Routine diagnostics for neural antibodies, clinical correlates, treatment and functional outcome.

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.

Psychosocial outcome in epilepsy after extratemporal surgery.

OBJECTIVE: Only limited data exist on psychosocial long-term outcome after epilepsy surgery in patients with extratemporal epilepsy. The aim of this study was to investigate psychosocial outcome after extratemporal epilepsy surgery and to assess factors predicting favorable outcome. METHOD: Sixty-five out of 104 eligible patients who had undergone extratemporal epilepsy surgery at our epilepsy center between 1990 and 2015 (mean age: 42.2. years; 75% of the resections in the frontal lobe) completed a questionnaire asking about seizure status, employment status, marital and living situation, driving status, depressive symptoms, and quality of life (QOL). Follow-up was on average 9.2years after surgery (range: 1-26years). RESULTS: Thirty-eight (58%) patients were free of disabling seizures (Engel class I), and 28 (43%) have not experienced any seizures after surgery (Engel class IA). Employment rate in the primary labor market remained at 45%, but more patients lost employment (14%) than gained employment (8%). Postoperative employment was predicted by preoperative employment (p=.007), seizure freedom (p=.025), older age at seizure onset (p=.018), younger age at follow-up (p=.035), and female gender (p=.048). Seizure-free patients were more likely to be driving; have a partner, particularly in males; and have lower depressive scores. Quality of life at follow-up was best predicted by employment (p=.012), partnership (p=.025), and seizure freedom (p=.025). In contrast, recurrence of seizures and early seizure onset were associated with poor psychosocial outcome, particularly in men. CONCLUSION: The study provides support that extratemporal surgery can lead to improved QOL and favorable psychosocial outcome. Seizure freedom is important but not the only determinant of good psychosocial outcome.

Immunoadsorption therapy in autoimmune encephalitides.

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.

Conjoint occurrence of GABAB receptor antibodies in Lambert-Eaton myasthenic syndrome with antibodies to the voltage gated calcium channel.

Antibodies (abs) to the GABAB receptor have been recently found to be responsible for immune-mediated encephalitis with dominant seizures. They are in approximately 50% of cases associated with small-cell lung cancer (SCLC). GABAB receptors are mainly located in the hippocampus, thalamus and cerebellum in the presynaptic and postsynaptic regions of synapses. The main function of these receptors is to reduce activity states of neurons. In some instances, GABAB receptor abs in these patients were accompanied by other antibodies, among them VGCC abs (Lancaster et al., 2010, Boronat et al., 2011). VGCC abs cause paraneoplastic Lambert Eaton myasthenic syndrome (LEMS) by reduction of presynaptic VGCCs (Titulaer et al., 2011). In the domain of CNS disease, VGCC abs have been found in association with paraneoplastic cerebellar ataxia (Mason et al., 1997) and rarely and at low titres also in other paraneoplastic encephalopathies together with Hu abs (Lennon et al., 1995). It has been a long-standing debate if abs in paraneoplastic conditions associate rather with the neurological syndrome or the tumour. Here, we describe the conjoint occurrence of abs to the GABAB receptor and to the VGCC in a patient with SCLC presenting only symptoms of the peripheral nervous system giving another example of the latter hypothesis.