The Value Of EAS-EMG And US-EMG In The Diagnosis And Differential Diagnosis Of Multiple System Atrophy

Background & Purpose Multiple system atrophy(MSA)is a central nervous system degenerative disease in adulthood,with atrophy in multiple anatomical lesions including pyramidal system,extrapyramidal system automatic nervous system and so on,as well as with characterized clinical manifestations.MSA is mainly seen in the elderly.With accelerated aging process,the number of MSA patients has been increased gradually.The clinical manifestations according to motor symptoms are mainly divided into two types: MSA-P type(Parkinson’s disease)with manifestation of enclosing and less Parkinson-like symptoms and MSA-C(cerebella ataxia)with manifestation of unstable motor coordination disorders and cerebella ataxia disorders.Among them,MSA-P type presenting with increased muscle tone as well as less tonic rigidity and bradykinesia,may be easily misdiagnosed as Parkinson disease(PD)or progressive supranuclear palsy(PSP).Meanwhile,it is difficult to identify MSA-C and Spinocerebellar ataxia(SCA),with ataxia as the major manifestation.The clinical identification of MSA and PD,especially in early diagnosis,has been a difficult problem both at home and abroad for many years.The main reason is that MSA and PD are lack of specific clinical symptoms.However,the existed MSA diagnostic criteria(2008 Gilman standard)relies only on clinical symptoms,while not on electrophysiological diagnosis or any other related reference indicators,leading to the lack of diagnosis and differential diagnosis of MSA and related diseases,which might be the reason of misdiagnosis.At home and abroad,there are still a lack of systematic studies on the identification methods of MSA and PD-related degenerative diseases.Therefore,whether objective indexes such as electrophysiology be increased or not,especially obtaining the cut-off value of differential diagnosis between MSA and other diseases by large sample cohort study to increase the diagnosis and differential diagnosis rate,has become a problem to be solved.In the field of electrophysiological examination of MSA,EAS-EMG and US-EMG tests have been carried out in foreign countries since the 90 s of the last century,and preliminary identification of the two has certain clinical value in the differential diagnosis of MSA.However,because of relatively less patients with lower acceptance level,there is no systematic study of large samples so far.Department of Neurology,Naval Medical College,Naval Medical University took the lead in China in 2000 to conduct anal sphincter electromyography(EAS-EMG)and then urethral sphincter electromyography(US-EMG)in 2010.After more than 10 years of study,it was found that electrophysiological indicators such as EAS-EMG may have value in the diagnosis of MSA and differential diagnosis between MSA and PD and a number of articles has been published.In China,some other departments also began this work refer to us.However,there are a few scholars who have doubt about the validity of EAS-EMG in the differential diagnosis between MSA and PD.Because the early part of our research is a retrospective study with small sample,the conclusion remains to be further validated by large sample cohort study,which is this study,to verify the value and reliability of EAS-EMG in the diagnosis and differential diagnosis of MSA and other diseases and to obtain the electrophysiological parameters of differential diagnosis between MSA and other diseases.Methods Combined with relevant literature at home and abroad,based on the full review and understanding of anal and urethral sphincter anatomical structure,EAS-EMG and US-EMG puncture standard operating procedures were established.MSA was diagnosed according to the new diagnostic criteria of MSA proposed by Gilman in 2008.Diagnosis of PD was based on the clinical diagnostic criteria of the Parkinson’s Disease Association in the UK.PSP meets the clinical diagnostic criteria of progressive supranuclear palsy in China.Diagnosis of SCA was based on the European Union of Neuroscience Associations(EFNS)as well as the consensus on diagnostic and management of adult chronic disorganization in adults published by the European Neurological Society(ENS)in the European Journal of Neurology in 2014.Patients were divided into five groups,including MSA,PD,PSP,SCA and control group.EAS-EMG and US-EMG were then performed on the patients.The mean duration of movement(MUPs),mean amplitude,polyphase wave percentage,phase shape as well as amplitude during strong contraction were recorded and analysed.The five groups of EMG parameters were statistically analyzed to assess the diagnostic and differential diagnostic value of EAS-EMG and US-EMG on MSA and other diseases as well as to obtain the cut-off value of differential diagnosis between MSA and other diseases.Results Five groups of patients,including 101 MSA patients(52 men,49 women)with mean age of 56 years and average duration 2.4 years,100 PD patients(65 men,35 women)with mean age of 64.7 years ± 10.0 and average duration 3.0 years,22 PSP patients(16 men,6 women)with mean age of 65.6 ± 7.7years and average duration 3.0 years,18 SCA patients(16 men,2 women)with mean age of 62.8 ± 7.2years and average duration 3.1 ± 2.7 years,as well as 23 patients in control group(14 men,9 women)with mean age of 61.5 years ± 11.3 and average duration 2.3 ± 1.8 years,were involved in the study.EAS-EMG results between MSA and other four groups: 99 cases with MSA,100 cases with PD,22 cases with PSP,17 cases with SCA and 23 cases in control group underwent EAS-EMG.The average MUP durations of MSA,PD,PSP,SCA and control group patients were,respectively,12.2 ms,9.8 ms,9.9 ms,10.3 ± 0.9 ms,and 9.5 ms.The average MUP amplitudes of MSA,PD,PSP,SCA patients and control group patients were,respectively,465.0 V,481 V,446.5 V,480 V and 450.1± 110.2 V.The average percentages of polyphasic MUPs of MSA,PD,PSP,SCA and control group patients were,respectively,37.1%,31.6%,33.5 % ± 16.4%,30.9 % ± 23.8 and 22.1% ±14.7%.The average amplitudes during strong contraction of MSA,PD,PSP,SCA and control group patients were,respectively,1.1 mV,1.45 mV,1.15 mV,1.5± 0.8mV,and 1.2mV.The ratios of simple phase and simple-mix phase during maximal voluntary contraction of MSA,PD,PSP,SCA and control group patients were,respectively,39.2 %,9.0 %,36.4 %,0.0 % and 4.3 %.There were significant differences for average MUP duration,average MUP amplitude,percentage of polyphasic MUPs,and the ratio of simple phase and simple-mix phase between MSA and PD by EAS-EMG.The average MUP duration of MSA showed significant difference compared with that of PSP.The average MUP duration,and the ratio of simple phase and simple-mix phase of MSA showed significant difference compared with that of SCA.The average MUP duration,and the ratio of simple phase,percentage of polyphasic MUPs and simple-mix phase of MSA showed significant difference compared with that of control group.US-EMG results between MSA and other four groups: 81 cases with MSA,96 cases with PD,15 cases with PSP,15 cases with SCA and 19 cases in control group underwent US-EMG.The average MUP durations of MSA,PD,PSP,SCA and control group patients were,respectively,11.5 ms,9.8ms,10.4 ± 1.5ms,10.1 ± 1.1ms and 9.2ms.The average MUP amplitudes of MSA,PD,PSP,SCA and control group patients were,respectively,290.0 V,296.0 V,322.0 V,418.7 ±166.1 V and 241.0 V.The average percentages of polyphasic MUPs of MSA,PD,PSP,SCA and control group patients were,respectively,14.3%,14.3 %,18.1 % ± 12.4%,10.0% and 0.0 %.The average amplitudes during strong contraction of MSA,PD,PSP,SCA and control group patients were,respectively,0.8 mV,0.8 mV,0.9 mV,1.3±0.6 mV and 0.9±0.6 mV.The ratios of simple phase and simple-mix phase during maximal voluntary contraction of MSA,PD,PSP,SCA and control group patients were,respectively,45.7 %,10.4%,13.3 %,0.0 % and 10.5%.The average MUP duration of MSA showed significant difference compared with that of PD,PSP,SCA and control group.The ratio of simple phase and simple-mix phase of MSA showed significant difference compared with that of PD,SCA and control group.There were no statistically significant differences in average MUP amplitude,percentage of polyphasic MUPs and amplitude during strong contraction among the five groups.Comparison of indexes obtained in EAS-EMG and US-EMG of MSA group: 99 cases with MSA underwent EAS-EMG while 81 cases with MSA underwent US-EMG.The statistical results suggest that EAS-EMG results revealed more obvious changes in average MUP amplitude,percentage of polyphasic MUPs,and amplitude during strong contraction than US-EMG for MSA cases.There was no statistically significant difference in other variables.Gender comparison of indexes obtained in US-EMG of MSA and PD group: All the indexes were compared between different genders.The average MUP duration,polyphase wave percentage as well as amplitude during strong contraction in US-EMG showed statistically significant difference in PD and MSA male patients compared with that of PD and MSA female ones.The cut-off value obtained in EAS-EMG and US-EMG: The cut-off value of average MUP duration and percentage of polyphasic MUPs for the differential diagnosis of MSA with PD in EAS-EMG were 10.9 ms and 40.9 %,respectively.The cut-off point of average MUP duration for distinguishing MSA from PD in US-EMG was 11.1 ms.The cut-off point of average MUP duration in differentiating MSA from PSP in EAS-EMG and US-EMG were 10.4 ms and 11.4ms,respectively.With the average MUP duration of EAS-EMG and US-EMG being applied jointly using parallel test,the sensitivity and specificity for distinguishing MSA from PD were 83.2 % and 71.8 %,while that for differentiating MSA from PSP were 93.1 % and 63.6%,respectively.Discussion Due to the striking overlap in clinical presentations between MSA and other neurodegenerative diseases such as Parkinson’s disease(PD),progressive supranuclear palsy(PSP)and diffuse Lewy-Body disease(DLBD),differential diagnosis is difficult and the accurate differential diagnosis depends on their prognostic and therapeutic implications.In our study,we found that EAS-EMG and US-EMG possessed practical values for the diagnosis and differential diagnosis of patients with MSA.Prevalence of this disease is very low ranging about3.4~4.9/100 thousands,and it took almost 3 years to have accumulated relatively bigger numbers of patients to identify the cut-off point for the diagnosis of MSA.Meanwhile,the sensitivity and specificity of the average MUP duration for the differential diagnosis of MSA with PD,as well as PSP were calculated at the optimal cut-off value.EAS-EMG was more sensitive than US-EMG in terms of diagnosis,and it showed more significant changes in most of the indexes except the amplitude when sphincter is under strong contraction than US-EMG.The combination of application of both EAS-EMG and US-EMG would improve the diagnosis rate of MSA.Because of the specific anatomic location of urethral sphincter,it is difficult to obtain data of percentage of polyphasic MUPs in US-EMG during changing location.Our previous studies showed that the parameter of average MUP amplitude was more sensitive in US-EMG than EAS-EMG for the diagnosis of MSA,which is inconsistent with the results in this study.It is probably because of the small amount of sample previously(only 9 cases)leading to data bias.It’s worth noticing that the sensitivity and specificity for differentiating MSA from PD in EAS-EMG were 75.8 % and 83.0 % when average MUP duration was more prolonged than 10.9 ms while those were 42.4% and 93.0% when percentage of polyphasic MUPs was more than 40.9%.The sensitivity and specificity for differentiating MSA from PD in US-EMG were 63.0 % and 86.5 % when average MUP duration was more prolonged than 11.1 ms,and the AUC of both them were more than 0.8,indicating they had higher value of clinical application.The sensitivity and specificity for average MUP duration in distinguishing MSA from PD would improve to 83.2 % and 71.8% if EAS-EMG and US-EMG were used jointly.In addition,with EAS-EMG and US-EMG being applied jointly,the sensitivity and specificity for average MUP duration in differentiating MSA from PSP would be increased to 93.1 % and 63.6%.As a result,EAS-EMG and US-EMG were used separately or jointly would both improve the differential diagnosis between MSA and other diseases including PD and PSP.In summary,our results confirm that EAS-EMG and US-EMG were highly sensitive and rather specific methods for the diagnosis and differential diagnosis of MSA,and combination of both could be helpful to improve the diagnostic sensitivity of MSA.Two electrophysiological methods could serve as a supplement and substitution for each other in case of examinations limited.On the other hand,although our sample size was large and the results gave us confidence in using EAS-EMG and US-EMG for the diagnosis and differential diagnosis of MSA,studies with even larger sample size may still need in the future.