Multiple Sclerosis

General Characteristics

Multiple sclerosis is a multifocal demyelinating disease – the disease causes the destruction of the myelin sheath of nerve fibers – scar-like lesions called sclerotic plaques form in the areas where the demyelination has occurred and block or distort the normal transmission of nerve impulses.

  • Incidence and prevalence vary geographically
    • fewer cases near the equator and larger numbers in the northern and southern latitudes
      • between 250,000 to 350,000 people with MS in the United States, with three times more cases among residents in the northern (versus southern) half of the country.
        • this distribution suggests an environmental contribution to the disease
    • MS is twice as likely to affect women than men
  • Two severity outcomes defined
    • Benign outcome: Full functioning for 15 years post onset
    • Malignant outcome: rapidly progressive course with significant disability or death soon after onset


  • Can be difficult to diagnose in early stages b/c of its presentation
  • Diagnosis requires the occurrence of 2 or more attacks each lasting a minimum of 24 hours and separated by at least a month.
  • The attacks must also be caused by lesions in 2 distinct areas of the CNS
  • Diagnosis rests on clinical grounds
  • 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


  • Actual etiology is unknown, but data implicates:
    • Genetic variables – 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
    • Environmental variables – siblings who develop MS do so in the same calendar year rather than at the same age
      • prevalence rates of MS decreases systematically as latitude of habitation nears the equator
      • 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
    • immunologic variables
    • 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


  • Corticosteriods, adrenocorticotropic hormone (ACTH) and other anti-inflammatory agents may be used during exacerbation to hasten remission
    • These drugs are known to produce mood changes and should be considered when assessing affective changes in patients with MS
  • Now introducing immunomodulators (e.g., interferon B-1-a) to treat, but even these still can’t arrest or cure

Disease Course

  • Deficits partially resolve as inflammation subsides; also can be suppressed with steroids, but with more attacks more plaques develop and permanent deficits occur
  • Approximately 50% have a mixed or generalized type, which involves the optic nerve, the brain, the cerebellum, and the spinal cord
  • 2/3 of people are diagnosed between the ages of 20-40 (average 30); although the transient and variable nature of MS symptoms make it difficult to diagnose (mean delay of 3.5 – 4 years from time of onset to diagnosis has been documented)
    • likely acquired before puberty however
      • onset before 15 rare
    • onset after 40 typically characterized by quicker progression and shorter length of survival
  • Typical lifespan following MS onset about 30 years, but this varies

Disease Categories

(Categories imprecise at best)

  1. Relapsing/Remitting (most common in early years – about 90%)
  2. Primary progressive
  3. Secondary progressive – initially relapsing-remitting course followed by progression with or without occasional relapses, minor remissions and plateaus
  4. Progressive relapsing (rarest) – progressive disease from onset with clear acute relapses, periods between relapses characterized by continuing progression

General Symptoms

  • Early symptoms commonly include:
    • Weakness in one or more limbs
    • Bladder dysfunction – includes urinary urgency, frequency, dysuria, nocturia, and incontinence
    • Optic neuritis (i.e., inflammation, demyelination or degeneration of the optic nerve)
      • results in temporary or total loss of vision, usually occurring over several hours or days
      • retrobulbar neuritis – optic neuritis that occurs far enough behind the optic disk that no early changes of the optic disk are visible by opthalmascope (MS is the most common cause for this)
    • Acute Myelitis (Transverse Myelitis) – common designation for an acutely evolving inflammatory-demyelinative lesion of the spinal cord, which often is expression of MS
    • Other neurological signs
      • e.g., vertigo, seizures, nystagmus, ataxia, diplopia, hemiplegia, deafness, neuropathy, aphasia and emotional changes
      • Charcot’s Triad: nystagmus, dysarthria, and tremor
      • Spinal Cord (3 I’s): incontinence, impotence, impairment of gait
  • Other common symptoms
    • spasticity
    • fatigue – one of the most common and debilitating complaints, affecting upto 90% of patients
    • psychiatric changes – including affective disturbances, psychoses and personality changes
      • believed to be due to the disease process rather than (only) a psychological response to the illness

Cognitive Symptoms

Cognitive symptoms have been reported in the early stages of the disease, but they become more evident as more white matter is affected

  • Overall prevalence of cognitive symptoms between 40-70%
    • Of the people with cognitive impairment, 80% of these folks have mild impairments
    • Even mild cognitive problems in MS are enough to interfere with day-to-day activities
  • Pattern of impairments more likely to resemble patients with frontal and subcortical lesions
  • Receptive and expressive language skills are generally spared (although mild deficits in naming and word generation are common)
  • Cognitive symptoms result from demyelination rather than gray matter lesions
  • Most common deficits are in memory, complex attention/speed of information processing and executive functions
  • basic cognitive profile (consistent with subcortical dementia, although because procedural memory spared might be considered White Matter Dementia):
    • little or no language deficit
    • impairment in retrieval from long-term memory, but normal recognition, immediate recall, and rates of forgetting
    • impaired abstract and conceptual reasoning, slowed rates of information processing
    • impaired attention
  • Intellectual Functioning
    • VIQ>PIQ (likely reflects motor impairments)
  • Memory Functioning
    • Some research suggests that memory impairments represent difficulties in retrieval, with storage, encoding, and recognition are generally spared (although this is a somewhat controversial finding)
  • Speed of Information Processing
    • While exaggerated by physical impairment, it also appears to cause an overall slowed speed of processing
    • May contribute to verbal memory impairments
    • commonly manifest as difficulty keeping up with conversations, work tasks
  • Attention
    • may be reflected as reduced span, impaired mental tracking, or slowed complex visuomotor tracking
  • Working memory deficits common
  • Executive Functions
    • Impairments similar to frontal lobe patients (e.g., problems with conceptual flexibility, abstraction, planning and problem solving)
    • Most common w/ chronic-progressive form
    • clinically evident in disinhibition and tangential speech, difficulty planning day-to-day activities, and problems organizing ideas in conversation and speech
  • Motor Slowing
    • Often seen early in course of disease
  • Visual Spatial Functions
    • Generally intact visual spatial skills but 10% to 20% of people with MS show higher order visual spatial processing problems(variable – impairments more related to exec. fxns and motor speed)
    • May be seen clinically as problems running into things while walking (e.g., walls, doors) or driving (e.g., curbs, posts) due to miscalculations
  • Typical areas of preserved functioning (again, may be variable): Memory storage, encoding, recogniton, simple auditory span; motor skill and implicit learing, language skills (aside from fluency), basic visual spatial functions

Affective and Behavioral Functioning

  • Depression is a common finding in people with MS
    • It is sometimes the first or most prominent symptom
    • People with MS have 50% lifetime risk of depression
      • May be exacerbated by high levels of perceived stress, low levels of perceived instrumental and emotional support, disease exacerbation and pharmocological treatment of disease associated with greater distress and depression
      • Notassociated with severity of neurological disability
  • Personality changes – also (rarely) includes euphoria
  • Anxiety also common, and found in about 25% of people with MS, but not well studied
    • May be prominent in early stages of disease when diagnosis and prognosis are unclear
    • comorbidity of anxiety and depression is more associated with somatic complaints and social dysfunction than either anxiety or depression alone
  • Emotional changes may be related to periventricular and frontal white matter lesions
    • Assocations between impairments in complex attention, information processing speed, and perhaps, executive functions and depression have been found
      • may have common neuroanatomical substrate

Differential Diagnosis

  • Dysmyelination
  • Number of conditions that can mimic MS
    • Guillain-Barre Syndrome – demyelinating disease of PNS
      • characterized by monophasic attack, lasting several weeks to months; no cog impairment
    • Leukodystrophies
      • Group of genetically transmitted illnesses
      • Usually manifest in children or adolescents, but sometimes later
      • Cause unremitting physical and mental deterioration
      • Two well-known: adrenoleukodystrophy (ALD) and metachromatic leukodystrophy (MLD)
    • Infections
    • Toxins – numerous toxins preferentially attack CNS myelin
      • Marchiafava-Bignami: possibly caused by substance in homemade red wine and results degeneration of CC
      • Chronic Toluene exposure
    • Lupus: produces CNS changes in only about 5% of cases