Hachiya Yasuo, Miyata Rie, Tanuma Naoyuki, Hongou Kazuhisa, Tanaka Keiko, Shimoda Konomi, Kanda Sachiko, Hoshino Ai, Hanafusa Yukiko, Kumada Satoko, Kurihara Eiji, Hayashi Masaharu
Department of Neuropediatrics, Tokyo Metropolitan Neurological Hospital, Tokyo, Japan.
Brain Dev. 2013 Aug;35(7):670-4. doi: 10.1016/j.braindev.2012.10.003. Epub 2012 Nov 9.
Although central nervous system (CNS) disorders associated with group-A beta-hemolytic streptococcal (GABHS) infection occur only rarely, Sydenham's chorea is a well-recognized disease that can arise following infection. Children may develop a tic, obsessive compulsive disorder (OCD), and extrapyramidal movement subsequent to GABHS infection. These disorders have been termed pediatric autoimmune neuropsychiatric disorders associated with streptococci (PANDAS). Herein we report one case each of acute disseminated encephalomyelitis (ADEM), PANDAS and subacute encephalitis associated with GABHS infection. To evaluate the pathogenesis of the CNS disorders associated with GABHS infection, we measured levels of neurotransmitters, cytokines, anti-neuronal autoantibodies, and performed immunohistochemistry using patient sera to stain human brain sections. All three cases showed psychiatric behavioral disorders. Immunotherapy was effective, and homovanillic acid levels in the cerebrospinal fluid (CSF) were elevated at the acute stage in all three cases. In each case of ADEM and PANDAS, immunohistochemistry demonstrated neuronal impairment in the basal ganglia during the acute stage. Neuronal immunoreactivity was visualized in the cerebral cortex at the acute stage in the case of subacute encephalitis. There was no direct correlation between immunoreactivity of patient sera on the brain sections and positivity of anti-neuronal autoantibodies or CSF biomarkers. The results suggest that autoimmune responses may modulate neurotransmission, and the use of patient serum for immunohistochemistry is a sensitive screening method for the detection of anti-neuronal autoantibodies in CNS disorders associated with GABHS infection.
虽然与A组β溶血性链球菌（GABHS）感染相关的中枢神经系统（CNS）疾病很少发生，但 Sydenham舞蹈病是一种公认的可在感染后出现的疾病。儿童在GABHS感染后可能会出现抽搐、强迫症（OCD）和锥体外系运动障碍。这些疾病被称为与链球菌相关的儿童自身免疫性神经精神疾病（PANDAS）。在此我们报告1例与GABHS感染相关的急性播散性脑脊髓炎（ADEM）、PANDAS和亚急性脑炎。为了评估与GABHS感染相关的中枢神经系统疾病的发病机制，我们测量了神经递质、细胞因子、抗神经元自身抗体的水平，并使用患者血清进行免疫组织化学染色人脑切片。所有3例均表现出精神行为障碍。免疫治疗有效，所有3例患者急性期脑脊液（CSF）中的高香草酸水平均升高。在ADEM和PANDAS的每例患者中，免疫组织化学显示急性期基底节存在神经元损伤。亚急性脑炎患者急性期大脑皮质可见神经元免疫反应性。患者血清在脑切片上的免疫反应性与抗神经元自身抗体或脑脊液生物标志物的阳性之间没有直接相关性。结果表明自身免疫反应可能调节神经传递，使用患者血清进行免疫组织化学是检测与GABHS感染相关的中枢神经系统疾病中抗神经元自身抗体的一种敏感筛查方法。
