(029) Progression of catatonia in anti-NMDA receptor encephalitis: lessons from five cases

Abstract: Background: Catatonia can occur in nearly one-third of patients with anti-NMDA receptor encephalitis (anti-NMDARE), but little consensus exists about its treatment approach. Five cases of catatonia secondary to anti-NMDARE are presented and the treatment outcomes are compared to the small body of literature currently available in this area.

Cases: We report five cases of patients who developed catatonia due to anti-NMDARE, all women ranging from age 21 to 38 years old (mean: 27.4 years old). All patients were confirmed to have anti-NMDAR antibodies in the CSF. Two patients presented with an ovarian cystic teratoma. Four of five patients had concurrent delirium. Three patients developed catatonia after receiving antipsychotic treatment for agitation. Lorazepam was used as first-line therapy to treat catatonia in all five patients. Every patient treated with lorazepam had initial improvement but not resolution of catatonic symptoms. In three patients, the catatonia worsened as their anti-NMDARE became more severe, and they stopped responding to lorazepam, leading to the lorazepam being discontinued; the catatonia eventually remitted days to weeks after immunomodulating treatment for these three patients. Lorazepam continued to be effective in a fourth patient, where it helped address autonomic instability in the setting of malignant catatonia, but the lorazepam needed to be reduced as it seemed to be worsening her comorbid delirium. In a fifth patient, catatonia did not improve along with her other symptoms of anti-NMDARE following immunomodulating treatment, and she needed electroconvulsive therapy to treat the catatonia into remission.

Discussion: As each patient’s anti-NMDARE worsened, lorazepam seemed to become less effective, which may reflect a natural progression of the disease course and underscores the importance of initiating treatment directed at the underlying cause of the catatonia. Catatonia in four out of five patients ultimately resolved due to immunomodulating treatment and not due to lorazepam.

Implications: We speculate that lorazepam for the treatment of catatonia may lose effectiveness as anti-NMDARE progresses, possibly due to the underlying disruption in NMDA signaling and related neural pathways. The importance of continuing symptomatic management with lorazepam while waiting for immunomodulatory treatment to address the underlying cause of catatonia should be explored using more rigorous methodology.

References:

1. Al-Diwani A, Handel A, Townsend L et al. The psychopathology of NMDAR-antibody encephalitis in adults: a systematic review and phenotypic analysis of individual patient data. Lancet Psychiatry. 2019 Mar;6(3):235-246.
2. Wu H, Wu C, Zhou Y et al. Catatonia in adult anti-NMDAR encephalitis: an observational cohort study. BMC Psychiatry. 2023 Feb 7;23(1):94.
3. Espinola-Nadurille M, Flores-Rivera J, Rivas-Alonso V et al. Catatonia in patients with anti-NMDA receptor encephalitis. Psychiatry Clin Neurosci. 2019;73(9):574–80.
4. Marques Macedo I, Gama Marques J. Catatonia secondary to anti-N-methyl-D-aspartate receptor (NMDAr) encephalitis: a review. CNS Spectr. 2020 Aug;25(4):475-492.

Presentation Eligibility: Not previously published or presented

Diversity, Equity, and Inclusion: Three of the five patients described in this case report come from marginalized communities that historically have not been represented adequately in clinical research, such as individuals that identify as Black or LGBTQ+. The presenters include an internal medicine/psychiatry resident and an early career C-L psychiatrist who primarily work with underserved communities in their clinical work, and a C-L psychiatrist with a background that is underrepresented in medicine; all of the presenters strive to bring a health equity-minded perspective into their scholarship.