Cohen: demyelinating, dizziness, trauma, mvmt disorders, NMJ diseases

Question 1

multiple sclerosis epidemiology

Answer 1

• most common cause of neurologic disability in young adults except for trauma
• mean age of attack is 29 years (rare <10 y/o, over age 55 )
• 70% women
• more common in northern hemisphere (first 15 years of life) - most common in whites/europeans

genetics: non mendelian, sex linked and not very familial

Question 2

signs of MS

Answer 2

may eventually have visual loss, diplopia, dysarthria, ataxia, paralysis, sensory loss, bladder and sexual dysfunction, and loss of cognitive abilities

sx during first attack:

1. visual loss/double vision - 49%
2. weakness - 42%
3. pareshtesias - 41%
4. incoordination
5. urinary problems

NOTE: depression is often seen even before they develop MS, often seen in HS

** optic neuritis! (can also be seen outside of MS)

Question 3

Pathology of MS?

Answer 3

• • Primarily a disease of MYELIN DESTRUCTION in oligodendrocytes, but eventually AXONS are destroyed, too in severe cases –> loss of axons correlates best w/ overall disability
• • AI disorder involving T-cell mediated attacks on CNS myelin, with formation of plaques (scars)

Other features:

• inflammation w/out T/B cell involvement
• Abs made that target Ags in myelin

Question 4

four common courses in MS?

Answer 4

1. benign MS: stable with some relapses, no progression
2. relapsing remitting * most common * stable periods, followed by progressive relapse periods
3. secondary chronic progressive: have period of relapsing/remiting followed by quick progression
4. primary progressive: progressive!

Question 5

clinical course of MS?

Answer 5

• variable for every pt!
• 80% relapsing/remitting
• prognosis is very variable: worse when sx begin in late 40’s-50’s
• shortens life expectancy by 5-10 years
• ** A majority will have some permanent impairment of gait, vision or urinary function
• Kurtzke’s Rule: 90% of disability in MS patients occurs within 10 years of initial diagnosis

Question 6

ddx of MS?

Answer 6

multiple attacks in time, and multiple attacks in different locations of the brain

With the help of MRI scans, the diagnosis can sometimes be made after a first known attack:

• MRI may show lesions in OTHER areas which would not cause the current symptoms/signs: i.e., the patient NOW has a clinical cerebellar deficit, but MRI of the cervical cord shows OLD lesions there, also
• Gadolinium enhancement helps reveal a RECENT area of demyelination on MRI scans

Diagnostic if - ** MRI shows: 9+ hyperintense T-2 lesions w/ one or more gadolinium-enchancing lesions, at least one lesion is in cerebellum/brain stem, at least 3 lesions are periventricular

ddx criteria:

• history of TWO or more known attacks Clinically isolated syndromes) in the brain or spinal cord, at TWO or more distinct times
• ‘MULTIPLE IN TIME AND SPACE (location)’

other diagnostic aids?

• Lumbar puncture: OLIGOCLONAL BANDS in >90% of patients eventually (more specific than white matter lesions on MRI)
• IgG bands each specific for one antigen
• Increased levels of myelin basic protein, or IgG index
• Increased WBCs, but always under 100/mmm

Question 7

optic neuritis

Answer 7

injury to optic nerve - results in painful , sudden loss of all or nearly all vision in one eye; painful when moving the eye, due to swelling of the nerve

• Patients lose vision in the middle of the visual field for that eye

Tests:
1. Pupillary reaction is usually lost; Marcus-Gunn pupillary reaction is seen: affected eye results in dilation of both eyes, d/t inability to send info back through CN II

• the inflammation is behind the retina, so examiner may not see anything at first; later the disc may be a lighter shade of yellow: PALLOR

** 1/2 of pts w/ optic neuritis will develop MS!

tx: IV corticosteroids

Question 8

Internuclear opthalmoplegia, INO

Answer 8

• When looking to one side, the ADDUCTING eye cannot reach the medial edge of the eye, and the ABDUCTING eye goes part-way, but has severe nystagmus
• Usually bilateral
• Caused by damage to the MEDIAL LONGITUDINAL FASCICULUS in the brain stem, linking nucleus of CN VI with the contralateral CN III
• Only two causes: multiple sclerosis (prolonged, or permanent impairment), or brain stem stroke (disappears in days)

** test: convergence is unimpaired, but then eyes turned to left the right eye lags and likewise to the right - results in nystagmus as well

Question 9

tx of MS?

Answer 9

… don’t think need to know

1. beta interferons: avenox, betaseron, rebif (tone down B and T cells in spinal cord, making them less likely to release IgG, suppress release of chemokines, block MMPs)
2. Gatiramer Acetate - for r/r MS, acts as a devoy w/ five repeating AA’s seen in CNS - results in immune attack on drug rather than CNS
3. Natalizumab - monoclonal ab which limits entrance of T cells into the CNS through inhibition of crossing the BBB
   * * increased risk of PML and infection w/ JC virus

symptomatic tx:
- corticosteroids, antispasmodics, antidepressants

Question 10

neuromyelitis optica (NMO)

Answer 10

** Optic neuritis and spinal cord demyelination (myelitis) without brain demyelination

• IT IS DEMYELINATING BUT A DISTINCT DISEASE FROM MULTIPLE SCLEROSIS - limited to optic nn. and spinal cord

** spinal cord shows severe damage AT THREE OR MORE LEVELS

• Patients may have respiratory crises when levels extend to C3 or C4, unusual in multiple sclerosis or even infectious myelitis
• CSF slightly abnormal, but there are seldom any oligoclonal bands, even when retested months later
• Involvement of optic nerves may be simultaneous

Pathogenesis:
** Most patients have serum antibodies to aquaphorin channels, in neuronal membranes, which allow passage of WATER

ddx:
1. Demyelination of the cord, extending along at least three vertebral segments, with optic neuritis, but no or very little brain involvement
2. ** Most patients have an antibody specific to NMO; NMO IgG antibody binds to a water channel in membranes, aquaphorin (100% specific for NMO, 70% have this ab)
3. Much better response to immunosuppressants such as azathioprine or prednisone than to interferons

Question 11

how is NMO distinct from MS?

Answer 11

• Wider range of ages, from infants to the very elderly, even in their 90s

Much more extensive demyelination of the spinal cord than that seen in MS, sometimes with large cavities and hemorrhages

Demyelination extends along at least 3 vertebral segments, sometimes the entire cord

Brain is usually uninvolved with few lesions seen on a brain MRI, except the optic nerve(s) and chiasm

Optic neuritis usually unilateral, but more commonly bilateral than in MS, and more severe loss of vision

Lumbar puncture often shows >50 WBC/mmm, and most don’t have oligoclonal bands

More likely to be a monophasic illness than MS, but many NMO cases do recur and progress

Optic neuritis usually occurs within months of myelitis, or even simultaneously

More likely to be seen shortly after an infection than is true of MS

Question 12

Demyelination of the peripheral nervous system

Answer 12

“Guillan Barre syndrome”

• • RAPIDLY worsening paralysis bringing the patient close to death in a few days - causing ascending paralysis
• • Auto-immune attack upon the roots of peripheral and sometimes cranial nerves
• • Usually follows a previous infection in the prior one to three weeks, commonly upper respiratory or gastrointestinal (may be due to Campylobacter jejuni), or surgery, trauma, vaccination, or no prior illness

sx:
- starts w/ paresthesias in hands and feet, sometimes face affecting motor nerves
- progressive weakness, that ascending over 4 weeks or less!
* * Deep tendon reflexes are nearly or completely lost within one week
- Abnormal cardiac function especially arrhythmias, syncope
- Death is generally through inhibition of respiration

outcome of GBS:

• only 5% die from cardiac /resp causes… 90% make full recovery
• younger pts. do better
• sometimes permanent weakness and sometimes paresthesiae and pain in the extremities

Question 13

ddx of GB?

Answer 13

Clinical picture is dramatic, with a rapid essentially motor polyneuropathy

Nerve conduction studies and electromyograms show decreased velocity of conduction and delayed F-waves, which measure conduction in a peripheral nerve to the spinal cord, and then back out again to the hand or foot muscle

Lumbar puncture will become abnormal, but usually this takes one week or more:
**Normal or slight elevation of white blood cells in CSF, but a SIGNIFICANT ELEVATION OF CSF PROTEIN = the classic CELLULAR CHEMICAL DISSOCIATION

Question 14

Chronic Inflammatory Demyelinating Polyneuropathy (CIDP)

Answer 14

A slower form of polyneuropathy, developing over 3 – 6 months, with milder weakness, sometimes more sensory complaints

More likely it is a distinct disease from GBS, rather than a variation

Reflexes are greatly diminsihed, increased CSF protein

Responds to oral corticosteroids, plasma exchange, IVIgG, while GBS does NOT respond to corticosteroids

Question 15

tx GBS?

Answer 15

Two treatments affect the immunoglobulins which seem to cause the disease:

1. PLASMA EXCHANGE: Plasma is filtered with removal of large proteinaceous components, including immunoglobulins; invasive with a central venous catheter, morbidity due to volume changes (wash out all proteins)
2. ** INTRAVENOUS IgG: newer, less invasive, but equally effective; sterile preparation of IgG from healthy volunteers, possibly attacks abnormal IgG causing Guillain-Barre Syndrome

Both treatments are most effective if begun in the first three weeks of the disease

Question 16

dizziness/light-headedness

Answer 16

= sense of altered orientation in space

most common cause is CV: hypotension

Question 17

Vertigo

Answer 17

= more than just spinning - the pts. has misperception of orientation to environ.
- sense of room spinning

most common causes:

1. “Peripheral”: Semicircular canals and utricle, saccule: benign paroxysmal positional vertigo, vestibular neuritis, Meniere’s Disease, trauma
2. “Central”: Brainstem and cerebellar: stroke, hemorrhage, multiple sclerosis, tumors, alcohol, degenerative disorders, migraine

Question 18

Benign Paroxysmal Positional Vertigo: BPPV

Answer 18

“Positional Vertigo” - when get out of bed in AM, they fall!

• Intermittent vertigo lasting less than a minute usually associated with changes in head position, especially looking up or down, “positioning vertigo”
• Often first noticed when GETTING OUT OF BED IN AM
• May cause nausea and vomiting if it is more than a few seconds in duration
• Walking is often partly impaired, but most patients CAN walk across a room, even if they can’t walk a straight line
• Sometimes a recent cold or upper respiratory infection can be recalled, but not always, or a recent trauma near one ear
• Patients get full relief by being still, lying or sitting in a certain position can help
• Typically lasts one to two weeks

Question 19

pathology of BPPV?

Answer 19

Thought to be due to detachment of the otolithic crystals of the maculae of the utricle or saccule detach and float into the posterior semicircular canal

The posterior semicircular canal is the lowest part of the labyrinth

Rapid head movements cause movement of these debris, activating the vestibular nerve, and giving the patient the sensation of vertigo

Question 20

BPPV ddx?

Answer 20

• Patients with BPPV may have had a recent illness or trauma
• No loss of HEARING with the vertigo
• Normal neurological examination except sometimes for prominent nystagmus, but patients are usually able to walk
• In particular, no cerebellar findings
• Happpike-maneuver: pt quickly goes from sitting to laying down with one side of head turned

Question 21

tx of BPPV?

Answer 21

• The Epley Maneuver may be curative, but can also worsen the vertigo

1. meclizine
2. scopolamine patch: anti-cholinergic
3. promethazine: anti-histamine/ anti-emetic
4. diazepam

Question 22

Meniere’s Disease

Answer 22

*** Recurrent attacks over years and often decades, of terrible vertigo, tinnitus(ringing) and a decline in hearing and a sense of fullness or pressure in one ear

*** Ultimately patients have HEARING LOSS

• Attacks are often minutes or hours long, and are separated by weeks or months with no vertigo at all between attacks
• Very debilitating, sudden attacks which completely immobilize patients

Pathology:
= Increased volume of endolymphatic fluid, causing bulging throughout the inner ear “ENDOLYMPHATIC HYDROPS”
- Membranes holding endolymph may rupture during an attack, and spill the potassium-rich liquid into the perilymph, damaging both the vestibular nerve and the cochlear hair cells

tx:
- during attaack meclizine, promethazine, or scopolamine patches can be used
- low salt diet, K+ sparing diuretic
- surgical drainage/repair

Question 23

central causes of dizziness?

Answer 23

• Vertigo arising from the brain, including the cerebellum, due to stroke, hemorrhage, tumors,
• Occasionally from cervical spine disease
• Post-traumatic, sometimes, especially trauma to the temporal lobes, brain stem, cerebellum
• As part of a degenerative disease: Alzheimer’s, Parkinson’s, Creutzfeldt-Jacob
• • Migraine: one of most common causes of intermittent vertigo in YA’s and children

Question 24

acoustic shwannoma

Answer 24

• benign tumor of the vestibular portion of the eighth cranial nerve: also called Vestibular Neuroma or Vestibular Schwannoma
• • Patients are more likely to complain of hearing loss at first, and later vertigo or headache and pressure in one ear
• • Usually a chronic sense of imbalance or vertigo rather than isolated, intermittent attacks of vertigo
• • ROARING TINNITUS becomes constant, sometimes with machine-like noises rather than simple ringing
• Originates close to the brainstem in the internal auditory canal, and may compress the seventh and fifth cranial nerves, and ultimately the brainstem if large enough

tx:
- surgery if significantly large
- gamma knife radiation for smaller tumors

** NOTE: if they are bilateral, then make ddx of Neurofibromatosis II

Question 25

cerebellar sx of disease?

Answer 25

1. Ataxia: Lack of coordination
   - Causes inability to walk with full control of direction, and increased falls in nearly all patients
2. INTENTION TREMOR: actually a loss of direction or an ability to control antagonistic muscles of the shoulder and arm, as the target is being approached:
   - Not like other tremors, since the oscillations can be in multiple planes, and vary in frequency

Question 26

strokes causing vertigo?

Answer 26

• disease of vertebral-basilar system, brainstem strokes (i.e. lateral medullary syndrome), cerebellar strokes

Note: cerebellar strokes are not seen on a head CT for 24 hours, unless hemorrhagic, so patients with cerebellar strokes can be sent home from clinics or hospitals with a potentially fatal condition

• have signs of cerebellar agnormalities often, and walking may be difficult
• h/a and diplopia
• Over 72 hours the size of the infarct will increase, and if the fourth ventricle is closed, patients may develop hydrocephalus and a fatal brainstem herniation

Question 27

what to order w/ LOC imaging?

Answer 27

CT or brain MRI

Question 28

Glasgow coma scale?

Answer 28

1. Minor (Mild): 9 to 13 on the GCS
2. Moderate: 8 to 12
3. Major (Severe): 7 and below

MVE 654 : motor, verbal, eye

Question 29

Cushing’s Reflex

Answer 29

any sudden lesion within the brain, trauma with or without hemorrhage, as well as expansion of a primary or metastatic tumor would cause:

1. Hypertension
2. Bradycardia

(dont correct them rapidly - best to let them run the course unless they are super severe)

Question 30

subdural hematoma

Answer 30

d/t tearing of bridging vv.

• more common and result of less severe trauma
• often seen in elderly w/ atrophy of brain, sometimes no trauma - often d/t falls
• CT shows “crescent shape”
• can be b/l

Chronic vs. acute:

• Considered “acute” if patients are seen within 72 hours of the suspected onset (appears hyperdense - white on CT)
• Considered “chronic” if at patients are seen at least 21 days from suspected onset (appears hypodense - dark on CT)

sx: include headache, confusion, hemiparesis but rarely total hemiplegia, seizures, and cranial nerve III palsies if large

tx:
- if there are deficits or its over 3 mm in thickness it will be drained
- overtime they usually shrink in volume
- hydroma = old, subdural or any other type of hemorrhage
- smaller hematomas: drained through “burr holes”
- larger hematomas: “craniotomy”

Question 31

epidural hematoma

Answer 31

• result severe, life threatening trauma; most pts. have skull fracture as well
• • d/t tear in middle meningeal artery
• compresses the brain more quickly d/t it being under pressure, and there are dural attachments in inner skull which limit the lateral spread!
• lose consciousness immediately or in a few hours
• commonly seen in MVA!!
• • CT shows LENS shape

“Lucid interval”
- lose consciousness, wake for a few hours, then lose consciousness a second time and they die! ie “ talk and die”

tx:
- surgical drainage always req’d - 100% death w/out
- surgeons drill burr holes

Question 32

Concussion

Answer 32

defined as “Head trauma producing a reversible decline in brain function, even without loss of consciousness”

• athletes should be removed and give 1-2 weeks recovery
• if suffered LOC, or persistent h/a - need a HEAD CT IMMEDIATELY!!!
• Some will develop a POST CONCUSSIVE SYNDROME of persistent headache, light headedness more than vertigo, depression, poor concentration, and irritability for weeks or months, which may be resistant to all forms of treatment

Question 33

Chronic Traumatic Encephalopathy (CTE)

Answer 33

• an irreversible brain disease cause by multiple “minor” head injuries including concussions
• see accumulation of Tau proteins!!!
• • patients are nearly all former athletes, especially professional football and hockey players, and boxers, or military veterans
• described as “punch drunk” - dysarthria, mental slowness, poor memory, and difficulty walking
• develop worsening dementia in a decade

** lots of pych problems first!

Levels of CTE:

• Early symptoms include irritability, easy anger, aggression, impulsivity, sometimes violent behavior, memory loss and inattention
• Ultimately a severe dementing illness, with poor judgement, lack of insight, inability to manage ones affairs, loss of language skills
• similar to FTD, sometimes look like they could have PD or ALS
• TX is best avoided!

Question 34

pathology of CTE

Answer 34

• severe atrophy of the brain, with widened sulci and large ventricles
• septum pellucidum between the two lateral ventricles is often damaged, as is the corpus callosum
• • accumulation of phosphorlyated TAU protein in frontal and temporal lobes **
• often found at bottom of sulci
• tau is also seen in AD
• no amyloid plaques
• Phosphorylated tau may undergo a conformational change and become toxic to neurons, leading to biochemical cascades and apoptosis

Question 35

four cardinal features of Parkinson’s Disease

Answer 35

Four Cardinal Features:

1. Resting tremor, usually beginning in one hand
   - oscillatory, to-and-fro, rhythmic, biphasic (slower than physio tremor)
   - 4-7 hertz frequency, may spread to head, jaws, leg
2. Bradykinesia, a slowness of movement, in initiating and executing movements, even in spontaneous facial expressions (stare)
   - “reptilian” or “masked” look w/ decreased rate of blinking
   - hard to swallow –> drooling
3. Dysequilibrium, or instability of gait and posture, leading to a higher risk of falls
   - fall backwards (retropulsion) when start walking
   - festination gait: try to “catch-up” w/ themselves, walk faster and faster
   - lack of arm swinging
4. Rigidity, especially later in the course of the illness
   - cramps, esp. in shoulders
   - “racheting”

(occasionally ddx made from just #1, but ideally have 3/4)

• there is no palsy or weakness
• eventual dementia

“kinesis paradoxica” - Occasionally under duresss, patients may walk or speak briefly with greater speed

Question 36

Other sx and signs of PD?

Answer 36

Sleep disorders, such as insomnia or REM Behavior Disorder

Loss of sense of smell

Autonomic problems, such as impotence, incontinence, hypotension

Cramps, pains especially in the back and shoulders

Depression, loss of usually activities, sometimes an early dementia

Smaller, incomprehensible handwriting

Loss of power of voice, with monotonous and hurried speech

Question 37

pathology of PD?

Answer 37

loss of substantia nigra –> loss of dopamine projection to striatum (caudate and putamen)
- futhermore see loss of other cells in brainstem, thalamus, cerebral hemispheres and autonomic ganglia

• see “Lewy bodies” - fibrils made of alpha-synuclein - that accumultate and cause degeneration, especially in the substantia nigra

** this is a clinical ddx - not yet seen w/ MRI

Question 38

Lewy Bodies

Answer 38

• Eosinophilic structures in the cytoplasm of neurons, especially in the substantia nigra, but in multiple other locations in the brains of Parkinson’s patients
• May be seen in the absence of Parkinson’s disease, including Lewy Body Disorder, or apparent Alzheimer’s Disease
• Contain increased amounts of alpha-synuclein
• Synuclein is a protein which helps facilitate the movement of synaptic vesicles to the end of the axon

Question 39

genetics of PD?

Answer 39

only 10% are herditary - usually present at younger ages

Some “PARK” genes are associated with Parkinson’s, in some families

PARK1 – PARK 11

A parkin protein has been discovered, of unknown function

Question 40

epidemiology of PD?

Answer 40

• Peak age of incidence 55 – 59 years, especially in the range of 40 – 70
• The older the age of onset, in general, the more rapid the deterioration
• higher in men, in those that live in rural areas, and those that don’t smoke/consume caffeine

** Approximately 50% of Parkinson’s Disease patient will die within @ 15 years

Question 41

tx of PD?

Answer 41

1. Dopamine agonist
   - Injection or oral intake of dopamine not helpful: dopamine DOES NOT cross the blood brain barrier
   - Levodopa DOES cross the BBB, and then it is converted to dopamine
   - “Levodopa/carbidopa” (sinemet) - most commonly prescribed** can cause nausea, hypotension, nightmares, dyskinesias, psychosis
   - effect may wear off in 5-10 years
2. Other D2 receptor agonists: Pramipaxole, ropinirole: used in younger pts, less dyskinesias, however not as effective.
   - may cause hypoTN, and behavioral changes, psychosis and hallucinations are more common
3. Amantadine: increases dopa release - as well as anticholinergic - loses effectiveness quickly
4. Monoamine oxidase and COMT: prolong the benefits of levodpoa by limiting degredation - help alleviate sx

Surgey for PD: surgical cuts or strong stimulation of the globus pallidus not super effective

• • DEEP BRAIN STIMULATION: of subthalamic nuclei is very effective - they lose function and no “misinformation” is given to the thalmus
• electrodes placed in skull

Question 42

psychiatric problems seen in PD?

Answer 42

1. DEMENTIA certainly does occur in PD, and is often a sign that patients are in their last years of life
   - Drugs for Alzheimer’s Disease can be helpful, including rivastigmine, an inhibitor of acetylcholine esterase in the brain
2. DEPRESSION is very common, right from the start, but is treatable
3. PSYCHOSIS is troubling, including violent/aggressive behavior

Question 43

drug-induced parkinsonism

Answer 43

Much less common in the past with tranquilizers such as phenothiazines (Mellaril, Prolixin, etc) and butyrophenones (haloperidol)

Less common with the “Atypical antipsychotics” such as olanzapine (Zyprexa), clozapine (Clozaril), or quetiapine (Seroquel) used much more than the older antipsychotics

Usually without the resting tremor, but with bradykinesia and stiffness and dysequilibrium

Somewhat responsive to anti-cholinergic drugs

***Perhaps most commonly found today with phenothiazines for nausea, reflux and gastroparesis, especially metoclopramide (Reglan)and promethazine (Phenergan)

Weeks might be needed for elimination of Parkinsonism after the offending drug is stopped

Question 44

Progressive Supranuclear Palsy- PSP

Answer 44

“pt. looks frightened, with extended posture, and very off balance!

• • Usually no tremor but severe dysequilibrium, FALLS ARE SEEN EARLY, AS IS CHOKING
• • Eventually there is a loss of speech, moderate dementia
• • PROGESSIVE LOSS OF EXTRA OCULAR MOVEMENTS, starting with vertical eye movements, then horizontal ones
• • Dystonic extension of the neck, puzzled look on face with a furrowed brow
• • Blink more frequently, but eyes seem prominent with fearful expression
• unable to swallow/talk w/in few years — usually die from aspiration pneumonia or from a fall

differences from PD and AD:

• NO tremors!
• have bradykinisea, dysequilibruim and falls
• slowly developing dementia, slower than AD
• live half as long as PD! this is worse :/

Pathology:
- degeneration of the entire brain stem, especially of the midbrain

Question 45

PSP tx?

Answer 45

No completely effective treatment exists for this degenerative disease

However, at least a quarter of the patients do respond to the drugs for Parkinson’s Disease, such as carbidopa/levodopa, and dopaminergic drugs

Question 46

Essential tremor

Answer 46

= “action tremor”

• the most common movement disorder seen in clinical practice
• 4-8 hertz or faster
• Symmetric in nearly all cases, mostly arms, sometimes the head, voice, but much less common in the legs
• possibly AD inheritence (80% have family hx)
• May be evident in childhood, and especially by the twenties, with some progression in most cases
• More rapidly disabling when it first appears at an elderly age
• Probably due to disease in the thalamus

PE:

• look at outstretched hands, or patient’s ability to flex arms and not quite touch the opposing fingers or the nose
• must rule out hyperTH and PD

Question 47

tx of essential tremor

Answer 47

Putting weights on the wrists may “dampen” the tremor

Patients should use heavier utensils

drinking alcohol may work for an hour or two to suppress essntial tumor

1. PROPANOLOL is commonly used, and helps most of the patients: not for asthmatics or patients with heart block
2. PRIMIDONE is also very helpful, but the first dose can cause severe confusion and disorientation

Question 48

Tics

Answer 48

Rapid movements (motor tics) or sounds (vocal tics)

Usually simple, as with sniffing, grunting, blinking, clearing the throat, protruding the chin, wrinkling the face, shrugging the shoulders

But sometimes more complicated movements of the limbs

Usually the patient is aware of tics, and can suppress them for a short time

Often develop in children, and may fade with time

Never a serious pathology, although parents may be worried; CNS imaging not indicated unless other findings

Question 49

Tourette’s syndrome

Answer 49

• ** combination of BOTH motor tics and vocal tics, starting before age 21
• Mostly tics of the head and shoulders
• Grunting, sniffing sounds, echolalia, and rarely obscenities
• Usually does not fade away with adolescence
• Many patients also have obsessive-compulsive disorder , and less often, depression

Pathology:

• derangement of dpoa at synapses is possible
• associated w/ OCD, and ADHD

tx?
- haloperidol or other D2 blockers, newer antipsychotics or clonidine

Question 50

Chorea

Answer 50

= irregular and variable mvmt disorder thats smooth and “dance like” writhing

** seen often in HD!

Less common causes:

1. Sydenham chorea: (St Vitus’ Dance) from untreated Group A streptococcal infections
   
   2. Rarely seen any more during pregnancy or from high dose oral contraceptives
   3. Can be hereditary in some infants, who are otherwise healthy

Question 51

Huntington Disease

Answer 51

• AD inheritence of trinucleotide CAG repeats –> increased Huntingtin gene product causes destruction of caudate and putamen (striatum)

begin expressing itself at almost any age, but most typically begins in the 40s and 50s

Progressive neurological and psychiatric disorder of the basal ganglia causing an incapacitating and fatal triad:

1. Movement disorder: including chorea, but also tremors, jerks. Clumsiness, “fidgetiness”
2. Cognitive loss: dementia
3. Psychiatric: agitation, depression, psychosis

** HD patients have a rapid downhill course, and often die in institutions, from suicide, infections or falls

Question 52

tx of HD?

Answer 52

• The chorea can be limited by dopaminergic blockers, which are also antipsychotics, and therefore control the agitation of patients
• These drugs cause sedation, hypotension and after years tardive dyskinesia: another movement disorder

** more effective treatment is now available for the chorea and other movements: TETRABENAZINE

Question 53

restless leg syndrome

Answer 53

• pts can’t stop moving or “kicking” their legs
• ddx. in 5% of middle aged and eldery people
• The patients have a painful, disturbing, “creepy, crawly” sensations deep inside both legs which can be partly relieved by continuous movement of the legs
• pts. “kick” in the night time
• Most patients have the onset as they approach bedtime, and it always interferes with the onset of sleep
• Other patients have this feeling continuously, or starting in the afternoon

Pathology:

• Nothing definitive has been found on MRIs, but autopsies do show reductions of total iron in the brain, especially the substantia nigra
• Patients do have reduced dopaminergic activity in the brainstem and basal ganglia, and may have reduced activity of tyrosine hydroxylase, which requires iron as a cofactor

Question 54

tx of RLS?

Answer 54

1. Dopamingeric drugs for PD:
   - Pramipexole seems more effective than Ropinirole
   - Levodopa/carbidopa may help but the benefit wears off quickly
2. Oral Iron supplements
3. Benzodiazepines, opiods,

Question 55

myasthenia gravis

Answer 55

• “weakening of muscle”

Pathology: immune mediated DESTRUCTION of AChR’s (more than just blocking)

• • thymic tumors present in 10-15%: thymomas
• • hyperplasia in 70% of thymus

Presentation:

1. increasing weakness over mos, but may present suddenly w/ diplopia or loss of speech or diff. swallowing
   - most pts. develop ptosis, diplopia + inability close eyes completely
2. fatiguing weakness of speech and swallowing
   - power of voice decreases, chewing and swallowing become more difficult
   - some. pts may have mm. weakness of limbs

Epidemiology:

• young women (20-30) OR older men (50-70)
• common w/ other AI disease - i.e SLE

Course of MG:

• if only have ocular sx for 2 years its unlikely to spread
• • more rarely have myasthenic crisis: severe impairment of swallowing, resp. impairment, aspiration pneumonia, require intubation

Question 56

ddx of MG?

Answer 56

• combo of b/l ptosis (often worse in one eye), extra-ocular palsies, weak voice, difficult w/ swallowing
• pts. often stronger in morning

** NO changes in reflexes, NO sensory changes, NO cerebellar involvement, NO ANS effects

ddx aids:

• Circulating antibodies to skeletal muscles in perhaps 80 – 90% of patients with generalized myasthenia
• Anti-striated muscle antibodies are more commonly positive in patients who have a thymoma than in patients who do not have a thymoma
• Nerve conduction studies show a DECREMENTAL RESPONSE
• CT or MRI of the chest to look for a thymoma

Question 57

Tensilon test

Answer 57

Tensilon (edrophonium) is a short-acting cholinesterase inhibitor, which allows acetylcholine to last longer at the NMJ (nicotinic as well as muscarinic), and therefore briefly overcome myasthenia gravis

Atropine, an anti-muscarinic, is first injected to limit bradycardia from muscarinic receptors (d/t ACH effecting all synapses)

Then 1-2 mg of Tensilon is given IV as a test

If no problems, up to 10 mg of Tensilon is given; maximum effect is seen in 1 to 5 minutes

Question 58

tx of MG?

Answer 58

1. Generally start with an oral cholinesterase inhibitor, such as pyridostigmine (Mestinon) 60mg, twice a day going slowly up to four or five times a day

Adverse effects: intestinal cramping, diarrhea, nausea, bradycardia, sweating

2. Many patients will also need corticosteroids, such as Prednisone

Question 59

tx of severe MG?

Answer 59

respond to plasmapheresis, which removes many of the patient’s own immunoglobulins

May also respond to intravenous IgG (IVIG)

Question 60

Amyotrophic Lateral Sclerosis clinical features

Answer 60

• • disease of upper and lower motor neurons, so increasing weakness is found in patients, often asymmetric (cranial nn, ventral roots, cortex, all atrophy)
• Predilection for certain muscles: the forearms and hands, tongue, larynx, pharynx, muscles of facial expression, lower extremity, respiratory muscles at the end
• • often NO involvement of extraocular mm. **

Early features:
- dysarthria (motor speech disorder), loss of hand fn, weak shoulder, foot drop, cramps, exercise intolerance, resp. failure, cognitive impairment

**Weakness, fasciculations, atrophy, yet increased deep tendon reflexes + babinski’s

ALS cognitive decline: (10% of pts)

• similar to frontotemporal problem - apathetic, impulsive, limiting in speech content as well as production, depressed, lacking in initiative
• labile and quickly changing moods (“pseudobulbar effect”) d/t diffuse brainstem disease

Question 61

pathology of ALS

Answer 61

Gradual cell death of both upper motor neurons and lower motor neurons

**Weakness, fasciculations, atrophy, yet increased deep tendon reflexes

• Prominent effects on lower brainstem and cervical spinal cord: speech may be impaired especially early in the course;
• Upper motor neurons: motor (frontal) cortex, via corticospinal tracts, to all levels of the brain stem and spinal cord
• Lower motor neurons: anterior horn of spinal cord to skeletal muscles

Question 62

Course of ALS?

Answer 62

Four known variations of the disease

1. Bulbar (brainstem) only
2. Upper motor neuron only
3. Lower motor neuron only
4. Upper and lower motor neurons simultaneously involved; the most common form of ALS

Prognosis is fatal in nearly all cases, typically within 5 years, especially if bulbar symptoms are prominent

Question 63

ddx of ALS?

Answer 63

• Worsening weakness, over months
• Frequent fasciculations, in the tongue as well as involved limbs, and worsening atrophy of the involved muscles
• loss of speech or inability to move the tongue
• fasciculations of the tongue
  Split hand: the lateral side (abductor pollicis brevis, first dorsal interosseous muscles) is usually more impaired than the medial side (abductor digiti minimi)
• No involvement of orbital or extraocular muscles (unlike MG)

ALS Diagnostic Criteria:

• evidence of UMN and LMN loss of fn in at least two levels
• UMN signs: increased DTRs, spasticity, babinski signs
• LMN signs: atrophy, weakness, fasciculation

DDx aids:

• EMG (electromyogram) - shows denervation in at least three limbs
• MRI is clear
• Blood tests show SOD1

Question 64

etiology of ALS?

Answer 64

SOD1: most patients have a mutation in this enzyme, Cu/Zn Superoxide Dismutase, but it may still be functional in ALS patients, clearing free radicals

Oxidative stress may occur, but not necessarily from a mutant form of SOD1

Question 65

tx of ALS?

Answer 65

Riluzole (Rilutek) is the only FDA-approved drug

Riluzole prolongs life, or time to respiratory failure, but only by approximately three months; possible hepatic damage, so serum ALT is monitored