Frequency and characteristics of isolated psychiatric episodes in anti–N-methyl-d-aspartate receptor encephalitis

Abstract

Importance: Patients with anti–N-methyl-D-aspartate receptor (NMDAR) encephalitis often develop prominent psychiatric manifestations. The frequency and type of isolated psychiatric episodes (pure psychiatric symptoms without neurological involvement) either as initial presentation of the disease or as relapse are unknown.

Objective: To determine the frequency, symptoms, and outcome of isolated psychiatric episodes in a cohort of patients with anti-NMDAR encephalitis.

Design, setting, and participants: Observational cohort of patients diagnosed during a5-year period (median follow-up, 2 years). A total of 571 patients with IgG antibodies against the NR1 subunit of the NMDAR were included in the study. Antibody studies were performed at the University of Pennsylvania and the University of Barcelona, and clinical information was obtained by us or referring physicians.

Main outcomes and measures: Frequency, type of symptoms, and outcome of patients with anti-NMDAR encephalitis and isolated psychiatric manifestations.

Results: Of 571 patients, 23 (4%) developed isolated psychiatric episodes, 5 at disease onset and 18 during relapse. For all 23 patients, age (median, 20 years), sex (91%female), and tumor association (43%; ovarian teratoma in all cases) were similar to the population at large.Predominant symptoms included delusional thinking (74%), mood disturbances (70%,usually manic), and aggression (57%). Brain magnetic resonance imaging findings were abnormal in 10 of 22 patients (45%) and cerebrospinal fluid analysis showed pleocytosis in 17 of 22 patients (77%). Eighty-three percent of the patients had full or substantial recovery after immunotherapy and tumor resection when appropriate. After relapse, 17 of 18 patients(94%) returned to a similar or better prerelapse functional level.

Conclusions and relevance: Isolated psychiatric episodes are rare but can occur as initial onset or relapse of anti-NMDAR encephalitis. Recognition of these episodes is important because they respond to immunotherapy. In patients with new-onset psychosis, having a history of encephalitis, subtle neurological symptoms, and/or abnormal results on ancillary tests should prompt screening for NMDAR antibodies.

Figure 1

Brain MRI of three patients with isolated psychiatric symptoms: (A) MRI of patient # 3 obtained at initial episode of encephalitis with pure psychiatric symptoms; note the FLAIR signal abnormalities in the left parietal lobe and adjacent to the splenium of the corpus callosum; (B) patient # 17, the MRI shows cortical and subcortical FLAIR changes in the right frontal lobe identified during a relapse of encephalitis manifesting with isolated psychiatric symptoms; (C) patient # 23, bilateral, extensive cortical and subcortical FLAIR changes identified during a relapse of encephalitis manifesting with isolated psychiatric symptoms.