Multiple sclerosis (MS) is a demyelinating disorder of the central nervous system (CNS), characterized clinically by episodes of focal disturbance of the optic nerves, brain, or spinal cord. The duration of discrete episodes is quite variable and remissions are common. Classic features include:76
The prevalence of MS varies greatly by region. Worldwide prevalence ranges from approximately 1 case per 100,000 in the Far East to more than 150 cases per 100,000 in parts of the United Kingdom.77 In the United States, prevalence ranges from approximately 10 cases per 100,000 to 170 cases per 100,000. MS presents most commonly in young adults, with a mean age of 30 years.78 Women are affected more commonly than men.
A detailed discussion of the pathophysiology of MS is beyond the scope of this material. The primarily affected cells in the CNS are oligodendrocytes, cells that produce a myelin sheath, surrounding axons and aiding conduction. It is not entirely clear whether the primary event in MS is an attack on the oligodendrocyte, the myelin sheath, or both.79 The classic lesion in the CNS in MS is a focal region of demyelination, referred to as a plaque. Large numbers of plaques may be found throughout the white matter of the brain or spinal cord. Clinical symptoms are determined by the location of the plaques. When they become numerous, plaques may become confluent.
The areas in the brain most commonly affected are the subcortical white matter and periventricular regions. In the spinal cord, subpial plaques are most common. Lesions throughout the brain stem and cerebellum are also common. Given the frequency of visual symptoms in MS, it is not surprising that the optic nerves are affected in virtually every case.80
Plaques at the junction of the cortex and white matter, or even in the gray matter itself, are less common, occurring in almost 25% of cases.81 These cortical or subcortical plaques may act as seizure foci. There are several reports of seizure onset or recurrent seizures correlating with new MS lesions or with active exacerbation of older plaques.82,83 Others have found no clear correlation.84
MS can cause virtually any neurologic deficit, based on the location of new and old plaques. This discussion is limited to seizures, which can occur at any time during the course of illness. In some cases, seizures may be the only clinical manifestation.83 Partial-onset seizures clearly predominate and occur more frequently than in the global epilepsy population.77,82
The diagnosis of MS requires signs or symptoms of multiple CNS lesions, separated in time and space. It also requires the exclusion of other disorders that may produce a similar clinical picture:
Diagnosis may be difficult at the time of presentation because the duration of the illness may be too short to produce multiple lesions and multiple signs or symptoms over time. Diagnostic testing to locate additional lesions and possibly subclinical signs may be helpful in making an early diagnosis in these cases.
Diagnostic testing includes MRI of the brain, spinal cord, or both. MS plaques are typically isodense or hypodense on T1-weighted scans and hyperintense on T2-weighted scans. Periventricular lesions are seen in up to 85% of MS patients,85 with involvement of the corpus callosum in up to 90%.86 Acute lesions usually demonstrate enhancement, presumably owing to disruption of the blood-brain barrier.
Evoked potential studies can be useful in defining subclinical lesions of the visual pathway, brain stem, or spinal cord. When abnormal, these tests typically reveal slowed central conduction, consistent with demyelination. Visual evoked potentials have been reported to be abnormal in up to 80% of MS cases.87
Examination of the spinal fluid usually demonstrates oligoclonal bands and increased intrathecal synthesis of IgG. During acute attacks, a mild pleocytosis may be present.
Many of the disorders that may present in a similar manner to MS do not manifest seizures frequently. Sarcoidosis and primary angiitis of the central nervous system (PACNS) manifest seizures more frequently than MS and should be considered earlier in the evaluation.
Between 1% and 4% of patients with MS may experience paroxysmal dysarthria and ataxia.88 These multiple brief episodes are marked by sudden onset of slurred speech and ataxia in one or more limbs. This entity may be confused with epileptic events based on its clinical characteristics. Interestingly, it responds well to anticonvulsive therapy, particularly carbamazepine.
Brief episodes of marked dystonic posturing of the arm, leg, or face on one side have also been reported.89 Often triggered by movement or tactile sensation, episodes may start abruptly and last for 30 seconds to several minutes. The movements are frequently painful. These episodes may be successfully treated with anticonvulsant drugs.
Treatment of acute exacerbations of MS is aimed at shortening the duration of individual attacks. The more commonly used immunosuppressive agents in MS are:
Relapses of prior symptoms may be due to a metabolic or infectious cause, the treatment of which yields resolution. Treatment of acute relapses frequently results in the resolution of acute seizures.
Chronic therapy is directed more toward the prevention of relapses and progression of disease. The relatively recent introduction of interferon beta-1b, interferon beta-1a, and copolymer-1 has reduced the frequency of relapses over time, but no current treatment has been shown to significantly alter the long-term outcome of the disease.
Seizures not related to an acute relapse of the underlying disorder typically respond well to traditional antiepileptic drugs.
MS can cause significant morbidity but tends to have much less effect on mortality. Given the wide variability and unpredictable nature of clinical signs and symptoms in MS, the prognosis is based on a patient's own clinical history. If the disease has been mild for 5 to 10 years, it is likely to remain mild for the next decade. If the patient is severely affected early in the illness, disability tends to be greater.90
Some have suggested that the occurrence or frequency of seizures does not significantly correlate with MS severity or evolution.91 Others have suggested that these patients fall into several major groups.77,83,92
Seizures in MS patients tend to have a good prognosis, with spontaneous resolution in almost half. In many of these cases, the seizures are thought to be related to acute exacerbations. In patients who have seizures that do not clearly correlate with the course of MS itself, antiepileptic drug therapy is quite effective. In patients who have a progressive cognitive decline associated with their seizures, the prognosis is somewhat worse, with a susceptibility to status epilepticus.
Reviewed and revised March 2004 by Steven C. Schachter, MD, epilepsy.com Editorial Board.
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