title: N-methyl-D-aspartate receptor encephalitis mediates loss of intrinsic activity measured by functional MRI.
abstract: Spontaneous brain activity is required for the development and maintenance of normal brain function. Many disease processes disrupt the organization of intrinsic brain activity, but few pervasively reduce the amplitude of resting state blood oxygen level dependent (BOLD) fMRI fluctuations. We report the case of a female with anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis, longitudinally studied during the course of her illness to determine the contribution of NMDAR signaling to spontaneous brain activity. Resting state BOLD fMRI was measured at the height of her illness and 18 weeks following discharge from hospital. Conventional resting state networks were defined using established methods. Correlation and covariance matrices were calculated by extracting the BOLD time series from regions of interest and calculating either the correlation or covariance quantity. The intrinsic activity was compared between visits, and to expected activity from 45 similarly aged healthy individuals. Near the height of the illness, the patient exhibited profound loss of consciousness, high-amplitude slowing of the electroencephalogram, and a severe reduction in the amplitude of spontaneous BOLD fMRI fluctuations. The patient's neurological status and measures of intrinsic activity improved following treatment. We conclude that NMDAR-mediated signaling plays a critical role in the mechanisms that give rise to organized spontaneous brain activity. Loss of intrinsic activity is associated with profound disruptions of consciousness and cognition.
authors.affiliation: Department of Neurology, School of Medicine, Washington University in St. Louis, 660 S Euclid Ave, St. Louis, MO, 63110, USA.
authors.forename: Matthew R
authors.initials: MR
authors.lastname: Brier
authors.affiliation: Department of Neurology, School of Medicine, Washington University in St. Louis, 660 S Euclid Ave, St. Louis, MO, 63110, USA.
authors.forename: Gregory S
authors.initials: GS
authors.lastname: Day
authors.affiliation: Department of Neurology, School of Medicine, Washington University in St. Louis, 660 S Euclid Ave, St. Louis, MO, 63110, USA.|Department of Radiology, School of Medicine, Washington University in St. Louis, St. Louis, MO, 63110, USA.
authors.forename: Abraham Z
authors.initials: AZ
authors.lastname: Snyder
authors.affiliation: Department of Neurology, School of Medicine, Washington University in St. Louis, 660 S Euclid Ave, St. Louis, MO, 63110, USA.
authors.forename: Aaron B
authors.initials: AB
authors.lastname: Tanenbaum
authors.affiliation: Department of Neurology, School of Medicine, Washington University in St. Louis, 660 S Euclid Ave, St. Louis, MO, 63110, USA. ancesb@neuro.wustl.edu.|Department of Radiology, School of Medicine, Washington University in St. Louis, St. Louis, MO, 63110, USA. ancesb@neuro.wustl.edu.
authors.forename: Beau M
authors.initials: BM
authors.lastname: Ances
mesh_terms: D060426:Anti-N-Methyl-D-Aspartate Receptor Encephalitis / Q000000981:diagnostic imaging* / Q000503:physiopathology* / Q000523:psychology; D001921:Brain / Q000000981:diagnostic imaging* / Q000503:physiopathology*; D002560:Cerebrovascular Circulation / Q000502:physiology; D018450:Disease Progression; D004569:Electroencephalography; D005260:Female; D006801:Humans; D008137:Longitudinal Studies; D008279:Magnetic Resonance Imaging; D009434:Neural Pathways / Q000000981:diagnostic imaging / Q000503:physiopathology; D010100:Oxygen / Q000097:blood; D012146:Rest; D014474:Unconsciousness / Q000000981:diagnostic imaging / Q000503:physiopathology / Q000523:psychology; D055815:Young Adult
chemical_list: D010100:Oxygen
keywords: Functional connectivity; NMDA receptor encephalitis; Resting-state; fMRI