Researchers Uncover a Possible Rare Cause of Epilepsy: Autoimmune Disease

Barbara Boughton

September 21, 2010

September 21, 2010 (San Francisco, California) — Some patients with cryptogenic partial seizures refractory to traditional antiepileptic medications may have "autoimmune epilepsy" — epilepsy characterized by the presence of autoimmune antibodies.

Although the incidence of this type of epilepsy is probably rare, patients with this condition may respond to immune-modulating therapy, according to new research presented at the American Neurological Association 135th Annual Meeting.

In the retrospective medical record review of the epilepsy monitoring unit at Mayo Clinic Hospital in Phoenix, Arizona — with a total of 1196 admissions from 2006 to 2009 — 6.9% of those patients who had partial-onset seizures and cryptogenic etiology (n = 159) tested positive for autoimmune antibodies.

Most of these identified patients received immune-modulating medications, and all had at least a 50% reduction in seizure frequency after therapies such as intravenous methylprednisolone or oral prednisone. However, these responses were not always long-lasting, said lead study author Matthew Hoerth, MD, a clinical neurophysiology fellow in the Department of Neurology at the Mayo Clinic in Phoenix.

"Although our review suggests that autoimmune epilepsy is rare, clinicians might want to think about screening patients for autoimmune antibodies if they have cryptogenic frequent partial seizures that are not responsive to antiepileptic therapy," he said.

Positive for Autoantibodies

Dr. Hoerth said the Mayo Clinic study was prompted when several patients treated in the epilepsy unit were found to test positive on autoantibody screening. "A review of the literature shows that a lot of immune-mediated diseases have epilepsy as a symptom of their disease — such as lupus and Crohn's disease — and several different antibodies are associated with seizures," he said.

Immune-mediated diseases with seizures tend to present with partial onset, Dr. Hoerth explained. So the researchers limited their review to those patients with partial-onset seizures and cryptogenic etiology. Patients with known autoimmune disorders were excluded from the review.

Almost 20% of patients with cryptogenic partial seizures were screened with a paraneoplastic antibody panel, and of these, 11 tested positive. Most of these patients had frequent symptoms — with up to 4 daily seizures — and commonly presented with vague cognitive symptoms such as confusion. Electrocardiograms of all the patients, however, were consistent with epilepsy, and most had tried more than 2 antiepileptic medications without success, Dr. Hoerth said.

Clinicians were able to treat 8 of the patients with immune-modulating therapy (2 were deceased before treatment could begin), and of these, all had at least an initial response to these medications. "The responses were not robust in all of the patients, but treatment with therapies such as [intravenous] steroids did seem to make a difference," Dr. Hoerth said.

Dr. Hoerth noted that more work needs to be done to understand the significance of these findings. Since the population in the study was highly selected, the percentage of patients in the review with autoimmune epilepsy may not reflect its true incidence, he added.

The researchers plan to do a prospective study to try to figure out which epilepsy patients should be tested for autoimmune antibodies and how they should be treated. "Over the next few years, we'll be learning a lot more about this phenomenon, and how to treat patients with positive autoimmune markers," Dr. Hoerth said.

Cause of Previously Unexplained Seizures?

"The study suggests that a small percentage, but an important percentage, of patients with partial-onset seizures may have autoimmune diseases," commented Dan Lowenstein, MD, professor and vice chair of the Department of Neurology at the University of California–San Francisco (UCSF) and director of the UCSF epilepsy center. "This study makes me wonder about a whole host of patients I've seen [with seizures] over the years with no obvious cause for their disease," he said.

Dr. Lowenstein noted that the Mayo Clinic study left some questions unanswered — for instance, how a clinician might plan long-term treatment for a patient with partial seizures, who tested positive for autoimmune antibodies, he said. Steroids — particularly those delivered intravenously — might not be appropriate for chronic disease.

"As the availability of screening assays increases, testing for autoimmune antibodies will probably become a more common part of the workup for patients," Dr. Lowenstein added. However, performing an entire paraneoplastic antibody panel is now fairly costly, he said.

Dr. Hoerth and Dr. Lowenstein have disclosed no relevant financial relationships.

American Neurological Association (ANA) 135th Annual Meeting: Abstract T-5. Presented September 14, 2010.


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