Demyelinating Disorders and Leukodystrophies

Demyelinating Disorders

• Myelin insulates axons, increasing conduction speed and efficiency.
• Oligodendrocytes myelinate the central nervous system.
• Schwann cells myelinate the peripheral nervous system.
• Demyelinating disorders involve destruction of myelin or oligodendrocytes, but axons are usually preserved.

Leukodystrophies

• Inherited mutations in enzymes affect myelin production or maintenance.
• Metachromatic leukodystrophy (MLD) is an autosomal recessive disorder due to arylsulfatase deficiency.
  • Sulfatides can't be broken down, accumulating in oligodendrocytes' lysosomes.
• Krabbe disease (autosomal recessive) is caused by a deficiency of galactocerebrosidase.
  • Galactocerebroside accumulates in macrophages.
• Adrenoleukodystrophy (X-linked) involves impaired coenzyme A addition to long-chain fatty acids.

Multiple Sclerosis (MS)

• Autoimmune destruction of CNS myelin and oligodendrocytes.
• Most common chronic CNS disease in young adults (20-30 years old), more common in women.
• Associated with HLA-DR2 and environmental triggers.
• More prevalent in regions away from the equator.
• Presents with relapsing neurological deficits (periods of remission).
• Clinical features can include blurred vision, vertigo, scanning speech, hemiparesis, lower extremity weakness, bowel/bladder dysfunction and sexual dysfunction.
• Diagnosis uses MRI (shows plaques/demyelination areas) and lumbar puncture (increased lymphocytes and immunoglobulins, oligoclonal IgG bands).
• Treatment for acute attacks involves high-dose steroids.
• Long-term treatment with interferon beta can slow disease progression.

Subacute Sclerosing Panencephalitis (SSPE)

• Progressive and debilitating encephalitis, often fatal.
• Caused by persistent measles virus infection (occurring in infancy), with neurological signs developing later in childhood.
• Characterized by viral inclusions in neurons and oligodendrocytes.

Progressive Multifocal Leukoencephalopathy (PML)

• JC virus infects oligodendrocytes (white matter).
• Immunosuppression (e.g., AIDS, leukemia) reactivates the virus.
• Presents with rapidly progressive neurological signs (e.g., visual loss, weakness, dementia).

Central Pontine Myelinolysis (CPM)

• Focal demyelination in the pons (anterior brain stem).
• Associated with rapid and significant correction of hyponatremia.
• Occurs in malnourished patients, such as alcoholics and those with liver disease.
• Characterized by acute bilateral paralysis (“locked-in” syndrome).

Explore the fascinating world of demyelinating disorders, including multiple sclerosis and various leukodystrophies. This quiz covers essential concepts such as the role of myelin, the types of cells involved in myelination, and the genetic mutations leading to these conditions. Test your knowledge on how these disorders affect the nervous system.