@article{52e069dd05d94dd89b00ad983266307b,
title = "Anti-N-methyl-D-aspartate receptor encephalitis with concurrent human herpes virus-6A deoxyribonucleic acid detection: An autopsy case",
abstract = "We report an autopsy case of anti-N-methyl-D-aspartate (NMDA) receptor (NMDAR) encephalitis with concurrent human herpes virus-6 (HHV-6) A deoxyribonucleic acid (DNA) detection in cerebrospinal fluid (CSF). A 38-year-old previously healthy Japanese man presented with a generalized seizure. Brain magnetic resonance imaging (MRI) findings were unremarkable, but CSF revealed pleocytosis. On Day 11, HHV-6 DNA was detected in CSF, and IgG antibodies against the NR1 subunit of the NMDAR (GluN1) were subsequently detected. Since HHV-6 encephalitis was initially suspected, the patient was treated with foscarnet and ganciclovir, but the HHV-6A copy number increased from 200 (Day 22) to 2000 copies/mL (Day 47), and the therapy was ineffective. As typical symptoms of anti-NMDAR encephalitis developed, we changed the patient's treatment to combat anti-NMDAR encephalitis. He was repeatedly treated with first-line immunotherapy, and GluN1 antibody titer decreased. He was not treated with second-line immunotherapy because of recurrent infections; he died on Day 310. Postmortem examinations did not show systemic tumors. Microscopic examination of the brain revealed only severe neuronal rarefaction in the hippocampal cornu ammonis (CA) 3–4 areas with gliosis. Early initiation of aggressive immunotherapy may be required in a refractory case of anti-NMDAR encephalitis, even with HHV-6A DNA detection, because the significance of this concurrent detection in autoimmune encephalitis remains unclear.",
keywords = "N-methyl-d-aspartate (NMDA), autoimmune diseases, encephalitis, human herpes virus-6 (HHV-6), neuropathology",
author = "Sho Shimohama and Takahiro Iizuka and Tsubasa Takizawa and Narumi Watanabe and Toshiki Tezuka and Kosuke Matsuda and Kazuhiro Yamanoi and Naomi Kanazawa and Yoshiki Kawamura and Tetsushi Yoshikawa and Tadaki Suzuki and Masaki Takao and Jin Nakahara and Yoshikane Izawa",
note = "Funding Information: We thank Prof. Josep Dalmau (Service of Neurology, IDIBAPS Hospital Clinic, University of Barcelona, Barcelona, Spain) for examining antibodies to NS antigens, including NMDA, AMPA, GABA(A), GABA(B), mGluR1, and mGluR5 receptors, and antibodies to LGI1 and Caspr2, DPPX, Neurexin3, and Iglon5 in this patient. We also thank the HHV-6 Foundation for a helpful discussion about the patient. We also thank Drs. Shun Iida and Harutaka Katano of National Institute of Infectious Diseases for pathological and molecular analysis. Funding Information: Dr. T. Iizuka has received research support from Astellas Pharma Inc. Dr. M. Takao received a grant‐in‐aid from the Japan Society for the Promotion of Science (JSPS) KAKENHI (Nos. 16H06277, 21K06417), a grant‐in‐aid from the Japan Agency for Medical Research and Development AMED (JP21wm0425019), and an intramural research grant for neurological and psychiatric disorders from the National Center of Neurology and Psychiatry. Dr. T. Suzuki received a grant‐in‐aid from the Japan Agency for Medical Research and Development AMED (JP22fk0108637). Other authors report no disclosures relevant to the manuscript. Funding Information: This work was supported in part by a grant‐in‐aid from the Japan Agency for Medical Research and Development AMED (JP21wm0425019, MT; JP22fk0108637, TS), JSPS KAKENHI (Grant Nos. 16H06277, 21K06417) (MT), and intramural funds from the National Center of Neurology and Psychiatry (MT). Publisher Copyright: {\textcopyright} 2022 Japanese Society of Neuropathology.",
year = "2023",
month = jun,
doi = "10.1111/neup.12881",
language = "English",
volume = "43",
pages = "257--261",
journal = "Neuropathology",
issn = "0919-6544",
publisher = "Wiley-Blackwell Publishing Ltd",
number = "3",
}
