Effective therapy for autoimmune drug-resistant epilepsy
MedWire News: Research points towards early immunotherapy as an effective treatment for medically intractable epilepsy when autoimmunity is identified as the basis of the drug resistance.
The study, published in the Archives of Neurology, shows that patients with autoimmune drug-resistant epilepsy had improved seizure outcomes after immunotherapy.
Seizures continue in one-third of patients who are treated with antiepileptic drugs (AEDs), explain Amy Quek (Mayo Clinic, Rochester, Minnesota, USA) and colleagues.
"Accumulating data support an autoimmune basis in patients with AED-resistant seizures… Identification of an immune basis is important because adjunctive immunotherapy may slow, halt, or even reverse the epileptogenic process in these patients," they write.
A total of 32 patients with epilepsy of suspected autoimmune etiology (based on neural antibody [91%], inflammatory cerebrospinal fluid [31%], or magnetic resonance imaging suggesting inflammation [63%]) were recruited. Most (81%) had failed treatment with two or more AEDs (median, three AEDs), and 26 patients (81%) had daily seizures; the rest of the cohort had at least one seizure per month.
Of these patients, 27 received immunotherapy: 12 received intravenous methylprednisolone (IVMP) alone, three received intravenous immune globulin (IVIg) alone, and 12 received combinations of IVMP, IVIg, cyclophosphamide, or plasmapheresis.
After a median of 17 months, 22 (81%) of these 27 patients reported clinical improvement after initiation of immunotherapy, and 18 were seizure free over a median of 10 months.
Neural antibodies were identified in 29 patients, of which the voltage-gated potassium channel antibody was the most common (found in 18 patients). Seven patients had antiglutamic acid decarboxylase 65 antibodies and four had antibodies against N-methyl-D-aspartate, Ma, or neuronal nicotinic acetylcholine receptors.
"The clinical spectrum of auto-immune epilepsy is still unknown… It is conceivable that we are only identifying patients with the most severe presentations in this heterogeneous group, and the burden of this entity remains underappreciated in patients with milder epilepsies," conclude Quek and team.
In an accompanying editorial, Gregory Bergey (The Johns Hopkins Hospital, Baltimore, Maryland, USA) suggests that trails to test which immunotherapy, for example, steroids, intravenous immunoglobulin, cyclosporine, or rituximab, is most effective would be an ethical way to further this research.
"We need an increased appreciation of the potential role of autoantibodies in refractory epilepsy so we are not overlooking treatable etiologies," he said.
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By Chloe McIvor