Effect of Clozapine on Anti-N-Methyl-D-Aspartate Receptor Encephalitis With Psychiatric Symptoms: A Series of Three Cases

Abstract

The main clinical manifestations of anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis are acute or subacute seizures, cognition impairment, and psychiatric symptoms. Nowadays, the scheme of antipsychotic therapy for this disease has not been established. This study reports three cases of anti-NMDAR encephalitis with psychiatric symptoms. The anti-NMDAR antibodies in cerebrospinal fluid (CSF) and serum were positive. The psychiatric symptoms still existed after intravenous immunoglobulin (IVIG) treatment; thus, clozapine was used for antipsychotic therapy. Case 1 was a 37-year-old man who suffered from bad mood and suicide behaviors for 1 month. Hallucination and delusion still existed after IVIG treatment and hormone therapy, and the symptoms were relieved when given clozapine for 12 months. Case 2 was a 28-year-old man who was admitted to our hospital due to injuring other people and destructive behaviors for 2 days. He showed irritability, bad temper, declined cognition, and severe delusion of persecution after IVIG treatment and hormone therapy, but the psychiatric symptoms disappeared when given clozapine for 3 months. Case 3 was a 23-year-old man who suffered from headache and babbing for 7 days. Symptoms such as irritability, bad temper, babbing, and injuring other people still existed after IVIG treatment and hormone therapy, but they disappeared when given clozapine for 2 months. Therefore, we suggest that during the treatment of anti-NMDAR encephalitis with psychiatric symptoms, if the anti-NMDAR antibodies in CSF and serum were positive, and psychiatric symptoms could not be controlled after IVIG and hormone therapy, clozapine may work.

Keywords: anti-NMDA receptor encephalitis; antipsychotic therapy; clozapine; hormone; intravenous immunoglobulin; psychiatric symptoms.

FIGURE 1

The anti-NMDA receptor (anti-NMDAR) antibodies in CSF (A,C,E,G,I) and serum (B,D,F,H,J). (A,B) Initial day in case 1. (C,D) Before treatment of clozapine in case 1. (E,F) After 18-month treatment of clozapine in case 1. (G,H) Before treatment of clozapine in case 2. (I,J) Before treatment of clozapine in case 3.

FIGURE 2

Initial electroencephalography (EEG) in case 1. EEG showed moderate slow-wave discharge, with medium-wave amplitude, appearing as a single emission or continuous occurrence in right sphenoidal electrode, frontal pole, frontal, and pretemporal regions.

FIGURE 3

Results of head MRI. (A,B) Head MRI showed encephalatrophy in case 1. (C,D) Head MRI showed long T1 and long T2 signal intensities in the left temporal lobe, and enhanced MRI stated irregular light enhancement in case 2. (A,C) T2WI; (B,D) T1-weighted sequence after gadolinium enhancement.

FIGURE 4

Clozapine plasma concentration. (A) Plasma concentration was 218.8 ng/ml in case 1. (B) Plasma concentration was 90.6 ng/ml in case 2. (C) Plasma concentration was 65.3 ng/ml in case 3. Asterisks (^∗) represent the chromatogram peak of clozapine.