Myelination Disorders

Question 1

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

Answer 1

• 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

Question 2

What is the difference between demyelination and dysmyelination?

Answer 2

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

Question 3

List the disorders of demyelination:

Answer 3

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

Question 4

What is the most common demyelinating disease of CNS?

Answer 4

Multiple Sclerosis

Question 5

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

Answer 5

• 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

Question 6

How is MS classified?

Answer 6

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)

Question 7

What is the gross pathology in MS?

Answer 7

• Plaques of demyelination – depressed, 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)

Question 8

What is the microscopic pathology in MS?

Answer 8

• 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)

Question 9

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

Answer 9

• 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

Question 10

Acute disseminated encephalomyelitis (ADEM):

• Clinical S/S
• Pathology
• Pathogenesis

Answer 10

• 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

Question 11

Define Neuromyelitis optica (Devic disease):

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

Answer 11

Relapsing synchronous bilateral optic neuritis & spinal cord lesions

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

Question 12

Neuromyelitis optica (Devic disease):

• Pathology
• Pathogenesis

Answer 12

• 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

Question 13

Central Pontine Myelinolysis (Osmotic demyelination syndrome)

• Definition
• Clincal S/S

Answer 13

• 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

Question 14

What causes central pontine myelinolysis?

Answer 14

• 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