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  1. What are the major disease manifestations and complications of multiple sclerosis?

  2. How are exacerbations of multiple sclerosis treated?

  3. What are treatment options for complicating symptoms of multiple sclerosis, such as fatigue, bladder dysfunction, and spasticity?

  4. What disease-modifying agents are available to treat multiple sclerosis? What are their major toxicities?

Multiple sclerosis (MS) is an autoimmune, T-cell-driven disease of the central nervous system characterized initially by demyelination and, eventually, by axonal destruction and neuronal loss. It is the most common neurologic disease in young adults.

The peak age of onset between 20 and 40 years, and it has a twofold higher incidence in women. It has long been observed that latitude of residence in childhood is a risk factor for the development of the disease. MS is rare in equatorial areas, and the prevalence rises sharply with increasing distance from the equator. The relation of MS prevalence to latitude and altitude suggests that increased sun exposure in childhood protects against MS, but more recent work favors a genetic predisposition to MS that is geographically clustered.

Genetic factors play a major role in the development of MS, and a family history is common. The major histocompatibility complex allele HLA-DRB1*1501 and two cytokine receptor genes, the interleukin 7 receptor alpha chain gene (IL7RA) and the interleukin 2 receptor alpha chain gene (IL2RA), have been implicated. Susceptibility to MS is likely polygenic, with the contribution of most genes to MS risk being relatively small. Clusters of MS cases have suggested an infectious trigger, although the search for a specific viral or bacterial cause of MS has been thus far fruitless.


Multiple sclerosis is characteristically a relapsing and remitting disease, but there is great variation in its course. Common presenting symptoms of MS are summarized in Table 213-1. Weakness, numbness, or both in one or more limbs are common first symptoms. Patients may have paresthesias in the extremities or a band-like tightness around the trunk or limbs. The legs may feel heavy or difficult to control. Neck flexion may cause a sensation of electric shocks in the shoulders, back, and occasionally in the thighs. This finding, known as the Lhermitte sign, may also be present in cervical spondylosis, vitamin B12 deficiency, radiation myelopathy, and other conditions affecting the cervical spine.

Table 213-1 Predominant Presenting Symptoms of Multiple Sclerosis

Certain acute or subacute clinical syndromes are particularly characteristic of MS, although they also occur in association with other diseases of the nervous system. Optic neuritis most often ...

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