Objective: To evaluate a trial of immunotherapy as an aid to diagnosis in suspected autoimmune epilepsy. Method:We reviewed the charts of 110 patients seen at our autoimmune neurology clinic with seizures as a chief complaint. Twenty-nine patients met the following inclusion criteria: (1) autoimmune epilepsy suspected based on the presence of $1 neural autoantibody (n 5 23), personal or family history or physical stigmata of autoimmunity, and frequent or medically intractable seizures; and (2) initiated a 6-to 12-week trial of IV methylprednisolone (IVMP), IV immune globulin (IVIg), or both. Patients were defined as responders if there was a 50% or greater reduction in seizure frequency.Results: Eighteen patients (62%) responded, of whom 10 (34%) became seizure-free; 52% improved with the first agent. Of those receiving a second agent after not responding to the first, 43% improved. A favorable response correlated with shorter interval between symptom onset and treatment initiation (median 9.5 vs 22 months; p 5 0.048). Responders included 14/16 (87.5%) patients with antibodies to plasma membrane antigens, 2/6 (33%) patients seropositive for glutamic acid decarboxylase 65 antibodies, and 2/6 (33%) patients without detectable antibodies. Of 13 responders followed for more than 6 months after initiating long-term oral immunosuppression, response was sustained in 11 (85%).Conclusions: These retrospective findings justify consideration of a trial of immunotherapy in patients with suspected autoimmune epilepsy. Classification of evidence:This study provides Class IV evidence that in patients with suspected autoimmune epilepsy, IVMP, IVIg, or both improve seizure control. Neurology ® 2014;82:1578-1586 GLOSSARY AED 5 antiepileptic drug; CASPR2 5 contactin-associated protein-like 2; CC 5 calcium channel; gAChR 5 neuronal acetylcholine receptor, ganglionic-type; GAD65 5 glutamic acid decarboxylase 65; IgG 5 immunoglobulin G; IVIg 5 IV immune globulin; IVMP 5 IV methylprednisolone; LGI1 5 leucine-rich, glioma-inactivated 1; PMA Abs 5 antibodies to neural plasma membrane antigen; VGKC 5 voltage-gated potassium channel.Approximately one-third of epilepsy cases are intractable to antiepileptic drug (AED) therapy.

Principal component analysis (PCA) by singular value decomposition (SVD) may be used to analyze an epoch of a multichannel electroencephalogram (EEG) into multiple linearly independent (temporally and spatially noncorrelated) components, or features; the original epoch of the EEG may be reconstructed as a linear combination of the components. The result of SVD includes the components, expressible as time series waveforms, and the factors that determine how much each component waveform contributes to each EEG channel. By omission of some component waveforms from the linear combination, a new EEG can be reconstructed, differing from the original in useful ways. For example, artifacts can be removed and features such as ictal or interictal discharges can be enhanced by suppressing the remainder of the EEG. We developed a variation of this technique in which the factors that reconstruct the modified EEG from the original are stored as a matrix. This matrix is applied to multichannel EEG at successive times to create a new EEG continuously in real time, without redoing the time-consuming SVD. This matrix acts as a spatial filter with useful properties. We successfully applied this method to remove artifacts, including ocular movement and electrocardiographic artifacts. Removal of myogenic artifacts was much less complete, but there was significant improvement in the ability to visualize underlying activity in the presence of myogenic artifacts. The major limitations of the method are its inability to completely separate some artifacts from cerebral activity, especially when both have similar amplitudes, and the possibility that a spatial filter may distort the distribution of activities that overlap with the artifacts being removed.

We propose a new integrative approach to characterize the structure of seizures in the space, time, and frequency domains. Such characterization leads to a new technical development for ictal source analysis for the presurgical evaluation of epilepsy patients. The present new ictal source analysis method consists of three parts. First, a three-dimensional source scanning procedure is performed by a spatio-temporal FINE source localization method to locate the multiple sources responsible for the time evolving ictal rhythms at their onsets. Next, the dynamic behavior of the sources is modeled by a multivariate autoregressive process (MVAR). Lastly, the causal interaction patterns among the sources as a function of frequency are estimated from the MVAR modeling of the source temporal dynamics. The causal interaction patterns indicate the dynamic communications between sources, which are useful to distinguish the primary sources responsible for the ictal onset from the secondary sources caused by the ictal propagation. The present ictal analysis strategy has been applied to a number of seizures from five epilepsy patients, and their results are consistent with observations from either MRI lesions or SPECT scans, which indicate its effectiveness. Each step of the ictal source analysis is statistically evaluated in order to guarantee the confidence in the results.

Results of this study modified our approach in patients with TLE. Interictal epileptiform discharges localized to one temporal lobe on serial routine EEGs or during LTM may be adequate to identify the epileptogenic zone in patients with MRI-identified unilateral medial temporal lobe atrophy.