NMDA型GluRサブユニット抗体陽性脳炎5症例の臨床的解析

NMDA-GluR Subunit Antibody-Positive Encephalitis: A Clinical Analysis of Five Cases

NMDA型GluRサブユニット抗体陽性脳炎5症例を経験した。主要症状は急速に変動する意識の変容，多彩な精神症状，行動異常，後弓反張，カタレプシー，顔面・口部を中心とする律動的・非律動的不随意運動，持続性部分てんかんとみなされる常同的律動的ミオクローヌス様運動，全般性・部分性てんかん，呼吸抑制などであった。MRIでは2症例に大脳皮質の肥厚を認め，脳波上急性期には多形性・単形性大徐波を認めたが，明らかなてんかん原性脳波所見は乏しかった。NMDA型GluRサブユニットであるGluN2BのN末端ペプチドに対する抗体量は髄液中で高値を呈した。5例中2例には卵巣奇形腫を認め摘出した。呼吸，痙攣コントロールに加え，ステロイドパルス療法，経静脈的免疫グロブリン大量療法，血漿交換療法を実施したが，最近の文献から，難治例には今後リツキシマブ，シクロホスファミド療法なども考慮すべきと思われる。

Abstract

Five consecutive cases of anti-NMDA-receptor encephalitis that we encountered were marked by a rapidly fluctuating level of consciousness associated with psychotic and delirious mental states. Opisthotonus, catatonia, and rhythmic and non-rhythmic involuntary movements of the mouth and jaw were also characteristic features of these particular cases. Serious and potentially fatal problems included epilepsia partialis continua, partial and generalized seizures, and respiratory depression, resembling the symptoms of encephalitis lethargica. An epidemic of encephalitis lethargica, also known of Economo encephalitis, occurred around 1917. Magnetic resonance imaging revealed edema of the neocortex in two cases and electroencephalography showed polymorphic and monomorphic delta slowing in the acute stage, although electroencephalographic seizure activity were not apparent. Routine cerebrospinal fluid analyses revealed lymphocyte-dominant pleocytosis in three cases, but antibodies against the NMDA-GluR subunit, GluN2B N-terminal, were at a high level in the fluid. All patients recovered without apparent sequelae. Two patients found to have ovarian teratoma underwent surgery for tumor removal. Treatments included pulse intravenous methylprednisolone, high-dose immunoglobulin, and plasma exchange together with seizure control and respiratory support. However, rituximab and or cyclophosphamide pulse therapy should also be considered for intractable cases, as indicated by recent reports.

(Received February 16, 2016; Accepted May 2, 2016; Published September 1, 2016)