Study On The Mechanism And Efficacy Of Repetitive Transcranial Magnetic Stimulation In The Treatment Of Parkinson’s Disease

Background: Parkinson’s disease(PD)is a neurodegenerative disease which occurs in the middle-aged and the elderly people.It is characterized by loss of degeneration of dopaminergic neurons in the substantia nigra and a significant decrease in the concentration of striatal dopaminergic transmitter.The clinical manifestations are mainly static tremor,bradykinesia,rigidity and postural instability,and often accompanied by non-motor symptoms such as depression,cognitive impairment and some autonomic symptoms,which seriously affect the quality of life,and bring the family and society a heavy burden.In 1994,Pascual-Leone first applied repetitive transcranial magnetic stimulation(rTMS)to the treatment of Parkinson’s disease,and achieved beneficial results.With the development of more and more clinical and basic research,many scholars explored the mechanism of rTMS in the treatment of PD through various ways and tried to find the best treatment protocols.Transcranial magnetic stimulation combined with electroencephalography(TMS-EEG)is an emerging technology that can be widely used in clinical practice.By monitoring the TMS-induced neuronal transients with high temporal resolution EEG,we can detect the excitability,connectivity,and neuronal oscillations of the cerebral cortex,which help us to explore the physiological mechanisms of neurological diseases.This study used TMS-EEG to assess the changes of TMS evoked potentials(TEPs)amplitude of PD patients after rTMS treatment,and explored the possible mechanisms of rTMS treatment of PD,which layed a foundation for further optimization of PD rTMS treatment.Methods: Thirty patients with PD were admitted to the Department of Neurology,Shenzhen People’s Hospital from November 2017 to November 2018 were randomly divided into rTMS high-frequency treatment group and rTMS low-frequency treatment group.The therapeutic effect was observed after 4 weeks of treatment.The patients were assessed and recorded using the Parkinson’s Disease Comprehensive Rating Scale(UPDRS),10-meter walking time,and the numbers of flipping upside down the palm within 30 seconds.The clinical efficacy was evaluated by using the reduction rate.TMS-EEG was used to detect the excitability of cerebral cortex before and after rTMS treatment.EEG data were processed by using the Matlab software.Statistical analysis was performed using SPSS19.0 statistical software.The significance level was P=0.05,and P<0.05 was considered statistically significant.Results: For the high-frequency treatment group,after 20 treatments,the UPDRS scale score and the 10-meter walking time decreased significantly than that before the treatment,and the numbers of flipping upside down the palm within 30 seconds increased,the difference was statistically significant(P<0.05).Among them,6 patients had a UPDRS reduction rate of more than 50%,which indicated the curative effect was significant.The other 5 patients had a UPDRS reduction rate of 10-50%,which indicated the curative effect was present.The UPDRS reduction rate after treatment in 4 patients was less than 10%,which indicated no effect.For the low-frequency treatment group,after 20 treatments,the UPDRS scale score and the 10-meter walking time decreased significantly than that before the treatment,and the numbers of flipping upside down the palm within 30 seconds increased,the difference was statistically significant(P<0.05).Among them,3 patients had a UPDRS reduction rate more than 50%,which indicated the effect was significant.The other 7 patients had a UPDRS reduction rate of 10-50% after the treatment,which indicated the curative effect was present.The UPDRS reduction rate after treatment in 5 patients was less than 10%,which indicated no significant effect.There was no significant difference of the efficacy between the high-frequency and low-frequency protocols(P>0.05).According to the UPDRS scoring rules,PD was divided into tremor-based type(TD-type)and postural instability/gait-disorder type(PIGD-type).It was found that the remission rate of high-frequency stimulation protocol for the PIGD-type was 87.5%,and that for TD-type was 57.1%,while low-frequency stimulation protocol had a remission rate of 50% for the PIGD-type and 77.8% for the TD-type.Compared the patients of effective before and after treatment in the high-frequency group,the TEPs amplitude induced by single-pulse TMS stimulation at the right M1 region increased at the left frontal lobe within 0.150-0.185 seconds after stimulation,the difference was statistically significant(P<0.001).Compared the patients of effective before and after treatment in the low-frequency group,the TEPs amplitude induced by the single-pulse TMS stimulation at the left M1 region decreased at the right frontal lobe within 0.206-0.245 seconds after stimulation,and the difference was statistically significant(P<0.001).Compared the low-frequency group and the high-frequency group,the TEPs amplitude induced by the single-pulse TMS stimulation at the right M1 area increased at the bilateral occipital lobes within 0.150-0.191 seconds after stimulation(P<0.001),and the TEPs amplitude induced by stimulation at the left M1 region decreased at the right frontal lobe within 0.207-0.249 seconds after stimulation,and the difference was statistically significant(P<0.001).Conclusion: High-frequency and low-frequency rTMS can both effectively improve the motor symptoms and daily living ability of PD patients.There was no significant difference between the two methods.Different subtypes of PD patients may be appropriate for different rTMS treatment modes.High-frequency and low-frequency rTMS may regulate cortical excitability of PD patients by exciting or inhibiting different neural circuits.TMS-EEG can better assess cortical excitability and can be widely used as a routine detection technique in the clinic.