Chronic Schizophrenia Later Diagnosed with Anti-NMDA Receptor Encephalitis: Case Report and Review of the Literature.

Abstract

Introduction Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis is an autoimmune disorder caused by Ig G auto-Ab directed against the NR1 subunit of the NMDA glutamate receptor (1). The binding of IgG antibodies induces a reversible internalization of the receptors (2). Decreased activity of NMDA receptors is known to be associated with both the positive and negative symptoms of schizophrenia (3). The early stages of the illness are characterized by psychiatric symptoms. As the illness progresses, neurologic symptoms emerge, and in the most severe stage of the illness, autonomic instability and respiratory collapse can occur. During the stage of the illness when psychiatric symptoms predominate in the presentation, anti-NMDAR encephalitis may be misattributed to a primary psychiatric disorder. Most of the literature thus far has described such misdiagnoses in patients with first-episode psychosis (4-6). There appear to be no documented cases of chronic schizophrenia that were definitely later reclassified as anti-NMDAR encephalitis. Here we report what we believe to be the first reported case of misdiagnosis of anti-NMDAR encephalitis as chronic schizophrenia. Case Report Ms. A is a 25-year-old female with a history of schizophrenia diagnosed four years prior and multiple subsequent psychiatric hospitalizations, who was evaluated in our medical emergency department, transferred from an outside psychiatric inpatient unit, for investigation of altered mental status (AMS), unilateral facial stiffness, and cough. Psychiatry was consulted. She was noted to be disorganized and agitated and had unilateral facial twitching. Her medications included lithium, divalproex sodium, clozapine, and the long-acting injectable formulation of paliperidone palmitate (last dose two weeks prior). An infectious workup was unremarkable. Intravenous lorazepam, given as empiric treatment for suspected catatonia, rendered no benefit. She was discharged back to the inpatient psychiatric facility. One week later she re-presented to this hospital with difficulty breathing and frothing at the mouth. She was noted to be conscious and awake, intermittently physically agitated, but nonverbal and not following commands or withdrawing from painful stimuli. Rhythmic orofacial grimacing was prominent with intermittent unilateral lead-pipe rigidity. She had autonomic instability with variable heart rate and blood pressures. Creatine kinase (CK) was initially elevated to 972 and peaked at 1,797. She was admitted to the medical intensive care unit (ICU) with neurology and psychiatry consulting. The differential diagnosis included delirium, severe antipsychotic-mediated extrapyramidal symptoms and neuroleptic malignant syndrome (NMS). Supportive care and amantadine were started for suspected NMS. Lumbar puncture (LP) showed mild elevation in the cerebrospinal fluid (CSF) white blood cell count (13/uL), with 98% lymphocyte predominance and normal protein and glucose. In