| Part One Therapeutic effect of repetitive transcranial magnetic stimulation on writer’s crampBackground:Focal hand dystonia (FHD) is a disorder characterized by involuntary contraction and co-contraction of muscles of the hand causing abnormal posturing and reduced fine motor control. Writer’s cramp is the most prevalent types of FHD. Because writer’s cramp will affect hand function and thus influence the work ability and career development of the patients, most of them have the desire for treatment. The current treatments mainly include oral medication and botulinum toxin injection. Oral medication is only valid for the mild patients. The efficacy of the treatment with botulinum toxin injection is less than that of the other focal dystonia, e.g. cervial dystonia and blepharospasm, and also accompanies obvious hand weakness. At present, the general understanding is that the mechanism of dystonia is related to loss of inhibition. Repetitive transcranial magnetic stimulation (rTMS) is a new type of noninvasive and safe neural regulation method and has been utilized by other researchers on dystonia. The preliminary results illustrate that low frequency rTMS might have the function of increase inhibition and improve symptoms.Objective:The current prospective study was to observe the treatment efficacy of rTMS for writer’s cramp, and investigate preliminarily the pathogenesis of dystonia and the treatment mechanism of rTMS through electrophysiological techniques and functional magnetic resonance imaging (fMRI).Methods:Fifteen primary writer’s cramp patients were enrolled in the study. Ten patients were allocated into the treatment group, and five patients were in the control group. In the treatment group,1Hz rTMS was performed at an intensity of90%resting motor threshold (RMT). Over the left premotor cortex1200stumuli per day were delivered for five consecutive days. fMRI scan, electrophysiological evaluation, clinic effect evaluation and patients’ self-evaluations had been performed before the first treatment and after five days of the treatment. The sham stimulations on the same sites were executed for control group. The evaluations are the same as that of the treatment group except fMRI. The fMRI of gender and age matched healthy volunteers had been acquired as healthy control.Results:Writer’s cramp rating scale (WCRS), Burke-Fahn-Marsden scale (BFM), writing time, RMT, MEP amplitude before and after the treatment in both treatment group and control group had no statistical significance. The WCRS and BFM scale and writing time between treatment group and control group have no statistical significance. But the variation of the WCRS, BFM movement scale and the MEP amplitude after rTMS in treatment group are obviously higher than that of control group. The differences of the subjective self-evaluations in these two groups have statistical significance (P=0.006). Before rTMS, the patients in treatment group exhibited higher activation in left primary sensorimotor cortex and lower activation in bilateral cerebellum and supplementary motor cortex (SMA) compared with healthy control (P<0.05, unc). After rTMS, the patients in treatment group exhibited a rTMS-related BOLD signal decrease in left M1and premotor cortex (PMd), and increase in bilateral cerebellum (P<0.05, unc). There was a positive correlation between cerebral activation pattern change and WCRS score decrease (r=0.5).Conclusions:Consecutive low frequency rTMS can improve writer’s cramp patients’subjective self-evaluations and has the improvement tendency on the corresponding scales, which suggests that rTMS has the improvement tendency on the clinical symptom of writer’s cramp. Further studies with enlarged sample numbers or with more sensitive observation criteria are suggested.With consecutive low frequency rTMS, MEP amplitude has the tendency of decrease, which suggests the tendency of decrease on the motor cortex excitability.After rTMS, the patients in treatment group exhibited a rTMS-related BOLD signal decrease in left M1, which suggests that rTMS may lead to reinforcement of intracortical inhibition and decreas of motor cortex activity. Part Two A pilot study on the therapeutic effect of repetitive transcranial magnetic stimulation for cervical dystoniaBackground:Cervical dystonia is the most common type of focal dystonia in clinics. It is characterized by phasic or sustained involuntary neck muscle contractions causing abnormal movements and postures of head and neck, often accompanied by dystonic tremor and pain. Serious cervical dystonia may result in functional disability. At present, botulinum toxin injection is the main treatment method for cervical dystonia. Because of the relatively sophisticated structure in the neck, and distinguished differences in various affected muscles of the patients, practiced injection skills are necessary. Some patients may also suffer loss of effect related to antibody. Repetitive transcranial magnetic stimulation (rTMS) is a new type of noninvasive and safe neural regulation method and has been demonstrated preliminary treatment effects on depression, pain and Parkinson disease, etc. The study for the effects of rTMS on cervical dystonia is limited. A case study and an open study indicate that rTMS might be effective for cervical dystonia, but lack of the comparison to sham stimulate, and can not eliminate the placebo effect.Objective:The current prospective study was to investigate the treatment efficacy of rTMS for cervical dystonia and compare the effect with botulinum toxin type A (BTX-A).Method:Twelve primary rotational cervical dystonia patients were enrolled in the study. Six patients were allocated in the treatment group, and the other six patients were in the control group. The whole research had two steps. Firstly, in the treatment group,1Hz rTMS was performed at an intensity of90%RMT. Over the premotor cortex of each side totally1600stimuli were delivered for5consecutive days. Sham stimulations had been given for control group on the same location. Before the first treatment and five days after the treatment, the evaluations had been performed, which included Tsui rating scale, TWSTRS, the ipsilateral and contralateral RMT, patients’ self-evaluations, etc. In the second step, botulinum toxin type A was used after the effects of the treatment group had vanished for one week. Before the first treatment and one month after the treatment, the same evaluations except RMT had been performed and were compared with that of the rTMS.Results:(1) The differences of Tsui rating scale, TWSTRS, the ipsilateral and contralateral RMT between before and after the treatment in both treatment group and control group were not with statistical significance. There were no statistical significance between treatment group and control group on the differences of Tsui rating scale, TWSTRS self-evaluations. But the variations of Tsui rating scale and TWSTRS after rTMS in treatment group are obviously higher than that of control group.(2) There are statistical significances on the improvements of Tsui rating scale and TWSTRS between before and after the BTX-A injection. rTMS and BTX-A have statistical significances on TWSTRS and the duration of effect. rTMS has no adverse effect. As to BTX-A, half of the patients may appear reversible adverse effect after the treatment.Conclusions:Consecutive low frequency rTMS has improvement tendency for clinic symptoms of cervical dystonia. It is highly recommended to enlarge the sample size for further study.No obvious change of RMT has been observed with consecutive low frequency rTMS.BTX-A surpasses rTMS on the clinic effects and the duration of effect but suffers from more adverse effect comparing to rTMS. |
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