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Flashcards in Myelination Disorders Deck (14):
1

  • What is responsible for axon myelination in CNS?
  • What are the components of myelin?

  • Oligodendrocyte
    • Analogous to Schwann cell in PNS
    • Small round dark nuclei with short processes (“oligo”)
    • Each oligodendrocyte provides a myelin sheath to several axons
  • Myelin components
    • Myelin basic protein (MBP)
      • Plasma membrane bound
    • Proteolipidprotein (PLP)
      • Structural component of myelin

2

What is the difference between demyelination and dysmyelination?

  1. Demyelination: destruction of myelin with relative preservation of axons
  2. Dysmyelination: failure to form myelin normally = leukodystrophy

3

List the disorders of demyelination:

  • Acquired disorders:
    • Multiple sclerosis (MS)
    • Acute disseminated encephalomyelitis (ADEM)
    • Central pontine myelinolysis (CPM)
    • Progressive multifocal leukoencephalopathy (PML) 
  • Inherited disorders:
    • Neuromyelitisoptica(NMO)

4

What is the most common demyelinating disease of CNS?

Multiple Sclerosis

5

  • Describe the pattern of demyelination in MS
  • Gender bias? 
  • Peak age of onset: 
  • Occurs more frequently in individuals living in ....

  • Demyelination is multifocal (disseminated in space) & lesions are of different ages (disseminated in time)
  • W > M
  • Peak age of onset: 20-40 years
  • Occurs more frequently in individuals living in northern climates

6

How is MS classified?

  1. Classic type 
    • Several subtypes are described
      • Various combinations of acute attacks with or without clinical recovery in between attacks and/or gradually progressive decline without episodes of recovery
  2. Rapidly progressive types
    • Acute (Marburg type)
    • Concentric sclerosis (Balo’sdisease)

7

What is the gross pathology in MS?

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  • Plaques of demyelinationdepressed, irregular, firm (“sclerosis”)
  • Usually occur in:
    • periventricular white matter
    • optic nerves and chiasm
    • brainstem and spinal cord tracts
    • cerebellum
    • Also occur in gray matter (but are fewer axons there so less frequent)

8

What is the microscopic pathology in MS?

  • Active plaque
    • Macrophages with myelin debris, perivascular lymphocytes, reactive astrocytes, relative preservation of axons
  • Inactive plaque
    • Few or no macrophages, few lymphocytes, myelin loss with axonal preservation, fibrillary astrocytes
  • Shadow plaque
    • Partial myelin absence (either due to incomplete myelin loss or partial remyelination)

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9

What is Acute disseminated encephalomyelitis (ADEM) and how does it occur?

  • Monophasic demyelinating disease, acute-onset
    • Associated with recent viral illness or immunization
      • Signs/symptoms occur 1-2 weeks following
    • Also call perivenous encephalomyelitis and post-infectious encephalomyelitis

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10

Acute disseminated encephalomyelitis (ADEM):

  • Clinical S/S 
  • Pathology 
  • Pathogenesis 

  • Clinical S/S:
    • Headache, lethargy, coma (diffuse brain involvement)
    • 80% complete recovery
  • Pathology
    • Perivenous demyelination with axonal preservation
    • Polymorphonuclear leukocytes early and lymphocytes later
  • Pathogenesis
    • Immune response to pathogen-associated antigens cross-reacts to myelin antigens that results in myelin damage

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11

Define Neuromyelitis optica (Devic disease): 

  • Gender Bias? 
  • Racial bias? 
  • Median age of onset: 

Relapsing synchronous bilateral optic neuritis & spinal cord lesions

  • W> M
  • Asians and African-Americans > Caucasians
  • Median age of onset: 39 years

12

Neuromyelitis optica (Devic disease): 

  • Pathology 
  • Pathogenesis  

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  • Pathology:
    • Necrosis (not just demyelination) with inflammatory cells
  • Pathogenesis:
    • Aquaporins (AQP4): Membrane water channels that help maintain astrocytic foot processes
    • Autoantibodies induce complement-dependent cytotoxicity, leukocyte infiltration, cytokine release, and blood-brain barrier breakdown
      • Lead to oligodendrocyte death, myelin loss
      • AQP4-specific IgG antibodies detectable in 60-90% of NMO patients

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13

Central Pontine Myelinolysis (Osmotic demyelination syndrome)

  • Definition 
  • Clincal S/S 

  • Monophasic process: loss of myelin with relative preservation of the axons & neurons in basis pontis
  • Clinical S/S:
    • Limb weakness (quadriplegia), gaze / speech abn, dysphagia, hypotension
    • May affect extrapontine sites

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14

What causes central pontine myelinolysis?

  • Most commonly associated with too rapid correction of hyponatremia
    • Mechanism poorly understood
    • Associated with :
      • Alcoholic liver damage
      • Post liver transplant
      • Chronic malnourishment/debilitation
      • Extensive skin burns