Multiple Sclerosis

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Definition of MS

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Multifocal demyelinating disease - causes the destruction of the myelin sheath of nerve fibers

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Sclerotic Plaques

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Scar-like lesions that form in the areas where the demyelination has occurred and block or distort the normal transmission of nerve impulses

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Diagnosis of MS

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Requires the occurrence of 2 or more attacks each lasting a minimum of 24 hours and separated by at least a month

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Diagnosis of MS

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The attacks must also be caused by lesions in 2 distinct areas of the CNS

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Diagnosis of MS

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Diagnosis rests on clinical grounds

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Diagnosis of MS

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MRI’s can be used to detect demyelinating plaques in the brain - BUT other disease can cause similar imaging patterns – e.g., AIDS and Lyme disease
 Plaques have predilection for periventricular white matter of brain (L/R hemisphere equally affected)
 Extent of plaques and total lesion area is related to cognitive fxing, but in general location of plaques is not predictive
• CSF analyses – can be used to detect oligoclonal abnormalities

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Etiology of MS

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Unknown. But data implicates genetic variables

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Etiology of MS - Genetic Factors

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1st degree relatives of affected individuals are 6-8 times more at risk than the general population, with siblings being most at risk; women:men = 2:1

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Etiology of MS - Genetic X Environmental Variables

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Siblings who develop MS do so in the same calendar year rather than at the same age

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Etiology of MS - Environmental Variables

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Prevalence rates of MS decreases systematically as latitude of habitation nears the equator

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Etiology of MS - Environmental Variables

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Those who move from high-risk latitude to a low-risk latitude (e.g. Europeans moving to South Africa) or vice-versa carry with them some of the risk from their place of origin if their movement occurs after the age of 15 --- disease acquisition is believed to occur before puberty

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Etiology of MS - Immunologic Variables

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Proposed explanations include a slow acting virus, a delayed reaction to a common virus, or an autoimmune reaction in which the body attacks its own tissues

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Treatment of MS

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Corticosteriods, adrenocorticotropic hormone (ACTH) and other anti-inflammatory agents may be used during exacerbation to hasten remission

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Treatment of MS - Side Effects

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These drugs are known to produce mood changes

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Treatment of MS - Newer Methods

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Newer immunomodulators (e.g., interferon B-1-a) to treat, but even these still can’t arrest or cure

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Course of MS

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Deficits partially resolve as inflammation subsides; also can be suppressed with steroids.

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Course of MS

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As more attacks occur more plaques develop and permanent deficits occur

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MS - Mixed or Generalized Type

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Affects approximately 50% and involves the optic nerve, the brain, the cerebellum, and the spinal cord

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MS - Age of Onset

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2/3 of people are diagnosed between the ages of 20-40 (average 30). Onset before age 15 is extremely rare

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MS - Age of Onset

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Onset after 40 is usually characterized by a faster progression of the degeneration process and shorter length of survival

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MS - First Episode

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After first episode, complete remission often occurs and most pts go years before recurrence

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MS - Delayed Diagnosis

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D/T the transient and variable nature of MS symptoms, mean delay of 3.5 –4 years from time of onset to diagnosis has been documented

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MS - Life Expectancy

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after onset of MS symptoms is generally estimated to be more than 30 years

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MS - 4 Types

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1. Relapsing/Remitting
2. Primary progressive
3. Secondary progressive
4. Progressive Relapsing

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MS - Relapsing/Remitting

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Most common in early years – about 90%

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MS - Primary Progressive Type

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Primary Progressive

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MS - Secondary Progressive Type

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Initially relapsing-remitting course followed by progression with or without occasional relapses, minor remissions and plateaus

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MS - Progressive Relapsing Type

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Rarest – progressive disease from onset with clear acute relapses, periods between relapses characterized by continuing progression

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MS Symptoms - General

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- Weakness in one or more limbs
- Bladder dysfunction - includes urinary urgency, frequency, dysuria, nocturia, and incontinence

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MS Symptoms - Optic Neuritis

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Inflammation, demyelination or degeneration of the optic nerve - Temporary or total loss of vision, usually occurring over several hours or days

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MS Symptoms - Retrobulbar Neuritis

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Optic neuritis that occurs far enough behind the optic disk that no early changes of the optic disk are visible by opthalmascope

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MS Symptoms - Acute Myelitis (Transverse Myelitis)

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Acutely evolving inflammatory-demyelinative lesion of the spinal cord,

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MS Symptoms - Other Neurological Signs

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vertigo, seizures, nystagmus, ataxia, diplopia, hemiplegia, deafness, neuropathy, aphasia and emotional changes

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MS Symptoms - Charcot’s Triad

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Nstagmus, dysarthria, and tremor

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MS Symptoms - Spinal Cord (3 I's)

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Incontinence, impotence, impairment of gait

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MS - Other common symptoms

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Spasticity

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MS Symptoms - Fatigue

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One of the most common and debilitating complaints, affecting up to 90% of patients

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MS Symptoms - Psychiatric Changes

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Affective disturbances, psychoses and personality changes - believed to be due to the disease process rather than (only) a psychological response to the illness

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MS - Cognitive Changes - General

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Cognitive symptoms have been reported in the early stages of the disease. More evident as more white matter is affected

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MS - Cognitive Changes - Prevalence

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40-70%

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MS - Cognitive Changes - Pattern

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Pattern of impairments more likely to resemble patients with frontal and subcortical lesions

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MS - Cognitive Changes - Language

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Receptive and expressive language skills are generally spared, although mild deficits in naming and word generation are common

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MS - Cognitive Changes - Secondary Memory

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Impairment in retrieval from long-term memory, but normal recognition, immediate recall, and rates of forgetting

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MS - Cognitive Changes - Executive Functions

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Impaired abstract and conceptual reasoning, slowed rates of information processing, impaired attention

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MS - Cognitive Changes -Intellectual Functioning

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VIQ > PIQ (likely reflects motor impairments)

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MS - Cognitive Changes - Speed of Information Processing

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While exaggerated by physical impairment, it also appears to cause an overall slowed speed of processing

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MS - Cognitive Changes - Attention/Tracking/Motor Speed

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Reduced span, impaired mental tracking, slowed complex visuomotor tracking, and Motor Slowing

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MS - Cognitive Changes - Executive Functions

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Impairments similar to frontal lobe patients (e.g., problems with conceptual flexibility) - Most common w/ chronic-progressive form

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MS - Intact Cognition

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Storage, encoding, recogniton, simple auditory span; motor skill and implicit learing, language skills (aside from fluency) visualspatial functions

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MS - Affective Functioning

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Depression is common and it is sometimes the first or most prominent symptom

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MS - Affective Functioning

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Also, rarely, includes euphoria

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MS - Etiology of Affective/Personality Changes

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May be related to periventricular and frontal white matter lesions

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MS - Differential DX - Guillain-Barre Syndrome

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Demyelinating disease of PNS
characterized by monophasic attack, lasting several weeks to months; no cog impairment

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MS - Differential DX - Leukodystrophies

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Group of genetically transmitted illnesses that usually manifest in children or adolescents, but sometimes later. Causes unremitting physical and mental deterioration
- Two well-known: adrenoleukodystrophy (ALD) and metachromatic leukodystrophy (MLD)

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MS - Differential DX - Toxins

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Numerous toxins preferentially attack CNS myelin
- Marchiafava-Bignami: possibly caused by substance in homemade red wine and results degeneration of CC
- Chronic Toluene exposure

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MS - Differential DX - Lupus:

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Produces CNS changes in only about 5% of cases initially, but later involves as many as 75%