MULTIPLE SCLEROSIS
DEFINITION:
A neurodegenerative disorder characterized by degeneration of
central nervous system (CNS) white matter with evidence of chronic
and remittent demyelination of the white matter.
EPIDEMIOLOGY:
- incidence: ?
- age of onset:
- of patients with Multiple Sclerosis (MS):
- 0.2-2% have onset of symptoms prior to 10 years of age
- risk factors:
- familial
- increased incidence of MS in family members, particularly
siblings
- F > M (2-4:1)
PATHOGENESIS:
- unknown etiology
- ? environmental factors, infection, altered immunity (an
autoimmune attack of the myelin sheath of nerve cells)
PATHOLOGY:
- dissolution of myelin sheaths without axonal or neuronal
damage
- demyelination occurs repeatedly and in noncontiguous regions
of the CNS
- sites of lesions:
- periventricular, cerebral & cerebellar white matter,
periaqueductal region of the brainstem, optic nerves, spinal
cord
- size of lesions:
- cells within lesions:
- few oligodendroglia, proliferating astrocytes, mononuclear
inflammatory cells
CLINICAL FEATURES:
- most common presenting symptoms:
- acute ataxia or unilateral weakness
- less common presenting symptoms:
- headaches
- severe, prolonged, generalized
- optic neuritis
- unilateral or bilateral
- diplopia, blurred vision, sudden visual loss
- paresthesias
- lower extremities, hands, feet, face
- others
- encephalopathy, hemiparesis, seizures
2. Exacerbations
- disseminated in time and space
- may persist for weeks to months
- separated by months to years
- initially followed by a partial or complete recovery but
with time greater degrees of residual dysfunction persists and
eventually enters into a progressive chronic phase
3. Complications
- progressive paraplegia
- increased intracranial pressure
- neurogenic bladder dysfunction
- Devic's Disease (neuromyelitis optica)
- combination of bilateral optic neuritis and transverse
myelitis
INVESTIGATIONS:
- progressive leukodystrophy
- areas of plaque formation and demyelination
2. Cerebral Spinal Fluid
- abnormalities found in 90% of patients with MS
- lymphocytic pleocytosis (<25 cells/uL)
- normal or slightly elevated protein (myelin-basic protein)
- altered immunoglobulins
- quantitive increase in IgG
- oligoclonal bands on electrophoresis
- note that the finding of myelin-basic protein and
oligoclonal banding are not specific for MS and diagnosis of
MS is on the basis of a clinical diagnosis in addition to
these findings
3. Evoked Potentials
- altered auditory, brainstem, visual, and peroneal
somatosensory
- (for myelitis) evoked potentials
MANAGEMENT:
- no treatment available to prevent demyelination
- treat movement disorders, UTI's, neurogenic bladder
dysfunction, and seizures
- physical therapy and psychotherapy
2. Medical
- for exacerbations
- prednisone 2mg/kg/d po x 1 wk then tapered over next 3
weeks
- ACTH
- may shorten the duration of acute attacks but do not
appear to affect the overall course of the disease
- other immunosuppressive measures
- cyclophosphamide, azothioprine, plasma exchange
3. Experimental
- mechanism of action:
- an immunomodulatory agent which down-regulates the
immune system
- may also correct the reduced suppressor activity
- given IM once a week
- has been found to reduce the number of relapses and slows
progression to functional disability
- also reduces lesion activity identified by MRI
- side effects:
- flu-like symptoms (fever, fatigue, muscle aches
2. Copolymer-1 (Cop-1)
- a synthetic polypeptide
- mechanism of action:
- a competitive inhibitor of myelin basic protein (the
proposed antigenic target of the autoimmune attack)
- enhances T-lymphocyte suppressor function
- reduces the number of relapses and slows progression to
functional disability
INTERNET LINKS:
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