Early-initiated immunotherapy may improve seizure outcomes in patients with characteristics of autoimmune epilepsy, according to a study in the March 26 online Archives of Neurology.
“Eighty-one percent [of patients] had significant improvement in seizure status, and 67% achieved seizure freedom, a majority of whom were antiepileptic drug [AED] resistant,” reported Amy M. L. Quek, MBBS, of the Mayo Clinic in Rochester, Minnesota, and colleagues.
Treating Medically Intractable Epilepsy
Previous studies have suggested that some patients who are unresponsive to AEDs may have autoimmune epilepsy and that immunotherapy may help to control their seizures. To further investigate the potential benefits of immunotherapy in such patients, Dr. Quek’s group searched the Mayo Clinic’s computerized diagnostic index and identified 32 patients who were diagnosed with autoimmune epilepsy after being evaluated in both the Autoimmune Neurology Clinic and Epilepsy Clinic between January 1, 2005, and December 31, 2010. Autoimmune etiology was suspected based on neural antibody detection (91%), inflammatory CSF (31%), or MRI suggesting inflammation (63%).
Of the 32 patients identified for inclusion in the study, all had partial seizures, 11 had an exclusive seizure presentation, and 21 had a predominant seizure presentation. Furthermore, the seizure semiologies of 12 patients varied or changed over time. Most patients (81%) experienced daily seizures and had failed treatment with two or more AEDs, and the remaining patients had at least one seizure per month.
After conducting EEGs on all 32 patients, the researchers found abnormalities that included interictal epileptiform discharges (20 patients), electrographic seizures (15 patients), and focal slowing (13 patients). Three of the 32 patients showed no EEG abnormalities, the investigators noted, and 15 (47%) patients showed normal head MRIs at the time of initial seizure evaluation.
Dr. Quek and colleagues also recorded neuropsychiatric manifestations at initial seizure evaluation, finding that 63% of patients had memory and cognitive difficulties, 25% had personality changes, and 19% had depression or anxiety.
Neural autoantibodies were identified in 29 patients, including voltage-gated potassium channel complex (VGKC) (56% of patients), glutamic acid decarboxylase 65 (22%), and collapsin response-mediator protein 5 (6%). Ma2, N-methyl-d-aspartate receptor, and ganglionic acetylcholine receptor were found in one patient each.
Response to Immunotherapy
To treat 27 patients in whom seizures persisted despite AED treatment, the researchers initiated immunotherapy with IV methylprednisolone (n=12); IV immune globulin alone (n=3); and combinations of IV methylprednisolone, IV immune globulin, plasmapheresis, or cyclophosphamide (n=12).
The patients were followed for a median of 17 months (range, three to 72 months), with 22 of the 27 patients (81%) showing clinical improvement at last follow-up. During a median 10-month period (range, two to 48 months), 18 patients (67%) were seizure free, and eight of those patients (44%) were seizure free within 12 weeks of initiation of immunotherapy.
Those who responded to immunotherapy had a four-month median time period from seizure onset to initiation of immunotherapy, compared with a 22-month period for nonresponders. In addition, one patient who was VGKC-positive experienced seizure freedom after thyroid cancer resection, and seizures resolved in another patient with VGKC antibodies after AED change alone.
Clinical Implications
Based on the study’s results, the researchers recommend immunotherapy in certain circumstances. “If autoimmune epilepsy is suspected, a trial of six to 12 weeks of immunotherapy … is justifiable in the absence of other treatment options and may serve as additional evidence of autoimmune etiology when a favorable seizure response is observed,” the investigators said. “Clinical experience suggests that immunotherapy should not be used alone to control seizures but should be used in combination with AEDs to optimize seizure control.”
In an accompanying editorial, Gregory K. Bergey, MD, Professor of Neurology, Johns Hopkins Hospital in Baltimore, noted that although the trial was not placebo controlled, the study’s reported rate of seizure freedom following immunotherapy warrants attention, especially when compared with low rates of seizure control in recent blinded trials of AEDs. “Perhaps the failure of new antiepileptic drugs is because some of these patients have autoimmune-mediated epilepsy,” he theorized. “What is the true scope of autoimmune epilepsy in our populations of drug-resistant epilepsy? This is not known, but certainly at present it is probably being underdiagnosed.”
—Lauren LeBano