Japanese encephalitis can trigger anti-N-methyl-d-aspartate receptor encephalitis

Abstract

Japanese encephalitis (JE) is usually a monophasic disease; however, in rare cases, patients with JE may have an early relapse after a partial recovery, giving rise to a biphasic pattern for the disease. In this study, we report three pediatric cases in which post-JE relapse was characterized by movement disorder and/or behavioral problems, and was related to anti-N-methyl-D-aspartate receptor (NMDAR) immunoglobulin G (IgG). Serum and cerebrospinal fluid were examined for anti-NMDAR IgG in three patients who had confirmed JE and then developed relapsing symptoms which were similar to those of anti-NMDAR encephalitis. The main symptoms of the two young children were choreoathetosis, irritability, and sleep disorder; while for the teenager, agitation, mutism, rigidity, and sleep disorder were the main symptoms. Samples of cerebrospinal fluid from all patients were positive for anti-NMDAR IgG, and all patients gradually improved with immunotherapy. Testing for NMDAR antibodies is highly recommend in patients with JE, especially those with a relapsing syndrome involving movement disorder and/or behavioral problems, as these patients may benefit from immunotherapy.

Japanese Encephalitis Virus-Induced Anti-N-Methyl-D-Aspartate Receptor Encephalitis: A Case Report and Review of Literature

“…A review of the English and Chinese literature, using the words: "Japanese encephalitis," "Japanese encephalitis virus," "anti-NMDAR encephalitis," and "NMDAR," identified only three articles describing JEV-associated anti-NMDARe, reporting on a total of five children including case induced by JE vaccination. [3][4][5] In a total of six cases, with an average age of onset of 6.4 years (range: 2-14 years), the median time between onset of JE and onset of anti-NMDARe was 26.8 days (range: 14-29 days). These findings thus revealed that the second phase of this disorder tends to occur in children after 2 to 4 weeks of JE or JE vaccination episodes.…”

“…1,2 Neurological sequelae or even death may occur in affected individuals, although it is usually a monophasic disease. 1,2 However, several studies have reported on patients with a biphasic disease characterized as JE followed by anti-Nmethyl-D-aspartate receptor encephalitis (anti-NMDARe) 3,4 or JE vaccination. 5 Here, we describe a boy with post-JE anti-NMDARe, presenting with biphasic disease similar to that in the previously reported cases, and we further provide a literature review.…”

Post-infectious neurological disorders

“…NMDA-R antibodies were present in three of these cases, while the other two were felt to have autoimmune encephalitis based upon negative JE virus testing and improvement with immunotherapy. 52,53 Larger, multi-center studies of JE patients are needed to determine the incidence of post-JE autoimmune encephalitis, and to identify other autoantibodies that may be associated with the disorder. Sydenham's chorea Acute rheumatic fever (ARF) is a multifocal inflammatory condition that presents in the weeks following GAS infection.…”

Arbovirus and seizures

“…Research by Yao et al showed that the expression of miR-16-1 and heat shock protein 70 was upregulated in astrocytes during the occurrence of epilepsy after JEV infection [16]. Another case report led by Ma et al showed that JEV infection can trigger anti-N-methyl-Daspartate receptor encephalitis [17]. This implies an autoimmunity-related mechanism underlying neuronal damage by JEV.…”