【作者】 叶玉琴；

【导师】 江新梅；

【作者基本信息】 吉林大学 ， 神经病学， 2011， 博士

【摘要】 吉兰-巴雷综合征(GBS)是最常见的周围神经系统自身免疫性疾病.主要表现为急性进展性对称性的周围神经损害：无力、腱反射减退或消失、疼痛麻木等。严重的患者可出现呼吸肌无力导致呼吸困难,严重威胁生命。GBS是一种常见的引起四肢瘫的周围神经系统疾病。早期诊断、治疗及预后是大家最关注的问题,而了解其发病机制、临床表现及相关检查对于早期诊断、治疗及判断预后有至关重要的作用。目前国外开始关注GBS的相关研究。但是还有很多相关问题未得到解决。如：早期甚至超早期神经电生理检测对GBS的早期诊断到底有多大意义?AMAN在中国北部地区是否真是主要发病类型?AMAN是否确实都存在神经轴突的损伤?AMAN预后是否确实都很差?AIDP是否存在一些其他特殊的神经电生理表现等?GBS早期治疗及晚期治疗、对轻型患者与中重型患者效果是否相同?儿童型GBS与成人型GBS到底有何不同,预后是否一样?国外开始关注这些问题,而在国内尚无大样本进行统计分析,无系统性的对该疾病进行研究。本研究针对这些问题收集中国东北部吉林省2006年1月至2010年10月在吉林大学第一医院住院的138例GBS患者及2007年爆发流行的26例GBS患者进行系统研究。方法：收集2006年1月至2010年10月于吉林大学第一医院住院的138例散发GBS患者及2007年爆发流行的26例GBS患者,分析其临床及神经电生理表现及治疗,跟踪6月观察预后等。同时将患者分为儿童组及成人组,分析儿童及成人GBS患者的临床、神经电生理及治疗预后等方面的差异。结果：1.138例散发患者中男性86例,女性52例,儿童患者33例,成人患者105例,平均年龄32岁。存在前驱感染者占59%,其中消化道感染者占63%。97%的患者出现肢体无力及腱反射减退,其中起病首发四肢无力者占51%,存在感觉障碍者仅占38%。起病呈中重型者(不能独立行走者)占72%;2.将患者神经电生理检查按时间分为超早期(7天内)、早期(8-14天)及2周后三组,比较不同时期电生理的异同。结果显示3组均主要表现为CMAP波幅降低(分别为70%,79%及85%)、F波异常(分别为47%,68%及62%)及H反射异常(55%,65%及53%)；3.按神经电生理检查结果将患者分为AMAN及AIDP组,发现AMAN患者33人(26%),AIDP患者66人(53%)。AIDP电生理上不仅存在CMAP波幅的降低,CMAP远端潜伏期及MCV也显著减慢,与AMAN存在明显差异。AIDP主要表现为下肢运动神经传导检测异常,上肢感觉神经传导检测异常而下肢腓肠神经相对不受累。AMAN与AIDP组患者起病呈中重型者分别为91%及74%。经IVIg治疗后短期内AMAN与AIDP组症状好转者分别为73%及90%。起病6月后AMAN与AIDP组轻型患者(能独立行走者)分别为82%及89%；4.135例患者应用IVIg治疗,症状好转者占84%。将患者按治疗时间分为2周内和2周后IVIg治疗组,结果显示2周内治疗组与2周后治疗组效果无显著差异。另将患者分为轻型及中重型患者治疗组,结果显示2组间也无显著差异；5.将138例患者分为儿童组及成人组,分析2组GBS患者临床、神经电生理及治疗预后的异同。儿童组33人,其中8岁以上者23例,起病存在前驱感染者仅占36%,而成人组为66%。儿童组起病与成人组均以四肢无力起病最为常见(分别为43%及53%),儿童组存在感觉异常者较成人少(分别为18%及44%),儿童组存在颅神经损害表现较成人多(分别为33%及23%),儿童组未见有呼吸衰竭者,儿童组起病较成人组重,中重型患者比例分别为82%及69%,儿童组应用IVIg治疗效果较成人组稍差(治疗好转比例分别为67%及91%)。儿童组与成人组在神经电生理上均主要表现为CMAP波幅降低、F波及H反射异常。经电生理分型,儿童组AMAN比例较成人组高(分别为38%及23%),儿童组中AMAN与AIDP起病中重型患者分别为91%及75%,6月时预后比较无显著差异,且与成人组预后比较也无显著差异。儿童组与成人组经ⅠVⅠg治疗后比较,治疗效果在AMAN儿童及成人患者中无明显差别,AIDP儿童患者治疗效果较成人患者差,但在儿童组中IVIg对AMAN的效果较AIDP稍差；6.2007年爆发流行的GBS患者均来自于吉林省长春市双阳区,均于2007年6月-7月的2周内集中发病,所有患者均有饮用生水史,73%的患者发病前1月内有腹泻史。54%的患者为AMAN且预后较AIDP差,1例患者发现空肠弯曲杆菌感染,3例患者血清CMV抗体阳性,2例患者血清EB病毒抗体阳性,8例患者血清科萨奇病毒抗体阳性,电生理上以CMAP波幅降低、F波及H反射异常最为常见,1月后复查电生理检查发现F波异常率较H反射明显降低,肌电上纤颤电位、正锐波的出现随时间推移出现率明显升高,且多见于预后不佳的患者。结论：1.临床上我国东北部吉林省GBS患者男性多见,以中青年居多,前驱感染以消化道感染最为常见。临床以四肢同时无力最为常见,AIDP是GBS主要类型。患者起病症状较重；2.超早期(7天内)神经电生理检查与早期(8-14天)及2周后检查结果类似,AIDP的神经电生理主要表现为下肢运动神经纤维受损,上肢感觉神经纤维受损而腓肠神经相对不受累,提示GBS超早期即可行神经电生理检查协助超早期诊断；3.AMAN发病比例明显高于国外,AMAN与AIDP预后基本类似,部分AMAN患者治疗后短期内症状甚至明显改善；4.IVIg治疗对GBS患者2周后治疗与2周内治疗效果类似,对轻型患者(能独立行走者)与中重型患者的效果也无明显差别,提示患者无论起病严重程度及起病时间长短均可进行IVIg治疗；5.GBS儿童患者与成人患者存在很多差异：儿童患者8岁以上多见,前驱感染者较少,极少出现主观感觉异常及呼吸衰竭,但颅神经受损较多且起病重于成人患者,AMAN的发病比例较成人高,IVIg治疗短期内效果不如成人明显。但儿童与成人患者神经电生理检查结果大体类似,AMAN与AIDP预后基本类似,但总体均较成人差,提示儿童患者应注意与成人不同的临床表现,早期诊断并改善治疗方案以期获得最佳治疗效果；6.2007年流行性GBS可能与各种病毒感染相关,与空肠弯曲菌关联不大。以AMAN为主要发病类型,且预后相对较差。在神经电生理方面F波恢复较H反射快,纤颤电位及正锐波的出现随时间推移出现率增高,且提示预后较差。更多还原

【Abstract】 Guillain-Barre syndrome (GBS) is an autoimmune disease affecting the peripheral nervous system. GBS is characterized by weakness, areflexia and numbness or a tingling sensation in the legs and arms. The patients may be chair or bed-bound, may need artificial ventilation. Early diagnosis, treatment and prognosis are very important to every patient while the mechanisms, clinical features and associated exams are important to early diagnosis and treatment. Some studies of GBS have been made in other countries but still many questions have been left such as:how much important of early or super-early neuroelectrophysiological examinations for GBS patients? Is it true that acute motor axonal neuropathy (AMAN) is the most common type in North China? If it is true that the damage of motor axon could be found in every AMAN and all AMAN patients had a bad recovery? Is there some special electrophysiological features in AIDP? Whether the effectiveness is the same between the mild and severe patients and treatment before or after 2 weeks? What is the difference between children and adult GBS patients? These questions have not been considered and we do not find systemic studies of GBS in our country. So we collected 138 sporadic GBS patients and 26 epidemic GBS patients who were admitted to the First Hospital of Jilin University between Jan 2006 and Dec 2010 in order to find some characteristics of GBS in Northeast China.Methods:A retrospective study were performed involving 138 sporadic GBS patients admitted to the First Hospital of Jilin University between Jan 2006 and Dec 2010 and 26 epidemic GBS patients broke out within 2 weeks in 2007. All patients come from Jilin province, Northeast China. Also we divided the sporadic patients into children and adult groups. The objective was to determine if there were some characteristics of GBS in Northeast China.Results:1. the sporadic patients group include 86 males and 52 females,33 children and 105 adults, there median age was 32 years.59% patients reported that they had an antecedent infection and 63% patients of them termed that they had suffered diarrhea. Notably,97% patients had motor weakness and reduced or absent deep tendon reflexes and 51% patients of them reported all limbs were involved simultaneously. Only 38% patients had sensory disturbances.72% patients could not walk independently.2. We divide 138 patients into 3 groups (within 1 week,8-14 days and after 2 weeks) according to the performing time of electrophysiological examinations. Low CMAP amplitude (70%,79% and 85%, retrospectively), abnormal F waves (47%,68% and 62%, retrospectively) and H reflexes (55%, 65% and 53%, retrospectively) were most common in all groups.3. electrophysiological findings subjected to the electrodiagnostic criteria, indicated that 33 patients (26%) exhibited features of AMAN and 66 patients (53%) were AIDP. Not only the low CMAP amplitude but also the slow CMAP latency and MCV were found in AIDP which were different notably from AMAN. Also the abnormal motor nerve conductive studies of lower extremities were most common in AIDP patients and with abnormal sensory nerve conductive studies of upper extremities without involvement of sural nerves.91% and 74% patients could not walk in AMAN and AIDP groups retrospectively.73% and 90% patients made some recovery after effective treatment in AMAN and AIDP groups.4.135 patients received IVIg treatment and 84% of them made some recovery. We divided them into 2 groups according to the time of treatment (within 2 weeks and after 2 weeks), also we divided them into mild group (could walk independently) and severe group. No significant difference were found between these groups.5.138 patients were divided into children and adult groups.23 of 33 children were older than 8 years. Only 36% of them while 66% adult patients had an antecedent infection. Symptoms onset with all limbs involvement were most common in two groups (43% and 53%). Sensory abnormalities were uncommon in children than in adult group (18% and 44%), but cranial nerve involvement were more common in children. Symptoms were more severe in children than in adult (82% and 69%), and the effective of IVIg were not significant in children than in adult (67% and 91%). Low CMAP amplitude, abnormal F waves and H reflexes were most common in two groups. The percent of AMAN were higher in children than in adult (38% and 23%). There were not significant difference between AMAN and AIDP children in recovery and also not different notably when compared with adult. But the AIDP children were not so effective with IVIg treatment when compared with adult patients. But IVIg treatment was more effective in AIDP children than in AMAN children.6. all 26 epidemic GBS patients with symptoms onset between 2 weeks in June and July of 2007 were residents of the Shuangyang District of Changchun City, Jilin province, China. All patients reported that they had drunk unboiled water and most,19/26 (73%) had suffered diarrhea within a month before GBS onset. 14 (54%) patients exhibited features of acute motor axonal neuropathy (AMAN) which associated with a longer illness. Only one patient tested positive for C. jejuni, and none tested positive for Salmonella, Shigella or fungi. Three patients’sera were positive for CMV antibodies; 2 patients’sera were positive for antibodies to EB virus; 8 patients’sera were positive for antibodies to Coxsackie virus. The abnormalities observable～1 month after GBS onset were similar to those evidenced at 10 days after onset, with the exception of F waves, which often recovered quickly, and fibrillation potentials and positive sharp waves which arose over time.Conclusion: 1. Most GBS patients were young males in Jilin province, Northeast China. And gastrointestinal infections were the most common antecedent infection. Clinically, all limbs were involved simultaneously were the most common features. The most common type of GBS was AIDP, which was the same as other countries. Most GBS patients were severe in Northeast China.2. As the electrophysiological features were almost the same in 3 groups (within 1 week,8-14 days and after 2 weeks), and the finding that the abnormal motor nerve conductive studies of lower extremities were most common in AIDP patients and with abnormal sensory nerve conductive studies of upper extremities without involvement of sural nerves. Electrophysiological examinations could be done in early even in super-early GBS.3. The percentage of AMAN was higher than in other countries, but there were not significant difference between AMAN and AIDP in recovery. Some AMAN patients could even make a significant recovery after given an effective treatment.4. Treatment with IVIg could be given regardless the time of GBS onset and the severe degree as there were not significant difference when compared between before and after 2 weeks and compared between mild and severe patients.5. There were many differences between children and adult patients. Most GBS children were older than 8 years, antecedent infection and sensory abnormalities were not so common, but cranial nerve involvement was more common than in adult patients. The percentage of AMAN was higher than adult patients and IVIg was not so effective in GBS children. But the electrophysiological features were almost the same. There were not significant difference between AMAN and AIDP in recovery and also not different notably when compared with adult. But the recovery of some GBS children was worse than adult patients. So as a clinician, we must give an early diagnosis and an effective treatment according to these clinical and electrophysiological characteristics.6. The outbreak of 2007 epidemic GBS may have been associated with various viral infections. The main subtype was AMAN, which was associated with a longer illness duration and a worse prognosis. F waves often recovered quickly than H reflexes, the development of fibrillation potentials and positives waves～1 month after GBS onset may accompany a longer duration of GBS disease.更多还原