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Refractory epilepsy may have autoimmune basis

NEW YORK (Reuters Health) – A significant number of patients with medically intractable seizures may have autoimmune epilepsy, a retrospective case series in Archives of Neurology suggests.

Among 32 patients with refractory epilepsy with a presumed autoimmune cause, 22 improved after immunotherapy, including 18 who became completely seizure-free.

“What we’re talking about is treatable neurology, we’re talking about reversible disease,” Dr. Sean J. Pittock of the Mayo Clinic in Rochester, Minnesota, the study’s senior author, told Reuters Health.

While the new report isn’t a randomized controlled trial, “it’s very compelling class 4 evidence,” said Dr. Gregory K. Bergey of The Johns Hopkins University School of Medicine in Baltimore, who authored an editorial on the study. He told Reuters Health, “The percentage that they got seizure-free is more than you would ever expect from a new drug trial or something of that nature.”

Based on the findings, Dr. Bergey added, neurologists should consider the possibility of an autoimmune etiology in patients with epilepsy that does not respond to standard treatment. “We should be thinking about this routinely in patients who have refractory epilepsy,” he said.

One-third of patients with epilepsy continue to have seizures despite optimal medical therapy, Dr. Pittock and his team note in their report. There is growing evidence, they add, that some of these patients may have autoimmune disease. For example, several autoantibodies targeting receptors and channels on brain cells have been identified, and the number of known neural autoantibodies is growing.

In the 32 patients in this report, Dr. Pittock and his team suspected an autoimmune etiology due to the presence of neural autoantibodies in 91%, inflammatory cerebrospinal fluid (CSF) in 31%, and signs of inflammation on magnetic resonance imaging in 63%.

Eighty-one percent had failed trials with at least two antiepileptic drugs.

Five of the patients did not receive immunotherapy. Two of these declined the treatment, two had symptom resolution with anti-epileptic drugs, and one was seizure-free after detection and treatment of a thyroid papillary carcinoma.

The remaining patients received IV immunotherapy, including methylprednisolone (12 patients); immune globulin (3); or combinations of steroids, immunoglobulin, cyclophosphamide, and plasmapheresis (12). They were followed for a median of 17 months.

Five of the 22 responders had relapses during follow-up; two of the five achieved seizure control with additional immunotherapy and antiseizure medication.

Fifteen patients who tested positive for voltage-gated potassium channel complex antibodies all responded to immunotherapy, as did three of five patients with glutamic acid decarboxylase 65 neural autoantibodies.

“When autoimmune epilepsy is suspected on clinical grounds, CSF evaluation and comprehensive screening for neural antibodies are indicated,” Dr. Pittock and his team write. “If autoimmune epilepsy is suspected, a trial of six to 12 weeks of immunotherapy (IVMP or IVIg daily for three days and then weekly) is justifiable in the absence of other treatment options and may serve as additional evidence for an autoimmune etiology when a favorable response is observed.”

It’s still unclear, Dr. Pittock noted, how long patients need to be kept on immunosuppressive treatment. The approach he and his colleagues take, he explained, is to start patients on a steroid-sparing treatment such as Imuran (azathioprine), and then gradually expand the interval between pulsed immunotherapy to see if it is possible to wean the patient off steroids.

“The message shouldn’t be that all epileptics should be started on steroids,” he added. “We want to be careful because we don’t want to get into a situation where everyone is getting treated with drugs that cause harm.” It’s also crucial, Dr. Pittock said, to objectively evaluate patients before and after immunotherapy is initiated, rather than relying on self-report to determine if the treatment works.

His paper was published online March 26.


Arch Neurol 2012.