吉兰巴雷综合征神经电生理研究

【作者】 孙青；

【导师】 崔丽英；

【作者基本信息】 北京协和医学院 ， 神经病学， 2013， 博士

【摘要】 第一部分吉兰巴雷综合征系列神经电生理研究目的：对吉兰巴雷综合征(GBS)患者进行系列的神经电生理随诊,明确急性炎性脱髓鞘性多发神经根神经病(AIDP)和急性运动轴索性神经病(AMAN)在病程的不同阶段其系列的神经电生理改变。依据目前的GBS分型诊断标准对GBS进行分型,研究系列神经电生理随诊后GBS分型的变化,并探讨分型发生改变的原因。研究传导阻滞在GBS中的转归,探讨传导阻滞潜在的病理生理机制。方法：连续收集北京协和医院2010年9月至2013年3月GBS患者21例,在发病2周和4周左右至少完成2次神经电生理检查,同时回顾性收集北京协和医院1997年至2010年至少完成2次神经电生理检查的GBS住院患者21例,共42例。收集患者临床资料和神经电生理测定参数,包括运动神经传导、感觉神经传导、F波和针极肌电图。利用Hadden等的GBS分型诊断标准对患者进行神经电生理分型：首先依据初次神经电生理检查将患者分为AIDP组、AMAN组、AMSAN组和未分型组；然后依据系列随诊的神经电生理检查再次分组。统计系列随诊后GBS分型发生改变的患者,并分析分型发生改变的原因。统计分析AIDP和AMAN患者的临床和神经电生理特点。分析传导阻滞在GBS中的转归及其原因。结果：42例患者中,初次神经电生理检查符合AIDP者26例(62%),AMAN者10例(24%),未分型者6例(14%)。系列随诊后符合AIDP者17例(40%),AMAN者16例(38%),未分型者3例(7%),分型待定者(神经传导异常快速恢复正常)6例(14%)。AIDP和AMAN两组患者差异具有统计学意义的临床症状是腹泻史(p=0.032)和麻木症状(p=0.015)。两组患者在面瘫、吞咽困难或构音障碍等临床症状上差异无统计学意义。两组患者Hughes评分最低分和发病第4周时Hughes评分差异无统计学意义(t=0.437, p=0.665; t=1.005, p=0.323)。两组患者呼吸机辅助呼吸比例和临床症状快速恢复比例差异无统计学意义(p=0.335；p=0.335)。6例神经传导快速恢复者与AIDP和AMAN患者相比,Hughes评分最低分差异均无统计学意义(t=0.455, p=0.653; t=0.149, p=0.883),但6例患者发病1月内Hughes评分改善均大于2分,发病第4周时Hughes评分与AIDP和AMAN患者相比,差异均有统计学意义(t=2.125, p=0.046; t=3.032, p=0.007)AIDP患者末端潜伏期(DML)延长在发病第1-2周开始出现,第3-5周达高峰,此后逐渐恢复；远端复合肌肉动作电位(dCMAP)波幅在发病第1周出现下降,在第2-3周最低,此后缓慢恢复。AIDP患者发病第1周F波出现率出现异常,F波平均潜伏期正常,此后F波出现率逐渐恢复,但F波潜伏期逐渐延长,发病第4周左右达高峰。AMAN患者CMAP波幅恢复速度有两种模式：一种是CMAP波幅持续维持在较低的水平,一种是CMAP波幅较快升高,这两种快慢不同的恢复模式可以存在于同—患者不同神经上。系列随诊GBS分型发生改变者多是初次神经电生理检查为AIDP者分型发生改变,或者是初次神经电生理检查未分型者系列随诊分型明确。11例AIDP患者分型发生改变,其原因包括传导阻滞演变为轴索变性(4例),传导阻滞快速恢复(5例),短暂性DML延长(2例)。结论：AIDP和AMAN患者病情严重程度和临床预后是相似的,电生理上AMAN患者CMAP波幅可以持续维持在很低的水平,也可以相对快速的恢复,AMAN潜在的病理生理机制不仅包括轴索变性,也包括可逆性传导障碍。系列神经电生理随诊GBS分型改变主要由AIDP组转变为AMAN组或者AIDP组神经电生理快速恢复,发生转变的原因包括传导阻滞演变为轴索变性、传导阻滞快速恢复和短暂的末端潜伏期的延长。第二部分Miller Fisher综合征和Bickerstaff脑干脑炎临床及电生理特点分析目的：总结Miller Fisher综合征(MFS)和Bickerstaff脑干脑炎(BBE)患者临床及电生理特点,并探索其发病机制。方法：回顾性分析北京协和医院2000年至2011年符合MFS诊断标准的患者(13例)和BBE诊断标准的患者(7例)的病历资料,收集患者临床资料和电生理测定参数,包括感觉和运动神经传导、针极肌电图、F波、皮肤交感反应(SSR)、脑干听觉诱发电位(BAEP)、瞬目反射等,统计MFS和BBE临床特点和各项电生理检查异常的患者比例。结果：MFS和BBE患者前驱感染以呼吸道症状为主,眼球活动障碍、面瘫、延髓部症状较常见,均有脑脊液蛋白细胞分离,都存在抗GQlb抗体。但临床上,BBE还有意识障碍等中枢神经系统受累表现。电生理上,MFS和BBE患者感觉神经受累比例分别为6/13、2/7,主要表现为感觉神经动作电位波幅明显下降,感觉神经传导速度轻度减慢或正常；运动神经受累比例分别为2/13、1/7,多表现为运动末端潜伏期轻度延长,复合肌肉动作电位波幅正常；肢体针极肌电图异常比例分别为1/7、0/4；F波出现率异常比例分别为3/13、5/7,部分患者可出现F波出现率明显下降,但可以恢复；SSR异常比例分别为1/2、1/3;瞬目反射异常比例分别为1/2、1/1,BBE患者表现为中枢性损害；脑干听觉诱发电位异常比例分别为3/5、1/4,均表现为I波潜伏期延长或波幅低。结论：MFS和BBE中枢神经系统和周围神经系统均可受累,但BBE以中枢神经系统受累更常见。MFS和BBE可能是中枢神经系统和周围神经系统受累程度不同的同一种疾病的连续疾病谱。更多还原

【Abstract】 Part1Serial electrophysiological study of Guillain-Barre syndromeObjective:To investigate the serial electrophysiological changes of acute inflammatory demyelinating polyneuropathies(AIDP) and acute motor axonal neuropathy(AMAN) through serial electrophysiological study of Guillain-Barre syndrome(GBS). To electrophysiologically classify GBS patients into AIDP and AMAN subtypes, investigate how serial recordings change the classification, and analyze the causes of classification changes. To investigate the serial electrophysiological changes of conduction block, and analyze the possible underlying mechanisms of conduction block.Methods:Prospectively collected21GBS patients in Peking Union Medical College Hospital between September2010and March2013, and performed at least two serial electrophysiological tests around the second and fourth week after disease onset. Retrospectively collected21GBS patients between1997and2010who had at least two serial electrophysiological recordings. The electrophysiological parameters included motor sensory nerve conduction, F waves and electromyography. Based on the first electrophysiological recordings, electrophysiologically classified GBS patients into AIDP and AMAN subtypes according to Hadden’s classification criteria. Analyzed how GBS patients changed the initial electrodiagnosis after serial electrophysiological recordings, and analyzed the causes of the changes. Compared and analyzed the clinical and electrophysiological characteristics of AIDP and AMAN patients. Analyzed the serial electrophysiological changes of conduction block.Results.At the first test,26of42patients(62%) fulfilled Hadden’s criteria for AIDP,10patients(24%) for AMAN and6patients(14%) were classified as equivocal. After follow-up,17patients(40%) were classified as AIDP,16patients(38%) as AMAN,3patients(7%) equivocal and6patients with rapid electrophysiological recovery(classification unclear). Clinically, preceding gastroenteritis were more common in AMAN group (p=0.032), and sensory symptoms were more common in AIDP group(p=0.015). Between the AIDP and AMAN groups, cranial nerve involvement did not differ significantly, and neither the nadir Hughes grade nor Hughes grade at the forth week differed significantly(t=0.437, p=0.665; t=1.005, p=0.323). Compared with AIDP and AMAN group, nadir Hughes grade of the6patients with rapid electrophysiological recovery did not differ significantly. However, all the6patients showed a markedly rapid clinical recovery(improved by two or more Hughes grades within one month), and compared with AIDP and AMAN group the Hughes grades at the forth week differed significantly(t=2.125, p=0.046; t=3.032, p=0.007).In AIDP group, distal motor latency(DML) prolongation appeared at week1-2, and became prominent at week3-5; The nadir of distal compound muscle action potential(dCMAP) amplitude decrease occurred at week1-2. In AIDP group, the early electrophysiological changes of F waves were decreased frequency with normal F wave latency, and F wave latency prolongation showed up later with nadir abnormality occurring at week4. There were two patterns of CMAP amplitude recovery in AMAN group:rapid increase and persistent at low level, and the two different recovery patterns were found in different nerves of the same patient.The majority of classification changes were from AIDP and equivocal groups by initial electrophysiological tests. The main reason was the recognition by serial recordings of reversible conduction failure(5patients), axonal degeneration(4patients) and transient prolongation of DML(2patients).Conclusion:The clinical severity and prognosis of the AIDP and AMAN groups are similar. In some AMAN patients, the CMAP amplitude can rapidly increase, which could not be explained by axonal degeneration. Besides axonal degeneration, reversible conduction failure might be another underlying mechanisms of AMAN.The causes of classification changes after serial electrophysiological study include:the length-dependent CMAP amplitude reduction, rapid resolve of conduction block, and transient prolongation of DML. Part2Clinical and electrophysiological study of Miller Fisher syndrome and Bickerstaff’s brainstem encephalitisObjective:To investigate the underlying mechanisms of Miller Fisher syndrome(MFS) and Bickerstaff’s brainstem encephalitis(BBE) through study of their clinical and electrophysiological characteristics.Methods:Retrospectively analyzed clinical and electrophysiological characteristics of13MFS and7BBE cases in Peking Union Medical College Hospital between2000and2011. The electrophysiological parameters included sensory and motor nerve conduction, electromyography, F wave, sympathetic skin response, brainstem auditory evoked potential and blink reflex.Results:MFS and BBE had similar clinical characteristics:respiratory symptoms were the most common infectious symptoms before disease onset; Ophthalmoplegia, facial palsy and bulbar symptoms were common; They both have cerebrospinal fluid albuminocytological dissociation and positive serum anti-GQlb antibody. However, BBE had more central nervous system lesion signs clinically such as conscious disturbance, positive Babinski’s sign and central facial palsy. Electrophysiologically, MFS and BBE also had similar electrophysiological features:sensory nerve abnormality ratios were6/13,2/7respectively, with prominently reduced sensory nerve active potential amplitude, normal or slightly slowed sensory conduction velocity; Motor nerves abnormality ratios were2/13,1/7respectively, with slightly prolonged distal motor latency and normal compound muscle action potential; Electromyography abnormality ratios were1/7,0/4respectively; F wave frequency abnormality ratios were3/13,5/7respectively, and in some cases, F wave frequency would restore; Blink reflex abnormality ratios were1/2,1/1respectively, with central involvement in BBE; BAEP abnormality ratios were3/5,1/4respectively, with wave I latency or amplitude abnormality.Conclusion: The similarities of clinical and electrophysiological features suggest that MFS and BBE have the same mechanism and they form a continuous spectrum with variable central nervous system and peripheral nervous system involvement.更多还原