Demyelinating Disorders PDF

# Demyelinating Disorders ## I. Basic Principles * Myelin insulates axons, improving the speed and efficiency of conduction. * Oligodendrocytes myelinate the central nervous system. * Schwann cells myelinate the peripheral nervous system. * Demyelinating disorders are characterized by dest...

# Demyelinating Disorders ## I. Basic Principles * Myelin insulates axons, improving the speed and efficiency of conduction. * Oligodendrocytes myelinate the central nervous system. * Schwann cells myelinate the peripheral nervous system. * Demyelinating disorders are characterized by destruction of myelin or oligodendrocytes; axons are generally preserved. ## II. Leukodystrophies * Inherited mutations in enzymes necessary for production or maintenance of myelin. * Metachromatic leukodystrophy is due to a deficiency of arylsulfatase (autosomal recessive); most common leukodystrophy. * Sulfatides cannot be degraded and accumulate in the lysosomes of oligodendrocytes (lysosomal storage disease). * Krabbe disease is due to a deficiency of galactocerebrosidase (autosomal recessive). * Galactocerebroside accumulates in macrophages. * Adrenoleukodystrophy is due to impaired addition of coenzyme A to long-chain fatty acids (X-linked defect). * Accumulation of fatty acids damages adrenal glands and white matter of the brain. * ## III. Multiple Sclerosis * Autoimmune destruction of CNS myelin and oligodendrocytes. * Most common chronic CNS disease of young adults (20-30 years of age); more commonly seen in women. * Associated with HLA-DR2. * More commonly seen in regions away from the equator. * Presents with relapsing neurologic deficits with periods of remission (multiple lesions in time and space). Clinical features include: * Blurred vision in one eye (optic nerve). * Vertigo and scanning speech mimicking alcohol intoxication (brainstem). * Internuclear ophthalmoplegia (medial longitudinal fasciculus). * Hemiparesis or unilateral loss of sensation (cerebral white matter, usually periventricular). * Lower extremity loss of sensation or weakness (spinal cord). * Bowel, bladder, and sexual dysfunction (autonomic nervous system). * Diagnosis is made by MRI and lumbar puncture. * MRI reveals plaques (areas of white matter demyelination). * Lumbar puncture shows increased lymphocytes, increased immunoglobulins with oligoclonal IgG bands on high resolution electrophoresis, and myelin basic protein. * Gross examination shows gray-appearing plaques in the white matter. * Treatment of acute attacks includes high-dose steroids. * Long-term treatment with interferon beta slows progression of disease. * ## IV. Subacute Sclerosing Panencephalitis * Progressive, debilitating encephalitis leading to death. * Due to slowly progressing, persistent infection of the brain by measles virus. * Infection occurs in infancy; neurologic signs arise years later (during childhood). * Characterized by viral inclusions within neurons (gray matter) and oligodendrocytes (white matter). ## V. Progressive Multifocal Leukoencephalopathy * JC virus infection of oligodendrocytes (white matter). * Immunosuppression (e.g., AIDS or leukemia) leads to reactivation of the latent virus. * Presents with rapidly progressive neurologic signs (visual loss, weakness, dementia) leading to death. ## VI. Central Pontine Myelinolysis * Focal demyelination of the pons (anterior brain stem). * Due to rapid intravenous correction of hyponatremia. * Occurs in severely malnourished patients (e.g., alcoholics and patients with liver disease). * Classically presents as acute bilateral paralysis ("locked in" syndrome).