Anti-NMDA Receptor Encephalitis, Autoimmunity, and Psychosis

Abstract

Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis is a recently-discovered synaptic autoimmune disorder in which auto-antibodies target NMDARs in the brain, leading to their removal from the synapse. Patients manifest with prominent psychiatric symptoms -and in particular psychosis -early in the disease course. This presentation converges with long-standing evidence on multiple fronts supporting the glutamatergic model of schizophrenia. We review mechanisms underlying disease in anti-NMDAR encephalitis, and discuss its role in furthering our understanding of neural circuit dysfunction in schizophrenia.

Paraneoplastic epilepsy

“…The cooccurrence of movement disorder with seizure is a characteristic feature of several paraneoplastic syndromes. Each antibody is associated with a specific type of movement disorder: GAD65 antibody-positive patients are typically associated with stiff person syndrome; patients with anti-NMDA receptor encephalitis often present with orobuccolingual dyskinesias; and parkinsonian features are usually observed in patients with antiMa2 and anti-CRMP5 antibody-positive PE [11][12][13][14][15]. Epilepsia partialis continua (EPC), a clinical syndrome with spontaneous regular or irregular clonic muscular twitching affecting a limited part of the body occurring for a minimum of 1 h, has been frequently reported in anti-Hu seropositive paraneoplastic encephalomyelitis [16][17][18][19][20].…”

“…Roughly 80% of patients with anti-NMDA receptor encephalitis are women [47]. The typical clinical stages are a viral-like prodrome followed by psychiatric symptoms, followed by neurologic complications (movement abnormalities, especially orofacial dyskinesias and seizures) before the recovery phase [13,76]. Over three-fourths of the patients developed seizures and/or SE during the first three weeks of symptom presentation in a series of 100 patients [22].…”

Antigen Presentation After Stroke

“…The majority of the autoantibodies against extracellular epitopes like NMDAR1, myelin oligodendrocyte glycoprotein, and contactin-associated protein-like 2 detected in healthy subjects or in patients with different neurological diseases, including stroke, are IgA-or IgM-positive, with very few IgG-positive samples [83]. In contrast, only IgG autoantibodies have been proven to be pathogenic in antibodymediated neurological autoimmune diseases, such as anti-NMDAR encephalitis [87], whereas the clinical significance of the presence of IgA or IgM autoantibodies is debated [88].…”

Les rétrovirus endogènes humains, une implication dans la schizophrénie et le trouble bipolaire

“…Depuis quelques années, de nombreuses études ont montré le rôle important d'anomalies immunoinflammatoires dans la physiopathologie des deux maladies, comme en témoigne l'importance des comorbidités auto-immunes que présentent les patients [2]. Certains cas de psychoses ont été directement reliés à l'activité d'autoanticorps anti-synapses, ces cas étant réversibles par un traitement immunomodulateur adapté [3]. Ces observations ont conduit à s'intéresser régions particulières de l'ADN humain, des copies non assemblées par les logiciels de séquençage, mais aussi des copies « non-ubiquitaires » (sans site d'insertion fixe dans l'ADN quand elles sont présentes) ont été identifiées dans des études portant sur la famille HERV-K [10,[14][15][16].…”