Hystero-epilepsy in the Tuesday Lessons and NMDA receptor function: A hypothesis for dissociative disorder.

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.