The Clinical Efficacy And Safety Study Of Continuous Theta Burst Transcranial Magnetic Stimulation On The Treatment Of Autism Spectrum Disorder

OBJECTIVE: To investigate the therapeutic effect,safety and feasibility of continuous theta burst transcranial magnetic stimulation（c TBS）in the treatment of children with autism spectrum disorder（ASD）.METHODS: Forty-six Han Chinese children with ASD who met the diagnostic criteria for autism spectrum disorders in the Diagnostic and Statistical Manual of Mental Disorders,5th edition（DSM-5）were selected.23 of these children were assigned to the c TBS treatment group,while the other 23 remained in the same treatment regime（no pseudo-stimulation）.Children in the c TBS group received 60 sessions of c TBS for 3 weeks,5 days per week,and their parents completed all scales to assess the severity of the child’s condition.Parents of the patients in the conventional group also completed the full scale to assess the severity of their children’s disease.The c TBS stimulation targets were the dorsolateral prefrontal cortex（DLPFC）and the primary motor cortex（M1）of the left cerebral hemisphere.The procedure was to first stimulate the M1 and DLPFC targets in the left hemisphere,and then repeat the stimulation of the M1 and DLPFC targets in the left hemisphere after a half-hour interval.The clinical symptoms and improvement of children with ASD were assessed at baseline,1 week in treatment,2 weeks in treatment,3 weeks in treatment（at the end of treatment）,at 1 month after treatment,and at 2 months after treatment using the parent-completed Autism Behavior Checklist（ABC）and Clancy Autism Behavior Scale（CABS）,respectively,and the results of the 2 groups were compared.Adverse events in this study were reported jointly by the child and parents,and at the end of each treatment,the child reported verbally the intensity of pain felt during the c TBS treatment on a scale from 0（no pain）to 10（intolerable pain）.In addition,children and parents could report adverse events at any time during and after treatment.In this study,the number of pain at the treatment site,hyperactivity,nosebleeds,seizures,nausea,skin breakdown,and other serious adverse events were recorded,as well as the reason for the subject’s shedding.RESULTS: Thirty-eight children with ASD eventually completed all treatments and evaluations,19 in both the c TBS-treated and conventional treatment groups.The mean age of the children was 6.11±1.62 years,of which 29（76.3%）were male,11（28.9%）has no siblings.,12（31.6%）were born by cesarean section,and 26（68.4%）were undergoing educational training.After 3 weeks of c TBS treatment,the ABC and CABS scores of children in the c TBS group decreased by 20.63 points（23%）and 3.68 points（19%）compared with the pre-treatment scores.The differences between the scores of 1)sensory stimuli sensorial;2)language;3)relating;4)body and object use;and 5)social self-help in the ABC scale were statistically significant（P < 0.05）.At the end of follow-up（2 months after treatment）,the ABC scale and CABS scale scores decreased by 17.84（20%）and 2.06（10%）points from baseline,with statistically significant differences from baseline scores（P < 0.05）.3 of the 23 children treated with c TBS（including4 detached children）reported pain at the treatment site at the time of treatment,and 1 parent reported pain at the treatment site after treatment.The parents of one child reported hyperactivity after treatment,but the symptoms of hyperactivity resolved on their own at the end of treatment,and neither pain nor hyperactivity required special treatment.CONCLUSIONS: Our exploratory trial demonstrates the safety and efficacy of 3-week c TBS treatment at DLPFC and M1 sites in the left hemisphere of the brain in children with autism spectrum disorder.We found preliminary evidence that after 60 c TBS treatments,the symptoms in children with ASD improved without serious adverse events.However,due to measurement bias on account of without the set of blind method and placebo and the efficacy evaluation indexes were highly subjective,and we held a conservative attitude towards this conclusion.In future work,we may recruit more children with ASD and conduct a randomized double-blind controlled trial to test the efficacy of c TBS in ASD population.