Department of Neurology, Dokkyo Medical University, Japan.
Med Hypotheses. 2021 May;150:110567. doi: 10.1016/j.mehy.2021.110567. Epub 2021 Mar 23.
Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis patients demonstrate characteristic multistage progression and movement disorders, which are analogous to hystero-epilepsy in Jean-Martin Charcot's Tuesday Lessons. First, based on a review of the Tuesday Lessons recorded by Charcot's pupils, we hypothesized that there were patients with anti-NMDAR encephalitis among those diagnosed with hystero-epilepsy in the nineteenth century. We found acute-onset multiple neuropsychiatric manifestations resembling anti-NMDAR encephalitis among patients with hystero-epilepsy. Patients with drug withdrawal syndrome, dissociative and conversion disorders and patients under hypnosis from the modern point of view were also identified. These results suggested that hystero-epilepsy in the Tuesday Lessons could encompass dissociative and conversion disorders, hypnosis, drug withdrawal syndrome, and anti-NMDAR encephalitis-like manifestations. Based on Charcot's observations and current progress in molecular biology, such as the identification of glutamate/NMDAR system dysfunction in drug withdrawal syndrome, we then hypothesized that patients with dissociative and conversion disorders and those under hypnosis could also have hypofunction of the glutamatergic system. The NMDAR hypofunction hypothesis is emerging as a pathogenesis of schizophrenia. NMDAR antagonists are known to evoke symptoms similar to schizophrenia, anti-NMDAR encephalitis and near-death experiences. In current clinical reports, spectrum disorders such as dissociative disorder and conversion disorder have been observed in patients with anti-NMDAR encephalitis. Our hypothesis will offer an expansion of the NMDAR hypofunction hypothesis from psychosis to functional neurological disorders and normal specific situations, such as hypnosis, thanatosis, and near-death experiences.
抗 N-甲基-D-天冬氨酸受体 (NMDAR) 脑炎患者表现出特征性的多阶段进展和运动障碍，类似于让·马丁·沙可（Jean-Martin Charcot）周二讲座中的癔症性癫痫。首先，基于对沙可学生记录的周二讲座的回顾，我们假设在 19 世纪诊断为癔症性癫痫的患者中存在抗 NMDAR 脑炎患者。我们发现了与抗 NMDAR 脑炎相似的急性发作性多种神经精神表现。还鉴定了具有戒断综合征、分离和转换障碍以及从现代观点来看处于催眠状态的患者。这些结果表明，周二讲座中的癔症性癫痫可能包括分离和转换障碍、催眠、戒断综合征以及类似抗 NMDAR 脑炎的表现。基于沙可的观察结果和当前分子生物学的进展，例如在戒断综合征中鉴定出谷氨酸/NMDAR 系统功能障碍，我们随后假设分离和转换障碍患者以及处于催眠状态的患者也可能存在谷氨酸能系统功能低下。NMDAR 功能低下假说正在成为精神分裂症的发病机制。已知 NMDAR 拮抗剂会引起类似于精神分裂症、抗 NMDAR 脑炎和濒死体验的症状。在当前的临床报告中，观察到抗 NMDAR 脑炎患者存在分离障碍和转换障碍等谱障碍。我们的假设将从精神病扩展到功能性神经障碍和正常特定情况，如催眠、濒死体验和濒死体验，为 NMDAR 功能低下假说提供了扩展。
