【作者】 周爽；

【导师】 崔丽英；

【作者基本信息】 北京协和医学院 ， 临床医学（专业学位）， 2013， 博士

【摘要】 背景：肌萎缩侧索硬化(amyotrophic lateral sclerosis,ALS)是一组选择性累及皮质锥体细胞、脑干运动神经元、锥体束及脊髓前角细胞的致死性神经系统变性疾病,目前病因未明,尚缺乏有效的治疗方法,预后不良。ALS病情进展隐匿,早期的漏诊和误诊率偏高。疾病呈进行性发展,逐渐出现咽喉肌、四肢及胸部肌肉的无力、萎缩,最终呼吸衰竭死亡。通过各种有效的检查手段,及早的明确ALS的诊断有极其重要的意义。ALS的诊断缺乏特异性的生物学指标,主要依靠临床症状和神经电生理检查特点进行诊断。同芯针肌电图测定在ALS的诊断中最为关键,感觉和运动神经传导测定具有重要的鉴别诊断价值。在临床实践中,有很多周围神经或下运动神经元疾病也可以表现为广泛神经源性损害的特点,本研究试图通过F波和运动神经传导测定方面的特点,研究其在ALS的诊断和鉴别诊断中的意义。目的：本研究主要通过回顾性研究ALS患者的临床及神经电生理特点,观察对比ALS患者正中神经、尺神经、胫后神经以及腓总神经F波及运动、感觉的传导,来评估病程、肌力等因素与下运动神经元损伤临床症状之间的联系。并试通过比较ALS患者和脊髓型颈椎病(cervical spondylotic myelopathy,CSM)/脊髓型腰椎病(lumbar spondylotic myelopathy, LSM)患者的神经电生理特点,探讨F波等电生理指标的鉴别诊断价值。方法：连续选取2012年6月至2013年4月期间就诊于北京协和医院门诊及病房,行肌电图检查且诊断为ALS的患者,同时选取此期间行肌电图及影像学检查诊断为CSM/LSM的患者,所有患者均建立病案资料库,记录姓名、性别、年龄、病程、发病部位、检查日期、诊断确定性、症状、体征、所检测肌肉的肌力分级及检测结果等。肌力分级采用MRC肌力分级法对拇短展肌、小指展肌、踇短展肌及趾短伸肌肌力进行测定,采用丹麦Medtronic公司的Keypoint肌电图仪对患者分别进行正中神经、尺神经、胫后神经、腓总神经的运动神经传导、感觉神经传导、F波传导测定。结果判断采用北京协和医院肌电图室根据不同年龄和神经测定的正常值作为对照进行判断。全部资料输入SPSS19.0数据库,进行数据统计学分析。结果：共收录ALS患者137名,分为临床确诊ALS(23例)、临床拟诊ALS(70例)、临床可能ALS(44例)。其中男性90例(65.7%),女性47例(34.3%),男女比为1.91：1,发病年龄25-75岁,平均发病年龄51.19±10.57岁。首发部位为脑干的24例(17.5%),颈段77例(56.2%),腰骶段36例(26.3%)。共收录CSM患者27例,男性21例(77.8%),女性6例(22.2%),发病年龄33-84岁,平均发病年龄53.67±12.78岁。共收录LSM患者32例,男性和女性各16例(50.00%),发病年龄16-84岁,平均发病年龄55.69±19.25岁。ALS患者正中神经和胫后神经的F波测定中,分别有87例(71.9%)和8例(33.3%)F波出现率降低,其中有46例(38%)和3例(12.5%)未引出F波,15例(12.4%)和11例(45.83%)F波平均潜伏期延长；且随肌力下降,F波出现率逐渐降低,F波出现率降低的比例和未引出F波的比例升高,F波平均潜伏期可以延长,F波离散程度亦可能增加,而F波传导速度的改变并不明显。相关性研究发现,F波出现率下降与MRC分级(P<0.05)、肌肉萎缩情况(P<0.05)和下运动神经元受损体征(P<0.05)明显相关。ALS患者运动神经传导测定中,共测定了正中神经134例、尺神经124例、胫后神经47例、腓总神经40例,分别有3例(2.23%)、1例(0.81%)、0例(0%)、4例(10.00%)未引出肯定波形。正中神经运动传导测定结果中,有31例(23.13%)出现了远端潜伏期的延长,92例(68.66%)出现了CMAP波幅的降低；尺神经运动传导测定结果中,有19例(15.32%)出现了远端潜伏期的延长,73例(58.87%)出现了CMAP波幅的降低；胫后神经运动传导测定结果中,有3例(6.38%)出现了远端潜伏期的延长,19例(40.43%)出现了CMAP波幅的降低；腓总神经运动传导测定结果中,有6例(15.00%)出现了远端潜伏期的延长,18例(45.00%)出现了CMAP波幅的降低；CMAP波幅下降与发病部位(P<0.001)、MRC肌力分级(P<0.001)及肌肉萎缩情况(P<0.001)明显相关。ALS患者感觉神经传导仅3例出现异常。ALS患者正中神经运动传导与CSM患者相比,DML(P<0.001)、CMAP波幅(P<0.001)、F波出现率(P<0.001)、F波传导速度(P<0.001)、F波平均潜伏期(P<0.05)均存在显著性差异。ALS患者胫后神经运动传导与LSM患者相比,DML(P<0.05)、CMAP波幅(P<0.001)、F波出现率(P<0.05)、F波平均潜伏期(P<0.05)均存在显著性差异。在相同肌力等级的情况下,ALS患者较CSM患者的运动传导潜伏期明显延长、CMAP波幅明显降低、F波出现率明显降低、F波平均潜伏期有所延长,而F波传导速度无明显差异。在相同肌力等级的情况下,ALS患者较LSM患者的运动传导潜伏期略有延长、CMAP波幅略有降低、F波出现率略降低、F波平均潜伏期略延长,但二者不具有明显的统计学差异。ALS患者F波出现率异常的平均病程为15.2±11.6月,远远早于CSM患者的35.0±37.0月,ALS患者最早出现F波出现率异常的病程仅2月,亦远远早于CSM患者的12月。ALS患者F波平均潜伏期延长的平均病程为15.0±14.2月,最早出现异常的患者病程4月；而CSM患者中极少出现F波平均潜伏期的延长。结论：ALS患者F波传导异常主要是出现率低、波形消失和潜伏期延长,也可出现F波离散性增大,并且与肌力下降和肌肉萎缩相关,但F波传导速度的改变并不明显。ALS患者运动神经传导以CMAP波幅下降为主要特点,可出现DML延长,并且与肌力的下降和萎缩相关；ALS患者存在明显的“分裂手”现象。仅有极少数ALS患者出现感觉传导的异常,且多于疾病的晚期出现。ALS患者于CSM/LSM患者相比,二者患者群的性别比、病程、锥体束征阳性率并没有显著的差异,但ALS患者运动传导DML、CMAP波幅、F波出现率、F波平均潜伏期均与CSM患者有明显差异且CMAP波幅下降可以作为二者鉴别诊断的一项参考指标。ALS患者出现F波出现率和平均潜伏期异常的时间远远早于CSM患者,在病程早期尤其是起病半年以内就出现F波出现率异常、F波平均潜伏期延长的患者,诊断上应该考虑ALS的可能。更多还原

【Abstract】 Background:Amyotrophic lateral sclerosis(ALS) is a neurodegenerative disease that result in progressive loss of bulbar and limb function. The pathogenesis of ALS remains unclear and there is no effective treatment. It may not draw your attention at the beginning of the disease, so many patients are misdiagnosed or never diagnosed. As the disease progresses, muscles of throat, limbs and thorax will become weaker and weaker until respiratory failure. So it is significance to make a definite diagnose early. The diagnosis of ALS depends on the clinical feature and electrophysiology, especially electromyography. Motor conduction studies are essential in the diagnosis of ALS. We research the feature of F-wave and moter conduction in patients of ALS and CSM/LSM, in order to make a clear diagnosis and differential diagnosis.Objective:To evaluate the relationship between the disease duration, muscle strength and the symptom of lower motor neuron, we retrospectively study the clinical and electrophysiological features in the patients that have been diagnosed ALS. We also compared the electrophysiological features between ALS and cervical spondylotic myelopathy (CSM)/lumbar spondylotic myelopathy (LSM) to make a clear differential diagnosis.Methods:We collected patients of confirmed ALS, CSM and LSM in Peking Union Medical College Hospital between June2012and April2013. Their clinical electrophysiological features including name, gender, age, disease duration, onset site, status of consent, pyramidal sign, myodynamia and result of nerve conduction and EMG were recorded and analyzed using statistical methods.Result:A total of137patients of ALS were recruited in our study including23definite ALS,70probable ALS and44possibleALS. The ratio of male:female in patients was1.91:1. The mean age of onset was51.19±10.57years. The onset site of disease were cervical myotomes (56.2%), lumbosacral myotomes (26.3%) and bulbar (17.5%).In the F-wave study among ALS patients in median nerve and posterior tibial nerve,87(71.9%) and8 (33.3%) had a low F-wave frequency,46(38%) and3(12.5%) had no F-wave,15(12.4%) and11(45.83%) had a prolonged F-wave mean latency. The patients who had a poor muscle strength had a lower F-wave frequency, higher ratio of no F-wave, prolonged F-wave mean latency, and increased F-wave dispersion than that have a better muscle strength. The reduction of F-wave frequency had a significant relationship with the UK Medical Research Council (MRC) scale (P<0.001) and atrophy of muscle (P <0.001).134median nerves,124ulnar nerves,47posterior tibial nerves and40common peroneal nerves were tested in the study of motor nerve conduction.3(3.23%) median nerves,1(0.81%) ulnar nerves,0(0%) posterior tibial nerves and4(10.00%) common peroneal nerves did not have a definite wave of motor conduction. In the motor conduction of median nerve,31(23.13%) had a prolongation of distal motor latency (DML), and92(68.66%) had a reduction of compound muscle action potential (CMAP) amplitude. In the motor conduction of ulnar nerve,19(15.32%) had a prolongation of DML, and73(58.87%) had a reduction of CMAP amplitude. In the motor conduction of posterior tibial nerve,3(6.38%) had a prolongation of DML, and19(40.43%) had a reduction of CMAP amplitude. In the motor conduction of common peroneal nerve,6(15.00%) had a prolongation of DML, and18(45.00%) had a reduction of CMAP amplitude. The reduction of CMAP amplitude had a significant relationship with onset site(P<0.001), the MRC scale(P<0.001)and atrophy of muscle(P<0.001). Only3patients had a abnormal sensory conduction.A total of27patients of CSM were recruited in our study. The mean age of onset was53.67±12.78years. A total of32patients of LSM were recruited in our study. The mean age of onset was55.69±19.25years. Compared with these patients, patients of ALS had a obviously prolonged DML (P<0.001), lower CMAP amplitude (P<0.001), lower F-wave frequency (P<0.001), slow F-wave velocity (P<0.001) and prolonged F-wave mean latency (P<0.05). Patients of ALS have a significantly prolonged DML, significantly lower CMAP amplitude, significantly lower F-wave frequency and prolonged F-wave latency than patients of CSM with the same MRC scale. Also, patients of ALS have a prolonged DML, lower CMAP amplitude, lower F-wave frequency and prolonged F-wave latency than patients of LSM with the same MRC scale. The mean disease duration of low F-wave frequency in ALS patients is15.2±11.6month, and that in CSM patients is35.0±37.0month. The shortest disease duration of ALS patient who have a low F-wave frequency is only2month, and that in CSM patients is12month. The mean disease duration of prolonged F-wave latency in ALS patients is15.0±14.2month, and the shortest of that is4month. But only one patient of CSM had a prolonged F-wave latency.Conclusion:Patients of ALS had a F-wave conduction feature of lower F-wave frequency, prolonged F-wave mean latency and increased F-wave dispersion. They had a strong correlation with muscle strength. But F-wave velocity only changed a little.They also had a motor nerve conduction feature of prolonged DML and lower CMAP amplitude. We found a high correlation between CMAP amplitude and both atrophy of muscle and strength as assessed by the MRC scale, but there was no correlation between CMAP amplitude and both pyramidal sign and disease duration. Split hands and split legs were exist in the ALS patients.A very few patients had a abnormal sensory nerve conduction and it always happened in the advanced stage of disease. Compared with CSM patients, ALS patients had a obviously prolonged DML,lower CMAP amplitude, lower F-wave frequency, slow F-wave velocity and prolonged F-wave mean latency. So we considerd CMAP amplitude could be a parameter for differential diagnosis of these two diseases. But the male female ratio, disease duration and pyramidal sign between this two groups did not have a significant different.The disease duration of ALS who had a low F-wave frequency or prolonged F-wave latency is much earlier than that of CSM.So the diagnosis of ALS should be considered if the patient had a low F-wave frequency or prolonged F-wave latency in the beginning of the disease or within6month.更多还原