The occurrence of seizures in systemic immune-mediated disorders demonstrates that epilepsy can be related to immunologic disorders. This raises the issues of whether immune mechanisms may be important in other, more common forms of epilepsy and whether immunotherapy merits further consideration.
Immunoglobulin therapy was first reported to be effective in epilepsy in 1977, when children with epilepsy were given intramuscular IgG to treat recurrent upper respiratory tract infections.93 Improvements in seizure frequency and behavior were noted. Subsequently, 16 children with Lennox-Gastaut syndrome were treated with intravenous IgG (IVIG), and significant improvement was seen in 8 of them.94 Since that time, several additional clinical trials have been published with similar results, reporting significant improvement in about half of cases.93
In 1994, the first double-blind, placebo-controlled trial of IVIG for the treatment of epilepsy was published.95 Three different dosages were evaluated in 61 patients with intractable epilepsy of various etiologies. Significant clinical improvement, defined as a reduction in seizures by at least 50% after 6 months, was reported in 52.5% of the IVIG group, compared to 27.8% of the placebo group, with a p value of .095. No dose relationship was identified.
There is emerging clinical evidence that IVIG may be of value in several refractory seizure conditions. The details regarding which patients and at what point of the illness it should be used need to be investigated further.
Rasmussen's syndrome, or chronic encephalitis and epilepsy, is a well-recognized and relatively stereotyped disorder, first described by Rasmussen in 1958.96,97 It is characterized by a progressive hemiparesis, intellectual decline, and intractable seizures, in association with pathologic changes suggestive of chronic encephalitis.97,98 At presentation, generalized seizures are most common, followed by simple partial and complex partial seizures.99 Approximately 20% of cases may present with status epilepticus.
As the illness evolves, partial seizures clearly predominate, occurring in 77% of cases.99 Epilepsia partialis continua has been reported to occur in more than 50% of cases at some time during the course of the disease.
The pathogenesis of Rasmussen's syndrome is unknown, but an association with autoantibodies to glutamate receptor GluR3 has been suggested.100,101 This has been supported by the finding of a simultaneous reduction in anti-GluR3 antibody titers, with clinical improvement in patients after total plasma exchange.102,103 This benefit is short-lived, suggesting reaccumulation of a pathogenic antibody.104,105
The treatment of Rasmussen's syndrome with high-dose steroid preparations has been somewhat effective, but the beneficial effects do not last long and periodic relapses are frequent.106,107 Treatment of this disorder with IVIG has been reported with initial improvement, but it is not consistently maintained.98,108
Reviewed and revised March 2004 by Steven C. Schachter, MD, epilepsy.com Editorial Board.
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