| Introduction:Non-motor symptoms(NMS),which impact severity of disease and quality of life,play important parts in Multiple System Atrophy(MSA).There is no enough NMS evaluation in scales like unified multiple system atrophy rating scale(UMSARS),etc.Besides,Non-motor symptom assessment scale for Parkinson’ s disease(NMSS)is not applicable for MSA.It is necessary to develop an instrument to assess the severity of MSA NMS and the effect of therapies in NMS.Most treatments of MSA are symptomatic,when it is no effective therapy throughout the world at present.Effect of traditional Chinese remedies should be evaluated,as it can relieve symptoms from multiple points.Furthermore,analysis of TCM syndrome pattern help discover the key mechanism of MSA and benefit treatment.Methods:Development of Multiple System Atrophy Non-motor Symptoms scale(MSA-NMSS),effect of traditional remedies(Wen Shen Jian Nao,warm kidney and nourish brain),analysis of TCM syndrome pattern comprised the three parts.First,the procedure of MSA-NMSS development,referring to patient-reported outcome(PRO)guideline,included constitution of items bank,formation of instrument for clinical study,clinical study,items winnowing,and evaluation of measurement properties.As conceptual framework,the instrument was to assess severity of MSA NMS,with quality of life as the ultimate objective.Constitution of items bank involved references,other rating scales like UMSARS and NMSS,etc.,PRO symptoms,which were collected with brainstorming method.And Delphi method was applied in items bank winnowing.After language testing and modification of items,instrument for clinical study formed.MSA-NMSS were assessed with both MSA patients and healthy controls in clinical study,while UMSARS was assessed with MSA patients at the same time.3 months after traditional remedies,MSA-NMSS were assessed with MSA patients the second time.Discrete trends method and stepwise regression analysis were applied in items winnowing.After that,exploratory factor analysis,which was to find the actual exited domains,and Pearson ’ s correlation coefficient,Coefficient alpha were performed.Measurement properties were evaluated then,which included reliability,validity,and ability to detect change.Coefficient alpha was applied in evaluation of reliability,while Pearson’s correlation coefficient and discriminated validity applied in validity,paired t-test or rank-sum test applied in ability to detect change.Secondly,MSA patients were assessed by UMSARS and progression(score of UMSARS/course)before and 12 months after the traditional remedies.They were observed at 1/2 month,1 month,3 months,6 months,12 months after the treatment,additionally 24 months,36 months,45 months as follow-up observations.Patients-report improved symptoms were also collected.Non-motor symptoms of MSA patients which involved frequency of urinary inconsistence,frequency of urination at night,frequency of urinary catheterization,as well as orthostatic and supine blood pressure,were estimated before and 3 months,6 months,12 months after the traditional remedies.Thirdly,distribution of syndrome elements were evaluated before and 3 months after the traditional remedies,as well as correlation between syndromes and course of the disease,syndromes and severity,syndromes and type of the disease of MSA patients.Results:a.The first part,there were 63 items in the bank which included 13 domains.Considering expert advice,37 items remained for clinical study after items winnowing by Delphi method,language testing,and modification of items.It collected 202 MSA patients in the clinical study,with 118 males and 84 females,96 MSA-C type,61 MSA-P type and 45 MSA-C&P(it was because which was the dominant type could not be identified).The patients were an average of 58.97±7.94 years of age,and 5.17±2.13 years of disease progress.It also collected 202 healthy controls,with 82 males and 120 females.The controls were an average of 61.96±7.86 years of age.There were 12 domains with 35 items in the instrument after items winnowing and modification of the result.The total Coefficient alpha was 0.854,which meant the internal consistency reliability was acceptable.Average of rank-sum in MSA patients was significantly different with that in healthy controls(p=0.000),which meant the instrument had good discriminated validity.Total score of MSA patients before and 3 months after traditional remedies were not significantly different with each other(p=0.619),however,the overall disability of UMSARS before and 3 months after traditional remedies were significantly different(p=0.005).The score of 3 months after treatment in domain 1 systemic symptoms,2 cognitive function,12 digestive system function were significantly higher than that before(p=0.044,0.000,0.001,respectively),and the score of 3 months after treatment in domain 4 sleep symptoms,9 defecation were significantly lower than that before(p=0.000,0.000,respectively).Both references and pilot study data showed traditional remedies can benefit blood pressure,vesicorectal disorder,insomnia,and rapid eye movement sleep behavior disorder,which dovetailed to the sleep symptoms and defecation in MSA-NMSS.It implied the instrument had acceptable ability to detect change.b.The second part,225 MSA patients were collected with 130 patients followed the observation.There were 75 males and 55 females,58 MSA-C type,39 MSA-P type and 33 MSA-C&P,112 probable MSA and 18 possible MSA,with an average of 59.10±8.08 years of age,4.61±2.18 years of disease progress.The progression of MSA was not increased from 1 month to 12 months after traditional remedies,with average of progression and overall disability(UMSARS)at 12 months after treatment 4/5 and 9/10 of that before treatment;as well as 24 months,36 months,and 45 months follow-up observations,with average of progression 4/5,3/5,2/5 of that before treatment,average of overall disability 9/10,7/10,2/5 of that before treatment,respectively.Traditional remedies slowed down progression of MSA at least 57.8%including the drop-out data(130/225).Patients-report improved symptoms mainly showed on orthostatic hypotension(44.6%improved),urinary and defecation(56.9%improved).Non-motor symptoms of 111 MSA patients were evaluated excluding the drop-out data.Frequency of urinary inconsistence and frequency of urination at night were relieved 2%and 9%3 months after traditional remedies,while frequency of urinary catheterization not.But then the three of them increased 12 months after treatment still,which were 10%,0.4%and 39%.Differences between orthostatic and supine hypotension before treatment were 23.80mmHg(systolic pressure)and 12.12mmHg(diastolic pressure).Compared with that,average differences after treatment were decreased,23.32mmHg and 11.88mmHg.c.The third part,194 MSA patients were collected for analysis of TCM syndrome pattern,with 114 males and 80 females,93 MSA-C,59 MSA-P and 42 MSA-C&P,160 probable MSA and 34 possible MSA.The patients were an average of 59.03±9.13 years of age,with 4.38±2.09 years of disease progress,and 42.64±16.11 points of UMSARS score on average.It showed mechanism of MSA was more deficiency and less excess,with more cold and less heat.There were more heat and blood deficiency,more phlegm and damp,with liver and heart disorders most frequently seen in MSA-P.Spleen deficiency was most frequently seen in MSA-C.And in MSA-C&P,there were more cold and Qi deficiency,more kidney deficiency and blood stasis,more phlegm and damp,and more stomach disorders,with Qi collapse only seen in MSA-C&P.Heat transformed to cold,while deficiency,kidney deficiency,liver and spleen disorders increased with the progress of MSA.After 3 months traditional Chinese remedies,key mechanism of MSA,which was yang deficiency of kidney,had not changed.It indicated TCM treatment principle of MSA was warming kidney and supporting Yang.Conclusion:MSA-NMSS had acceptable reliability,good validity,and acceptable ability to detect change.Traditional Chinese remedies mostly slowed down progression of MSA(at least 58%),mainly on non-motor symptoms,especially orthostatic hypotension.Key mechanism of MSA was Yang deficiency of kidney,with warming kidney and supporting Yang as the principle of TCM treatment. |
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