【摘要】：第一部分F波在肌萎縮側(cè)索硬化和肯尼迪病診斷和鑒別診斷的意義研究背景：肌萎縮側(cè)索硬化(amyotrophic lateral sclerosis, ALS)是一種選擇性累及大腦皮質(zhì)腦干和脊髓運動神經(jīng)元的快速進(jìn)展性神經(jīng)系統(tǒng)變性疾病,主要臨床表現(xiàn)包括進(jìn)行性肌肉無力萎縮、延髓麻痹和錐體束征。目前ALS病因尚未明確且缺乏有效的治療辦法,患者預(yù)后不良。ALS診斷需要上、下運動神經(jīng)元同時受累的證據(jù),目前尚缺乏特異性的生物學(xué)標(biāo)記物。ALS病情進(jìn)展隱匿,臨床表現(xiàn)具有異質(zhì)性,早期容易誤診漏診,例如一些ALS患者上運動神經(jīng)元受累體征出現(xiàn)于病程晚期或無上運動神經(jīng)元受累體征,臨床上有時難以與肯尼迪病(Kennedy disease, KD)鑒別。既往研究顯示ALS和KD在感覺神經(jīng)傳導(dǎo)、針級肌電圖、皮層興奮性測試、血清肌酸激酶水平和臨床表現(xiàn)上存在差異。至今缺乏關(guān)于ALS和KD的F波特點比較的研究。目的：本研究擬通過比較ALS患者和正常受試者尺神經(jīng)F波參數(shù)差異并分析ALS患者上、下運動神經(jīng)元功能異常對F波參數(shù)的影響來探討ALS中F波的特點；并試圖通過分析和比較ALS患者和KD患者正中神經(jīng)、尺神經(jīng)、脛神經(jīng)和腓神經(jīng)F波特點的差異,探討F波在ALS和KD診斷和鑒別診斷中的價值。方法：連續(xù)入組自2013年9月至2014年7月期間就診于我院神經(jīng)科門診的82：名ALS患者,所有患者建立病案數(shù)據(jù)庫,記錄患者姓名、性別、年齡、病程、發(fā)病部位、癥狀、體征及所檢測肌肉的MRC肌力分級等。50名年齡和性別匹配的健康志愿者作為正常對照組。以受試者尺神經(jīng)為研究對象,對ALS患者和正常對照組行尺神經(jīng)運動神經(jīng)傳導(dǎo)和F波檢測。比較ALS患者與正常對照組尺神經(jīng)F波參數(shù)差異,并使用Logistic回歸分析評估ALS患者尺神經(jīng)F波參數(shù)與上肢錐體束征和小指展肌MRC肌力分級(MRC5級、MRC4級和MRC3級)的關(guān)系。連續(xù)入組自2013年9月至2014年12月就診于我院神經(jīng)科門診的37名以下運動神經(jīng)元受累為主的男性ALS患者和同時期就診于我院神經(jīng)科門診的32名KD患者；30名男性健康志愿者作為正常對照組。比較ALS患者、KD患者和正常對照組雙側(cè)正中神經(jīng)、尺神經(jīng)、脛神經(jīng)和腓神經(jīng)F波參數(shù)差異。結(jié)果：ALS患者與正常對照組尺神經(jīng)F波參數(shù)的比較研究發(fā)現(xiàn),與正常對照組相比,ALS患者尺神經(jīng)平均(P=0.040)和最大(P)0.001)F波波幅、平均(P0.001)和最大(P0.001)F/M波幅比、重復(fù)神經(jīng)元指數(shù)(P0.001)、重復(fù)F波指數(shù)(P0.001)和巨大F波出現(xiàn)率(P0.001)增高,F波時間離散度(P0.001)、最短F波潛伏期(P0.001)延長,F波時限(P=0.004)縮短,F波出現(xiàn)率(P0.001)降低,差異均有統(tǒng)計學(xué)意義。ALS患者尺神經(jīng)F波最短潛伏期(P0.001)和F波出現(xiàn)率(P0.001)與小指展肌MRC肌力分級顯著相關(guān)；F波平均(P0.001)和最大波幅(P=0.002)與上肢錐體束征顯著相關(guān)；平均(MRC,P0.001;錐體束征,P0.001)和最大(MRC,P=0.001;錐體束征,P=0.002)F／M波幅比、F波時限(MRC,P0.001;錐體束征,P=0.047)、重復(fù)神經(jīng)元指數(shù)(MRC,P0.001;錐體束征,P=0.009)和重復(fù)F波指數(shù)(MRC,P0.001；錐體束征,P=0.002)與小指展肌MRC肌力分級及上肢錐體束征顯著相關(guān)。ALS患者與KD患者F波參數(shù)的比較研究發(fā)現(xiàn),與ALS患者和正常對照組相比,KD患者正中神經(jīng)、尺神經(jīng)、脛神經(jīng)和腓神經(jīng)最大F波波幅、巨大F波出現(xiàn)率和出現(xiàn)巨大F波受試者比率均增高,差異有統(tǒng)計學(xué)意義。與ALS患者相比,巨大F波可出現(xiàn)于KD患者多條神經(jīng)且傾向于對稱分布。在所測F波參數(shù)中,出現(xiàn)巨大F波神經(jīng)數(shù)量是區(qū)分ALS和KD最有效參數(shù),曲線下面積為0.908(95%可信區(qū)間：0.835-0.982)。受試者≥3條神經(jīng)出現(xiàn)巨大F波區(qū)分ALS和KD敏感性和特異性較高,分別為85%和81%。ALS患者(r=0.107,P=0.529)和KD患者(r=0.162,P=0.418)巨大F波總出現(xiàn)率與病程相關(guān)性無統(tǒng)計學(xué)意義。結(jié)論：F波參數(shù)受上、下運動神經(jīng)元功能影響,可反映脊髓運動神經(jīng)元池的完整性和興奮性。F波有助于鑒別ALS和KD,不受患者病程影響。對于下運動神經(jīng)元受累為主的男性ALS患者,如果巨大F波出現(xiàn)率顯著增加,尤其是在正中神經(jīng)和腓神經(jīng),以及多條神經(jīng)記錄到巨大F波(三3條)或巨大F波對稱分布于左右側(cè)相同神經(jīng)需考慮KD診斷,建議行KD基因檢測。第二部分肌萎縮側(cè)索硬化分裂手現(xiàn)象的電生理學(xué)研究和機(jī)制探討研究背景：肌萎縮側(cè)索硬化(amyotrophic lateral sclerosis, ALS)分裂手現(xiàn)象是指拇短展肌(abductor pollicis brevis, APB)和第一骨間肌受累重于小指展肌(abductor digiti minimi, ADM),是ALS的特異性臨床表現(xiàn)。既往研究顯示中樞機(jī)制和周圍軸索機(jī)制可能參與了ALS分裂手現(xiàn)象的發(fā)生,尚無研究顯示支配APB和ADM的脊髓運動神經(jīng)元池功能異常是否符合ALS分裂手現(xiàn)象。目的：本研究擬通過F波檢測探討ALS中支配APB和ADM的脊髓運動神經(jīng)元池功能異常是否符合ALS分裂手現(xiàn)象,參與ALS分裂手現(xiàn)象的發(fā)生。方法：研究納入2013年9月至2014年3月在北京協(xié)和醫(yī)院神經(jīng)科門診就診的40名ALS患者,根據(jù)ALS患者手部肌肉受累情況分為兩組,一組為手部肌肉萎縮無力明顯的ALS患者,一組為手部肌肉無明顯萎縮無力的ALS患者。20名健康志愿者作為正常對照組。對受試者正中神經(jīng)和尺神經(jīng)進(jìn)行運動神經(jīng)傳導(dǎo)檢測和F波測定。比較APB和ADM記錄的F波參數(shù)。分析的F波參數(shù)包括F波潛伏期、F波出現(xiàn)率、F波波幅F/M波幅比、重復(fù)神經(jīng)元指數(shù)和重復(fù)F波指數(shù)。結(jié)果：正常受試者APB和ADM記錄的F波參數(shù)相比,F波出現(xiàn)率(P0.05)、重復(fù)神經(jīng)元指數(shù)(P0.001)和重復(fù)F波指數(shù)(P0.001)存在差異,有統(tǒng)計學(xué)意義。ALS患者無明顯肌肉無力萎縮的上肢APB記錄的F波與正常對照組APB記錄的F波相比,F波出現(xiàn)率顯著降低(P0.001)、重復(fù)神經(jīng)元指數(shù)(P0.001)和重復(fù)F波指數(shù)(P0.001)顯著增高,差異有統(tǒng)計學(xué)意義,而ALS患者ADM記錄的F波參數(shù)相對正常。ALS患者出現(xiàn)肌肉萎縮無力臨床表現(xiàn)的上肢APB與ADM記錄的F波參數(shù)比較,平均F波波幅(P0.05)、F/M波幅比(P0.05)、F波出現(xiàn)率(P0.001)、重復(fù)神經(jīng)元指數(shù)(P0.05)和重復(fù)F波指數(shù)(P0.05)存在差異,有統(tǒng)計學(xué)意義。APB和ADM脊髓運動神經(jīng)元池功能異常的電生理學(xué)差異是ALS的特異性表現(xiàn)。APB記錄的F波出現(xiàn)率(P=0.002)、重復(fù)神經(jīng)元指數(shù)(P0.001)和重復(fù)F波指數(shù)(P0.001)有助于區(qū)分ALS患者和正常受試者,診斷價值優(yōu)于ADM/APB復(fù)合肌肉動作電位波幅比。結(jié)論：正常受試者和ALS患者APB和ADM記錄的F波參數(shù)差異符合分裂手現(xiàn)象,可能脊髓運動神經(jīng)元池功能異常參與了ALS分裂手現(xiàn)象的發(fā)生。F波有助于發(fā)現(xiàn)ALS患者脊髓前角細(xì)胞的亞臨床病變,有助于ALS的診斷和鑒別診斷。第三部分肌萎縮側(cè)索硬化、肯尼迪病、遠(yuǎn)端肌萎縮型頸椎病和平山病電生理特點的比較研究背景：肌萎縮側(cè)索硬化(amyotrophic lateral sclerosis, ALS)是快速進(jìn)展的神經(jīng)系統(tǒng)變性病,臨床診斷需要上、下運動神經(jīng)元同時受累的證據(jù)。但是在疾病早期,肌肉無力萎縮可能局限于ALS患者手部小肌肉,為了早期明確診斷需注意排除有類似臨床表現(xiàn)的一些疾病如遠(yuǎn)端肌萎縮型頸椎病(cervical spondylotic amyotrophy, CSA)、平山病(Hirayama disease, HD)和肯尼迪病(Kennedy disease, KD)。目的：研究旨在探討ALS、遠(yuǎn)端型CSA、 HD和KD患者神經(jīng)傳導(dǎo)檢查的特點以及手部肌肉受累的差異。方法：回顧性分析北京協(xié)和醫(yī)院肌電圖室2000年至2014年符合ALS診斷標(biāo)準(zhǔn)的患者(200例)、符合遠(yuǎn)端型CSA診斷標(biāo)準(zhǔn)的患者(95例)、符合HD診斷標(biāo)準(zhǔn)的患者(88例)和符合KD診斷標(biāo)準(zhǔn)的患者(43例)的病歷資料,收集患者臨床資料和上肢神經(jīng)傳導(dǎo)檢查結(jié)果。150名健康志愿者作為正常對照組。結(jié)果：ALS患者小指展�。炊陶辜�(abductor digiti minimi/abductor pollicis brevis, ADM/APB)復(fù)合肌肉動作電位(compound muscle action potential, CMAP)波幅比(3.52±0.60,P0.001)高于正常對照組(1.00±0.24),差異有統(tǒng)計學(xué)意義。遠(yuǎn)端型CSA患者(0.93±0.77,P0.001)和HD患者(0.63±0.52,P0.001)ADM/APB CMAP波幅比低于正常對照組,差異有統(tǒng)計學(xué)意義。遠(yuǎn)端型CSA患者APB CMAP波幅(9.91±5.05mV,P=0.005)低于HD患者(12.07±4.88mV),差異有統(tǒng)計學(xué)意義。HD患者ADM/APB CMAP波幅比低于遠(yuǎn)端型CSA,差異有統(tǒng)計學(xué)意義(P0.001)。KD患者ADM/APB CMAP波幅比(1.06±0.40,P=0.862)與正常對照組相比差異無統(tǒng)計學(xué)意義。APB CMAP消失或異常增高的ADM/APB CMAP波幅比(≥4.5)僅見于ALS患者。ALS患者、遠(yuǎn)端型CSA和HD患者正中神經(jīng)和尺神經(jīng)的感覺神經(jīng)動作電位波幅和感覺神經(jīng)傳導(dǎo)速度均在正常范圍。KD患者感覺神經(jīng)動作電位波幅異常率為81%,感覺神經(jīng)傳導(dǎo)速度異常率為9.3%。結(jié)論：ALS患者、遠(yuǎn)端型CSA患者、HD患者和KD患者手部小肌肉萎縮的差異反映了疾病不同的病理生理機(jī)制。神經(jīng)傳導(dǎo)檢查特別是ADM/APB CMAP波幅比有助于診斷和鑒別診斷ALS及與ALS有類似臨床表現(xiàn)的疾病。
[Abstract]:Part 1 the significance of F wave in the diagnosis and differential diagnosis of amyotrophic lateral sclerosis and Kennedy's disease: amyotrophic lateral sclerosis (amyotrophic lateral sclerosis, ALS) is a rapid progressive neurodegenerative disease involving the cerebral cortex and spinal motor neurons of the cerebral cortex. The main clinical manifestations include progressive disease. Weak muscle atrophy, medulla paralysis and pyramidal tract sign. The etiology of ALS is not yet clear and lack of effective treatment. The patient has poor prognosis,.ALS diagnosis needs, the evidence of the simultaneous involvement of the lower motor neurons, the lack of specific biological markers,.ALS, is inactive, the clinical manifestation is heterogeneous, and early misdiagnosis. Missed diagnosis, for example, the signs of motor neuron involvement in some ALS patients appear at the late stage of the course of the disease or the sign of no upper motor neuron, and it is sometimes difficult to identify with Kennedy's disease (Kennedy disease, KD). Previous studies showed that ALS and KD were in sensory nerve conduction, needle level electromyography, cortical excitability test, serum creatine kinase level and clinical level. There is a difference in performance. So far, there is a lack of research on the comparison of the characteristics of the F wave of ALS and KD. Objective: To explore the characteristics of F wave in ALS by comparing the differences in the F wave parameters of the ulnar nerve in ALS patients and normal subjects and analyzing the effects of the dysfunction of the lower motor neurons on the F wave parameters in the ALS patients, and to try to analyze and compare the AL of the ALS. The difference between the median nerve, the ulnar nerve, the tibial nerve and the F wave of the peroneal nerve in S patients and KD patients, and to explore the value of the F wave in the diagnosis and differential diagnosis of ALS and KD. Methods: 82 consecutive patients from September 2013 to July 2014 were enrolled in the neurology department of our hospital, named ALS patients, the patient established a database of medical records, and recorded the name of the patient. Different age, age, course of disease, location, symptoms, signs, and MRC muscular strength classification of.50 were used as normal control group. The ulnar nerve conduction and F wave test were performed on the ulnar nerve in the subjects of the subjects and the ALS patients and the normal control group. Compared with the normal control group, the patients with ALS were compared with the normal control group. The parameter difference of nerve F wave and Logistic regression analysis were used to evaluate the relationship between the F wave parameters of the ulnar nerve in ALS patients and the pyramidal tract sign of the upper limb and the MRC muscle strength classification of the small finger abductor muscle (MRC5, MRC4 and MRC3). From September 2013 to December 2014, the group of 37 men with motor neuron involvement in the Department of Neurology Department of our hospital were diagnosed as the male ALS. 32 KD patients and 30 male healthy volunteers were treated in the Department of Neurology in our hospital as a normal control group. The F wave parameters of the median nerve, ulnar nerve, tibial nerve and peroneal nerve of the patients with ALS, KD and normal control were compared. Results: the comparison of the F wave parameters of the ulnar nerve between the ALS patients and the normal control group was compared with the normal control group. Compared with the normal control group, the average (P=0.040) and the maximum (P) 0.001) F wave amplitude of the ALS patients, the average (P0.001) and the maximum (P0.001) F/M amplitude ratio, the repeat neuron index (P0.001), the repetition of the F wave index (P0.001) and the large F wave occurrence rate (P0.001) increased. P=0.004) shortened and F wave occurrence rate (P0.001) decreased. The difference was statistically significant in the shortest latency (P0.001) and F wave occurrence rate (P0.001) of the ulnar nerve in.ALS patients and the MRC muscle strength classification of the small finger abductor muscle; F wave mean (P0.001) and maximum amplitude (P=0.002) were significantly related to the pyramidal tract of the upper limb. 1) and the maximum (MRC, P=0.001; pyramidal sign, P=0.002) F / M amplitude ratio, F wave time limit (MRC, P0.001; pyramidal tract sign, P=0.047), repeat neuron index (MRC, P0.001; pyramidal tract sign, P=0.009) and repeated exponential wave index (pyramidal tract sign) Compared with the ALS patients and the normal control group, the maximum F wave amplitude of the median nerve, the ulnar nerve, the tibial nerve and the peroneal nerve in the patients with KD was compared with that of the normal control group. The rate of the huge F wave and the ratio of the huge F wave subjects increased, and the difference was statistically significant. Compared with the ALS patients, the huge F wave could appear in the multiple nerves of KD patients and tend to be inclined to the KD patients. In the measured F wave parameters, the number of large F wave nerves appeared to be the most effective parameter to distinguish between ALS and KD. The area under the curve was 0.908 (95% confidence interval: 0.835-0.982). The subjects with more than 3 neurons showed great F waves to distinguish between ALS and KD sensitivity and specificity, respectively, 85% and 81%.ALS (r=0.107, P=0.529) and KD patients, respectively. 0.418) there is no statistical significance in the correlation between the total emergence rate of the huge F wave and the course of the disease. Conclusion: the parameters of the F wave and the function of the lower motor neurons can reflect the integrity of the spinal cord motor neuron pool and the excitatory.F wave, which can help identify the ALS and KD, and are not affected by the patient's course. For the male ALS patients who are mainly involved in the involvement of the lower transport neurons, if they are huge The incidence of large F waves increased significantly, especially in the median and peroneal nerves, as well as the multiple nerve recording of the huge F wave (three 3) or the huge F wave symmetrically distributed on the left and right side of the KD diagnosis. KD gene detection was recommended. The electrophysiological study and mechanism research background of the second part of the amyotrophic lateral sclerosis Amyotrophic lateral sclerosis (ALS) cleft hand phenomenon refers to the specific clinical manifestations of the abductor pollicis (abductor pollicis brevis, APB) and the first interosseous muscle (abductor digiti minimi, ADM). Previous studies have shown that the central mechanism and the peripheral axonal mechanism may be involved in the division. No study has shown whether the dysfunction of the spinal motor neuron pool dominating APB and ADM conforms to the ALS cleavage phenomenon. Objective: To investigate whether the dysfunction of the spinal motor neuron pool in the spinal cord motor neurons, which dominates APB and ADM in ALS, is conformed to the phenomenon of ALS splitting hand and to participate in the occurrence of ALS split hand phenomenon by F wave detection. 40 ALS patients in the Peking Union Medical College Hospital neurology department from September 2013 to March 2014 were divided into two groups according to the muscle involvement of the hands of the ALS patients. A group of ALS patients with weak muscle atrophy in hand, and a group of.20 healthy volunteers for ALS patients with no atrophy and weakness of the hand muscles as normal controls Motor nerve conduction detection and F wave measurement were performed on the median nerve and ulnar nerve in the subjects. F wave parameters recorded by APB and ADM were compared. The F wave parameters included the F wave incubation period, the F wave occurrence rate, the F/M amplitude ratio of F wave amplitude, the repeat neuron index and the repeated F wave index. The occurrence rate (P0.05), the repeated neuron index (P0.001) and the repeated F wave index (P0.001) were different. The F wave of the APB recorded in the upper limb of the.ALS patients with no obvious muscle weakness was significantly lower than the F wave recorded in the normal control group APB, and the F wave rate was significantly decreased (P0.001), and the repeated neuron index (P0.001) and repeated exponential wave index were observed. The difference was statistically significant, while the F wave parameters in the ADM records of the ALS patients were compared with the F wave parameters of the APB and ADM records of the upper limbs of the normal.ALS patients with atrophy and weakness of the muscles, the average F wave amplitude (P0.05), the F/M amplitude ratio (P0.05), the F wave occurrence rate, the repeated neuron index and the repeated exponential wave index. In the difference, the electrophysiological difference between.APB and ADM spinal motor neuron pool dysfunction is the specificity of ALS, the F wave occurrence rate of the.APB record (P=0.002), the repeat neuron index (P0.001) and the repeated F wave index (P0.001) help to distinguish between ALS and normal subjects, and the diagnostic value is better than the ADM/APB complex muscle movement. The amplitude ratio of potential wave amplitude. Conclusion: the difference of F wave parameters recorded by APB and ADM in normal subjects and ALS patients is in accordance with the split hand phenomenon. The abnormal involvement of the spinal motor neuron pool function in the occurrence of.F wave of the ALS split hand phenomenon is helpful to the detection of subclinical pathological changes of the spinal cord anterior horn cells in ALS patients, which is helpful for the diagnosis and differential diagnosis of ALS. Third parts are helpful. Comparative study on the electrophysiological characteristics of amyotrophic lateral sclerosis, Kennedy's disease, distal amyotrophic cervical spondylosis and Pingshan disease: amyotrophic lateral sclerosis (ALS) is a rapid progressive neurodegenerative disease, clinical diagnosis needs, and the evidence of simultaneous involvement of the lower transport neurons. But in the early stages of the disease, Muscle weakness may be limited to small hand muscles in ALS patients. For early diagnosis, attention should be paid to eliminating some of the diseases with similar clinical manifestations such as cervical spondylotic amyotrophy (CSA), Hirayama disease, HD, and Kennedy's disease (Kennedy disease, KD). S, the characteristics of nerve conduction examination in patients with distal CSA, HD and KD, and the difference in the involvement of the hand muscles. Methods: a retrospective analysis of the patients (200 cases) that met the ALS diagnostic criteria from 2000 to 2014 of Peking Union Medical College Hospital, which conforms to the distal CSA diagnostic criteria (95 cases), patients with HD diagnostic criteria (88 cases) and accords with KD diagnosis. The patient's medical records of 43 patients (43 cases), the patient's clinical data and the results of the upper limb nerve conduction examination were used as the normal control group. Results: the ALS patient's small finger abductor / pollicis abductor (abductor digiti minimi/abductor pollicis brevis, ADM/APB) complex muscle action potential (compound muscle action potent) Ial, CMAP) amplitude ratio (3.52 + 0.60, P0.001) was higher than that of normal control group (1 + 0.24), and the difference was statistically significant. The CMAP amplitude ratio of ADM/APB in distal CSA patients (0.93 + 0.77, P0.001) and HD patients (0.63 + 0.52, P0.001) was lower than that in normal control group, and the difference was statistically significant. The difference was statistically significant in patients (12.07 4.88mV). The amplitude ratio of ADM/APB CMAP in.HD patients was lower than that of distal CSA, and the difference was statistically significant (P0.001) the CMAP amplitude ratio of ADM/APB CMAP (1.06 + 0.40, P=0.862) was not statistically significant compared with that of the normal control group. The sensory nerve action potential wave amplitude and sensory nerve conduction velocity of the median nerve and the ulnar nerve in patients with.ALS, distal CSA and HD were 81%, and the abnormal rate of sensory nerve conduction velocity in.KD patients was 9.3%.: ALS patients, distal CSA patients, HD patients and KD patients hands. The difference in small muscle atrophy reflects the different pathophysiological mechanisms of the disease. The nerve conduction examination, especially the amplitude ratio of ADM/APB CMAP, helps to diagnose and differentiate between ALS and the disease that has similar clinical manifestations with ALS.
【學(xué)位授予單位】：北京協(xié)和醫(yī)學(xué)院
【學(xué)位級別】：博士
【學(xué)位授予年份】：2016
【分類號】：R744.8

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