white matter disease; "separate lesions in time and space"
Etiology
: etiology and pathogenesis are not established but there are environmental, genetic, and immune factors
Epidemiology
: age: 20 – 40 years old
affects twice as many women as men
risk in general population is 0.1%; risk for people with affected mother is 3-5%
more common in northern latitudes; geographic risk conferred before age 15
Definition
: demyelinating disorder characterized by distinct episodes of neurologic deficits that are separated in time, attributable to white matter lesions that are separated in space
Topology
: preferentially affects white matter, but may extend into gray matter
autoimmune disease, which attacks myelin sheath that surrounds axons within the CNS and the optic nerves
axonal demyelination leads to poor conduction of neural impulses
acute MS lesions are characterized by perivascular infiltration of mononuclear white cells
glial fibrillary proliferation found in chronic healed MS plaques
both genetic and environmental factors play a role in its pathogenesis
Multiple well-circumscribed irregularly shaped plaques with firmer consistency than surrounding white matter (sclerosis)
Active plaque –
myelin breakdown, perivascular cuffs; accumulation of white cells around blood vessels.
Inactive plaque –
no myelin,
ß in oligodendrocytes, astrocyte proliferation and gliosis
Pathologic dynamics
:
Patterns of demyelination: pathogenetic mechanisms leading to demyelination may be fundamentally distinct in different groups of MS patients
Remyelination: We know partial remyelination can occur after destruction, why not full?
(1) Presence of inhibitory local environment may prevent spontaneous repair
(2) Absence of endogenous cells or factors required for new myelin synthesis
Symptoms and Signs
Common: lesions of white matter
visual loss / optic nerve
double vision / brainstem
ataxia / brainstem or cerebellum
hemiparesis / corticospinal tract
incontinence and paraparesis / spinal cord
Uncommon: lesions of gray matter
seizures / cerebral cortex
aphasia / language areas
chorea / basal ganglia
Ý
body temperature exacerbate symptoms by causing further reduction in marginal axonal function
Uhthoff’s Symptom
: heat induced vision loss
Positive Symptoms
: due to aberrant discharges from irritable axons
L’hermitte’s Sign
Þ electrical sensation that runs down the back of neck when flexed
Photopsias
Þ flashes of light induced by eye movements; facial pain (trigeminal neuralgia) and dystonic spasms
Optic Neuritis
– typically presents as acute, painful visual loss in one eye
75% of young women and 35% of young men with optic neuritis develop MS; 60% of people with MS get optic neuritis
optic nerve involvement found in 90% of autopsies of people with MS
Detection: visual blurring, color loss
Time Course of MS
(1) Relapsing-remitting
Þ most common; attacks develop over days to weeks, reach a plateau, begin to improve spontaneously; neurological deficits accumulate over time
(2) Primary progressive
Þ continual progression; 30% of cases; most common in late onset
(3) Secondary progressive
Þ begin as relapsing-remitting form and then become continually progressive
highly variable disease: level of neurological disability correlates with the number of symptomatic attacks in patients with relapasing-remitting disease and the number of plaques seen on neuroimaging
bad prognostic signs: primary progressive disease, motor involvement and numerous lesions on 1st MRI exam
progression of disease after diagnosis: 10 years- 50% continue to work; 15 years- 50% require cane; 25 years- 50% wheelchair bound; average age of death of MS patients is 65 years old
Diagnosis
Separate lesions in space and time; no definitive test
History: can not use history alone
Þ need objective evidence
Neurologic Exam
MRI Scan (most sensitive lab test for subclinical lesions, shows acuteness of plaque); characteristic Unidentified Bright Objects (UBO); gadolinium enhanced T1 most sensitive exam; lesions come and go faster than clinical signs and correlation between lesions and disability is weak
CSF Analysis: evidence of immunological process in CNS (
Ý IgG); 80% sensitive but nonspecific; normal WBC and glucose; slight Ý in protein
Evoked Potentials: used to identify silent lesions; not commonly used any more
Diagnosis
: at least one attack of neurologic dysfunction, with clinical evidence of attacks in more than one area
diagnostic pitfalls: degenerative disease, stroke; repeated damage mapped to same location suggests structural lesion
Treatment
Betaseron (
b -interferon 1b) and Avonex (b -interferon 1a): ß rate of MS attacks and MRI lesions; side effects include flu like symptoms and injection site reactions
Copoxone (Copolymer 1): similar in composition to myelin basic protein and may act by desensitize the immune system; less effective than
b -interferon drugs in reducing MS exacerbations
Betaseron, Avonex and Copoxone are very expensive and require regular injections
IV steroids:
ß severity and duration of attacks; usually reserved for severe attacks