卵巢畸胎瘤合并抗N-甲基-D-天冬氨酸受体脑炎的临床特点分析

Comparison of Clinical Features in Female anti-NMDAR Encephalitis Patients with and without Ovarian Teratoma

目的探讨卵巢畸胎瘤合并抗N-甲基-D-天冬氨酸受体(NMDAR)脑炎患者的临床特点、治疗及预后。方法回顾性分析2013年2月至2018年2月诊断为抗NMDAR脑炎且合并或无合并卵巢畸胎瘤的35例女性患者的临床资料。随访其预后,通过改良Rankin量表(mRS)评估患者不同阶段的神经功能情况。结果合并畸胎瘤的抗NMDAR脑炎患者病毒感染样前驱症状及脑脊液淋巴细胞反应比例较低,脑脊液抗NMDAR抗体强阳性比例较高(3+~4+)。伴有畸胎瘤患者中复杂部分性癫发作常见,1例出现非惊厥性癫持续状态。所有患者均接受免疫治疗。其中伴有卵巢畸胎瘤的抗NMDAR脑炎患者入院时的平均mRS评分、需要一线及二线免疫治疗联合控制的比例、首次出院后第1和18个月以及末次随访的mRS评分均低于无合并畸胎瘤的抗NMDAR脑炎患者,且术后抗NMDAR脑炎的复发率更低。结论是否合并畸胎瘤对脑脊液抗NMDAR滴度及细胞学检测结果有所影响,提示可能存在不同的发病机制;合并卵巢畸胎瘤的抗NMDAR脑炎患者多数症状较轻,及时手术切除畸胎瘤有助于改善预后并防止复发。

Aim To investigate the differences in clinical features of female anti-NMDAR encephalitis patients with or without ovarian teratoma.Methods The electronic medical data from Huashan Hospital and enrolled female patients diagnosed with anti-NMDAR encephalitis were retrospectively analyzed. According to the past disease history or results of routine screening of teratoma and follow-up pathological diagnosis,the patients were divided into anti-NMDAR patients with or without ovarian teratoma.Their clinical features and auxiliary examinations during hospitalizations were analyzed and compared,and the further follow-up studies were carried out and modified Rankin score ( mRS) was used to evaluate the prognosis.Results 18 patients diagnosed with anti-NMDAR encephalitis were confirmed to have ovarian teratoma,while 17 patients with anti-NMDAR encephalitis didn't show any sign of associated tumor.In patients with teratoma,the cerebrospinal fluid ( CSF) tested for anti-NMDAR antibodies were more likely to show strong positive response ( 3 + or 4 +) than those without teratoma ( 11 /18 vs.3 /17,P = 0.015 3). For patients without teratoma,viral prodrome ( 12 /17 vs.5 /18,P = 0.018 4) and pleocytosis in CSF ( 8 / 17 vs.1 /18,P = 0.007 2) were more frequent than the patients with teratoma.As for seizure type, complex partial seizures were more commonly seen in patients with teratoma ( 9 /18 vs.2 /17,P =0.027 5), one of them even presented with non convulsive status epilepticus.All of them received one or multiple immunotherapy.A combination of first-line and second-line immunotherapy were more commonly used in patients without ovarian teratoma ( 13 /17 vs.4 /18,P = 0.0022 ) and a higher initial mRS was also observed in this group [( 4.82 ± 0.39) vs.( 4.39 ± 0.70),P = 0.0311].Patients with teratoma usually have surgical procedures 1 and 18 months later after discharge and they were less likely to have relapse of encephalitis than those without teratoma.They tend to have better prognosis at 12 month,18 month and last follow-up [12 month follow-up:( 3.41 ± 0.36) vs.( 2.10 ± 0.42),P = 0.021 5;18 month followup:( 3.27 ± 0.45) vs.( 1.87 ± 0.48),P = 0.048 8;last follow-up:( 3.20 ± 0.51) vs.( 1.78 ± 0.42), P = 0.048 3].The differences in age,clinical manifestations,seizure frequency and recurrence, antiepileptic treatment,ICU admission as well as abnormalities in brain MRI,electroencephalogram and other CSF examinations were not statistically different between the two groups ( P > 0.05).Conclusion The difference in anti-NMDAR antibody titrates and occurrence of pleocytosis may indicate distinctive pathogenesis in anti-NMDAR encephalitis patients with or without teratoma.Patients with teratoma may present with milder neurological symptoms and tend to have better outcome after tumor removal.