Demyelinating Diseases Flashcards
Are demyelinating diseases inherited or acquired?
Acquired
What happens in demyelinating diseases?
Damage to myelin with relative preservation of axons
What is multiple sclerosis?
Episodes of neurological deficits that are separated in time & space that affect white matter
- This means that the lesions are in different areas of the CNS and are in different stages of regression
Describe the frequency of relapses, the neurological state, and recovery in MS
- Episodes are of variable duration (weeks, months, years)
- Gradual partial recovery of neuro fxn with steady deterioration over time
- Freq of relapses tend to decrease during the course
What are common neurological S&S of MS?
- Unilateral visual impairment (frequently the initial symptom)
- Optic neuritis (20-50% of people w optic neuritis develop MS)
- Ataxia, nystagmus
- Motor & sensory impairment of trunk & limbs, spasticity, loss of bladder control
Is MS more common in males or females?
How do genetics & environmental factors play a role?
What mutations do you see that cause susceptibility to MS?
Women x2 more than men
Env: Inc incidence further away from the equator (Vit D deficiency?)
Genetics: Higher chance if first-degree relative has it
- DR2, IL-2, IL-7
What role does inflammation play in MS and what cells are involved?
Chronic inflammation with disease initiated by CD4 Th1 & Th17 cells that react against self myelin antigens & secrete cytokines
- Th1 cells secrete IFN gamma which activates macrophages (macrophages eat myelin)
- Th17 cells promote recruitment of leukocytes
- Demyelination cause by these activated leukocytes & their products
What is the morphology of MS? What does it look like grossly in the brain? What are some specific things you see?
What is sclerosis like compared to the rest of it?
What parts of the brain do you see this affecting the most?
White matter with some extension into grey matter
- Gross: Multiple, well-circumscribed and slightly depressed, glassy, grey-tan, irregularly shaped plaques
- Sclerosis is firmer than surrounding white matter
- Sharply defined boarders, adjacent to lateral ventricles, corpus callosum (thinning), optic nerves & chiasm, brainstem, ascending and descending fiber tracts, cerebellum, spinal cord
What stain do we use for MS and how does this appear?
Luxol fast blue PAS
- Myelin will stain blue
What is an active plaque? What is the histo of an active plaque in MS?
Active plaque has ongoing myelin b/d
- Abundant foamy macrophages w lipid-rich, PAS + debris
- Small vein mononuclear (inflammatory) infiltrates at outer edge of the plaque
- Preservation of axons w/i plaque & depletion of oligodendrocytes
What is an inactive plaque? What is the histo of an inactive plaque in MS?
Quiescent (dormant) with no inflammation
- No myelin, dec in oligo- nuclei, slight dec in axons
What are CSF findings for MS?
- Mildly elevated protein
- Moderate pleocytosis
- IgG increased
- Oligoclonal IgG bands (gamma region) in immunoelectrophoresis
What is neuromyelitis optica (NMO)? (2)
Synchronous bilateral optic neuritis & spinal cord demyelination
What does the CSF show in NMO?
Neurophils w increased opening pressure, can be cloudy
What causes NMO?
Antibodies to aquaporin 4 which are the major water channel of astrocytes (harms integrity of BBB)
Tx of NMO?
- Plasmapheresis
- Glucocorticoids or plasma exchange for acute attack
What is acute disseminated encephalomyelitis (ADEM)?
Diffuse monophasic demyelinating disease that follows wither a viral infection or immunization
- “Perivenous encephalomyelitis”
- Monophasic means that all demyelination happens at the same time (unlike MS)
What are the sx of ADEM and how soon do they start appearing?
- H/A
- Lethargy
- Coma
- 20% die and the rest recover completely
- Sx follow 1-2 weeks after viral inf or immunization
What is the morphology of ADEM?
Grayish discoloration around white matter vessels
- Myelin loss w relative preservation of axons
- Accumulation of lipid-laden macrophages
What is acute necrotizing hemorrhagic encephalomyelitis?
CNS demyelination in young adults and children that follows recent URI; more severe– fatal in most cases with significant deficits in survivors
What is central pontine myelinolysis (osmotic demyelination syndrome)?
Loss of myelin in a roughly symmetric pattern involving the basis pontis & portions of the pontine tegmentum
- Myelin loss w/o inflammation
What are sx of central pontine myelinolysis?
- Acute paralysis
- Dysphagia
- Dysarthria
- Diplopia
- Loss of consciousness
- Can lead to “locked-in syndrome”
What causes central pontine myelinolysis to happen?
Overly rapid correction of hyponatremia
- 2-6 days after
