnitus, vertigo. CN 5, 9, and 10 are often
involved.

vi. Parasites
1. Malaria, toxo, trypanosomiasis, amebic infection, strongyloidiasis, trichinosis,
onchocercaiasis (4th leading cause of blindness in the world), many others

vii. Bioterrorism
1. Anthrax:
a. 95% is cutaneous, with 80-90% healing on their own. But inhalation → 50% get

meningoencephalitis!
b. Fever, headache, vomiting, delirium, seizures, myclonus, increased tone, focal
abnormalities.
c. Tx = IV cipro or doxycycline, plus other abx
2. Botulism: starts with diplopia, blurred vision, ptosis. Followed by dysarthria, dysphagia,
flaccid paralysis. Tx = antitoxin and supportive care.

Inherently Multifocal Diseases

1. Multiple Sclerosis
a. Can begin in early childhood or later in life. If minimal disability after 5 yrs, better prognosis
b. Dx = 2+ CNS lesions separated in space and time. Can look for other diagnosis (e.g., lupus), but that is
rare.
c. Diagnostic testing - not specific for MS (just signals CNS inflammation), but helpful.
i. IgG index = (IgG in CSF/albumin in CSF)/ (IgG in serum/albumin in serum) - ratio to albumin
ensures that the increase in IgG isn’t just a generalized increase in protein, and ratio to serum
ensures it’s not a systemic inflammation with passive migration of IgG into CSF
ii. Oligoclonal bands = antibodies are produced by one or more clones of plasma cells. Bands
present in CSF but not serum → active inflammation in the nervous system

21
 iii. Evoked potentials tests - visual, auditory, and somatosensory - stimulate patient while
monitoring with EEG. Keep repeating → the “noise” will average out, but the signal related to
stimulation will reinforce. Compare that wave to normal controls or to the patient on the other
side. Can see how long the stimulus took to generate a signal → estimate conduction speed and

myelination.
d. Different patterns:
i. Relapsing remitting - 85% start out this way, but by ten years 50% are secondary progressive
ii. Primary progressive
iii. Secondary progressive - initially R-R, then progressive
iv. Progressive-relapsing - progression from onset, but with clear superimposed relapses followed by
partial or full recovery. Continuing progression between relapses.
e. Symptoms
i. Lhermitte’s phenomenon = neck flexion → electric sensation down the back and into the limbs.

Can hapen with any condition affecting the posterior columns of the spinal cord, including B12
deficiency or extrinsic cord compression
ii. In addition to the typical symptoms, can also get paroxysmal symptoms = seizures, trigeminal
neuralgia, intermittent pain, 20 seconds of dysarthria or ataxia, and dystonic episodes
f. Differential dx:
i. Lupus
ii. Acute disseminated encephalomyelitis (ADEM) - abrupt multifocal condition that progresses
over several hours, usually with fever, headache, stiff neck, and depressed consciousness. Kids
> adults, usually antecedent infection or vaccination. Some patients end up with MS, but not all.
iii. Neuromyelitis optic = Devic’s syndrome
1. Specific autoantibody to aquaporin 4. Get optic neuritis and/or transverse myelitis that
extends over more spinal segments than a typical MS lesion
2. Risk of MS is high if lots of white matter lesions → give glatiramir or interferon beta
g. Treatment - can reduce relapses by ⅓ and slow disease progression (but do not halt or reverse)
i. Inteferon-beta: Rebif, avonex, betaseron. Decrease frequency of relapses and slow progression.
Cause flu-like symptoms.
ii. Glatiramir acetate. Subq every day.
iii. Natalizumab/tasabri - monoclonal antibody against a T cell integrin. 1/1000 chance of PML. IV
once per month.
iv. Mitoxantrone - not first line and can only use for 3 years because of cardiotoxicity. The only one
with FDA approval for secondary progressive. IV every three months.

2. Connective Tissue Diseases

a. Lupus
i. The CT disease most often associated with neurologic dysfunction - 50-75% of patients.
ii. Most often neuropsych abnormalities - cognitive impairment, psychosis, altered consciousness.
Also seizure, focal deficits from stroke or focal inflammation.
iii. Most common peripheral lesion is distal, symmetric polyneuropathy

b. Rheumatoid Arthritis
i. Most common = compression of spinal cord from spine arthritis.
ii. Peripheral nerve involvement is common (10%) - mononeuropathy multiplex or distal sensory
motor neuropathy.
iii. Rheumatoid nodules form in meninges, usually asymptomatic.

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 c. Sjogren’s
i. PNS more common than CNS - most distinctive is pure sensory neuropathy affecting dorsal root
ganglia - lose proprioception, etc. Lots of other neuropathies are possible, many patterns. Can
also have focal myositis.
ii. CNS complications in < 10% - psychiatric, cognitive, seizures, focal deficits, meningoencephalitis,
anything

d. Progressive Systemic Sclerosis/Scleroderma

i. Trigeminal neuropathy, peripheral entrapment (esp carpal tunnel), diffuse muscle weakness
ii. Rarely hits CNS

e. Mixed CT disease
i. Trigeminal neuralgia and TG sensory neuropathy are common. Can also have psych issues,
movement disorders, and seizures.

f. Behcet’s disease
i. Immune mediated small vessel vasculitis → recurrent oral aphthous ulcers, genital ulcers, and
uveitis.
ii. CNS - aseptic meningitis is most common. Also can have focal lesions at any level of the nervous
system (esp brainstem and basal ganglia), usually simultaneous and multifocal - often confused
with MS!
iii. Neuro symptoms - ⅓ get cerebral venous thrombosis

g. Polyarteritis Nodosa
i. Necrotizing vasculitis of small and medium sized vessels, especially at branch points
ii. 80% have neuro symptoms, especially PNS - classic is mononeuropathy multiplex. Can also
have stroke, headache, encephalopathy (acute or chronic), lots of others.
iii. Churg strauss and Wegener’s can present similarly - use cyclophosphamide for Wegner’s
iv. Can also have Primary Angiitis of the CNS or Primary Peripheral Nervous System Angiitis

3. Sarcoidosis
a. Noncaseating granulomas in many organs. Affects nervous system in 5%. Can look like TB -
parenchymal granulomas or meningeal involvement.
b. Most common = transient unilateral or bilateral facial nerve palsy. In the parenchyma, can hit the

hypothalamus → diabetes insipidus, endocrine abnormalities

c. Often affects muscles. Can affect peripheral motor and/or sensory nerves
d. Dx: Serum ACE is typically high, but not sensitive or specific. CSF ACE is especially likely to abnormal,
but still okay in 40% of sarcoid patients with neuro symptoms
e. Tx: steroids, maybe immune suppression

4. Coagulation Disorders
a. Hemophilia → hemorrhages, can happen in the nervous system
b. Primary hypercoagulability is associated with venous thromboembolism, treat with anticoagulants
c. Secondary hypercoagulability (from meds, cancer, pregnancy, CHF, trauma, diabetes, nephrotic syndrome,

vasculitis). Can lead to nonbacterial thrombotic endocarditis → stroke

d. Antiphospholipid antibodies (anti-cardiolipin, lupus anticoagulant) are seen in lupus and other CT disease,
infection, cancer, with drugs - warfarin is no better than aspirin
e. Thrombotic thrombocytopenic purpura - plasma exchange.

23
CHAPTER 11: ACUTE MENTAL STATUS CHANGES

Acute mental status changes can be focal (aphasia, neglect, hallucinations) or diffuse (delirium, stupor, etc). This chapter
focuses on diffuse.

Vocabulary
● Delirium - mildest form. Inattentiveness and confusion.
● Coma: eyes closed, no conscious response to stimuli, can’t arouse
● Encephalopathy: any state of altered level of consciousness or clouded sensorium
● Minimally conscious state - minimal but definite awareness of self or environment
● Obtundation: Appear to be asleep, but can respond sluggishly to verbal or slightly painful stimuli
● Stupor - like deep sleep, aroused only by vigorous and repeated stimulation, and then have reduced alertness
● Vegetative state - absence of behavioral evidence for awareness of self or the environment, preserved capacity
for spontaneous or stimulated arousal (e.g., sleep wake cycle)

Consciousness = arousal (ARAS), awareness (prefrontal cortex and connections), and cognition (widespread cortical
networks)

Evaluation
1. ABCs: Check and then monitor closely, risk for hypoventilation and aspiration. If failing → intubate
2. Evaluate metabolic brain emergencies with oxygen, glucose (hypo or hyper), naloxone: treat empirically for
hypoxemia, hypoglycemia, and give naloxone.
a. Oxygen
i. Check ABGs (pulse oximetry first).
ii. Although 100% oxygen can cause respiratory arrest in patients with chronic CO2 retention who
depend on hypoxia for respiratory drive, this situation is rare and less of a risk than the danger of
not correcting hypoxemia
b. Glucose
i. E.g, patient could be hypoglycemic if took normal insulin/oral meds but then was NPO for a
procedure
ii. Give thiamine with dextrose solution if any concern about deficiency - avoids precipitating or
inducing Wernicke’s encephalopathy
c. Drugs/alcohol
i. Naloxone for opiates
ii. Flumazenil for benzodiazepines.
iii. Always remember delirium tremens! Comes on 3-4 days after last drink. Give benzodiazepenes.
Withdrawal from benzo’s and barbituates can also cause tremors and agitation.
3. Evaluate structural brain injury with pupils, doll’s eyes, motor asymmetry
a. Pupils constrict with anticholinergics and sympathomimetics, dilate with cholinergics, cholinesterase
inhibitors, and opiates
b. Herniation:
i. Lateral mass → uncal herniation = medial temporal lobe goes over the free tentorial edge →
blown pupil on same side, later get ispilateral CN3 palsy
ii. Medial mass → transtentorial herniation = pressure on thalamus, then midbrain - disrupts
sympathetic and parasympathetics → both pupils are fixed, don’t react to light
iii. If herniation reaches pons, will disrupt VOR.
→ RULE: If VOR is disrupted but pupils are fine, no herniation is present! Metabolic/toxic
cause - VOR is very sensitive to toxins and metabolic problems, especially benzo’s and
barbituates

24
 c. If pupils and doll’s eye are both abnormal → herniation OR toxic/metabolic problem
4. Other electrolytes, renal, hepatic, temperature: hypo- and hypernatremia, hypocalcemia, hypomagnesemia,
hepatic, uremia.
a. Tetany → suggests hypoCa or hypo Mg
5. Everything else
a. Drugs, meds, seizure (can be tough to recognize!), infection, lupus, primary angiitis of the CNS

Head trauma
1. Indications for head CT:
a. GSC < 15
b. focal abnormalities
c. declining or fluctuating alertness
d. CSF leak
e. Suspected basilar skull fracture (periorbital or temporal ecchymoses)
f. Vomiting
g. Age > 65
h. Persistent retrograde amnesia
i. Seizure
2. If no need for surgery, can go home. Family should wake the patient every 2 hours for the first twelve hours - go
back to ED if reduced responsiveness, severe headache, nausea, vomiting
3. Post concussive syndrome - lots of different symptoms, can last days or several years

Increased Intracranial Pressure

● Encourage venous drainage - remove cervical collar if possible, elevate head of the bed, minimize ventilator
pressures (improves pressure gradient)
● Hyperventilation reduces ICP in 2-30 mins, but transient and risk of ischemia from too much vasoconstriction.
General target is 35 mm Hg of CO2
● Hyperosmotic agents - hypertonic saline, mannitol. Don’t cross the BBB, pull fluid out of brain parenchyma and
into blood vessels, then osmotic diuresis. But transient effect because the agents do eventually cross the BBB.
● Paralytic agents/sedatives (e.g., pentobarbitol) reduce toxic byproducts of brain metabolism
● Induced hypothermia can slow metabolism - improves outcomes with hypoxic ischemic events, not trauma
● Tumors and abscesses - can use steriods for ICP, work by decreasing edema. Doesn’t work for trauma.

Brain death: No response to noxious stimuli other than spinal reflexes. No brainstem reflexes. Cause of coma must be
known and be irreversible

CHAPTER 18: HEADACHE

1. Headache emergencies: SAH and bacterial meningitis

a. Watch for a severe headache that is qualitatively different, or is accompanied by fever, stiff neck, or
focal neuro abnormality not documented with patient’s previous headaches. Can be either SAH or
meningitis!
i. SAH usually has faster onset of pain, meningitis usually has more fever, but there are exceptions
b. Empiric meningitis treatment with cefotaxime/ceftriaxone and vancomycin (for resistant strep pneumo). If
IC’ed, add ampicillin for listeria.
c. Diagnosis:
i. Do CT first, but if that will delay by an hour, skip to LP. Do LP if CT negative - CT misses 5% of
SAHs. Watch for xanthochromia - indicates RBCs are starting to break down, have been around
for > 12 hours (not from LP trauma)
ii. Normal CSF pressure < 200 mm H20, normal protein = 15-45 mg/dL, normal glucose > 50% of
serum

25
2. Other secondary causes of headache
a. Viral meningitis or encephalitis
i. Both have fever, headache, stiff neck, mental status changes, seizures, but vary in severity of
specific symptoms
ii. Viral meningitis
1. Usually caused by enteroviruses that enter the blood from the intestines/ Not really an
emergency, because no treatment
2. Fever, headache, stiff neck >> mental status changes. Less likely to have seizures.
iii. Viral encephalitis
1. Usually caused by arborviruses via insect vector.
2. Mental status changes > fever, headache, stiff neck. More likely to have seizures. 10% of
patients with WNV get flaccid paralysis because it hits motor neurons in the anterior horn
of the spinal cord
3. No treatment for most kinds - big exception is herpes encephalitis (acyclovir)

b. Fungal or Tuberculous Meningitis

i. More indolent than viral meningitis - can smolder for months or years
ii. CSF findings are between viral and bacterial

c. Mass lesions
i. Get an MRI if new headaches (< 1 year), focal findings, or papilledema
ii. If current headaches have happened for a year, and no focal findings or papilledema, just
reassure - no imaging necessary

d. Giant Cell/Temporal Arteritis

i. Medium and large arteries. Patients > 50 y/o.
ii. Present with focal deficits, head pain that is dull and superficial - often in temporal region, but can
be anywhere, unilateral or bilateral. Temporal artery tenderness and jaw or tongue claudication.
Often absent temporal pulses. 40-50% have polymyalgia rheumatica = pain and stiffness in
limbs
iii. Permanent blindness in 50% untreated.
iv. Diagnosis: ESR, CRP, temporal biopsy (do even if bloodwork is negative if suspicions are high) -
false negatives are common, so if suspicion is high, repeat biopsy on the other side

e. Idiopathic Intracranial Hypertension = Psuedotumor Cerebri

i. ICP is high for no known reason. Most common in obese women in childbearing years,
ii. Diffuse headache, transient or persistant visual symptoms, papilledema. Sometimes worse

moving from sitting → standing or lying down → sitting. Sometimes unilateral or bilateral CN6

palsies.
iii. Dx: Must have imaging to rule out mass lesion, LP to document increased ICP and exclude
inflammatory disease.
iv. Generally self-limited, but can cause permanent vision loss! Treat with acetazolamide.
Topiramate also inhibits carbonic anhydrase (and causes weight loss!).
1. Can do lumpoperitoneal shunting or fenestration of the optic nerve sheath if don’t
respond to meds.

f. Spontaneous Intracranial Hypertension

i. Like an LP headache, but no known cause. Symptoms include postural headache (best when
flat), can have visual symptoms, dizziness, nausea, hyperacusis, tinnitus, or mental status
changes.
26
 ii. Sometimes have a CSF leak - usually resolves on its own after a few weeks, but if it doesn’t, try
hydration, caffeine, steroids, intrathecal or epidural saline infusion, or epidural blood patch. Can
repair surgically if need be.

g. Cerebral Venous Thrombosis

i. Headaches, focal neuro symptoms, often seizures.
ii. Risk when coagulation disorder or severe dehydration.
iii. Dx with MRI and MRV (venography)
iv. Treat with heparin

h. Arterial dissection
i. Headache or neckpain after recent trauma or cervical manipulation. Anticoagulate for at least
three months.

i. Systemic Conditions: infections, AI, cancer, endocrine, metabolic, medications

j. Sinus disease:
i. Acute sinusitis - worsened with changes in head position. Often nasal discharge, etc. but maybe
not if sphenoid sinusitis - doesn’t communicate with nasal pasages. High risk of meningitis with
spenoid sinusitis.
ii. Chronic sinusitis - unclear if causes headaches. Tx is the same as tension and migraine

k. TMJ disease
i. Correlation between chewing and headaches, joint is easily dislocated on exam.
ii. Treat with soft diet, move to jaw bracing and surgery

Primary headaches

1. Migraine and tension headaches

a. Lots of overlap between the two, and the same meds are used for both

2. Cluster headaches
a. Clusters usually last 4-8 weeks, with headaches for 30 mins to 2 hours, explosive onset. Prefer to sit up.
Usually at night, often during REM sleep. Men > women.
b. Unilateral, always on the same side (migraine can switch). Autonomic sx.
c. Oxygen is the most effective treatment - other migraine meds work, too.

3. Trigeminal Neuralgia
a. Usually benign, but can be assoc’ed with structural lesions - common in MS. Can be associated with
dental disease/microabscesses.
b. Usually doesn’t wake people from sleep
c. Do MRI of the posterior fossa if patient is < 50, focal abnormalities, or if symptoms began or changed in
character within two years.
d. Tx = carbamazepine, various surgeries if that fails

4. Glossopharyngeal Neuralgia
a. Similar to trigeminal, but start in the oropharynx and extends up and back towards the ear. Frequently
awakens people from sleep - unlike trigeminal neuralgia
b. Can be triggered by swallowing (especially sour or spicy food), yawning, sneezing, coughing, cold liquids,
or touching the ear

27
 5. Chronic Paroxysmal Hemicrania and related conditions
a. CPH: Short hedaches (ave 13 mins) that occur frequently throughout the day and throughout the year.
Treat with indomethacin. Women > men.
b. Short Lasting Unilateral Neuralgiform Headache with Conjunctival Injection and Tearing (SUNCT)
i. Pain 5-120 seconds, typically 15-30 seconds. Average 28 attacks per day.
ii. Similar to CPH, but does not respond to indomethacin
c. Ice Pick/Primary Stabbing Headaches - brief paroxysms of stabbing pain, last < 1 second. Common in
patients with migraine, but can happen without other headache. Treat with indomethacin.
d. Hemicrania Continua - continuous unilateral headache with attacks of more intense pain accompanied
by autonomic symptoms

CHAPTER 13: VISUAL SYMPTOMS

Diplopia → problem with eye alignment, vs. loss of vision itself

Monocular Vision Loss

1. Young people - NMO, trauma.
a. NMO - vision loss over 7-10 days, eye pain worse with movement. Lesions on MRI → 50% chance of

getting MS within 5 years. Normal MRI → 10% risk. Optic disc will be slightly pale. Tx is steroids, just
quickens recovery, doesn’t affect long term outcome. If abnormal MRI, begin disease modifying agents

(glatiramir, interferon beta)

2. Older patients:
a. Acute - acute glaucoma, retinal detachment, acute ischemic optic neuropathy
i. Acute glaucoma - sudden vision loss w/ severe eye and face pain, nausea, vomiting, and dilation
of the pupil
ii. Retinal detachment - diabetes, myopia, intraocular inflammation, cataract surgery, trauma (even
jogging)
iii. Acute ischemic optic neuropathy - sometimes caused by Giant Cell Arteritis
b. Chronic - cataracts and macular degeneration

Transient Vision Loss - Monocular or Binocular

Caused by ischemia, migraine, or increased ICP
1. Ischemia:
a. Monocular vision loss - atherosclerotic disease of the ispilateral carotid artery. Vision loss progresses
over minutes, improves over minutes to one hour
b. Half of visual field - cortical TIA
2. Increased ICP - visual loss can be positional → alters ICP. Look for bilateral disc edema with normal optic nerve

functioning.

Binocular Vision Loss

1. Heteronymous (bitemporal) hemianopia - lose nasal half of each retina from lesion affecting the chiasm.
a. Caused by pituitary adenoma, suprasellar meningioma, craniopharyngioma, glioma, and internal carotid
artery aneurysm.

Diplopia
● Can result from lesions anywhere in the ocular motor system. Also diseases of the muscle or neuromuscular
junction, masses in the orbit, etc.
● 4th nerve lesion - can’t look down and in (towards nostril). Often compensate by tilting the entire head in the
direction that the affected eye can’t move
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 ● Must figure out if the lesion is within the brainstem (intra-axial) or outside the brainstem, affecting CNs after they
have already exited → examine for limb weakness, sensory changes, ataxia, hyperreflexia.
○ Extra axial process affecting multiple CNs: almost always caused by meningeal cancer or meningeal
inflammation. Examine the CSF, consider meningeal biopsy
○ Extra axial process affecting one CN: Usually compression (require urgent treatment) or focal ischemia
(e.g., diabetes → small vessel ischemia).
■ Ischemia - will cause loss of eye CN3 eye movements but the pupil remains normal!
● For small vessel disease, no treatment available, but gradual improvement in 50%. Do an
MRI
■ Compression → CN3 blown pupil - see with herniation, expanding arterial aneurysm.

CHAPTER 14: DIZZINESS AND DISEQUILIBRIUM

Dizziness can mean lightheadedness/presyncope (global cerebral hypoperfusion), vertigo = any false sensation of
movement (from central or peripheral vestibular dysfunction), balance difficulty, clumsiness, confusion, or malaise.

Nystagmus cold water test: Cold water in one ear mimics a destructive lesion → decreased input to that side (suppose

the right). Then get slow deviation of the eyes to the right, followed by fast beat of nystagmus to the left (side with
increased input). Nystagmus is named after fast component.

Central vertigo Peripheral Vertigo

Associated symptoms Dysarthria, dysphagia, diplopia, limb Hearing loss and tinnitus are frequent
numbness, weakness, ataxia from - vestibular and cochlear nerves travel
brainstem and cerebellum together to the brainstem
involvement

Usually no hearing loss - auditory

pathways go bilateral as soon as they
enter the brainstem.

Nystagmus Multidirectional - changes according Unidirectional.

to direction of gaze
Usually has both translational
Pure horizontal, pure vertical, or pure component (horizontal or vertical) and
rotational. rotational component.
Fast beat away from the side of the
lesion

Subjective sense of vertigo Vertigo is greatest with peripheral

lesions

Testing to determine if lesion is central or peripheral

1. Audiogram for unilateral hearing loss
2. Brainstem evoked potentials - not reliable enough to be useful
3. Imaging of posterior fossa and the skull, especially auditory canal

Central Vertigo
1. Getting worse - neoplasm, abscess
29
 2. Acute - trauma or vascular process
3. Recurrent, transient spells - TIA, migraine, seizure, paroxysmal manifestations of MS. Can have migraine without
headache!
a. Migraine may be the most common cause of dizziness dating back several months or longer without
features of common peripheral disorder or exam suggesting a structural lesion.

Peripheral vertigo
1. Getting worse - inflammation, cancer (meningioma, vestibular nerve schwanoma), toxins (aminoglycosides,
cisplatin)
2. Recurrent
a. Benign paroxysmal positional vertigo (BPPV):
i. Most common cause of recurrent vertigo. Brief episodes whenever the head is in certain
positions. No vertigo in other positions.
ii. Usually caused by calcium carbonate particles (otoliths) that get dislodged from the otolith
membrane → get stuck in semicircular canal. Maybe after trauma or labyrinthitis, usually cause is

unknown. Can rarely be a central problem.

iii. Dx: tortional and upbeat nystagmus when the head moves in the problematic direction.
iv. Can treat posterior canal stones with the Epley maneuver
b. Meniere’s Disease
i. Episodic vertigo and tinnitus with hearing loss. Hearing loss is fluctuating and reversible early on,
but later progressive. Episodes begin with sensation of fullness and pressure in one ear. May
have nausea, vomiting, and ataxia. Attacks happen weeks, months, or years apart.
ii. Increased endolymph volume in the labyrinth - can happen after labyrinthitis but usually
idiopathic.
iii. Tx: restrict salt, diuretics. If that fails, can do ablative therapy - knock out the vestibular
nerve. Easiest way is intratympanic gentamicin injection, but doesn’t always work and 25%
chance of hearing loss. Labyrinthectomy is effective, but also hearing loss - best when already
have impaired hearing. Vestibular nerve section is most likely to preserve hearing, but more
complicated, less reliable
c. Perilymph fistula
i. Episodes of vertigo brought on by sneezing, coughing, loud noises (Tullio’s phenomenon),
exertion, or airplanes. Small tear in oval or round window. Usually gets better with rest.
d. Dehiscence of the superior semicircular canal
i. Thin or absent temporal bone over the superior semi-circular canal → episodes of vertigo brought

on by sneezing, coughing, loud noise, together with mild low-frequency hearing loss and
hypersensitivity to bone-conducted sounds (even eyeball movement!)
ii. Surgery if really bad, otherwise conservative management
e. Vestibular paroxysmia
i. Vestibular nerve compression or irritation → brief episodes (seconds-minutes) of vertigo with

hearing loss, hyperacusis, or tinnitus.

ii. Tx = carbamazepine (like TG neuralgia)
3. Single episode
a. Acute labyrinthitis -
i. Sudden or subacute onset of severe vertigo, nausea, vomiting, imbalance, sometimes with
hearing loss and tinnitus.
ii. Associated with bacterial and viral infection
b. Acute idiopathic unilateral peripheral vestibulopathy = acute vestibular syndrome = vestibular
neuritis

30
 i. Intense vertigo that is worse when head moves, but still present at rest. Nausea and vomiting.
Normal hearing!
ii. Presumed to be viral or post viral, associated with HSV1

Disequilibrium
Involves visual, proprioceptive, and vestibular pathways. People with proprioceptive or vestibular impairment especially rely
on vision → Romberg is a useful screen.

CHAPTER 15: BACK PAIN AND NECK PAIN

Emergencies
1. Get an urgent MRI if rapidly progressive damage to the spinal cord or multiple nerve roots - could be metastasis,
epidural abscess, primary tumor, hematoma, acute disc herniation
2. Get an MRI in person with history of cancer who now has back pain
a. If metastasis is compressing the cord - give high dose steroids, do decompression surgery, then
radiation. If not compressing the cord or there are multiple lesions, then just do radiation.

Non-urgent indications for surgery

1. Spinal cord compression
2. Compression of 1+ nerve roots → persistent motor deficits or abnormal control of bladder or bowel
3. Lumbar spinal stenosis
4. Mass lesions of unknown etiology
5. Pain refractory to all nonsurgical treatment, if pain corresponds to structural lesion distribution

Musculoskeletal Pain
Diffuse - no signs or symptoms to suggest damage to individual nerve roots. Generally caused by excessive stress on
bones, muscles, and CT. Usually improves with time. Continue with ordinary activities - not bed rest! Treat with PT, heat,
US, pain meds, TCAs, gabapentin, etc.

Disc herniation
● Generally:
○ Risk of neuro impairment is greatest with midline herniation.
○ Degree of pain/neuro impairment seems to be related to inflammation - can have symptoms resolve while
imaging stays the same, of have imaging showing herniation with no symptoms
○ Tx: maybe bed rest, epidural injections, surgery. Surgery helps people to recover faster, but doesn’t affect
long term outcomes
● Lumbosacral herniation
○ Sudden pain in the low back during heavy lifting, later radiates to one lower extremity in the L5 or S1
distribution. May have weakness and hyporeflexia in the affected distribution
■ L5-S1 herniation affects S1 distribution
○ Worse when sitting, worse with cough, sneezing, or straining during bowel movements
○ Straight leg sign usually present - pain with passive flexion of the hip while knee is extended. Worsened
by dorsiflexion of the ankle, relieved by knee flexion. Sensitive but not specific.
○ Central herniation - can compress the cauda equina → diffuse LE weakness and numbness, loss of bladder
and bowel control
● Cervical disc herniation
○ Rapid head turning, but sometimes no obvious cause. Pain conforms to the distribution of one root - goes
into the arm or medial scapula. May also have weakness, atrophy, and hyporeflexia. May have little or no
pain!
○ Central herniation - can press on the spinal cord, affecting function of the LEs, bladder, or bowels.
31
Spinal stenosis
● Growth of bones → narrowing of canal
● Cervical stenosis - looks like disc herniation, same management
● Lumbar stenosis → neurogenic claudication = pain in the low back or legs provoked by standing and relieved
by bending over or sitting down. Pain is related to position, not exertion - walking is no worse than standing, riding
a bike may be okay. Usually requires surgery

CHAPTER 16: INCONTINENCE

Background
Enough urine volume → triggering of micturition reflex, which is normally inhibited until a convenient time. Pontine
micturition center coordinates the reflex
1. contract detrusor muscle - parasympathetic S2-S4. Can inhibit with anticholinergic meds (oxybutinin)
2. relax bladder neck internal sphincter - decrease sympathetic input from T10-L2
3. relax external sphincter
Voluntary sphincter relaxation is S2-S4.

Urologic causes
1. Stress Incontinence
a. Weakness of pelvic floor muscles → urethra herniates through pelvic floor → creates pressure gradient in

the abdomen/pelvis vs. distal urethra.

b. Leak small amounts of urine when abdominal pressure increases
c. More common in women than men, unless men have surgerical injury
d. Tx: pelvic floor exercises, pessaries, surgery
2. Functional incontinence - can’t make it to the bathroom in time because of mobility or cognitive issues
3. Damaged urinary sphincter - can’t maintain tight seal. Can be neurologic or from surgery or trauma

Neurologic causes
1. UMN problem → spastic bladder = urge incontinence. Get sudden, uncontrollable urge to void, with complete
emptying of bladder
2. LMD problem → flaccid bladder = overflow incontinence. Typical of diabetic polyneuropathy, cauda equina
syndrome.
a. Can also get overflow incontinence with UMN below the pontine micturition center - get spastic
bladder and destrusor-external sphincter dyssynergia, where bladder contracts against a closed
sphincter, often causing ureteral reflux.

CHAPTER 17: PEDIATRIC NEUROLOGY

Hypotonic Infants
Babies have hypotonia from lesions ANYWHERE in the motor pathway, not just with LMN lesions. If the problem is UMN,
eventually spasticity will develop.
● Peripheral lesion: severe weakness > hypotonia, reduced/absent reflexes
● Spinal lesion or higher: hypotonia >> weakness, brisk reflexes

Spinal Muscular Atrophies: Hereditary LMN disease b/c of mutation in Survival Motor Neuron 1 gene (SMN1)
● SMA 1: Acute, fulminant form - begins at birth or within the first six months of life. Marked
reduction/disappearance of fetal movements during the last months of pregnancy. No tremor.

32
 ● SMA2: begins between 6-18 months. Postural or kinetic tremor is common.
● SMA3: begins 5-15 years. Postural or kinetic tremor is common.

Infant botulism
Constipation is typical

Developmental delay and regression

One time events (trauma, etc) can halt or slow forward progress, but does not usually result in backward movement.
Regression implies an ongoing disease process.

Cerebral palsy
Nonpgrogressive (static) abnormality of control of movement/posture due to CNS dysfunction that is prenatal and not
degenerative.

Widespread cognitive delay without motor involvement: autism, uncontrolled general seizures, ADHD

Global developmental delay affecting motor, language, cognition, social interaction: usually infectious, toxic, or hypoxic-
ischemic injury. Less often - genetic.
● Most common inherited form: Fragile X syndrome. Long triplet repeat → defective FMRP
○ Normally FMRP associates with RNA-inducing silencing complex to degrade proteins in the dendrites.
When that doesn’t happen, proteins are continuously made regardless of synaptic activity.
○ Get MR, autism, and ADHD, characteristic facial features, joint abnormalities, and impaired motor skills.
○ Short triplet repeats → Fragile X tremor ataxia syndrome. The FMRP gains function and
sequesters/perturbes nuclear proteins

Paroxysmal symptoms
Most common cause of sudden and recurrent focal symptoms = seizures and migraines. Kids don’t get strokes as much.
Others: breath holding spells, night terrors, narcolepsy/cataplexy, tics, syncope, psychogenic spells, benign paroxysmal
vertigo

1. Headaches
Cyclical vomiting (alternating n/v) and periodic abdominal pain are two variants of migraine seen almost exclusively in
kids. They often overlap. May have no headache! But 75% will get headache later in life, and cyclical vomiting responds to
typical migraine meds.

2. Seizures
● In babies, immature nervous system doesn’t propagate epileptic charges as in adults → classic tonic-clonic
convulsions are rare. Generally get brief episodes of hypertonia, atonia, or local tonic-clonic movements.
● Others: infantile spasms, benign, rolandic epilepsy

3. Breath holding spells: small kids often hold breath while crying → can cause seizure. Usually start 6-18 months, disappear

by 5-6 yrs. Just educate and reassure, no treatment

4. Benign paroxysmal vertigo: Vertigo, vomiting, nystagmus, diffuse pallor. Usually few minutes, can be hours. May fall,
but no loss of consciousness. Onset 1-4 years. Become less severe/frequent and either disappear or replaced with
migraine

5. Tics: Might change the tic behaviors over time, can suppress voluntarily, no impaired awareness (contrast seizure)
● Can be brought on by hyperthyroidism - weight loss, change in exercise tolerance, behavioral changes
33
 ● Family history of tics, ADD, or OCD → suggests tourettes
● Treatment: Pimozide, fluphenazine, haloperiodl, clonidine, guanfacine

Abnormal Gait
If symmetric→ spasticity, weakness, or ataxia are most common

1. Ataxia: Most often occurs with infection or nonspecfic febrile illness.

● VZV is the most common - most often 1-5 years old. Sudden truncal ataxia → deteriorating gait. ½ have
nystagmus, tremors in limbs, head, trunk. Symptoms usually resolve in several months, but sometimes have
permanent residual effects. Can also have symptoms after live vaccine.
● Neuroblastoma → paraneoplastic syndrome with ataxia, myoclonus, and opsoclonus (irregular,
multidirectional eye movements)
● Toxins - antihistamines! heavy metals, mercury, AEDs, etc.
● Posterior fossa tumors - can have acute ataxia, but progressive more likely
● Friedrich’s, ataxia telangectasia, etc.

CHAPTER 18: GERIATRIC NEUROLOGY

Mental status changes

1. Difficulty thinking of words but relative sparing of vocabulary,
2. General slowing of central processes, and
3. Decline in recent memory and ability to learn new info with relative sparing of remote memory

Cranial nerve changes:

1. Impaired upward gaze b/c of supranuclear problems (VOR is fine)
2. Jerky or saccadic pursuit from impaired smooth pursuit
3. Ptosis is common - muscle and skin stretches out

Motor
1. Can’t stand on one leg with eyes closed
2. Decreased muscle bulk
3. Decreased coordination

Reflexes - decreased DTRs, so 20% no longer have detectable ankle reflexes. Positive Babinski is never normal.

Sensation - lose vibration at the toes, also position/light touch/and pain deteriorate to a lesser degree

Gait disturbances: Most common = cervical stenosis, polyneuropathy, mechanical problems (fractures)

Miscellaneous

Adrenal leukodystrophy
● X-linked condition → hits boys. Most common peroxismal disorder. Can’t transport Very Long Chain FA’s into the
peroxisomes for breakdown → VLFAs build up and interfere with leydig cells of the testes, CNS, and adrenal
cortex.
● Manifests with cognitive and behavioral problems (often dx as ADHD, will respond to ritalin) and/or seizures.
Total disability within 6 months to 2 years. Progressive weakness, blindness, death in 5-10 years.

34
Krabbe disease = globoid cell leukodystrophy
● Rare AR disorder, deficiency in galactocerebrosidase. Enables liposomes to hydrolize galactolipids formed
during white matter myelination. End up with globoid cells and decreased myelin in PNS and CNS.
Accumulate psychosine and galactocerebroside
● Usually presents by 6 months, but 10% in adulthood. Get peripheral motor sensory neuropathy.
○ Infant onset: irritability, dev delay or regression, spasticity, axial hypotonia, no reflexes, optic atrophy,
microcephaly, seizures. Death by 2 years
○ Juvenile: weakness, loss of skills, vision loss. Death 2-7 years later
○ Adult: Loss of manual dexterity, burning paresthesias in the extremities, weakness, predominantly
peripheral motor and sensory loss with scoliosis and muscle atrophy. Sometimes intellectual deterioration

Metachromatic leukodystrophy
● Lysosomal storage disease → deficient arylsulfatase A → cerebroside sulfate accumulation → CNS and PNS
demyelination
● Infantile, juvenile, or adult onset

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