| Background and Aims:Epilepsy is a highly prevalent neurological disorder with a variety of causes and clinical manifestations.However,about one third of patients do not achieve seizure control despite of sufficient medical therapy.Surgical intervention is a treatment option in certain patients suffering from refractory epilepsy,but it is invasive and not suitable for all patients.Therefore,it is needed to find safe and effective treatments to control intractable seizures.Transcranial magnetic stimulation(TMS)is a new emerging therapy method that can potentially offer individuals a safe and noninvasive alternative to epilepsy surgery.In repetitive transcranial magnetic stimulation(rTMS),pulses are applied with specific repetitive protocols that are able to induce neuromodulatory changes outlasting the duration of the stimulation train.The induced effects are highly dependent on the frequency and/or pattern of the applied stimuli,with facilitatory effects on cortical excitability with high-frequency rTMS(HF-rTMS;>5 Hz)stimulation and a reduction in cortical excitability with low-frequency rTMS(LF-rTMS;?1 Hz).Based on the physics of TMS,either a hyperexcitable epileptogenic focus is targeted infocal epilepsy or relevant network structures in multifocal or generalized epilepsy,for example,vertex or cerebellum.We investigated the potential therapeutic role of high-frequency cerebellar rTMS in patients affected by refractory epilepsy.Methods:We enrolled 87 patients between September 2014 and September 2017,who had been diagnosed refractory epilepsy in Qilu Hospital of Shandong University.In the study,individuals were randomized to treatment group(n=44)and control group(n=43).Patients in treatment group received high-frequency(20 Hz),high intensity rTMS(90%rMT)for bilateral cerebellar stimulation.one thousand and two hundred stimuli per day were given at bilateral cerebellar for 5 consecutive days,continuous treatment 2 cycles.The control group used the same method for "shame stimulation".Finally,we evaluated the number of seizures and interictal epileptiform discharges(IEDs)in patients before and after rTMS.Results:In the course of the study,one patient loss to follow-up in treatment group,and eventually 86 patients completed the study.The baseline period lasted 3 months,the numbers of mean weekly seizure frequency at baseline and during the follow-up period were assessed in our study.For patients in treatment group,the average seizure frequency after 1,2 and 3 months of follow-up respectively was 2.1(2.1±0.9)/month,1.5(1.5±0.8)/month and 5.5(5.5±1.4)/month,which was significantly reduced compared to 6.6(6.6± 1.2)/month at baseline(p<0.05).In contrast,patients receiving"shame stimulation" did not show a significant change of seizure frequency after rTMS treatment(follow up)compared to baseline level.The active rTMS decreased the mean frequency of seizures after 1,2 and 3 months of follow-up respectively by 67.33%(95%CI:63.27%,71.40%),76.47%(95%CI:72.57%,80.37%),17.76%(95%CI:13.06%,22.45%).In the visual EEG analysis,the IED baseline frequency was 10.3(10.3±2.7)events/min in treatment group,decreased to 6.8(6.8±1.7)events/min at the end of the rTMS period(p<0.05),whereas patients in control group did not show a significant change of IED after rTMS treatment.None of the patients complained of obvious discomfort during the treatment and follow-up.Conclusion:High-frequency cerebellar rTMS reduced seizure frequency and interictal epileptiform discharges in patients with refractory epilepsy,the efficacy lasts at least 8-12 weeks,with no obvious discomfort. |
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