Ma Congcong, Wang Chengze, Zhang Qiaoman, Lian Yajun
Department of Neurology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, Henan Province, China Email
J Pain Res. 2019 Jan 30;12:519-526. doi: 10.2147/JPR.S189301. eCollection 2019.
Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis patients often present with psychiatric symptoms, cognitive dysfunction, epilepsy and memory deficits. A previous study has suggested that headache can occurr during the early stages of anti-NMDAR encephalitis. However, the exact association between headache and anti-NMDAR encephalitis has hardly been investigated, apart from a few case studies. This is probably due to the severity of encephalitis symptoms, and the mechanism underlying headache-associated anti-NMDAR encephalitis remains largely unclear.
This study aimed to investigate the role of prodromal headache in 28 patients diagnosed with anti-NMDAR encephalitis.
Clinical data related to the prodromal headache characteristics of anti-NMDAR encephalitis patients were prospectively collected from January first 2017 to June first 2018. Autoimmune antibodies in the cerebrospinal fluid (CSF) of anti-NMDAR encephalitis patients were detected by an indirect immunofluorescence staining kit. The differences between age, sex, clinical symptoms (fever, epilepsy, psychiatric symptoms, cognitive impairment, disturbance of consciousness), CSF, brain MRI abnormalities, and modified Rankin Scale (mRS) score were compared between patients with and without headache. In addition, the association of headache severity with brain MRI abnormalities, antibody titers, and mRS score was examined.
Twenty-eight patients with anti-NMDAR encephalitis (median, 29 years; range, 15-62 years) reported headache. Among them, 18 (64%) were female, 24 (86%) had fever, 21 (75%) were positive for serum virus antibody, 19 (68%) had severe pain intensity (scored 4-7 out of 10 on the visual analog scale), 18 (64%) presented with pulsating character, and 5 (18%) patients accompanied by vomiting. Moreover, headache was detected in the frontal lobe of 14 (50%) patients and temporal lobe of 12 (43%) patients. Encephalitic symptoms (psychiatric symptoms, cognitive dysfunction, epilepsy, and memory deficits) appeared in 23 patients at average 5.5 days (range, 1-21 days) followed by headache attack. In five patients, the headache was lasted for 21 days.
Prodromal headache is commonly found in the temporal lobe and frontal lobe of young patients, and hardly accompanied by vomiting. Headache is rapidly substituted by encephalitis symptoms in the majority of patients, while gradually relieved in a few patients after the recovering from encephalitis symptoms. The results strongly suggest that the NR1 subunit of NMDAR is involved in prodromal headache. In sum, the symptom of prodromal headache is crucial for the diagnosis of anti-NMDAR encephalitis.
抗N-甲基-D-天冬氨酸受体（NMDAR）脑炎患者常出现精神症状、认知功能障碍、癫痫和记忆缺陷。先前的一项研究表明，抗NMDAR脑炎早期可出现头痛。然而，除少数病例研究外，头痛与抗NMDAR脑炎的确切关联几乎未被研究。这可能是由于脑炎症状严重，且头痛相关性抗NMDAR脑炎的潜在机制仍不清楚。
本研究旨在调查前驱性头痛在28例诊断为抗NMDAR脑炎患者中的作用。
前瞻性收集2017年1月1日至2018年6月1日抗NMDAR脑炎患者前驱性头痛特征的临床资料。采用间接免疫荧光染色试剂盒检测抗NMDAR脑炎患者脑脊液（CSF）中的自身免疫抗体。比较有头痛和无头痛患者在年龄、性别、临床症状（发热、癫痫、精神症状、认知障碍、意识障碍）、脑脊液、脑MRI异常及改良Rankin量表（mRS）评分方面的差异。此外，还检查了头痛严重程度与脑MRI异常、抗体滴度及mRS评分的相关性。
28例抗NMDAR脑炎患者（中位年龄29岁；范围15 - 62岁）报告有头痛。其中，女性18例（64%），发热24例（86%），血清病毒抗体阳性21例（75%），19例（68%）疼痛程度严重（视觉模拟量表评分为4 - 7分），18例（64%）呈搏动性，5例（18%）伴有呕吐。此外，14例（50%）患者的头痛出现在额叶，12例（43%）出现在颞叶。23例患者在头痛发作后平均5.5天（范围1 - 21天）出现脑炎症状（精神症状、认知功能障碍、癫痫和记忆缺陷）。5例患者头痛持续21天。
前驱性头痛常见于年轻患者的颞叶和额叶，很少伴有呕吐。大多数患者头痛迅速被脑炎症状取代，少数患者在脑炎症状恢复后逐渐缓解。结果强烈提示NMDAR的NR1亚基参与前驱性头痛。总之，前驱性头痛症状对抗NMDAR脑炎的诊断至关重要。
