Efficacy And Safety Study Of LF-rTMS And ITBS In The Treatment Of SCA3/MJD Patients

Background:Spinocerebellar ataxia type 3/Machado-Joseph disease(SCA3/MJD)is the most common subtype of spinocerebellar ataxias(SCAs)in mainland China.Since the pathogenesis of SCA3/MJD has not been fully explained,there is no evidence-based treatment presently.Previous studies have reported that transcranial magnetic stimulation(TMS)could alleviate ataxia symptoms of SCAs.However,sample sizes of most studies were small,and few studies specifically targeting SCA3/MJD patients.Besides,previous studies did not compare the efficacy of different stimulation patterns.Therefore,the related research with larger sample size of SCA3/MJD patients and the comparison between different stimulation patterns are urgent scientific issues,which has important clinical guiding significance.Objective:The purpose of this study was to investigate the efficacy and safety of low frequency repetitive TMS(LF-rTMS)and intermittent theta burst stimulation(iTBS)in the treatment of SCA3/MJD patients,and to compare the therapeutic difference between these two stimulation patterns.Methods:A total of 120 SCA3/MJD patients in mainland China were recruited,including mild and moderate-to-severe patients,and these patients were randomly divided into three groups by block:LF-rTMS group(n=40),iTBS group(n=40)and sham-stimulation group(n=40).Patients were assessed by scales before and after treatment,including the Assessment and Rating of Ataxia(SARA),the International Cooperative Ataxia Rating Scale(ICARS),the 10-meter Walk Test(10m WT),the 9-Hole Peg Test(9-HPT)and the PATA Rate Test(PRT).All patients received 10sessions treatment(once a day,five days per week for two weeks).In this study,intention-to-treat analysis was used for data analysis,andχ~2test was used to compare categorical variables between groups.Paired t-test and Wilcoxon rank sum test were used to compare the outcome measures before and after treatment in each group.Two-way ANOVA and Friedman rank sum test were used to compare the therapeutic differences among three groups.Independent t-test was used to compare the therapeutic differences between mild and moderate-to-severe patients.p<0.05 indicated that the difference was statistically significant.Results:1.In this study,there were 11 drop-outs,and no significant difference was found in the drop-out rate among the three groups(p=0.378).A total of 12 patients had mild and transient side effects,and no significant difference was found in the incidence of side effects among the three groups(p=0.483).2.In LF-rTMS group,the SARA and ICARS scores were decreased after treatment(p<0.001).The usual speed walking time of the 10m WT was shortened(p=0.008),and the PATA rate was increased(p=0.010).3.In iTBS group,the scores of SARA and ICARS were decreased after treatment(p<0.001).Both the usual and fastest speed walking time of 10m WT were shortened(p=0.011,p=0.009,respectively).Furthermore,the 9-HPT completion time in the non-dominant hand was shortened(p<0.001),and the improvement of PATA rate was significant(p=0.008).4.In sham-stimulation group,the SARA score(p=0.766),ICARS score(p=0.676),10m WT walking time(usual speed,p=0.284;fastest speed,p=0.267),9-HPT completion time(dominant hand,p=0.474;non-dominant hand,p=0.651)and the PATA rate(p=0.064)had no significant difference before and after treatment.5.The scores of SARA and ICARS in both LF-rTMS group and iTBS group were decreased after treatment compared with sham-stimulation group(LF-rTMS group vs sham-stimulation group:p<0.001;iTBS group vs sham-stimulation group:p<0.001),but no significant difference was found between LF-rTMS and iTBS group(p=1.000).In addition,the time that patients in iTBS group performed the9-HPT using non-dominant hand was shortened compared with sham-stimulation group(p=0.037).6.There was no significant difference in the reduction of SARA and ICARS scores between mild and moderate-to-severe patients in three groups[(LF-rTMS group:SARA score,p=0.389;ICARS score,p=0.747);(iTBS group:SARA score,p=0.684;ICARS score,p=0.609);(sham-stimulation:SARA score,p=0.556;ICARS score,p=0.343)].Conclusions:1.Both LF-rTMS and iTBS stimulation patterns were safe in the treatment of SCA3/MJD patients.2.Both LF-rTMS and iTBS stimulation patterns could alleviate ataxia symptoms of SCA3/MJD patients,and the therapeutic efficacy has no significant difference between these two patterns.28 figures,5 tables,74 references...