Myelin Disorders Flashcards
what are the three types of myelin disorders & how are they dfefined?
- hypomyelinating: arrest in myelin production
- dysmyelination: abnormal myelin production
- demyelinating: desctruction of existing myelin
what is the key role of myelin?
- faciliates electrical conduction by
- increasing membrance resistance
- decreasing membrane capacitance
(R and C inversely related)
myelin in the CNS
- is what “kind”?
- made by what cells?
- contains which proteins?
- compact myelin
- made by: oligodendrocytes
- contains:
- PLP (proteolipid protein)
- MBP (myelin basic protein)
myelin in the PNS
- is what “kind” of myelin
- made by what cells
- includes what proteins
- compact myelin
- made by: schwann cells
- contains
- MPZ (myelin protein zero)
- PMP-22 (peripheral myelin protein-22)
which myelin disorders are dysmyelinating diseases?
what does this mean?
= abnormal myelin production
- frontal leukodystrophies
- Alexander’s Disease
- metachromatic leukodystrophy
- posterior leukodystrophys
- Krabbe’s disease
- Adrenoleukodystrophy
alexander’s disease
- what kind of myelination disorder?
- cause?
- presentation?
- dysmeylination disorder - frontal leukodystrophy
- cause: GFAP mutation leading to rosenthal fiber accumulation
- presentation: infant with megalencephaly (enlarged brain)
metachromatic leukodystrophy
- what kind of myelination disorder
- cause
- presentation
- dysmyelination disorder - frontal leukodystrophy
- causse: arysulftase A deficiency leading to cerebroside sulfate accumulation, impairing both
- CNS myelination
- PNS myelination
- presentation:
- juveline onset: development regression + seizures
- adult onset: dementia + peripheral neuropathy + cholecystitis
krabbe’s disease
- what kind of myelination disorder?
- cause
- presentation
- dysmyelination disease
- cause: galactocerebroside B-galactosidase deficiency
- presentation: a lot goes wrong
adrenoleukodystrophy
- what kind of myeliantion disorder
- cause
- presentation
- dysmyelination disease - posteiror leukodystrophy
- cause: adrenal neuropathy -> high plasma VLCFAS
- presentation: adrenal insufficiency, +
- childhood onset: behavior issues
- adult onset: spasticity
which type of dysmyelination disorders leads to infants with megalencephaly?
Alexander’s Disease
(frontal leukodystrophy)
which dysmyelination disease involves cerebroside sulfate accumulation?
metachromatic leukodystrophy
frontal leukodystrophy
which dysmyelination disorder can be diagnosed with high plasma VLCFAs?
adrenoluekodystrophy
posterior leukodystrophy
list the mutation associated with each dysmyelination disease
- Alexanders: GFAP
- Metachromatic leukodstrophy: arylsulfatase A
- Krabbe: galacterocerbrosidase B-galactosidase
multiple sclerosis - pathogenesis
autoreactive lymphocytes
- inflammatory response of Th-1, Th-17 & B-cells, causing
- myelin dstruction + axonal destruction of the
- gray + white matter
what are the major risk factors for MS?
- Epstein Barr Virtus
- Vit-D deficiency / low sunlight
- smoking
- adolescent obesity
- high amplitudes
explain the role of amplitude in pre-disposition to MS
- geographic affect on MS risk depends on age of moving
- moving before 15 yo: adopt risks of new location (high or low altitude)
- moving after 15 yo: adopt risks of initial location (high or low altidude)
high altitude = higher MS risk
what are the three categorizations of MS based on dissemination in time?
- relapsing remitting (m/c): initial episode -> followed by relapses & remission
- secondary progressive: initial episode -> remission -> gradual worsening
- primary progressive: no initial episode -> gradual worsening
what is a clinically isolated syndrome (CIS)?
what are the clinical actively syndromes seen in MS?
definition: a solitary demylinating event lasting at least 24 hours
- optic neuritis
- brainstem
- cerebellar
- transverse myelitis
what is a radiologicaly isolated syndrome (RIS)?
an abnormal MRI in the absence of clinical symptoms
tends to preceed CIS
what are the common ocular manifesations of MS?
- optic neuritis
- optic atrophy (following optic neuritis)
- internuclear opahtlmoplegia
optic neuritis in MS
- demographics affected
- clinical presentation
- findings on work-up
- demographic: F, 30s-40s
- clinical presentation:
-
rapid monocular vision loss of
- depth perception
- color saturation
- pain on extraocular movement
-
rapid monocular vision loss of
- work-up:
- PE:
- significant edema
- normal fundus
- nosplinter hemorrhages
- MRI: < 50% enhancement of optic nerve length
- PE:
describe the type of vision loss caused by optic neuritis in MS
- rapid onset
- monocular
- decreasing perception of:
- depth
- saturation
what two key ocular manifestations are NOT seen in optic neuritis?
- an abnormal fundus
- splinter hemorrhages
identify
optic atrophy
MS
internuclear opathalmolplegia in MS
- presentation
- mechanism
- presentation: inability to adduct the eye (unilateral or bilateral)
- cause: injury to MLF
- carries fibers to oculomotor nucleus (CNIII), which
- innervates the ipsilateral medial rectus, which
- adducts ipsilateral eye
list the risk of MS development based on clinical findings
- low risk: CIS + normal brain MRI
- medium risk: RIS w/ either spinal cord lesions OR oligoclonal bands
- high risk: either
- CIS + abnormal MRI (2+ lesions)
- smokers
- low Vit-D levels
- < 30 yrs old
- very high risk: CIS + abnormal MRI involving new disease activity
pts with at what risk for developing MS are treated?
high risk and very high risk
(high risk tx with disease modifying therapy)
which factors are associated with an aggresive presentation of MS?
- male, AA, onset > 40 years
- risk factors for eveloping MS:
- obesity
- smoking
- Vit D
- risk factors for eveloping MS:
what set of criteria must be met to make a diagnosis of MS?
McDonald Criteria
- dissemination in time: more than one attack
- dissemination in space: a lesion that
- is at least 3mm in the long axis
- at least 2 of the following areas:
- cortical
- juxtacortical
- paraventircal
- spinal cord: hemicord transverse myelitis
describes the lesions (plaques) that characterize multiple sclerosis
- > 3mm lesions
- cortical / juxtacortical - ovoid
- paraventricular - perpendicular, flame shaped
- tranverse myelitis (spinal)
- involves only one vertebral segment
- hemicord & NOT in central canal
MS treatment
what are the roles of DMTs (disease modifying treatments)?
- NOT for symptom improvement
- serve to delay progression from CIS to MS
MS treatment
what is the management for patients who refuse DMTs?
annual MRIs for 5 years
MS treatment
which DMTs increase PML risk?
- natalizumab
- fingolimod
- rituximab
- ocreliazumab
- dimethyl fumarate
DO follow no rules
MS treatment
when shoud switching therapies be considered?
- 1 or more relapses
- 1 year of worsening diasability
- 2 or more new MRI lesions
MS treatment
which MS patients should NOT be treated?
- CIS with normal MRIs [low risk]
- CIS/MIS with NEDA [no evidence of disease activity] while off therapy for 2 years
MS treatment
treatment for acute flares?
methylprednisone
progressive multifocal leukoencephlopathy (PML)
- definition
- cause
- demographics
- MRI
- treatment:
- definition: potentially fatal demyelination
- cause: JC virus reactivation
- demographics: I/C - HIV, transplants, chemo, natalizumab
- MRI: gray white junction lesions that dont follow vascular territories
- treatment:
- PML: plasma exchange (qod x 5)
- PML IRIS: high dose steroids (IVMP 1g/day x 5)
identify
MS lesions
flame like, perpendicular to ventricles
identify
MS lesions
cortical - ovoid shaped
identify
PML-IRIS
neuromyelitis optica (NMO)
- cause
- presentation
- MRI
- cause: antibodies to aquaporin-4, a water channel on astrocyte foot processes
- presentation:
- binocular optic neuritis (with > 50% optic nerve enhancement)
- area-postrema syndrome: hiccups & N&V
- MRI: large lesions that follow ependymal lines
- brain - including diencephalon
- spinal cord - LETM (longidutinally extensive transverse myelitis)
- affects at least 3 segments
- +/- complete, including central canal
- may involve medulla
identify
neuromyeltis optica (NMO)
lesions in diencephalon
identify
neuromyelitis optica (NMO)
advancing LEMN coinciding with vomitting (area postrema) syndrome
identify
neuromyelitis optica (NMO)
lesions that that are large (here - tumefactive lesions, which are > 2cm) and don’t obey ependymal lines
contrast the ocular presentations of
- MS
- NMO
- MS
- monocular
- optic nerve enhancement < 50%
- NMO
- binocular
- optic nerve enhancement > 50%
contrast the lesions seen in
- MS
- NMO
- MS
- brain: does not follow ependyma - ovoid, flame shaped
- spinal cord (transverse myelitis)
- hemicord
- not including central canal
- one vertebral segment
- NMO
- brain: follows ependyma, often includes diencehpalon, can be large
- spinal cord: (LETM)
- possibly complete
- includes central canal
- multiple vertebral levels -:> possibly up to medulla
compare & contrast NMO based on
- general prevalence
- age of onset
- co-existing autoimmunity
- nature of optic neuritis
- nature of myelitis
- presence of diencephalon syndrome
- presence of dawson’s fingers
- presence of tumefactive lesions
- CSF features
area postrema syndrome
- presents how?
- is part of which syndrome? why?
- presentation: hiccups, nausea & vomitting
- NMO: d/t LETM, which can affect the medulla
MOG antibody disease
- cause
- age of onset
- presentation
- MRI
- cause: myelin oligodendrocyte glycoprotein antibody disease
- age of onset: 25
- presentation: binocular optic neurtiis + significant optic disc edema
- MRI:
- brain: involve gray matter
- spinal cord (transverse mylitis)
- LETM (affects multiple vertebral levels)
- has a predilection for the conus medullaris
- involves central canal - including gray matter
- RARELY RECURRENT.
ADEM
- cause: triggered by inflammation - often viral infection
- age of onset: children m/c (age 5-8 yo)
- presentation: demylination + ENCEPHALOPATHY
- MRI:
- brain: involve gray matter (basal ganglia)
- spinal cord (myelitis): rarely seen
how does tranverse myelitis
- present clinically?
- appear on MRI in each demylination disease?
- present: flaccid paralysis with decreased reflexes
- lesions on MRI:
- MS: single vertebral level, hemicord, no central canal
- NMO: LETM that can include medulla, central canal involved
- MOG: LETM w/ conus medullaris, central canal involved (up to gray matter), rarely recurrent
- ADEM: spinal cord involvement rare
which demylination disease can affect the gray matter of the brain?
explain
- ADEM (basal ganglia involvement)
- MOG antibody disease
which demylenation disease commonly presents with optic disc edema?
MOG antibody disease
can occur in MS, but is insignificant
which demylination disease presents with spinal cord lesions that have a predilection for the conus medularis?
MOG antibody disease
which demylinating disease presents with LETM that typically does not recurr?
MOG antibody disease
list the m/c age group affected by each demylinating disease
- MS: 30-50, rarely > 60
- NMO: > 40, often > 60
- ADEM: children m/c
- MOG antibody disease: ~25
