PRIMARY DISEASE OF MYELIN

MYELIN DISEASES TIM SMITH, MD


Objectives:

1. Learn the clinical features, epidemiology and pathology of MS.

2. Know that CPM can be caused by correction of hyponatremia.

3. Realize that the leukodystrophies have subsets that occur at different ages, have variable heredity, and that they are metabolic defects involving enzymes affecting
myelin production and maintenance.
4. Learn the clinical features and pathology of PML.

5. Describe the differences clinically and pathologically between PML, the leukodystrophies and MS.


Robbins 7th ed. pp. 837-839.

page 284 Tim Smith, MD Myelin Diseases PRIMARY DISEASES OF MYELIN

I. Multiple Sclerosis (MS) - the most common demyelinating disease of CNS A. Epidemiology 1. Genetic factors - European extraction, HLA class II associations, increased risk in identical twins even more than for other family
members, spouse at no increased risk 2. Temperate climate (increased toward poles, decreased toward equator)- risk defined in first 15 years of life (a disease of Yankees) 3. Peak 18-40 years of age, female > male
B. Pathogenesis - presumed autoimmune - inciting factor?

C. Animal models 1. Experimental allergic encephalomyelitis (EAE) - inject animals with myelin components or lymphocytes sensitized to myelin - T-cell
mediated 2. Virally induced demyelination
D. Clinical course 1. Definition: distinct episodes separated in time and attributable to white matter lesions separated in space 2. Varies from slowly progressive (relapsing and remitting - most common course), to quickly progressive, to mildly progressive, to localized
forms such as neuromyelitis optica with bilateral optic neuritis and very
destructive lesions in the spinal cord 3. Common symptoms - visual impairment, limb weakness, double vision, vertigo, ataxia, dysesthesias, bladder dysfunction 4. Exam - nystagmus, internuclear ophthalmoplegia, weakness, spasticity, hyperreflexia, extensor plantar response, tremor, ataxia, dysarthria 5. CSF a. Slightly increased protein, small number lymphocytes and plasma cells b. Protein electrophoresis (with matching serum specimen) - oligoclonal bands 6. MRI scans show multiple lesions
7. Evoked potentials
E. Gross pathology - white matter (less often grey matter) plaques - sharply defined, translucent grey, especially around ventricles
F. Microscopic pathology - sharply defined plaques 1. Active plaques - myelin breakdown, macrophages, perivascular
lymphocytes, axons relatively spared
2. Inactive plaques - gliosis, axons relatively spared, very little
remyelination
G. Treatment supportive (immunosuppression, antispasmodics, synthetic polypeptides mimicking myelin) page 285 Tim Smith, MD Myelin Diseases II. Acute disseminated encephalomyelitis - postinfectious encephalomyelitis - rare A. Immune mediated

B. Post viral 2-4 days (measles, chickenpox, rubella) or post vaccinal 10-13 days (smallpox, typhoid)
C. Usually monophasic - fever, seizure, coma, focal signs - fatal 15-20% - severe neurologic sequelae
D. Pathology - perivascular demyelination, edema, necrosis, hemorrhage
III. Central pontine myelinolysis (CPM)
A. Correction of hyponatremia (often in an alcoholic); also seen after liver transplant (osmotic problem?)
B. Rapidly progressive corticospinal (flaccid quadriplegia) and corticobulbar (facial and oropharyngeal weakness) symptoms
C. The center of the basis pontis (and sometimes portions of the tegmentum) show damage to the myelin with relative sparing of axons.
IV. Leukodystrophies - most hereditary - metabolic defect interfering with generation or maintenance of myelin
A. Types 1. Metachromatic a. Autosomal recessive
b. Enzyme deficiency - arylsulfatase A - accumulation of sulfatides esp. cerebroside sulfate c. Subtypes - congenital, late infantile (commonest), juvenile and adult d. Clinical features - gait changes, bulbar palsy; eventually blind, deaf and demented 2. Krabbe's - globoid cell leukodystrophy a. Autosomal recessive
b. Enzyme deficiency - galactocerebroside

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