CAJ | 학술논문

目的探讨复发性抗N-甲基-D-天冬氨酸(NMDA)受体脑炎的临床特点、诊断与诊疗.方法回顾2011年6月至2014年11月在北京协和医院神经科收治的复发性抗NMDA受体脑炎16例,分析症状学、脑脊液学、神经影像学、免疫学和肿瘤学等特点及治疗方案.结果男5例,女11例,平均21.2岁.首次发病的起病症状包括:精神症状10例,不自主运动2例,癫痫发作3例,近记忆力减退1例;主要症状数:2 ～8个(平均5.8个);入ICU救治43.8％;改良Rankin评分(mRS)平均4.56;1例于首次发病时发现卵巢畸胎瘤并行切.16例共发生复发32次,多次复发者8例,平均复发间隔5.0个月.复发时症状数1～7个,其中以单一症状复发者11例次,多症状复发者21例次;复发期平均症状数2.59个/例次,低于初次发病(P＜0.05).复发期mRS评分1～5分,平均2.69,低于初次发病(P＜0.05).2例复发时出现不同于首次发病时的新症状.复发期脑脊液抗NMDA受体抗体阳性率为100％,血清抗NMDA受体抗体阳性率为53.1％.复发期脑电图异常12例.头MRI首次发病检查中8例异常,复发时原有病灶均消失,7例见新病灶.5例于复发期行头PET,均有异常.2例于复发期发现卵巢畸胎瘤并手术切除.16例给予一线免疫治疗,12例加用二线免疫治疗.全部病例经免疫治疗后病情缓解,mRS评分0～2分,平均0.78分.结论抗NMDA受体脑炎具有一次复发和多次复发的可能性,即使切除畸胎瘤仍有可能复发.多数患者在复发时症状较轻.症状学、脑脊液抗体检测和神经影像学等为判断和评估复发的重要方法.为预防复发,选择长程免疫治疗方案是必要的,并需要遵循个体化的原则.
목적 탐토복발성항N-갑기-D-천동안산(NMDA)수체뇌염적림상특점、진단여진료.방법 회고2011년6월지2014년11월재북경협화의원신경과수치적복발성항NMDA수체뇌염16례,분석증상학、뇌척액학、신경영상학、면역학화종류학등특점급치료방안.결과 남5례,녀11례,평균21.2세.수차발병적기병증상포괄:정신증상10례,불자주운동2례,전간발작3례,근기억력감퇴1례;주요증상수:2 ～8개(평균5.8개);입ICU구치43.8％;개량Rankin평분(mRS)평균4.56;1례우수차발병시발현란소기태류병행절.16례공발생복발32차,다차복발자8례,평균복발간격5.0개월.복발시증상수1～7개,기중이단일증상복발자11례차,다증상복발자21례차;복발기평균증상수2.59개/례차,저우초차발병(P＜0.05).복발기mRS평분1～5분,평균2.69,저우초차발병(P＜0.05).2례복발시출현불동우수차발병시적신증상.복발기뇌척액항NMDA수체항체양성솔위100％,혈청항NMDA수체항체양성솔위53.1％.복발기뇌전도이상12례.두MRI수차발병검사중8례이상,복발시원유병조균소실,7례견신병조.5례우복발기행두PET,균유이상.2례우복발기발현란소기태류병수술절제.16례급여일선면역치료,12례가용이선면역치료.전부병례경면역치료후병정완해,mRS평분0～2분,평균0.78분.결론 항NMDA수체뇌염구유일차복발화다차복발적가능성,즉사절제기태류잉유가능복발.다수환자재복발시증상교경.증상학、뇌척액항체검측화신경영상학등위판단화평고복발적중요방법.위예방복발,선택장정면역치료방안시필요적,병수요준순개체화적원칙.
Objective With the discovery of more patients with anti-N-methyl-D-aspartate (antiNMDAR) encephalitis,frequent clinical relapses pose a new challenge to neurologists.Methods Retrospective reviews were conducted for 16 hospitalized patients with relapsing anti-NMDAR encephalitis at our hospital from June 2011 until November 2014.Their clinical data including symptoms,cerebrospinal fluid (CSF) profiles,neuroimaging findings and relapsing treatment were compared with those initial episodes.Results There were 11 females and 5 males with a mean onset time of 21.2 (10-34) years.For initial episodes,the mean number of major symptoms was 5.8 and the mean modified Rankin score (mRS) 4.56.And 7 (43.8％) cases were admitted into intensive care unit (ICU).All received first-line immunotherapy and only one case second-line immunotherapy.Ovarian teratoma was detected and resected in only one case of initial episode.Among 32 relapses,8 cases (50％) had multiple (2-4) relapses.There was a median delay of 5.0 (0.5-18) months for relapses.Relapses were common upon pausing or reducing immunotherapy,usually monotherapy with corticosteroids.Compared with initial episodes,relapses were less severe (mean mRS 2.69,mean number of symptom 2.59) and only 2 cases were admitted into ICU during relapses.Presentation of relapses were partial symptoms of initial episode.However,two patients had new symptoms of brain stem involvement.Brain magnetic resonance imaging (MRI) of 8 cases showed abnormality initially during initial episode and disappearance at relapses while new lesions appeared in 7 patients including 3 cases with CNS demyelinating features of central nervous system (CNS) on MRI.The positivity rate of anti-NMDAR antibody was 100％ in CSF and 53.1％ in sera during relapses.Anti-AQP4 and NMO-Ig were positive in one case with brain stem involvement.All cases received first-line immunotherapy and 12 chronic second-line immunotherapy.Two cases of ovarian teratoma were detected on reassessment during relapse and then resected.Conclusion Inadequacy of second-line and chronic immunotherapy,occult teratoma and potential demyelination may contribute to a relapse of anti-NMDAR encephalitis.And its proper management should follow the recommendations of guidelines.