GABA(B)R and AMPAR abs are well associated with LE. GABA(B)R abs lead to severe clinical, neuroradiological and EEG abnormalities with poorer outcome.

There is a need for diagnostic biomarkers of epilepsy and status epilepticus to support clinical examination, electroencephalography and neuroimaging. Extracellular microRNAs may be potentially ideal biomarkers since some are expressed uniquely within specific brain regions and cell types. Cerebrospinal fluid offers a source of microRNA biomarkers with the advantage of being in close contact with the target tissue and sites of pathology. Here we profiled microRNA levels in cerebrospinal fluid from patients with temporal lobe epilepsy or status epilepticus, and compared findings to matched controls. Differential expression of 20 microRNAs was detected between patient groups and controls. A validation phase included an expanded cohort and samples from patients with other neurological diseases. This identified lower levels of miR-19b in temporal lobe epilepsy compared to controls, status epilepticus and other neurological diseases. Levels of miR-451a were higher in status epilepticus compared to other groups whereas miR-21-5p differed in status epilepticus compared to temporal lobe epilepsy but not to other neurological diseases. Targets of these microRNAs include proteins regulating neuronal death, tissue remodelling, gliosis and inflammation. The present study indicates cerebrospinal fluid contains microRNAs that can support differential diagnosis of temporal lobe epilepsy and status epilepticus from other neurological and non-neurological diseases.

Only higher CASPR2 serum antibody titres indicate anti-CASPR2 encephalitis, and diagnostic accuracy increases if MRI findings are considered. Anti-CASPR2 encephalitis has characteristic features and a favourable outcome with immunotherapy.

Objective:It was hypothesized that in encephalitides with autoantibodies directed to CNS surface antigens an antibody-removing intervention might speed up recovery.Methods:The outcome of autoimmune encephalitis in 19 patients with antibodies against surface antigens (leucine-rich, glioma inactivated 1 [LGI1], n = 3; contactin-associated protein-2 [CASPR2], n = 4; NMDA receptor [NMDAR], n = 7) and intracellular antigens (glutamic acid decarboxylase [GAD], n = 5) after immunoadsorption in addition to corticosteroid therapy was evaluated retrospectively. Modified Rankin scale (mRS) scores and data on seizures, memory, and antibody titers directly after immunoadsorption (early follow-up) and after a median of 4 months (late follow-up) were compiled.Results:Immediately after immunoadsorption, 9 of 14 patients with antibodies against LGI1, CASPR2, or NMDAR (64%), but none with GAD antibodies, had improved by at least one mRS point. Five of the 7 patients with LGI1 or CASRP2 antibodies had become seizure-free, and 2 patients with NMDAR antibodies had a memory improvement of more than 1 SD of a normal control population. At late follow-up, 12 of 14 patients with surface antibodies had improved (86%), and none of the patients with GAD antibodies.Conclusions:It is suggested that addition of immunoadsorption to immunosuppression therapy in patients with surface antibodies may accelerate recovery. This supports the pathogenic role of surface antibodies.Classification of evidence:This study provides Class IV evidence that immunoadsorption combined with immunosuppression therapy is effective in patients with autoimmune encephalitis with surface antibodies.

The results support the view that in selected older patients, epilepsy surgery shows equal or even higher success rates as compared to younger patients. However, patients of older age may be at greater risk for postoperative hygroma and memory deficits, especially after dominant temporal lobe resections.

Objective To determine frequencies, interlaboratory reproducibility, clinical ratings, and prognostic implications of neural antibodies in a routine laboratory setting in patients with suspected neuropsychiatric autoimmune conditions. Methods Earliest available samples from 10,919 patients were tested for a broad panel of neural antibodies. Sera that reacted with leucine-rich glioma-inactivated protein 1 (LGI1), contactin-associated protein-2 (CASPR2), or the voltage-gated potassium channel (VGKC) complex were retested for LGI1 and CASPR2 antibodies by another laboratory. Physicians in charge of patients with positive antibody results retrospectively reported on clinical, treatment, and outcome parameters. Results Positive results were obtained for 576 patients (5.3%). Median disease duration was 6 months (interquartile range 0.6–46 months). In most patients, antibodies were detected both in CSF and serum. However, in 16 (28%) patients with N-methyl-d-aspartate receptor (NMDAR) antibodies, this diagnosis could be made only in cerebrospinal fluid (CSF). The two laboratories agreed largely on LGI1 and CASPR2 antibody diagnoses (κ = 0.95). The clinicians (413 responses, 71.7%) rated two-thirds of the antibody-positive patients as autoimmune. Antibodies against the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR), NMDAR (CSF or high serum titer), γ-aminobutyric acid-B receptor (GABABR), and LGI1 had ≥ 90% positive ratings, whereas antibodies against the glycine receptor, VGKC complex, or otherwise unspecified neuropil had ≤ 40% positive ratings. Of the patients with surface antibodies, 64% improved after ≥ 3 months, mostly with ≥ 1 immunotherapy intervention. Conclusions This novel approach starting from routine diagnostics in a dedicated laboratory provides reliable and useful results with therapeutic implications. Counseling should consider clinical presentation, demographic features, and antibody titers of the individual patient.

Summary Objective To examine the long‐term outcome of psychological status, personality, and health‐related quality of life (HRQoL) in patients with psychogenic nonepileptic seizures (PNES) and to define predictors of favorable outcome of cessation of PNES. Method Patients diagnosed with PNES during video–electroencephalography (EEG) monitoring at the Erlangen Epilepsy Center were contacted 1‐16 years after communicating the diagnosis. Follow‐up information from each participant was obtained by interview (PNES outcome) and by self‐reported questionnaires of psychological symptoms (Beck Depression Inventory‐II, Symptom Checklist‐90‐Standard, Dissociative Symptoms questionnaire), personality traits (Freiburg Personality Inventory‐Revised), and HRQoL (36‐Item Short Form Health Survey). Results Fifty‐two patients participated in the study (mean age ± standard deviation [SD] 40.5 ± 14.0 years; 75% female, follow‐up: 5.3 ± 4.2 years). Nineteen patients (37%) were free of PNES for the past 12 months. Patients with persisting PNES were older at disease onset (32.9 vs 22.3 years, P < 0.01) and diagnosis (40.5 vs 27.2 years, P < 0.001), and showed worse psychological functioning, lower extraversion and life satisfaction, and higher inhibitedness and worse HRQoL than PNES‐free patients. Patients with cessation of PNES were within the normal range in all dimensions. Cessation of PNES was best predicted by younger age at PNES onset and higher extraversion. Significance Outcome of PNES is poor, psychopathology is high, and HRQoL is low in patients with persistent PNES but may normalize with PNES cessation. High introversion and older age at PNES onset are risk factors for persistent PNES.

Objective: Despite bioequivalence, the exchangeability of antiepileptic drugs in clinical settings is disputed. Therefore, we investigated the risk for recurrent seizures after switching the manufacturer of the same drug in a large German cohort. Methods: Anonymous patient data from practice neurologists throughout Germany between 2011 and 2016 were collected using the IMS Disease Analyzer database (QuintilesIMS, Frankfurt, Germany). People with epilepsy were included if at least 2 prescriptions within 360 days and 1 within 180 days prior to the index date were available. The cohort was separated into a seizure group and seizure-free controls. Both groups were matched 1:1 according to age, gender, insurance status, and treating physician. The risk for breakthrough seizures after a manufacturer switch of the same antiepileptic drug was analyzed using multivariate regression models. Results: A total of 3,530 people with epilepsy were included (each group, n = 1,765; age = 53.7 ± 19.8 years). Patients with seizures had switched the drug manufacturer more often than controls (26.8% vs 14.2%; odds ratio [OR] = 1.35, 95% confidence interval [CI] = 1.08-1.69, p = 0.009), both from branded to generic (5.5% vs 2.4%; OR = 1.85, 95% CI = 1.30-2.64, p < 0.001) and between generic drugs (14.7% vs 7.1%; OR = 1.45, 95% CI = 1.13-1.87, p = 0.004). Interpretation: In previously seizure-free patients, switching the manufacturer of antiepileptic medications was associated with a higher risk for seizure recurrence. Our retrospective approach does not allow us to determine whether other changes in medical care at the same time could contribute to the recurrence. However, it would be prudent to avoid switching the manufacturer of anticonvulsants in seizure-free patients. ANN NEUROL 2018;84:918-925