VIENNA — A sizable minority of patients with drug-resistant epilepsy were found to have autoantibodies to neural antigens, and many of them responded to steroids and other immunomodulatory drugs, a researcher said here.
Among 72 patients who underwent a variety of assays for neural autoantibodies, 14 tested positive for at least one — and of eight who then underwent immune-targeted treatment, six showed at least a 50% reduction in seizure frequency, reported Raffaele Iorio, MD, of Catholic University in Rome.
“Testing for neural-specific antibodies should be considered in the workup of patients with AED (anti-epileptic drug) resistant epilepsy due to unknown cause,” he told attendees at theWorld Congress of Neurology.
But some of the antibodies assayed in the study are generally considered oncogenic, and Iorio acknowledged that their presence may actually signal an occult tumor.
Past studies have implicated immune system factors in the genesis of epilepsy, some of them involving antibodies against proteins within the central nervous system, Iorio said.
For the current study, he and colleagues enrolled 35 patients with seizures of unknown cause that were associated with other neurologic abnormalities, including movement disorders, cognitive impairment psychiatric disturbances such as delirium, or recognized autoimmune diseases. The group also recruited 37 other patients with AED-resistant epilepsy.
Clinical samples were tested with immunohistochemistry, immunoblot, and cell-based assays for immunoglobulin G (IgG) reactivity with a variety of antigens related on one hand to neurotransmitter receptors and to known onconeural antigens on the other.
Three patients among the 35 with epilepsy and accompanying neurologic abnormalities tested positive for one of these antigens: one with IgG specific for the Hu onco-antigen, one reacting with the GAD65 synaptic protein, and one reacting with an unknown intracellular CNS protein.
In the AED-resistant patients, five tested positive for specific synaptic antigens and six others had IgG reactive with unknown synaptic or intracellular proteins.
Among 69 healthy subjects, none showed any IgG reactivity in the assays, Iorio said.
Across both patient groups, those with positive test results more often had focal seizures centered in temporal regions (79% versus 47% of IgG-negative patients, P=0.04) and were more often AED-resistant (79% versus 47%, P=0.04). Positive test results were also associated with a greater likelihood of T2 hyperintense lesions seen on MRI scans (29% versus 5%,P=0.02), which Iorio said was suggestive of an inflammatory condition.
Eleven of the IgG-positive patients were offered immunotherapies based on intravenous methylprednisolone plus other treatments — donor immunoglobulins, rituximab (Rituxan), or plasmapheresis followed by oral steroids. Six had at least 50% reduction in seizure frequency from baseline, one patient had a reduction between 20% and 50%, and one had no meaningful response, Iorio reported.
Session moderator Reetta Kälviäinen, MD, director of the Kuopio Epilepsy Center in Finland, said that reactivity with onconeural antigens could suggest a tumoral cause of seizures.
“[Immunological involvement] is a new area for us in epilepsy,” she said, emphasizing that seeking the underlying cause of seizures is paramount. In the case of the patient testing positive for Hu, “there could be a tumor somewhere…this is where we are going now — etiology first — and this [study] is an excellent example.”
Iorio told MedPage Today that his group had considered a malignant etiology in the Hu-positive patient, and had conducted a wide range of imaging and other tests that all came up negative. Nevertheless, he said, such a cause cannot be ruled out.
The study had no commercial funding. Iorio said he had no conflict of interest.
Kälviäinen reported relationships with UCB Pharma, Eisai, Lundbeck, GlaxoSmithKline, Medtronic, Pfizer, and Orion.