LGI1-antibody encephalitis is characterised by frequent, multifocal clinical and subclinical seizures.

PURPOSE: To describe clinical and electrographic characteristics of seizures LGI1-antibody encephalitis, and their correlations with two-year outcomes. METHODS: Video-electroencephalography recordings were performed on a cohort of 16 consecutive patients with LGI1-antibodies from two UK neuroscience-centers over five-years. RESULTS: From 14 of 16 patients (13 males; age-range 53-92years), 86 faciobrachial dystonic seizures were recorded at a median frequency of 0.4 per hour (range 0.1-9.8), and ictal EEG changes accompanied 5/86 events. In addition, 11/16 patients showed 53 other seizures - subclinical (n=18), motor (n=16), or sensory (n=19) - at a median of 0.1 per hour (range 0.1-2) associated with temporal and frontal discharges. The sensory events were most commonly thermal sensations or body-shuddering, and the motor events were frequently automatisms or vocalisations. Furthermore, multifocal interictal epileptiform discharges, from temporal, frontal and parietal regions, and interictal slow-wave activity were observed in 25% and 69% of patients, respectively. Higher observed seizure frequency correlated with poorer functional recovery at two-years (p=0.001). CONCLUSIONS: Multiple frequent seizure semiologies, in addition to numerous subclinical seizures and interictal epileptiform discharges, are hallmarks of LGI1-antibody encephalitis. High overall seizure frequency may predict more limited long-term recovery. These observations should encourage closer monitoring and proactive treatment of seizure activity in these patients.

Impaired neuromuscular transmission and response to acetylcholinesterase inhibitors in centronuclear myopathies.

Many clinical features of autosomal centronuclear myopathies (CNM) and X-linked myotubular myopathy (XLMTM) are common to congenital myasthenic syndromes (CMS). We describe three children whose clinical and electrophysiological findings originally suggested CMS, in whom CNM was diagnosed pathologically, though not yet genetically characterised. A fourth case, with XLMTM, also showed electrophysiological features of a neuromuscular transmission defect. Three (including the XLMTM case) showed improved strength with acetylcholinesterase inhibitor treatment. We also studied neuromuscular junction structure and function in the MTM1 knockdown zebrafish model of XLMTM, demonstrating abnormal neuromuscular junction organization; anticholinesterase therapy resulted in marked clinical response. These observations suggest that a neuromuscular transmission defect may accompany CNM and contribute to muscle weakness. Muscle biopsy should be considered in infants suspected to have CMS, especially if treatment response is incomplete, or no CMS gene mutation is identified. Treatment with acetylcholinesterase inhibitors may benefit some CNM patients. This warrants further confirmation.