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.

Objective:To characterize the clinical features and MRI abnormalities of leucine-rich glioma-inactivated 1 (LGI1)-autoantibody (Ab) faciobrachial dystonic seizures (FBDS).Methods:Forty-eight patients with LGI1-Ab encephalopathy were retrospectively identified by searching our clinical and serologic database from January 1, 2002, to June 1, 2015. Of these, 26 met inclusion criteria for this case series: LGI1-Ab seropositivity and FBDS. In a separate analysis of all 48 patients initially identified, the MRIs of patients with (n = 26) and without (n = 22) FBDS were compared by 2 neuroradiologists blinded to the clinical details.Results:The median age of the 26 included patients was 62.5 years (range 37–78); 65% were men. FBDS involved arm (26), face (22), and leg (12). Ten were previously diagnosed as psychogenic. Ictal EEGs were normal in 20 of 23 assessed. Basal ganglia T1 and T2 signal abnormalities were detected in 11 patients (42%), with excellent agreement between neuroradiologists (κ scores of 0.86 and 0.93, respectively), and included T1 hyperintensity alone (2), T2 hyperintensity alone (1), or both (8). The T1 hyperintensities persisted longer than the T2 hyperintensities (median 11 weeks vs 1 week, p = 0.02). Improvement with immunotherapy (18/18) was more frequent than with antiepileptic medications (10/24). A separate analysis of all 48 patients initially identified with LGI1-Ab encephalopathy showed that basal ganglia MRI abnormalities were present in 11 of 26 with FBDS but not present in those without FBDS (0/22) (p < 0.001). In contrast, mesial temporal MRI abnormalities were less common among those with FBDS (42%) than those without (91%) (p < 0.001).Conclusions:Basal ganglia T1 hyperintensity is a clinically useful MRI biomarker of LGI1-Ab FBDS and suggests a basal ganglia localization.

APE and RITE scores can aid diagnosis, treatment, and prognostication of autoimmune epilepsy. A PowerPoint slide summarizing this article is available for download in the Supporting Information section here.

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.

Expression of the immediate-early gene c-fos has been advanced as a marker of neuronal activity in the adult nervous system. We sought to test the validity of c-fos mRNA expression as a marker of neuronal activity during seizures and to elucidate specific neurotransmitter receptors whose activation was necessary for seizure-evoked c-fos mRNA expression. We correlated c-fos mRNA expression, measured with in situ hybridization, with kindled seizure-induced firing of hippocampal dentate granule cells or substantia nigra pars compacta and pars reticulata neurons. We found that the occurrence of seizure-evoked synchronous action potentials during the seizure exhibited a perfect qualitative correlation with the presence of c-fos mRNA expression in the granule cells 30 min following the seizure (Fisher's exact test, p = 0.002). However, there was no quantitative correlation between the number of seizure-induced population action potentials and the magnitude of c-fos mRNA expression in the granule cells. In the substantia nigra, where neuronal populations have previously been demonstrated to exhibit synchronous firing during kindled seizures, no induction of c-fos mRNA was detected in either pars compacta or pars reticulata. Pretreatment with antagonists of the NMDA subtype of glutamate receptor selectively and markedly decreased seizure-induced c-fos mRNA expression in the dentate granule cells, despite increasing the number of granule cell population action potentials. These findings illustrate the complexity of the relationship between c-fos induction and neuronal burst firing during kindled seizures.(ABSTRACT TRUNCATED AT 250 WORDS)