Immunotherapy Helps Epileptic Patients With Neural Antibodies

Daniel M. Keller, PhD

September 27, 2013

VIENNA, Austria — A proportion of patients with epilepsy whose disease is resistant to antiepileptic drugs (AEDs) have autoantibodies against neural components. Immune-directed therapy in these patients substantially reduces seizure frequency for many, a new study suggests.

"In general, patients with antibodies targeting synaptic antigens — cell surface antigens — showed a dramatic response to antibody-depleting therapy like plasmapheresis or immunoglobulins, while patients with antibodies targeting intracellular antigens respond less frequently to immunotherapy," lead author Raffaele Iorio, MD, from the Institute of Neurology in the Department of Geriatrics, Neurosciences, and Orthopedics at the Catholic University in Rome, Italy, concluded.

He reported findings here at the XXI World Congress of Neurology (WCN).

About 30% of patients do not achieve control of their epilepsy with AEDs, and certain epilepsy syndromes characterized predominantly by seizures may have an immunologic cause. In this analysis, Dr. Iorio evaluated the frequency of neural autoantibodies in patients with epilepsy of unknown causes and assessed the response to immunotherapy in patients with neural autoantibodies and AED-resistant disease.

Patients were classified into 2 groups. Group 1 had epilepsy that was of unknown cause but was associated with a psychiatric disturbance, a movement disorder, cognitive impairment, or an associated autoimmune disease, such as lupus, Sjögren's syndrome, or myasthenia gravis (group 1, n = 35).

Dr. Raffaele Iorio

Group 2 (n = 37) included patients with AED-resistant epilepsy. Excluded from both groups were individuals with structural/metabolic epilepsy or genetic causes of epilepsy. The groups were well matched for age of epilepsy onset (mean, 29 to 31 years) and sex (about 60% to 65% women).

All samples were tested on a mouse brain substrate by immunohistochemistry for antibodies binding to synaptic antigens or to intracellular antigens. Cell-based assays or immunoblots using recombinant onconeural antigens were used to identify antibodies to specific antigens.

Dr. Iorio said only 3 patients (9%) in group 1 had at least 1 neural-specific autoantibody vs 11 patients (28%) in group 2. The patients with neural-specific autoantibodies (n = 14) and the ones without the autoantibodies (n = 58) did not significantly differ in sex composition, age, disease duration, prevalence of associated autoimmune diseases, or generalized seizures. They did differ, however, in some neurologic characteristics.

Clinical Characteristics of Epileptic Patients With and Without Neural-Specific Autoantibodies

Characteristic Neural-Specific Autoantibody–Positive (n = 14), n (%) Neural-Specific Autoantibody–Negative (n = 58), n (%) P Value
Temporal seizures 11 (79) 27 (47) .039
AED-resistant 11 (79) 27 (47) .039
T2 hyperintense lesions on MRI 4 (29) 3 (5) .023


Immunotherapy Benefited Majority With Autoantibodies

Of the 11 patients with AED-resistant epilepsy who had at least 1 neural-specific antibody, 8 agreed to be treated with immunotherapy: 5 with intravenous (IV) steroids and IV immunoglobulin monthly for 6 months; 1 with IV methylprednisolone, IV immunoglobulin, and rituximab; and 2 with IV steroids, 5 cycles of plasmapheresis, and oral steroids.

"Six patients, the majority of patients, showed dramatic reductions in frequency [of seizures] at 3 months of follow-up while 1 patient showed just a moderate response, and another patient showed no response," Dr. Iorio reported. The 6 patients had a reduction in seizure frequency of 50% or greater at 3 months, 1 had a reduction of 20% to 50%, and 1 a reduction of less than 20%.

He concluded that immunotherapy in patients with AED-resistant epilepsy and neural antibodies is beneficial and recommended consideration of testing for neural antibodies in patients with AED-resistant epilepsy of unknown cause as the presence of such antibodies may predict a response to immunotherapy.

Important Step Forward

Session chair Reeta Kälviäinen, MD, from the Kuopio Epilepsy Center and professor of clinical epileptology at the University of Eastern Finland in Kuopio, commented to Medscape Medical News that the study results are "a very important step forward." Immunotherapy is being used for status epilepticus in the acute setting, even before antibody test results are back, with continuation of immunotherapy if the test results are positive.

"I think this [study] is a natural next step [for] chronic cases," she said. "In fact, this was one of the first studies that I saw really looking at this kind of approach in chronic cases."

Changes are in the works to reclassify the causes of epilepsy on the basis of genetics, structural damage, and autoimmune diseases. "It's not a small number" of epileptic patients who exhibit autoantibodies, Dr. Kälviäinen said. "We have sort of neglected that."

She noted that for longer-term therapy, immunoglobulins and drugs such as rituximab are indicated. Corticosteroids have unacceptable adverse effects, and plasmapheresis is impractical.

Dr. Iorio has disclosed no relevant financial relationships. Dr. Kälviäinen has served on scientific advisory boards for UCB Pharma, Eisai, Lundbeck, GlaxoSmithKline, and Fennomedical and has received funding for travel and speaker honoraria from UCB Pharma, Eisai, GlaxoSmithKline, Medtronic, Pfizer, Orion, and Fennomedical, and institutional research funding from UCB Pharma and GlaxoSmithKline.

XXI World Congress of Neurology (WNC). Free Papers Session 1. Presented September 22, 2013.


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