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

Ping Yang,Tianhao Huang,Bin Zhou,Gaoya Zhou,Feng Li,Erwen Tu,Shuaishuai Xia,Liang Li,Yong Zhu,Huiyong Huang

doi:10.3389/fnins.2019.00315

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.

Highlights

Anti-N-methyl-D-aspartate receptor encephalitis is an autoimmune encephalitis induced by anti-NMDAR (Jiang et al, 2018). Dalmau et al (2007) reported anti-NMDAR as the pathogenic antibody and diagnostic marker of this disease in 2007
Head-enhanced magnetic resonance imaging (MRI) showed encephalatrophy (Figures 3A,B), and no epileptic waves were found in EEG
Anti-NMDAR encephalitis may initially present with multiple psychiatric symptoms, which results in being misdiagnosed as primary psychiatric disease (Dalmau et al, 2008)

Summary

INTRODUCTION

Anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis is an autoimmune encephalitis induced by anti-NMDAR (Jiang et al, 2018). Dalmau et al (2007) reported anti-NMDAR as the pathogenic antibody and diagnostic marker of this disease in 2007. The number of newly diagnosed cases of anti-NMDAR encephalitis has exceeded that of enterovirus encephalitis and herpes simplex encephalitis (Gable et al, 2012) It often combined with psychiatric symptoms, such as severe hallucination, delusion, and aggressive behaviors (Warren et al, 2018). Head-enhanced magnetic resonance imaging (MRI) showed encephalatrophy (Figures 3A,B), and no epileptic waves were found in EEG He was given clozapine (50–300 mg/day), with 218.8 ng/ml plasma concentration. The patient was given clozapine (25–300 mg/day), with 90.6 ng/ml plasma concentration (Figure 4B; Zhou et al, 2004), and all the psychiatric symptoms disappeared completely 3 months later. (2–4 mg/day, 30 days), the patient still showed visual hallucination and aggressive behaviors He was given clozapine (50–100 mg/day), with 65.3 ng/ml plasma concentration (Figure 4C; Zhou et al, 2004).

DISCUSSION

Findings

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