Prevalence of N-Methyl-d-Aspartate Receptor antibody (NMDAR-Ab) encephalitis in patients with first episode psychosis and treatment resistant schizophrenia on clozapine, a population based study.

ABSTRACT

INTRODUCTION: N-methyl-d-aspartate receptor antibody (NMDAR-Ab) encephalitis consensus criteria has recently been defined. We aimed to examine the prevalence of NMDAR-Ab encephalitis in patients with first episode psychosis (FEP) and treatment resistant schizophrenia (TRS) on clozapine, using clinical investigations, antibody testing and to retrospectively apply diagnostic consensus criteria. METHODS: Adult (18-65 years old) cases of FEP meeting inclusion criteria were recruited over three years and assessed using the Structured Clinical Interview for DSM-IV disorders (SCID). NMDAR-Ab was identified using a live cell-based assay (L-CBA). Seropositive cases were clinically investigated for features of encephalitis including neuro-imaging, EEG and CSF where possible. Serum was retested using immunohistochemistry (IHC) as part of diagnostic criteria guidelines. A cohort of patients with TRS was also recruited. RESULTS: 112 FEP patients were recruited over 3 years. NMDAR-Ab seroprevalence was 4/112 (3.5%) cases. One case (<1%) was diagnosed with definite NMDAR-Ab encephalitis and treated with immunotherapy. One of the three other seropositive cases met criteria for probable encephalitis. However all three were ultimately diagnosed with mood disorders with psychotic features. None have developed neurological features at three year follow up. 1/100 (1%) of patients with TRS was 100 patients with TRS were recruited. One case (1%) seropositive for NMDAR-Ab but did not meet criteria for encephalitis. CONCLUSIONS: NMDAR-Ab encephalitis as defined by consensus guidelines occured rarely in psychiatric services in this study. Further studies are needed to establish pathogenicity of serum NMDAR-Ab antibodies. Psychiatric services should be aware of the clinical features of encephalitis.