肛门括约肌肌电图对多系统萎缩和帕金森病的诊断和鉴别诊断价值

【作者】 王含；

【导师】 崔丽英；

【作者基本信息】 中国协和医科大学 ， 神经病学， 2007， 博士

【摘要】 第一部分ASEMG鉴别诊断MSA的运动单位平均时限研究:335例MSA及相关疾病的ASEMG分析背景和目的肛门括约肌肌电图(anal sphincter electromyography,ASEMG)是多系统萎缩(multiple system atrophy,MSA)的一项重要的辅助检查手段,同时也用于其它神经系统疾病的鉴别,如帕金森病(Parkinson’s disease,PD)、帕金森综合征(Parkinson syndrome,PDS)、体位性低血压(Orthostatic Hypotension,OH)、小脑性共济失调(Cerebella Ataxia,CA)和圆锥马尾综合征(Cauda Equina Lesion,CEL)。运动单位平均时限(mean duration,MD)是其中的主要观测指标,“大于10ms”被公认为ASEMG异常的判断标准,但由此得出的“神经源性损害”的结论也可见于上述各种疾病,因而对MSA的诊断不具有最佳的特异性。国外研究曾提示平均时限13ms对鉴别MSA和PD具有较好的灵敏度和特异度,但对MSA与其它疾病的鉴别尚无报导。本研究将在较大样本的病例研究基础上,分析平均时限等参数在各组疾病中的分布特点,探讨ASEMG对于MSA与上述疾病鉴别诊断的应用价值。方法自2003年11月起,对所有在北京协和医院神经科肌电图室接受ASEMG检查的患者进行相关资料登记,前瞻性的建立北京协和医院神经科的ASEMG数据库。从中选择资料完整的初诊为MSA(possible43例,probable85例)、PD(44例)、PDS(76例)、OH(20例)、CA(10例)、CEL(36例)、及正常对照者(18例)的ASEMG结果(共计335例)进行回顾性分析。比较分析平均时限等各常规参数在各组间的差异,根据ROC曲线得出不同参数对于MSA与各组疾病鉴别的灵敏度和特异度。结果MSA-probable组患者的平均时限为15.69±2.66ms,与PD(12.40±1.44),PDS(12.60±1.79),CA(12.46±2.25),OH(12.91±1.79),CEL(13.24±2.49)和正常对照(11.56±1.59ms)之间的差异均有显著性意义(P＜0.001),其余各常规参数中仅平均时限超过10ms%和平均相在MSA组与正常对照间有显著性差异。平均时限等各常规参数在其余各组患者间均无显著性差异。MSA-probable组的卫星电位出现率为24.96%±11.55%,明显高于PD(10.18%±7.78%),PDS(11.29%±8.78%),CA(10.40%±6.43%),0H(12.98%±8.41%),CEL(13.33%±10.35%)(P＜0.001)。ROC曲线坐标显示,若以平均时限10ms为分界点,则MSA组与各疾病组鉴别的灵敏度98.8%-100%,但特异度为4.5%-10%;若以13.70ms为分界点,MSA与各组疾病鉴别的灵敏度均为73.8%%,特异度分别为PD81.8%、PDS78.4%、CA80%、OH70%和CEL66.7%;若以卫星电位出现率20.87%为分界点,相应的灵敏度为58.3%,特异度分别为PD91.9%、PDS89.2%、CA100%、OH80%、CEL80.6%。若同时考虑平均时限(10ms、13.7ms)和SP出现率(10%、15%、20%),发现10ms+20%和13.7ms+10%的联合标准对于鉴别MSA和PD具有较好的灵敏度(80%,80%),特异度前者更佳(81%和66.7%)。结论ASEMG有助于MSA与其他神经系统变性病等相关疾病的诊断及鉴别,但以平均时限10ms作为MSA和其它疾病的分界点特异性较差,需将平均时限标准提高至13.7ms以上方能具有较好的特异度。MSA患者在ASEMG上更容易出现卫星电位,SP出现率可资MSA与其它疾病的鉴别。联合考察平均时限和SP出现率更有助于区分MSA和PD。本研究创新点(1)首次在国内建立了大样本的ASEMG数据库。(2)首次同时对MSA与多种疾病进行病例对照研究。(3)首次通过大样本的病例资料明确提出平均时限10ms不适于MSA和其他疾病的鉴别,肯定了SP对于MSA与其它疾病鉴别的价值。第二部分肛门括约肌电图的卫星电位对MSA和PD的鉴别诊断价值背景和目的多系统萎缩(multiple system atrophy,MSA)与帕金森病(Parkinson’sdisease,PD)早期在临床上极易混淆,临床误诊率很高。肛门括约肌肌电图(analsphincter electromyography,ASEMG)可能有助于这两种疾病的早期鉴别(5年内),但其珍断价值仍有争议。国外的学者曾报道过MSA患者的ASEMG中出现卫星电位(satellite potential,SP)的现象,但其对于MSA与PD鉴别的价值未见报道。通过前一部分研究,我们发现并初步证实了SP出现率对两者的鉴别诊断价值。本研究即旨在深入分析ASEMG中SP在MSA和PD中的电生理特点,进一步探讨SP在两者早期鉴别诊断中的意义。方法本研究选择2004年11月至2006年11月间经随诊证实的拟诊MSA(probable-MSA)患者54例和PD患者20例,采用两种SP定义(主波-卫星间距＞1ms和＞5ms),分析比较ASEMG中SP出现的情况和特点,包括卫星电位的个数、卫星电位出现率;含卫星电位运动单位的平均时限;卫星电位的平均潜伏期;主波-卫星平均间距;出现卫星电位的运动单位主波的平均时限。对卫星电位的出现率、平均潜伏期和平均问期与病程进行相关性分析。根据标准化MSA量表-Ⅳ(UMSA-Ⅳ),对MSA患者的预后和SP出现率进行COX回归分析。结果依照不同卫星电位定义得出的各参数在MSA和PD间的差异均有显著性意义。MSA和PD组患者SP出现率分别为:1ms定义时,30.41%±12.54%(9.50-55.00%)和9.61%±7.94%(0-25%)(p＜0.001);5ms定义时,15.87%±11.92%(0-45%)和4.17%±5.09%(0-15%)。无论采用何种SP定义,含SP的MUAP个数、平均SP个数、SP出现率以及平均时限在MSA组(MSA-P或MSA-C)与PD组间的差异均有统计学意义,主波与SP的间距在两组间的差异均无显著性意义。若采用1ms定义,则当SP出现率为15%时,MSA与PD鉴别的灵敏度为83.3%,特异度为85%;当SP出现率为21%时,相应的灵敏度和特异度分别为70.4%和90%。若采用5ms定义,则当SP出现率为9.76%时,灵敏度为70.4%,特异度为80%。无论病程早晚(3年以内或以上)、无论采用何种卫星电位的定义(1ms或5ms),SP出现率在MSA和PD组问的差异均有显著性意义(p＜0.001),SP出现率与病程间未见正相关的关系。SP出现率与UMSA-Ⅳ评分间的相关性无显著性意义。结论1ms和5ms标准的卫星电位定义均可以用于MSA和PD的鉴别,SP出现率是最重要的鉴别参数,具有比较理想的灵敏度和特异度,在病程早期(3年以内)就可以具有重要的诊断价值。SP出现率不能做为预测MSA预后的单一指标。创新点:(1)首次对ASEMG的卫星电位采用标准化的定义进行量化分析。(2)首次在MSA和PD中分析比较SP,从全新的角度重新诠释了ASEMG对于两者鉴别诊断的价值。国际上尚无类似报道。更多还原

【Abstract】 PART 1: The Study of Mean Duration in Anal Sphincter Electromyography: Overview of 335 Cases of Multiple System Atrophy and Related Neurological DiseasesBackground and Objectives Anal sphincter electromyography (ASEMG) is an important diagnostic tool in multiple system atrophy (MSA). The mean duration of motor unit action potential (MUAP) exceeding 10ms has been widely accepted as the main criteria for "neurogenic impairment". However, longer duration of MUAP than 10ms could also present in other diseases, such as Parkinson’s disease (PD), Parkinson’s syndrome and cauda equine lesion, etc. The value of ASEMG, therefore, is challenged for its low specificity. It has been reported that the mean duration longer than 13 ms could be more specific in differentiating MSA from PD while satellite potentials (SP) seem special in MSA patients, but the related studies with a large sample size is lacking.Methods We established an ASEMG data bank prospectively since the end of 2003. 335 cases with intact data were selected from the data bank, including 131 patients with MSA, 44 with PD, 76 with PDS, 36 with cauda equine lesion (CEL), 10 with cerebella ataxia (CA), 20 with orthostatic hypotension (OH) and 18 patients as normal control. The results of the ASEMG were reviewed retrospectively. Sensitivity and specificity of mean duration and SP rate or their combined use in differentiating MSA-probable from PD and other related diseases were evaluated by ROC curves.Results The mean duration was significantly longer in MSA-probable (15.69±2.66ms) than in PD (12.40±1.44), PDS (12.60±1.79), CA(12.46±2.25), OH (12.91±1.79), CEL (13.24±2.49) and normal control (11.56±1.59 )(P<0.001). No statistical difference was found among the patients groups. The SP rate of MSA-probable (24.00%±11.89%) was higher than PD (10.18%±7.78%), PDS (11.29%±8.78%), CA (10.40%±6.43%), OH (12.98%±8.41%), CEL (13.33%±10.35%) and normal control (6.83%±6.98%) (P<0.001) . When the cut-off level of 10ms in MD was employed, the sensitivity of MD in differentiating MSA from other diseases was high (98.8%-100%), while the specificity was lower than 10%. The specificity of MD in differentiating MSA-probable from PD,PDS, and CA could be improved (81.8,78.4,and 80, respectively) with the sensitivity of 73.8%, if 13.7 ms was accepted as the cut-off level. When a cut-off level of 20.87% was adopted, the sensitivity of SP rate in differentiating MSA-probable from other diseases was 58.7% while the specificity was 91.9% in differentiating MSA-probable from PD and more than 80% from other disease. If MD and SP rate were combined, the sensitivity and specificity could be 80 % and 81%(MD>10ms ,SP rate >20%), or 80% and 66.7%( MD>13.7ms,SP rate>l 0%).Conclusion ASEMG is valuable in differentiating MSA-probable from PD and other neurological diseases. 13.7ms is more specific as a cut-off value of MD than 10ms. SP rate was helpful in differentiating MSA from other related diseases. The combined use of MD and SP rate had a higher sensitivity and specificity in differentiating MSA from PD than their use separately. PART 2: The Value of Satellite Potential in Anal Sphincter Electromyography in the differentiation between Multiple System Atrophy and Parkinson’s DiseaseBackground and Objectives It’s difficult to differentiate multiple system atrophy (MSA) from Parkinson’s disease (PD) in their early stage. Anal sphincter electromyography (ASEMG) was reported to be helpful for the differentiated diagnosis within the first five years after onset. However, it’s still controversial. In our previous studies, Satelite Potential (SP) was found to be of diagnostic value in MSA. In this study, we aimed to further elaborate the features of SP in MSA and PD. We also investigated the value of SP in the differentiation between MSA and PD.Methods Fifty-four patients with probable MSA and twenty patients with PD presented in PUMC hospital during the period of 2004 and 2006 were enrolled in this study. The SP was defined as the spikes appearing preceding or following the main component of a MUAP and separated from it by an almost constant, isoelectrical interval of 1 ms or 5 ms. We analyzed the features of SP, which included the SP number, SP rate, the mean duration of MUAP with SP, the SP latency, the interval between the main spike and SP, the mean spike duration of MUAP with SP, in the two patient groups. The mean duration of MUAP with SP and the SP rate with ideal sensitivity and specificity in differentiating MSA from PD were determined according to the ROC curve. The uniformed MSA rating scale-IV (UMSA-IV) was used for the evaluation of the patient prognosis. The correlation between SP rate and prognosis rating score was determined by COX regression analysis.Results All the parameters were significantly different between MSA and PD whether the isoelectrical interval was accepted as 1ms or 5ms. The SP rate in MSA and PD was 30.41%±12.54% (9.50-55.00%) versus 9.61%±7.94%(0-25%)(P<0.001), when 1ms was accepted as the isoelectrical interval. If 5ms was accepted, the SP rate was 15.87%±11.92%(0-45%) versus 4.17±5.09%(0-15%) correspondingly (P<0.001). With the 1ms criterion being used, the SP rate, ideal sensitivity and specificity in differentiating MSA from PD were 15%,83.3% and 85% or 21%,70.4%,and 90%. When the 5ms criterion was adopted, they are 9.76%, 70.4%, and 80%. The significant difference of SP rate in MSA and PD was independent on the disease duration and the isoelectrical interval criterion. The SP rate and prognosis rating scale was not correlated statistically.Conclusion Both 1ms and 5ms could be accepted as the isoelectrical interval of SP in ASEMG. The SP rate is the most important parameter with an ideal sensitivity and specificity in differentiating MSA from PD, even within the first 3 years after onset. The prognosis of MSA couldn’t be predicted by the SP alone.更多还原