重复经颅磁刺激治疗慢性神经病理性疼痛

目的探讨重复经颅磁刺激（rTMS）对慢性神经病理性疼痛的疗效和安全性。方法回顾性分析4例慢性神经病理性疼痛病人的资料,其中丘脑痛3例,臂丛神经撕脱伤后疼痛1例,均经正规药物治疗效果欠佳,给予运动皮质10Hz的rTMS（1000次刺激）治疗,每个疗程5d,共3个疗程。分别于治疗前、每个疗程后以及全部疗程结束后1个月、6个月和1年采用视觉模拟疼痛评分（VAS）、汉密尔顿抑郁评分（HAMD）和汉密尔顿焦虑评分（HAMA）来评估疗效。结果全部疗程结束后,疗效满意3例,疗效差l例。疗效满意病人中,随访1年后复发2例。副作用为治疗期间头面部轻度疼痛1例。结论rTMS对部分慢性神经病理性疼痛安全有效．尤其是面部和肢体疼痛的病人。但其疗效不持久,可作为运动皮质电刺激的测试方法。     

重复经颅磁刺激治疗伴躯体疼痛抑郁症患者的疗效观察

目的探讨重复经颅磁刺激（rTMS）治疗伴有躯体疼痛的抑郁症患者的临床疗效和安全性。方法将60例伴有躯体疼痛的抑郁症患者随机分为两组,各30例,均给予度洛西汀口服8周,研究组同时联用rTMS,对照组则予假性rTMS刺激4周,观察8周。于治疗前及治疗后第1,2,3,4,8周应用汉密尔顿抑郁量表（HAMD）、医学结局研究用疼痛量表（MOSPM）和治疗中出现的不良反应量表（TESS）评定两组的治疗效果和安全性。结果治疗结束后两组的MOSPM和HAMD评分均较治疗前显著下降（P〈0．05）;治疗第1,2,3,4周,研究组的MOSPM评分低于对照组,差异有统计学意义（P〈0．05）;治疗第2,3,4周,研究组的HAMD评分低于对照组而显效率高于对照组,差异有统计学意义（P〈0．05）;治疗第8周,两组患者的MOSPM和HAMD评分及显效率差异均无统计学意义（P〉0．05）,治疗期间无严重不良反应发生。结论rTMS能有效治疗伴躯体疼痛的抑郁症,迅速缓解疼痛改善抑郁症状,早期疗效优于单一度洛西汀治疗,且安全性高。     

Effect of 5 Hz repetitive transcranial magnetic stimulation on cognition during a Go/NoGo task

Repetitive transcranial magnetic stimulation (rTMS) has been developed as a novel tool for modulating cognition by delivering stimulation in the brain. However, the effects of rTMS on cognition are still controversial. This randomized, sham-controlled, crossover study was designed to determine whether rTMS of the left dorsolateral prefrontal cortex (DLPFC) interferes with the Go/NoGo task and whether personal parameters such as age affect rTMS. A total of 24 healthy subjects (12 male and 12 female, aged 20-37 years) underwent one session of active rTMS followed by sham rTMS (total of 1600 pulses, 100% of motor threshold, 5 Hz, 8 s), or vice versa. The results did not show any differences between active and sham rTMS stimulation in terms of performance accuracy, response speed, or choice reaction time (cRT) implicating that short-term rTMS will not enhance or deteriorate cognition. However, percentage cRT shortening induced by active rTMS was negatively correlated with age (r = -0.57, P = 0.005), whereas that induced by sham rTMS was not (r = -0.23, P > 0.05), suggesting that cognition of younger subjects might have greater modulation by active stimulation than older ones. This finding may help explain some of the controversies or paradoxical results observed in studies of the effect of left DLPFC rTMS on cognition.     

Efficacy of repetitive transcranial magnetic stimulation in depression: A review of the evidence

Repetitive transcranial magnetic stimulation (rTMS) is a novel treatment in psychiatry. We reviewed all published evidence on the efficacy of this treatment option in depressive disorders. An extensive electronic and manual search for eligible research reports identified only 12 studies that met the predetermined criteria for inclusion. rTMS was administered differently in most studies, and patient characteristics varied widely. A formal meta-analysis of the studies was thus not possible. Instead, we conducted a qualitative evaluation of the included studies. The antidepressive efficacy was not consistent, and where efficacy was demonstrated, it was modest in most studies. Some patients had good but transient responses to rTMS. Treatment gains were not maintained beyond the treatment period. Comparisons with electroconvulsive therapy (ECT) indicated the superiority of ECT. More, larger and more carefully designed studies are needed to demonstrate convincingly a clinically relevant effect of rTMS. We conclude that there is insufficient evidence for rTMS as a valid treatment for depression at present.     

High-frequency repetitive transcranial magnetic stimulation over the primary motor cortex relieves musculoskeletal pain in patients with Parkinson's disease: A randomized controlled trial

BackgroundPain is common in Parkinson's disease, and there is no effective treatment. We conducted a clinical trial to determine whether high-frequency repetitive transcranial magnetic stimulation over the primary motor cortex alleviates musculoskeletal pain in patients with Parkinson's disease.MethodsIn this single-center and double-blind trial, 52 patients with Parkinson's disease and musculoskeletal pain were randomly allocated to 26-member groups receiving 5 sessions of either 20-Hz repetitive transcranial magnetic stimulation or sham stimulation over the primary motor cortex. The participants underwent assessments in the “ON” medication state at baseline, after the fifth session, and at 2- and 4-week follow-up timepoints. The primary outcomes were pain scores on a numeric rating scale. The secondary outcomes were scores on clinical scales assessing motor symptoms, depression, anxiety, autonomic symptoms, sleep quality, and the overall severity of Parkinson's disease.ResultsAnalyses revealed significant group × time interactions for numeric rating scale pain scores (p < 0.001), motor symptom scores (p < 0.001), depression scores (p = 0.009), anxiety scores (p = 0.013), and overall disease severity scores (p < 0.001). Post hoc analyses confirmed that the repetitive transcranial magnetic stimulation group, but not the sham stimulation group, exhibited significant improvements in numeric rating scale pain scores, motor symptom scores, depression scores, anxiety scores, and overall disease severity scores.ConclusionHigh-frequency repetitive transcranial magnetic stimulation over the primary motor cortex may be an effective adjunct therapy for alleviating musculoskeletal pain in patients with Parkinson's disease.     

Non pharmacological treatment for neuropathic pain: Invasive and non-invasive cortical stimulation

The use of medications in chronic neuropathic pain may be limited with regard to efficacy and tolerance. Therefore, non-pharmacological approaches, using electrical stimulation of the cortex has been proposed as an alternative. First, in the early nineties, surgically-implanted epidural motor cortex stimulation (EMCS) was proven to be effective to relieve refractory neuropathic pain. Later, non-invasive stimulation techniques were found to produce similar analgesic effects, at least by means of repetitive transcranial magnetic stimulation (rTMS) targeting the primary motor cortex (M1). Following “high-frequency” rTMS (e.g., stimulation frequency ranging from 5 to 20 Hz) delivered to the precentral gyrus (e.g., M1 region), it is possible to obtain an analgesic effect via the modulation of several remote brain regions involved in nociceptive information processing or control. This pain reduction can last for weeks beyond the time of the stimulation, especially if repeated sessions are performed, probably related to processes of long-term synaptic plasticity. Transcranial direct current stimulation (tDCS), another form of transcranial stimulation, using low-intensity electrical currents, generally delivered by a pair of large electrodes, has also shown some efficacy to improve patients with chronic pain syndromes. The mechanism of action of tDCS differs from that of EMCS and rTMS, but the cortical target is the same, which is M1. Although the level of evidence of therapeutic efficacy in the context of neuropathic pain is lower for tDCS than for rTMS, interesting perspectives are opened by using at-home tDCS protocols for long-term management. Now, there is a scientific basis for recommending both EMCS and rTMS of M1 to treat refractory chronic neuropathic pain, but their application in clinical practice remains limited due to practical and regulatory issues.     

导航经颅磁刺激定位手运动功能区初步研究

目的探讨导航经颅磁刺激定位双手运动功能区的准确性和安全性。方法采用导航经颅磁刺激对10例右利手的健康志愿者双手第一骨间背侧肌进行刺激,定位双手运动功能区及其边界,记录阳性位点坐标和运动诱发电位,并计算双手运动功能区面积。结果 10例受试者均成功定位双手运动功能区,主要定位于中央前回"Ω"区及其周围;右手运动功能区面积大于左手[(6.22±0.76)cm2对(4.30±0.40)cm~2;t=7.078,P=0.000];其中4例表现出困倦,无一例出现头痛、癫发作等不良反应。结论导航经颅磁刺激定位手运动功能区准确、安全,可作为术前定位运动功能区和研究运动功能重塑的辅助方法。     

Multi-modality mapping of motor cortex: comparing echoplanar BOLD fMRI and transcranial magnetic stimulation

Summary Multiple non-invasive methods of imaging brain function are now available for presurgical planning and neurobiological research. As these new methods become available, it is important to understand their relative advantages and liabilities, as well as how the information gained compares across different methods. A current and future trend in neurobiological studies as well as presurgical planning is to combine information from different imaging techniques. Multi-modal integration may perhaps give more powerful information than each modality alone, especially when one of the methods is transcranial magnetic stimulation (TMS), with its ability to non-invasively activate the brain. As an initial venture in cross comparing new imaging methods, we performed the following 2 studies, locating motor cortex with echoplanar BOLD fMRI and TMS. The two methods can be readily integrated, with concurring results, although each have important limitations.     

Augmentative repetitive navigated transcranial magnetic stimulation (rTMS) in drug-resistant bipolar depression

Objectives:  The efficacy of transcranial magnetic stimulation (TMS) has been poorly investigated in bipolar depression. The present study aimed to assess the efficacy of low-frequency repetitive TMS (rTMS) of the right dorsolateral prefrontal cortex (DLPFC) combined with brain navigation in a sample of bipolar depressed subjects.
Methods:  Eleven subjects with bipolar I or bipolar II disorder and major depressive episode who did not respond to previous pharmacological treatment were treated with three weeks of open-label rTMS at 1 Hz, 110% of motor threshold, 300 stimuli/day.
Results:  All subjects completed the trial showing a statistically significant improvement on the 21-item Hamilton Depression Rating Scale (HAM-D), Montgomery-Åsberg Depression Rating Scale, and Clinical Global Impression severity of illness scale (ANOVAs with repeated measures: F  =   22.36, p < 0.0001; F  =   12.66, p < 0.0001; and F  =   10.41, p < 0.0001, respectively). In addition, stimulation response, defined as an endpoint HAM-D score reduction of ≥50% compared to baseline, was achieved by 6 out of 11 subjects, 4 of whom were considered remitters (HAM-D endpoint score ≤ 8). Partial response (endpoint HAM-D score reduction between 25% and 50%) was achieved by 3/11 patients. No manic/hypomanic activation was detected during the treatment according to Young Mania Rating Scale scores (ANOVAs with repeated measures: F  =   0.62, p = 0.61). Side effects were slight and were limited to the first days of treatment.
Conclusions:  Augmentative low-frequency rTMS of the right DLPFC combined with brain navigation was effective and well tolerated in a small sample of drug-resistant bipolar depressive patients, even though the lack of a sham controlled group limits confidence in the results.     

Deconvolution of transcranial magnetic stimulation (TMS) maps

Summary. Transcranial magnetic stimulation (TMS) is a noninvasive method for local stimulation of cerebral cortex using a small coil's pulsed magnetic field. TMS response maps consist of measured responses to stimulations at points on a scalp-referenced grid and are used to study the topography of the brain's inhibitory and excitatory response. Because the magnetic field distributions of stimulation coils are 1–2 centimeters wide and 2–3 centimeters long, and the induced electric fields are even broader, the resolution of TMS maps is limited and the actual region of cortical stimulation is poorly defined. To better characterize the activation pattern, a practical mathematical procedure was developed for deconvolving a spherical model approximation of the coil's induced electric field distribution (here measured in a phantom) from the TMS response maps. This procedure offers an integrated, internally consistent method for processing TMS response maps to estimate the spatial distribution of motor cortex activations and inhibitions. Received February 7, 2000; accepted July 3, 2000     

BOLD fMRI response to direct stimulation (transcranial magnetic stimulation) of the motor cortex shows no decline with age

Previous studies using BOLD fMRI to examine age-related changes in cortical activation used tasks that relied on peripheral systems to activate the brain. They were unable to distinguish between alterations due to age-related changes in the periphery and actual changes in cortical physiology. Transcranial magnetic stimulation (TMS), which allows direct, noninvasive stimulation of cortical neurons, was interleaved with BOLD fMRI to study 6 young and 5 old subjects. Three different tasks were compared: direct stimulation by TMS, indirect active stimulation produced by a motor task, and indirect passive stimulation produced by hearing the TMS coil discharge.Direct neuronal stimulation by TMS produced similar fMRI signal increases in both groups, suggesting that cortical physiology itself may not necessarily decline with age.     

重复经颅磁刺激治疗帕金森病的临床研究

目的 探讨低频重复经颅磁刺激（rTMS）对帕金森病（PD）的治疗作用。方法 将45例PD患者随机分为治疗组30例，假刺激组15例。治疗组给予频率1Hz、刺激强度为110％静息阈值的rTMS，每日1次，治疗10d，并在治疗后1个月和3个月时随访。采用UPDRS评分、木插板试验、记时运动试验和10m折返运动试验进行疗效评价，评价前患者停服抗PD药物至少12h。结果治疗组治疗结束后UPDRS总分及Ⅰ、Ⅱ和Ⅲ分较治疗前均明显降低（均P〈0.01），患者木插板所用的平均时间明显减少（P〈0．01），记时运动1min平均运动次数明显增加（P〈0．01），行走速度明显增快（P〈0．01），随访3个月仍低于治疗前（P〈0．05）。治疗后3个月生活满意度（L-S1B）无明显变化，而生活质量评分（PDQ）则明显降低（P〈0．05）。假刺激组治疗前后木插板试验、记时运动试验和10m折返运动均无明显变化。结论 低频rTMS可以改善PD患者的临床症状，提高患者生活质量。     

导航经颅磁刺激定位国人右利手汉字示图书写功能区

目的运用导航经颅磁刺激探索国人右利手汉字图示书写功能区的皮层定位,并分析研究该技术下与手运动中枢的皮层位置关系。方法对10例健康受试者完成汉字示图书写的任务,在进行书写的同时予以导航下经颅磁刺激,根据出现书写障碍的阳性位点,测绘书写功能区的区域和面积;通过导航经颅磁刺激刺激右手运动功能区出现运动诱发电位,记录右手肌肉肌电数据和阳性刺激坐标,计算右手运动功能区面积,进行书写功能区与右手运动功能区大小和距离的对比。结果 10例健康汉语母语受试者均可以在导航经颅磁刺激下定位书写中枢。书写功能区的皮层定位较为固定,阳性位点主要位于额中回后部(86%,55/64)。书写功能区面积小于右手运动功能区的面积,差异具有统计学意义(161.03 mm~2±62.58 mm~2 vs.589.50 mm~2±227.34 mm~2,t=-4.050,P0.001)。书写功能区的位置与手运动区的皮层定位存在一定距离(d=12.58 mm±2.71 mm),并没有功能区的重合。结论导航经颅磁刺激技术可以辅助定位示图书写功能区位置,并且书写功能区与手运动功能区没有重合。     

Treatment of chronic intractable atypical facial pain using peripheral subcutaneous field stimulation

Introduction: Atypical facial pain (ATFP) is challenging to manage and there are few proven therapies available. We present a case report describing application of peripheral subcutaneous field stimulation (PSFS) to a patient with chronic intractable ATFP which conventional treatment failed to ameliorate. Methods: The patient underwent an uneventful PSFS trial with percutaneous placement of two temporary eight‐electrode leads (Medtronic Inc, Minneapolis, MN, USA) placed subdermally over the left mandible. Results: After experiencing excellent pain relief over the next two days, the patient was implanted with permanent leads and rechargeable generator two and a half weeks later and reported sustained pain relief at 12‐month follow‐up visit. Discussion: Peripheral subcutaneous field stimulation provides an effective treatment option for patients suffering from chronic ATFP who have failed conservative treatment. PSFS may provide pain relief with advantages over conservative treatments and more invasive techniques. Conclusion: Peripheral subcutaneous field stimulation offers an alternative treatment option to select patients with intractable ATFP.     

Pilot study of repetitive transcranial magnetic stimulation in patients with chemotherapy-induced peripheral neuropathy

ObjectiveChemotherapy-induced peripheral neuropathy (CIPN) is one of the intractable long-term side effects of anticancer medications and results in pain and dysesthesia. Repetitive transcranial magnetic stimulation (rTMS) of the primary motor cortex has been demonstrated to provide effective relief for intractable neuropathic pain. The objective of this study was to investigate the effects of rTMS treatment on CIPN in cancer patients.Materials and methodsEleven female patients with breast cancer or gynecologic cancer (mean age 64.8 [standard deviation 7.8]) who had neuropathic pain and/or peripheral sensory neuropathy, with a minimum two grade severity based on the scale of the National Cancer Institutes’ Common Terminology Criteria for Adverse Events (version 4.0) were enrolled. Patients received rTMS (5-Hz; 500 pulses/session; figure-8 coil) on their primary motor cortex corresponding to the target extremity. The intensity of pain and dysesthesia for all extremities was evaluated using a visual analog scale for pain, dysesthesia, and the Japanese version of the short-form McGill Pain Questionnaire 2 (SFMPQ2).ResultsrTMS for target extremity significantly decreased the visual analog scale of pain and dysesthesia. The intensity of pain measured by the SFMPQ2 was also decreased in the target extremity. Regarding non-target extremities, only dysesthesia significantly decreased as a result of rTMS. No adverse events were observed.ConclusionThis is an initial report demonstrating the potential of rTMS for the treatment of CIPN. We suggest rTMS could be potentially beneficial and effective as a treatment for pain and dysesthesia in patients with CIPN.     

Therapeutic effect of repetitive transcranial magnetic stimulation on motor function in Parkinson''s disease patients

Cortical excitability of the primary motor cortex is altered in patients with Parkinson's disease (PD). Therefore, modulation of cortical excitability by high frequency repetitive transcranial magnetic stimulation (rTMS) of the motor cortex might result in beneficial effects on motor functions in PD. The present study aims to evaluate the effect of rTMS of the motor cortex on motor functions in patients with PD. Thirty-six unmedicated PD patients were included consecutively in this study. The patients were assigned in a randomized pattern to one of two groups, one group receiving real-rTMS (suprathreshold 5-Hz, 2000 pulses once a day for 10 consecutive days) and the second group receiving sham-rTMS using closed envelopes. Total motor section of Unified Parkinson's Disease Rating Scale (UPDRS), walking speed, and self-assessment scale were performed for each patient before rTMS and after the first, fifth, 10th sessions, and then after 1 month. Evaluation of these measures was performed blindly without knowing the type of rTMS. anova for repeated measurements revealed a significant time effect for the total motor UPDRS, walking speed and self-assessment scale during the course of the study in the group of patients receiving real-rTMS (P = 0.0001, 0.001, and 0.002), while no significant changes were observed in the group receiving sham-rTMS except in self-assessment scale (P = 0.019). A 10-day course of real-rTMS resulted in statistically significant long-term improvement of the motor functions in comparison with the sham-rTMS. The rTMS could have a therapeutic role of for PD patients.     

Long-term treatment of chronic orofacial,pudendal, and central neuropathic limb pain with repetitive transcranial magnetic stimulation of the motor cortex

ObjectiveTo assess the long-term analgesic effects of high-frequency repetitive transcranial magnetic stimulation (rTMS) of the motor cortex in patients with chronic pain syndrome.MethodsThe study included 57 patients (orofacial pain, n = 26, pudendal neuralgia, n = 18, and neuropathic limb pain, n = 13) with an “induction phase” of 12 daily rTMS sessions for 3 weeks, followed by a “maintenance phase” of bi-monthly sessions for the next five months.ResultsAll pain measures significantly decreased from baseline to the end of the induction phase. Analgesic response, defined as pain intensity decrease ≥ 30% compared to baseline, was observed in 39 patients (68%), who could be differentiated from non-responders from the 7th rTMS session. At the end of the maintenance phase (D180), 27 patients (47%) were still responders. Anxio-depressive symptoms and quality of life also improved. The analgesic response at the end of the induction phase was associated with lower pain score at baseline, and the response at the end of the maintenance phase was associated with lower anxio-depressive score at baseline.ConclusionThe analgesic efficacy of motor cortex rTMS can be maintained in the long term in various chronic pain conditions. Patients with high pain level and severe anxio-depressive symptoms may have a less favorable profile to respond to the procedure.SignificanceThe overall impact of rTMS treatment on daily life requires a multidimensional evaluation that goes beyond the analgesic effect that can be achieved.     

诊断性经颅磁刺激研究进展

经颅磁刺激是一种无创性神经电生理学技术,经颅磁刺激运动诱发电位已广泛应用于运动皮质兴奋性与皮质延髓束、皮质脊髓束传导功能的评价。近年随着对磁刺激原理的深入了解和刺激线圈、刺激模式的不断多样化,经颅磁刺激在神经病学临床诊断中的应用不断拓展,逐渐形成更加科学和标准化的运动诱发电位操作流程。本文拟对诊断性经颅磁刺激常规刺激模式研究进展、特殊模式刺激方案,以及经颅磁刺激与脑电图、f MRI的联合应用进行综述。     

Descending volleys generated by efficacious epidural motor cortex stimulation in patients with chronic neuropathic pain

Epidural motor cortex stimulation (EMCS) is a therapeutic option for chronic, drug-resistant neuropathic pain, but its mechanisms of action remain poorly understood. In two patients with refractory hand pain successfully treated by EMCS, the presence of implanted epidural cervical electrodes for spinal cord stimulation permitted to study the descending volleys generated by EMCS in order to better appraise the neural circuits involved in EMCS effects. Direct and indirect volleys (D- and I-waves) were produced depending on electrode polarity and montage and stimulus intensity. At low-intensity, anodal monopolar EMCS generated D-waves, suggesting direct activation of corticospinal fibers, whereas cathodal EMCS generated I2-waves, suggesting transsynaptic activation of corticospinal tract. The bipolar electrode configuration used in chronic EMCS to produce maximal pain relief generated mostly I3-waves. This result suggests that EMCS induces analgesia by activating top–down controls originating from intracortical horizontal fibers or interneurons but not by stimulating directly the pyramidal tract. The descending volleys elicited by bipolar EMCS are close to those elicited by transcranial magnetic stimulation using a coil with posteroanterior orientation. Different pathways are activated by EMCS according to stimulus intensity and electrode montage and polarity. Special attention should be paid to these parameters when programming EMCS for pain treatment.