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Multiple Sclerosis

Contributed by: Yasmin Qaseem, Baylor College of Medicine, 1 Baylor Plaza, Houston, Tx 77030
  • Multiple sclerosis is an autoimmune inflammatory demyelinating disease that yields neurological deficits that localize to different parts of the CNS and chronically progresses over a lifetime, often punctuated by acute exacerbations. The traditional patient is a young woman of Northern European descent.
  • Multiple Sclerosis is likely an autoimmune disease triggered by unknown environmental factors in those with a genetic predisposition. Some have speculated that the environmental factor may be a virus. Risk factors include Northern European descent, female gender, and a family history. Onset is typically between the second and fourth decades. Moving from northern to southern latitudes before the age of 15 has been shown to be protective.
  • Pathogenesis of MS appears to involve autoimmune attack of myelin-producing oligodendrocytes, resulting in inflammation and surrounding edema. Over time there is progressive loss of white matter in the CNS, which can be detected on imaging or can manifest clinically as neurological deficits. Importantly, demyelination is multifocal, and thus clinical neurological symptoms will localize to different anatomical parts of the CNS.
Clinical Consequences and Diagnosis
  • Overview
    • The key aspect of MS is evidence of white matter injury, either clinically or by imaging, that localizes to different anatomical regions of the CNS. As the disease is progressive, evidence of injury manifests at different points in life. As a result, MS can be thought of as white matter injury that is “separated in space and time”.
  • Optic Neuritis
    • This symptom of disease presents as acute pain and loss of vision in one eye. Bilateral involvement may occur more rarely.
  • Internuclear Opthalmoplegia
    • Due to demyelination of the medial longitudinal fasciculus, this condition prevents ocular adduction. However, convergence remains intact. This may present bilaterally.
  • Upper Motor Neuron Signs
    • These typically manifest as spasticity, hyperreflexia and even clonus. Patients also present with problems with gait and coordination.
  • Neuropathy
    • Patients often experience pain and alterations in sensation. Additionally, Lhermitte phenomenon is commonly described as an “electric shock” felt down the back.
  • Autonomic Involvement
    • Bowel and bladder incontinence is frequently experienced in patients with MS secondary to sphincter dysfunction. Sensitivity to heat may also occur and can worsen MS symptoms.
Natural History
  • Overview
    • MS can evolve with different tempos and a variety of sub-groups have been identified depending on the disease's natural history
  • Clinically Isolated Syndrome
    • The initial episode involving a neurologic deficit lasting over 24 hours
  • Relapsing-Remitting
    • Acute exacerbations of disease with a complete return to baseline functioning
  • Secondary Progressive
    • Disease that is initially of the relapsing-remitting course that then becomes progressive without return to baseline
  • Primary Progressive
    • Continually progressive disease that may have periods of without improvement
Imaging and Labs
  • Both imaging studies and labs can help solidify a diagnosis of MS. MRI is the traditional imaging modality and shows lesions in white matter. Lumbar puncture can show the presence of oligoclonal IgG bands or an increased IgG index. Visual evoked potentials (VEP) can also be performed if the diagnosis is in question and will show a delayed response.
  • Overview
    • Treatment of MS can be separated into therapies that aim to target acute exacerbations and “disease modifying therapies” which aim to alter the progressive natural history of the disease or prevent flares. Importantly, no curative treatment has been found for MS.
  • Acute Treatment
    • Acute treatment is typically undertaken with IV steroids which may reduce the severity and duration of flares.
  • Disease Modifying Therapies
    • Disease modifying therapies aim to reduce the progressive nature of the disease and reduce the number of acute exacerbations. These drugs are typically immunomodulators. The original disease modifying therapy was interferon although a number of new drugs have been developed that target various aspects of the suspected autoimmune response
Further Reading
  • Goldenberg, M. "Multiple sclerosis review." Pharmacy and Therapeutics 37.3 (2012): 175.
  • Nylander, A. and Hafler, M “Multiple Sclerosis.” The Journal of Clinical Investigation 122.4 (2012): 1180.
  • McDonald, W. Ian, et al. "Recommended diagnostic criteria for multiple sclerosis: guidelines from the International Panel on the diagnosis of multiple sclerosis." Annals of neurology 50.1 (2001): 121-127.
  • Lublin, Fred D., and Stephen C. Reingold. "Defining the clinical course of multiple sclerosis results of an international survey." Neurology 46.4 (1996): 907-911.

To cite this article
Qaseem, Y, “Multiple Sclerosis” in Pathway Medicine: An Introduction to Clinical Medicine", (2015).