原因か偶然か？ジフテリア・百日せき・破傷風・ポリオ混合ワクチン追加免疫接種後の抗NMDA受容体脳炎

Anti-NMDA receptor encephalitis after TdaP–IPV booster vaccination: cause or coincidence?

ETTER TO THE EDITORS

Anti-NMDA receptor encephalitis after TdaP–IPV booster vaccination: cause or coincidence?
Caroline Hofmann • Marc-Oliver Baur • Horst Schroten
Received: 5 September 2010 / Accepted: 13 September 2010 / Published online: 30 September 2010

Springer-Verlag 2010

Dear Sirs,

Anti-NMDA receptor encephalitis is a recently described autoimmune disorder mediated by antibodies to the NR1 subunit of the N-methyl-D-aspartate receptor. It was first
recognized as a paraneoplastic syndrome in young women with ovarian teratoma [1]. Further studies have shown that about 40% of the patients with anti-NMDA receptor
encephalitis do not have a clinically detectable tumor, and men and children are also affected [2]. The mechanisms triggering the disorder, especially in patients without an
associated neoplasm are unknown. The high incidence of prodromal viral-like symptoms suggests a possible infection triggering the autoimmune response [3].

We report about a 15-year-old female patient who was diagnosed with anti-NMDA receptor encephalitis after receiving a booster vaccination against tetanus/diphtheria/pertussis and polio (TdaP-IPV).

破傷風・ジフテリア・百日咳・ポリオ（TdaP-IPV）の追加免疫ワクチン接種後に抗NMDA受容体と診断された１５歳女性患者について報告する。

Within the first 24 h after the injection she developed a low-grade fever and general fatigue.

注射後２４時間以内に、患者は低度の発熱と全身の疲労を発症した。

During the following weeks, her family observed an unusual need for sleep.

続く数週間の間、家族は、患者の睡眠時間が異常に増加していることに気が付いた。

Psychiatric symptoms became apparent 5 weeks after the immunization and included disorganized thinking and hallucinations.

精神症状は、ワクチン接種の５週間後に明らかとなり、思考の混乱と幻覚などが表れた。

Within a few days she became increasingly agitated with orofacial dyskinesia, opistotonic posturing, and choreic movements of the upper extremity.

数日以内に、口腔顔面ジスキネジア、後弓反張、上肢の舞踏病運動を示し、極度に興奮しやすくなった。

She grew unresponsive to verbal commands and required intensive care treatment due to autonomic instability.

患者は、言語による命令に応答しなくなり、自律神経不安定のため、集中治療処置が必要となった。

The unique pattern of clinical symptoms led to the consideration of anti-NMDA receptor encephalitis, which was confirmed by the detection of anti-NMDAR antibodies in plasma and cerebrospinal fluid. Other possible causes of encephalopathy including intoxication,infectious and metabolic diseases were ruled out; repetitive brain scans showed no abnormalities. After confirming the diagnosis, an extensive tumor search was performed without any proof of malignancy; biopsy of a prominent ovarian cyst revealed no teratoma.

The onset of prodromal symptoms shortly after the immunization is intriguing and suggests the vaccination as a possible trigger of anti-NMDA receptor encephalitis.

ワクチン後まもなく現れた前駆的症状の発症は、興味深いものであり、ワクチンが抗NMDA受容体脳炎の引き金となった可能性を示唆する。

Neurological adverse events including autoimmune disorders have been discussed in literature for many years; a definite causal association between vaccination and disease was seldom established. For example, the 1976 swine influenza vaccine was associated with an increased frequency of Guillain-Barre Syndrome (GBS) [4]. A recent study about the safety of TdaP vaccination in adolescents revealed no increased risk of neurological adverse events [5], even though rare cases of GBS have been reported. To our knowledge, this is the first possible case of vaccination associated anti-NMDA receptor encephalitis. Therefore, not only infectious agents and tumor antigens but also vaccines should be considered as a possible trigger of immune response in this recently described disorder.

Conflict of interest None.

References
1. Dalmau J, Gleichmann AJ et al (2008) Anti-NMDA-receptor encephalitis: case series and analysis of the effect of antibodies. Lancet Neurol 7(12):1091–1098 C. Hofmann (&)
University Children’s Hospital Heidelberg, Heidelberg, Germany e-mail: caroline.hofmann@med.uni-heidelberg.de M.-O. Baur H. Schroten Department of Pediatrics, University Hospital Mannheim, Mannheim, Germany 123 J Neurol (2011) 258:500–501 DOI 10.1007/s00415-010-5757-3

2. Vincent A, Bien CG (2008) Anti-NMDA-receptor encephalitis: a cause of psychiatric, seizure, and movement disorders in young adults. Lancet Neurol 7(12):1074–1075

3. Florance NR, Davis RL et al (2009) Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis in children and adolescents. Ann Neurol 66(1):11–18

4. Toplak N, Avcin T (2009) Influenza and autoimmunity. Contemporary challenges