Multiple sclerosis is initially characterized by weakness, numbness, tingling, or unsteadiness in a limb; spastic paraparesis may follow. This common neurologic disorder of unknown cause has its greatest incidence in young adults.
Epidemiologic studies indicate that multiple sclerosis is much more common in persons of western European lineage who live in temperate zones. No population with a high risk for multiple sclerosis exists between latitudes 40 °N and 40 °S.
Genetic, dietary, and climatic factors cannot account for these differences. There may be a familial incidence of the disease, since affected relatives are sometimes reported. The strong association between multiple sclerosis and specific HLA antigens (HLA-DR2) provides support for a theory of genetic predisposition. Many believe that the disease has an immunologic basis. Pathologically, Focal-often perivenular-areas of demyelination with reactive gliosis are found scattered in the white matter of brain and spinal cord and in the optic nerves.
A. Symptoms and Signs: The common initial presentation is weakness, numbness, tingling, or unsteadiness in a limb; spastic paraparesis; retrobulbar neuritis; diplopia; disequilibrium; or a sphincter disturbance such as urinary urgency or hesitancy. Symptoms may disappear after a few days or weeks, although examination often reveals a residual deficit.
In most patients, there is an interval of months or years after the initial episode before new symptoms develop or the original ones recur. Eventually, however, relapses and usually incomplete remissions lead to increasing disability, with weakness, spasticity, and ataxia of the limbs, impaired vision, and urinary incontinence. The findings on examination at this stage commonly include optic atrophy, nystagmus, dysarthria, and pyramidal, sensory, or cerebellar deficits in some or all of the limbs.
Less commonly, symptoms are steadily progressive from their onset, and disability develops at a relatively early stage. The diagnosis cannot be made with confidence unless the total clinical picture indicates involvement of different parts of the central nervous system at different times.
A number of factors (eg, infection, trauma) may precipitate or trigger exacerbations. Relapses are also more likely during the 2 or 3 months following pregnancy, possibly because of the increased demands and stresses that occur in the postpartum period.
B. Imaging: MRI of the brain or cervical cord is often helpful in demonstrating the presence of a multiplicity of lesions. CT scans are less helpful.
In patients presenting with myelopathy alone and in whom there is no clinical or laboratory evidence of more widespread disease, myelography or MRI may be necessary to exclude a congenital or acquired surgically treatable lesion. The foramen magnum region must be visualized to exclude the possibility of Arnold-Chiari malformation, in which part of the cerebellum and the lower brain stem are displaced into the cervical canal and produce mixed pyramidal and cerebellar deficits in the limbs.
C. Laboratory and Other Studies: A definitive diagnosis can never be based solely on the laboratory findings. If there is clinical evidence of only a single lesion in the central nervous system, multiple sclerosiscannot properly be diagnosed unless it can be shown that other regions are affected subclinically. The electrocerebral responses evoked by monocular visual stimulation with a checkerboard pattern stimulus, by monaural click stimulation, and by electrical stimulation of a sensory or mixed peripheral nerve have been used to detect subclinical involvement of the visual, brain stem auditory, and somatosensory pathways, respectively. Other disorders may also be characterized by multifocal electrophysiologic abnormalities.
There may be mild lymphocytosis or a slightly increased protein concentration in the cerebrospinal fluid, especially soon after an acute relapse. Elevated IgG in cerebrospinal fluid and discrete bands of IgG (oligoclonal bands) are present in many patients. The presence of such bands is not specific, however, since they have been found in a variety of inflammatory neurologic disorders and occasionally in patients with vascular or neoplastic disorders of the nervous system.
At least partial recovery from acute exacerbations can reasonably be expected, but further relapses may occur without warning, and there is no means of preventing progression of the disorder. Some disability is likely to result eventually, but about half of all patients are without significant disability even 10 years after onset of symptoms.
Recovery from acute relapses may be hastened by treatment with corticosteroids, but the extent of recovery is unchanged. A high dose (eg, prednisone, 60 or 80 mg) is given daily for 1 week, after which medication is tapered over the following 2 or 3 weeks. Such a regimen is often preceded by methylprednisolone, 1 g intravenously for 3 days. Long-term treatment with steroids provides no benefit and does not prevent further relapses.
Several recent studies have suggested that intensive immunosuppressive therapy with cyclophosphamide or azathioprine may help to arrest the course of chronic progressive active multiple sclerosis. The evidence of benefit is incomplete, however, and further clinical trials are in progress. There is little evidence that plasmapheresis enhances any beneficial effects of immunosuppression in multiple sclerosis, and its role in the management of the various clinical forms of the disease is uncertain. In patients with relapsing-remitting multiple sclerosis, treatment with beta interferon has been shown to reduce the annual exacerbation rate, and further studies of this approach are proceeding. Finally, preliminary studies suggest that Cop 1 (a random polymer-simulating myelin basic protein) may be beneficial in patients with the exacerbating-remitting form of multiple sclerosis, and further evaluation of this approach seems warranted.
Treatment for spasticity and for neurogenic bladder may be needed in advanced cases. Excessive fatigue must be avoided, and patients should rest during periods of acute relapse.
10240:22:1 Beck RW et al: A randomized, controlled trial of corticosteroids in the treatment of acute optic neuritis. N Engl J Med 1992;326:581. (Intravenous methylprednisolone followed by oral prednisone speeds recovery after optic neuritis.)
10240:22:2 Hughes RAC: Immunotherapy for multiple sclerosis. J Neurol Neurosurg Psychiatry 1994;57:3.
10240:22:3 IFNB Multiple Sclerosis Study Group: Interferon beta-1b is effective in relapsing-remitting multiple sclerosis. Neurology 1993;43:655. (Double-blind controlled trial.)