Demyelinating Diseases B&B

Question 1

who is the classic demographic affected by multiple sclerosis? what is the most common presenting symptom?

Answer 1

white women in 20s-30s

autoimmune demyelination in CNS, relapsing/remitting (most commonly), fatigue most common symptom (esp. after hot shower!) - but any neuro symptom is possible!

Question 2

white woman in 20’s-30’s presenting to physician with complain of extreme fatigue, especially after a hot shower… what are you thinking?

Answer 2

multiple sclerosis: autoimmune demyelination in CNS, relapsing/remitting (most commonly), fatigue most common symptom (esp. after hot shower!)

Question 3

multiple sclerosis is often classified as a Type ____ hypersensitivity

Answer 3

Type IV: T cells react to myelin antigens (myelin basic protein), IFN-y recruits macrophages

Question 4

besides fatigue, what are 3 classic symptoms of multiple sclerosis?

Answer 4

1. optic neuritis - pain/ loss of vision
2. MLF (medial longitudinal fasciculus) syndrome - one eye cannot move medially on lateral gaze
3. bladder dysfunction - spastic bladder or overflow incontinence (failure to sense load)

Question 5

what does CSF of multiple sclerosis patients show?

Answer 5

high protein + oligoclonal bands (highly suggestive, greater risk of relapse)

recall MRI is gold standard for diagnosis (see periventricular plaques)

Question 6

describe the pathology and presentation of Guillain-Barré syndrome

Answer 6

acute inflammatory demyelinating radiculopathy (days-weeks): autoimmune destruction of Schwann cells —> ascending muscle weakness (mild/no paresthesias) + autonomic dysfunction

50%+ patients present with facial muscle weakness, high risk of respiratory failure

symptoms resolve weeks-months

Question 7

what are the 2 infections that cause Guillain-Barre?

Answer 7

1. campylobacter jejuni: presents with bloody diarrhea
2. cytomegalovirus: immunosuppressed patient (esp. transplant patients)

acute inflammatory demyelinating radiculopathy (days-weeks): autoimmune destruction of Schwann cells —> ascending muscle weakness (mild/no paresthesias) + autonomic dysfunction

Question 8

pt with recent history of bloody diarrhea OR transplant surgery presenting with rapidly progressive ascending muscle weakness + autonomic dysfunction =

Answer 8

Guillain Barre: classically caused by campylobacter jejuni (bloody diarrhea) or CMV (transplant/immunosuppressed)

Question 9

with what infection is PML associated, and how does it present?

Answer 9

PML = progressive multifocal leukoenceophalopathy: severe demyelinating disease of CNS due to reactivation of latent JC virus in immunocompromised (HIV) patients (CD4 <200)

imaging shows multiple white matter lesions due to destruction of oligodendrocytes (poor prognosis)

causes slow onset encephalopathy - alerted mental status, focal neural deficits

Question 10

when does postinfectious encephalomyelitis occur, and what does histology show?

Answer 10

acute onset of multifocal neurological symptoms with rapid deterioration weeks after infection (varicella, measles) or vaccination (rabies, small pox)

histology shows perivenous inflammatory infiltration

imaging shows dark circles due to demyelination

Question 11

what is the cause and presentation of Charcot-Marie-Tooth disease?

Answer 11

aka hereditary motor and sensory neuropathy (HMSN): progressive peripheral nerve disorder, onset late childhood/adolescence, due to defective production of nerve proteins or myelin

—> bilateral leg muscle wasting (stork-like contour), foot drop, foot deformities (pes cavus), falls/clumsiness

Question 12

young patient with weakness (mostly legs) + severe deformities of lower legs/ feet = which demyelinating disease?

Answer 12

Charcot-Marie-Tooth: aka hereditary motor and sensory neuropathy (HMSN): progressive peripheral nerve disorder, onset late childhood/adolescence, due to defective production of nerve proteins or myelin

may have pes cavus foot deformities or claw hands

Question 13

what is the cause and presentation of metachromatic leukodystrophy?

Answer 13

rare AR lysosomal storage disease due to deficiency of arylsulfatase A —> buildup of sulfatides impairs myelin production (CNS + PNS)

3 forms: late infantile, juvenile, adult

Question 14

rare AR lysosomal storage disease due to deficiency of arylsulfatase A

Answer 14

metachromatic leukodystrophy

—> buildup of sulfatides impairs myelin production (CNS + PNS)

Question 15

Krabbe’s disease

Answer 15

autosomal recessive lysosomal storage disease - deficiency of galactocerebrosidase

buildup of galactocerebroside damages myelin sheath —> presents in infancy with progressive motor/sensory problems, developmental delay, limb spasticity, hypotonia, absent reflexes, microcephaly

Question 16

autosomal recessive lysosomal storage disease causing deficiency of galactocerebrosidase

Answer 16

Krabbe’s disease: buildup of galactocerebroside damages myelin sheath

—> presents in infancy with progressive motor/sensory problems, developmental delay, limb spasticity, hypotonia, absent reflexes, microcephaly

Question 17

3 mo infant presents at wellness appointment and shows signs of developmental delay. PE is significant for microcephaly, absent reflexes, and limb spasticity. CSF shows elevated levels of galactocerebroside. What is the diagnosis?

Answer 17

Krabbe’s disease: autosomal recessive lysosomal storage disease - deficiency of galactocerebrosidase

buildup of galactocerebroside damages myelin sheath —> presents in infancy with progressive motor/sensory problems, developmental delay, limb spasticity, hypotonia, absent reflexes, microcephaly