Neuropsychological And Psychopathological Profile Of Anti-Nmdar Encephalitis: A Possible Pathophysiological Model For Pediatric Neuropsychiatric Disorders

Arch Clin Neuropsychol. 2019 Nov 27;34(8):1309-1319. doi: 10.1093/arclin/acy088.


Objective: Anti-N-methyl-d-aspartate receptor (NMDAR) encephalitis is a severe, but treatable, autoimmune disorder, characterized by autoantibodies causing hypofunction of blocking NMDA receptors leading to a unique constellation of cognitive, motor, and psychiatric symptoms. Neuropsychological and psychopathological outcome has not been fully explored, particularly in children. Aim of this study was to investigate pediatric anti-NMDAR encephalitis as a model of impairment of the complex frontal-subcortical circuits who are implicated in several of the childhood neuropsychiatric disorders.

Method: Seven children diagnosed with anti-NMDAR encephalitis at our department underwent an evaluation of the global mental functioning before discharge, a neuropsychological and psychological/behavioral standardized examination within one month after discharge and subsequently were followed up longitudinally for mean 35 months (range 24-48 months). Collected neuropsychological data were evaluated retrospectively.

Results: Deficits in attention, executive functions and/or visual motor functions involving executive functions were seen in all children within one month after discharge. These deficits were long lasting in about a half of the patients. In addition, four patients developed persistent psychopathological dysfunctions: difficulties to regulate their own behavior, impulsivity, hyperactivity, irritability, apathy, and obsessive-compulsive symptoms.

Conclusions: Our data are in line with research suggesting a crucial role of the executive functions impairments in cognitive outcome disturbance of anti-NMDAR encephalitis. We found also behavioral and psychological deficits pointing to a more comprehensive framework of frontal-subcortical dysfunction, in which the NMDA mediated transmission appear to have a role, as suggested by neurobiological, pharmacological, and neuroimaging studies.

Keywords: Behavioral; Executive functions; Frontal-subcortical circuits, NMDAR encephalitis; Psychological.

MeSH terms

  • Adolescent
  • Anti-N-Methyl-D-Aspartate Receptor Encephalitis / physiopathology*
  • Anti-N-Methyl-D-Aspartate Receptor Encephalitis / psychology*
  • Attention Deficit Disorder with Hyperactivity / etiology
  • Attention Deficit Disorder with Hyperactivity / psychology
  • Child
  • Child Behavior
  • Child Behavior Disorders / etiology
  • Child Behavior Disorders / physiopathology
  • Child Behavior Disorders / psychology
  • Child, Preschool
  • Executive Function
  • Female
  • Follow-Up Studies
  • Frontal Lobe / physiopathology
  • Humans
  • Longitudinal Studies
  • Male
  • Mental Disorders / etiology
  • Mental Disorders / physiopathology*
  • Mental Disorders / psychology*
  • Mental Processes
  • Nervous System Diseases / etiology
  • Nervous System Diseases / physiopathology*
  • Nervous System Diseases / psychology*
  • Neuropsychological Tests
  • Retrospective Studies