| Objective: To explore the clinical efficacy of central nerve stimulation combined with peripheral nerve stimulation based on multimodal parameters of behavior assessment,neuroelectrophysiology,and brain perfusion CT and identify the best combination of neuromodulation techniques in patients with pDOC after brain injury.Methods: The study include two randomized controlled trial(RCT).The study of the efficacy of tDCS combined with MNS in pDOC patients and the study on the efficacy of r TMS combined with MNS in pDOC patients.The tDCS combined MNS study included a total of 75 pDOC patients divided into three groups: tDCS group,MNS group,and tDCS+MNS group.The study of r TMS combined with MNS included 75 pDOC patients divided into three groups :r TMS group,MNS group and r TMS+MNS group.The tDCS group,MNS group,r TMS group,tDCS+MNS group and r TMS+MNS group were given tDCS stimulation,MNS stimulation,r TMS stimulation,tDCS+MNS stimulation and r TMS+MNS stimulation in addition to conventional rehabilitation treatment,respectively.We assessed the Coma Recovery Scale-Revised score(CRS-R),Glasgow coma scale(GCS),Full Outline of Unresponsiveness Score(FOUR),Electroencephalograph(EEG),Somatosensory evoked potential(SEP),brainstem auditory evoked potential(brainstem auditory evoked potential,BAEP),Visual evoked potential(VEP)and Perfusion CT(p CT)before treatment and at week 4 after treatment.In addition,the wake-up rate,and Glasgow Outcome Scale Extended(GOS-E)at 6 months after treatment were also recorded.The latency and amplitude of N20 and Judson’s grade were recorded in SEP;the latency and amplitude of Ⅰ and Ⅴ waves and HALL’s grade were recorded in BAEP;Brain p CT was used to record Cerebral Blood Flow(CBF)and Cerebral Blood velocity(CBV)in four regions of interest(ROI): frontal lobe,temporal lobe,occipital lobe and basal ganglia region(BGR).The two RCT trials were statistically analyzed respectively.The clinical efficacy of the r TMS+MNS group and the tDCS+MNS group was compared.Results: 1.Before the intervention,There were no significant differences in CRS-R,GCS,FOUR score,EEG grade,EEG grading,SEP,BAEP,VEP,CBF and CBV in the four ROI before intervention.There were characteristic improvements in CRS-R,GCS,FOUR,EEG grading,EEG grading,SEP,BAEP,VEP,CBF and CBV in the four ROI in the three groups before and after treatment,and the differences were statistically significant.The tDCS combined MNS group had more characteristic improvements in CRS-R,GCS score,SEP,BAEP,VEP,CBF in the four ROI than that in the tDCS group and the MNS group,and the differences were statistically significant.There was no significant difference in the improvement of consciousness level between the tDCS group and the MNS group except for the changes of V wave latency.The wake-up rate in the tDCS combined with MNS group was 70.8%,which was higher than 54.2% in the tDCS group and 56% in the MNS group.GOS-E showed that the proportion of good outcomes in the tDCS combined MNS group was 58.3%,which was higher than 50% in the tDCS group and 44% in the MNS group.2.Before treatment,there were no statistically significant differences in CRS-R,GCS,FOUR score,EEG grading,SEP,BAEP,VEP,CBF and CBV in the four ROI among the three groups before intervention.The CRS-R,GCS,FOUR,EEG grading,SEP,BAEP,VEP,CBF and CBV in the four ROI of the brain were significantly improved in the three groups before and after treatment.The r TMS combined MNS group had more characteristic improvements in CRS-R,GCS score,EEG grading,SEP,BAEP,VEP,CBF in the four ROI than that in the r TMS group and the MNS group,with statistically significant differences.There was no significant difference in the improvement of conscious behavior scores between the r TMS group and the MNS group except for the changes of cerebral blood flow in the frontal lobe.In the analysis of the wake-up rate,the effective rate of the r TMS combined with MNS group was 72%,which was higher than that of the r TMS group(48%)and the MNS group(56%).GOS-E showed that the proportion of good outcomes in the r TMS combined MNS group was 66.7%,which was higher than that in the r TMS group(58.3%)and the MNS group(48%).3.Before the intervention,there were no statistically significant differences between the tDCS combined MNS group and the r TMS combined MNS group at baseline levels such as age,duration of pDOC,gender,etiology,diagnosis,hypertension,and pupillary reflex.Among the outcome indicators,there were no statistically significant differences in behavioral assessment,EEG grading,SEP,BAEP,VEP,CBF and CBV in the four ROI between the two groups before intervention.The behavior assessment,EEG,SEP,BAEP,VEP,CBF and CBV of the four ROI were improved in the two groups before and after treatment,and the differences were statistically significant.Although,there were no significant differences in behavioral,neuroelectrophysiological,awakening rate and GOS-E characteristic improvement between the two groups,r TMS combined MNS can better improve cerebral blood flow in frontal lobe than tDCS+MNS.Conclusion: 1.Both MNS and tDCS can improve the consciousness level of pDOC patients,and there is no significant difference in the wake-promoting effect between the MNS alone and tDCS alone,but MNS can reduce the latency of V wave.The combined MNS and tDCS stimulation can significantly improve the consciousness level of pDOC patients than MNS or tDCS alone.2.Both r TMS and MNS have a wake-promoting effect on pDOC patients,and there is no significant difference in clinical efficacy between the r TMS alone and MNS alone,but r TMS can improve frontal CBF.r TMS combined with MNS can improve the level of consciousness of patients more than MNS or r TMS alone.3.r TMS combined with MNS and tDCS combined with MNS can both improve the level of consciousness of pDOC patients,and there is no significant difference in the improvement of consciousness level between the two groups,but r TMS combined with MNS can better improve the cerebral blood flow in the frontal lobe. |