Department of Neurology, Kitasato University School of Medicine, Sagamihara, Japan.
Department of Neurology, Kagoshima City Medical Association Hospital, Kagoshima, Japan.
Brain Behav. 2018 Jul;8(7):e01012. doi: 10.1002/brb3.1012. Epub 2018 Jun 1.
To investigate the nature of prodromal headache in anti-NMDA receptor (NMDAR) encephalitis.
Retrospective review of the clinical information of 39 patients with anti-NMDAR encephalitis admitted between January 1999 and September 2017. Five patients with an atypical presentation were excluded. Thus, in 34 patients (median 27 years [range, 12-47 years]; 28 [82%] female), the clinical features were compared between patients who initially reported headache and those who did not report.
Twenty-two patients (65%) reported headache either transiently (n = 5) or continuously (n = 17). Encephalitic symptoms (psychobehavioral memory alterations, seizure, dyskinesias, or altered level of consciousness) developed in 20 patients with median 5.5 days (range, 1-29 days) after headache onset. In one patient, NMDAR antibodies were detected in CSF 3 days after headache onset. Patients with headache had more frequently fever (14/22 [64%] vs. 2/12 [17%] p = 0.013) and higher CSF pleocytosis (median white blood cells 79/μl [range, 6-311/μl] vs. 30/μl [range, 2-69/μl], p = 0.035) than those without headache, but there was no difference in gender, age at onset, seizure, migraine, CSF oligoclonal band detection, elevated IgG index, tumor association, or brain MRI abnormalities between them.
Headache often developed with fever and pleocytosis, but it was rapidly replaced by psychiatric symptoms. Based on current knowledge on the antibody-mediated mechanisms that cause a decrease of synaptic NMDAR through crosslinking and internalization leading to a state mimicking "dissociative anesthesia," we speculated that prodromal headache is not likely caused by direct effect of the autoantibodies but rather meningeal inflammation (noninfectious aseptic meningitis) that occurs in parallel to intrathecal antibody synthesis as an epiphenomenon of NMDAR autoimmunity. Psychobehavioral alterations following headache is an important clue to the diagnosis.
探讨抗 N-甲基-D-天冬氨酸受体（NMDAR）脑炎前驱性头痛的性质。
回顾性分析 1999 年 1 月至 2017 年 9 月期间收治的 39 例抗 NMDAR 脑炎患者的临床资料。排除 5 例表现不典型的患者。因此，在 34 例患者（中位年龄 27 岁[范围，12-47 岁]；28 例[82%]为女性）中，比较了最初报告头痛和未报告头痛患者的临床特征。
22 例（65%）患者报告头痛，其中 5 例为短暂性头痛，17 例为持续性头痛。20 例患者在头痛发作后中位 5.5 天（范围，1-29 天）出现脑炎症状（精神行为记忆改变、癫痫发作、运动障碍或意识水平改变）。1 例患者在头痛发作后 3 天检测到脑脊液中存在 NMDAR 抗体。有头痛的患者更常出现发热（14/22 [64%] vs. 2/12 [17%]，p=0.013）和更高的脑脊液白细胞增多（中位数白细胞 79/μl[范围，6-311/μl] vs. 30/μl[范围，2-69/μl]，p=0.035），但两组间性别、发病年龄、癫痫发作、偏头痛、脑脊液寡克隆带检测、升高的 IgG 指数、肿瘤相关、或脑 MRI 异常均无差异。
头痛常伴有发热和白细胞增多，但很快被精神症状取代。基于目前对抗体介导的机制的认识，该机制通过交联和内化导致突触 NMDAR 减少，从而模拟“分离性麻醉”状态，我们推测前驱性头痛不是由自身抗体的直接作用引起，而是脑膜炎症（非感染性无菌性脑膜炎）引起，它与鞘内抗体合成平行发生，是 NMDAR 自身免疫的一种表现。头痛后出现的精神行为改变是诊断的一个重要线索。
