Spinal Cord Stimulation With Interleaved Pulses: A Randomized,Controlled Trial

Objectives. The development of multicontact electrodes and programmable, implanted pulse generators has increased the therapeutic success of spinal cord stimulation (SCS) by enhancing the ability to capture and maintain pain/paresthesia overlap. This study sought to determine if interleaved stimulation and/or frequency doubling improves pain/paresthesia overlap in patients with failed back surgery syndrome. Methods. Using a patient‐interactive computer system that quantifies SCS performance and presents stimulation settings in randomized, double‐blind fashion, we compared the effect on pain/paresthesia overlap of interleaved stimulation (rapidly interleaved pulse trains using two different contact combinations) vs. standard treatment with a single contact combination, controlling for frequency doubling. Stimulation amplitude (charge per phase, as determined by varying pulse voltage or width) was adjusted to a subjectively comfortable intensity (usage amplitude), which was maintained for all trials in each patient. The number of percutaneous spinal electrodes used (one or two) and the phase angle between interleaved pulses were additional study variables. Results. Multivariate analysis of 266 test results from 15 patients revealed a statistically significant (p ≤ 0.05) association between increased computer‐calculated pain/paresthesia overlap and 1) high‐ and low‐frequency interleaved stimulation using two combinations of contacts and 2) frequency doubling using one combination. We found no significant effect for electrode configuration (single or dual), pulse width matching, or phase angle. Conclusions. The statistically significant advantages we observed for SCS with interleaved stimulation are explained, at least in part, by the effects of frequency doubling. These findings have important implications for the design and adjustment of pulse generators.     

Cerebellar Transcranial Direct Current Stimulation in Children with Developmental Coordination Disorder: A Randomized,Double-Blind,Sham-Controlled Pilot Study

Journal of Autism and Developmental Disorders - Evidence-based therapeutic options for children with developmental coordination disorder (DCD) are scarce. This work explored the effects of...     

A Double-blind,Randomized Trial of Deep Repetitive Transcranial Magnetic Stimulation (rTMS) for Autism Spectrum Disorder

BackgroundBiomedical treatment options for autism spectrum disorder (ASD) are extremely limited. Repetitive transcranial magnetic stimulation (rTMS) is a safe and efficacious technique when targeting specific areas of cortical dysfunction in major depressive disorder, and a similar approach could yield therapeutic benefits in ASD, if applied to relevant cortical regions.ObjectiveThe aim of this study was to examine whether deep rTMS to bilateral dorsomedial prefrontal cortex improves social relating in ASD.Methods28 adults diagnosed with either autistic disorder (high-functioning) or Asperger's disorder completed a prospective, double-blind, randomized, placebo-controlled design with 2 weeks of daily weekday treatment. This involved deep rTMS to bilateral dorsomedial prefrontal cortex (5 Hz, 10-s train duration, 20-s inter-train interval) for 15 min (1500 pulses per session) using a HAUT-Coil. The sham rTMS coil was encased in the same helmet of the active deep rTMS coil, but no effective field was delivered into the brain. Assessments were conducted before, after, and one month following treatment.ResultsParticipants in the active condition showed a near significant reduction in self-reported social relating symptoms from pre-treatment to one month follow-up, and a significant reduction in social relating symptoms (relative to sham participants) for both post-treatment assessments. Those in the active condition also showed a reduction in self-oriented anxiety during difficult and emotional social situations from pre-treatment to one month follow-up. There were no changes for those in the sham condition.ConclusionDeep rTMS to bilateral dorsomedial prefrontal cortex yielded a reduction in social relating impairment and socially-related anxiety. Further research in this area should employ extended rTMS protocols that approximate those used in depression in an attempt to replicate and amplify the clinical response.     

Transcranial Magnetic Stimulation Versus Transcutaneous Neuromuscular Electrical Stimulation in Post Stroke Dysphagia: A Clinical Randomized Controlled Trial

ObjectivesTo evaluate the efficacy of high-frequency repeated transcranial magnetic stimulation (rTMS) applied contralesionally versus transcutaneous neuromuscular electrical stimulation (TNES) in acute post-stroke dysphagic patients.Materials and methodsA randomized, parallel, comparative, controlled trial was conducted on patients with acute ischemic stroke who were admitted to our department. Fifteen patients received rTMS, 15 patients received TNES, and 15 patients were recruited as a control group. Between the second and tenth days after a stroke, patients were enrolled. The study and follow-up periods were completed by all patients.ResultsAmong the screened patients, 45 (31.47%) right-handed patients were diagnosed with post-stroke dysphagia with a mean age of 60.53 ± 8.23 years. Immediately after intervention both rTMS and TNES groups significantly improve the swallowing disturbance questionnaire (SDQ) and penetration aspiration scale (PAS), compared to the control (p < 0.001 and p = 0.027), respectively. rTMS was more effective than TNES in reducing SDQ and PAS (p < 0.05). rTMS and TNES improved the Yale Pharyngeal Residue Severity Rating Scale (YPRSRS) significantly (p = 0.002); however, their efficacy was comparable (p > 0.05). A significant (p < 0.001) strong negative correlation was observed between the grade of weakness and all scores.ConclusionOur findings showed that high-frequency rTMS and TNES effectively improved the clinical condition of acute post-stroke dysphagic patients in terms of swallowing disturbance assessed by SDQ, pharyngeal residue assessed by YPRSRS, and the severity of penetration and aspiration events evaluated by PAS, compared to the controls. The outcomes of high-frequency rTMS were more favorable than those of TNES in terms of SDQ and PAS.     

Transcranial Magnetic Stimulation in Neurology: What We Have Learned From Randomized Controlled Studies

Background. Initially developed to excite peripheral nerves, magnetic stimulation was quickly recognized as a valuable tool to noninvasively activate the cerebral cortex. The subsequent discovery that repetitive transcranial magnetic stimulation (rTMS) could have long‐lasting effects on cortical excitability spawned a broad interest in the use of this technique as a new therapeutic method in a variety of neuropsychiatric disorders. Although the current outcomes from initial trials include some conflicting results, initial evidence supports that rTMS might have a therapeutic value in different neurologic conditions. Methods. We reviewed the results of clinical trials of rTMS on four different disorders: stroke, Parkinson's disease, chronic refractory pain, and epilepsy. We reviewed randomized, controlled studies only in order to obtain the strongest evidence for the clinical effects of rTMS. Results. An extensive literature review revealed 32 articles that met our criteria. From these studies, we found evidence for the therapeutic efficacy of rTMS, particularly in the relief of chronic pain and motor neurorehabilitation in single hemisphere stroke patients. Repetitive TMS also seems to have a therapeutic effect on motor function in Parkinson's disease, but the evidence is somewhat confounded by the uncontrolled variability of multiple factors. Lastly, only two randomized, sham‐controlled studies have been performed for epilepsy; although evidence indicates rTMS may reduce seizure frequency in patients with neocortical foci, more research is needed to confirm these initial findings. Conclusions. There is mounting evidence for the efficacy of rTMS in the short‐term treatment of certain neurologic conditions. More long‐term research is needed in order to properly evaluate the effects of this method in a clinical setting.     

Spinal Cord Stimulation vs. Conventional Medical Management: A Prospective,Randomized, Controlled,Multicenter Study of Patients with Failed Back Surgery Syndrome (PROCESS Study)

Introduction. Since its first application in 1967, numerous case series indicate that spinal cord stimulation (SCS) is an effective treatment for the management of failed back surgery syndrome (FBSS). However, only one randomized controlled trial has demonstrated that SCS provides more effective pain relief than re‐operation and conventional medical management. The PROCESS randomized, controlled, multicenter trial aims to assess the clinical effectiveness and cost‐effectiveness of SCS when added to conventional medical management compared to conventional medical management alone in patients with FBSS. Methods/Design. A total of 100 FBSS patients with predominantly neuropathic leg pain will be recruited from 12 centers and randomized to receive either conventional medical management alone or in combination with SCS for a period of 24 months. Patients will be evaluated at 1, 3, 6, 9, 12, 18, and 24 months. At the 6‐month visit, patients will be classified as successful (≥  50% pain relief in the legs) or unsuccessful (< 50% pain relief in the legs). If the results of the randomized treatment are unsuccessful, patients can cross over to the alternative treatment arm. Discussion. This paper highlights the rationale, design, methods, and challenges of an ongoing prospective, randomized, controlled, multicenter clinical trial that has been undertaken to obtain conclusive evidence of the clinical efficacy and cost‐effectiveness of an SCS system in patients with FBSS.     

Non-invasive Cerebellar Stimulation: Moving Towards Clinical Applications for Cerebellar and Extra-Cerebellar Disorders

The field of non-invasive stimulation of the cerebellum is quickly expanding. The anatomical structure of the cerebellum with a high density of neurons in the superficial layer, its electrical properties, and its participation in numerous closed-loop circuits involved in motor, cognitive, and affective operations both in children and in adults make of the cerebellum a target with very high potential for neuromodulation of both cerebellar and extra-cerebellar disorders, in neurology, psychiatry, and neurosurgery. A common research effort is required to extract the optimal parameters of stimulation and to identify how non-invasive stimulation of the cerebellum modifies cerebellar plasticity and functional connectivity in remote cortical and subcortical areas. A patient stratification should be considered.     

加巴喷丁治疗癫癎的随机双盲研究

目的评价加巴喷丁在癫癎治疗中的有效性和安全性.方法采用多中心随机双盲研究,用加巴喷丁添加治疗各型癫癎,观察有效性和安全性.结果随机入组病例236例,进入疗效分析的为205例.服用加巴喷丁的病人每4周随访时的癫癎发作次数均减少,且在用药后第12周与对照组的差别有统计意义.治疗有效率在用药后第12、20周与对照组的差别有统计意义,且在全身强直阵挛发作者和部分性发作继发全身性发作者中更明显.安全性两组无差异.结论加巴喷丁在添加治疗癫癎的疗效显示较安慰剂组在减神舶G龇⒆鞔问椭瘟朴行实确矫婢薪虾玫牧菩?同时也是一个安全性较好的药物.     

Effect of Chronic Cortical Stimulation on Chronic Severe Tinnitus: A Prospective Randomized Double-blind Cross-over Trial and Long-term Follow Up

BackgroundChronic severe tinnitus can be greatly detrimental to quality of life. Some authors have reported benefit of repetitive transcranial magnetic stimulation, others of electrical cortical stimulation by stimulating the Heschl's gyrus or secondary auditory areas.ObjectiveTo evaluate the efficacy of chronic electrical epidural stimulation of the auditory cortex on severe and disabling tinnitus.MethodIn this double-blind randomized cross-over, patients with chronic (at least 2 years), severe (Strukturierte Tinnitus-Interview, STI score > 19), unilateral or strongly lateralized tinnitus were included. After open-phase stimulation for 4 months, patients were randomized into 2 groups for double-blind stimulation with cross-over between significant and non-significant phases and wash-out in between. Each of the 3 phases was 2 weeks in duration. Patients were chronically stimulated and followed if not explanted. A decrease of STI score >35% was considered as clinically significant.ResultsNone of the 9 patients included achieved significant improvement during the double-blind phase. Four were explanted, 2 owing to lack of effect, one for breast cancer under the stimulator, and another for psychiatric decompensation. Five are still stimulated. Three felt slight to great subjective effectiveness, the remaining 2 reported benefits and still requested stimulation.ConclusionsThis study did not find an objective efficiency of chronic cortical stimulation for severe and resistant tinnitus. The discordance between the results in double-blind and open evaluations could be related to a placebo effect of surgery, but may also be explained by a poorly defined target, a too short randomized phase, or inappropriate outcome measures.Clinical trial reference: NCT00486577     

Transcranial Magnetic Stimulation Combined with Speech and Language Training in Early Aphasia Rehabilitation: A Randomized Double-Blind Controlled Pilot Study

Abstract

Background: Functional neuroimaging studies with poststroke aphasia patients have shown increased activation of the unaffected hemisphere, which hypothetically reflects a maladaptive strategy of brain reorganization. Objective: We investigated whether repetitive transcranial magnetic stimulation (rTMS) inhibiting the right-hemisphere homologue of Broca’s area improves language restitution if combined with speech/language therapy. Methods: Forty aphasic patients during the subacute phase of ischemic stroke were randomized to a 3-week aphasia rehabilitation protocol in combination with real or sham rTMS. Naming, repetition, and comprehension were assessed using the Boston Diagnostic Aphasia Examination at baseline, immediately after therapy, and 15 weeks after completing treatment. Results: Although language functions improved in both experimental and control groups after 3 weeks, only slight group differences in degree of recovery were revealed between patients receiving rTMS and control participants. Follow-up revealed that severely aphasic rTMS patients demonstrated significantly greater improvement than patients receiving sham stimulation in repetition. Conclusions: Inhibitory rTMS applied to the right frontal language homologue is not effective for all poststroke aphasia patients, although it might benefit selected patients.     

α7-烟碱型乙酰胆碱受体激动剂对精神分裂症认知缺陷和阴性症状治疗:随机双盲对照研究的meta分析

背景:现有α7-烟碱型乙酰胆碱受体激动剂(α7-nAChR受体激动剂)对精神分裂症的认知障碍和阴性症状治疗的临床研究结果不尽一致.目的:评估α7-烟碱型乙酰胆碱受体激动剂在治疗精神分裂症认知缺损和阴性症状的临床疗效和安全性.方法:PubMed、Embase、ClinicalTrials.gov、CochraneLibrary和中国知网、万方、VIP数据库进行文献检索,检索时间截止于2017年5月26日.M eta分析双盲随机对照试验中α7-nAChR受体激动剂的作用,评估α7-nAChR受体激动剂对精神分裂症的总体认知功能和阴性症状的临床疗效.通过计算药物和安慰剂之间的平均差(SMDs),评估α7-nAChR受体激动剂能否作为有效的抗精神病药物.结果:8个低偏倚研究纳入了meta分析.我们没有发现α7乙酰受体激动剂对精神分裂症患者的认知障碍(SMD=-0.10(-0.46,0.25),=88％)和阴性症状(SMD=0.13(-0.04,0.30),I2=64％)有明显疗效.敏感性分析也印证了此结果.药物总体安全且耐受性良好,在不良事件(RR=1.02,[0.85,1.23])和脱落率(RR=1.04,[0.61,1.78])与安慰剂对照无显著差异.根据GRADE评级,该meta分析结果的证据强度为“中”.结论:α7-nAChR受体激动剂可能不是有效地改善精神分裂症患者总体认知障碍和的阴性症状的药物.     

Cerebellar Stimulation: Regional Effects on a Thalamocortical System

Regional effects of electrical stimulation of the cerebellar surface were quantitatively analyzed. Computer controlled stimulus sequences were delivered to ventrolateral thalamus and evoked responses recorded from ipsilateral sensorimotor cortex in the cat. Threshold and excitability profiles were produced with an on-line computer, and their modification by cerebellar stimulation was determined. The results of electrical stimulation of the cerebellar surface were: (1) depressed excitability from paramedian lobule and lobulus simplex; (2) uniquely elevated thresholds from paramedian lobule; and (3) a profound and long-lasting depression of excitability following termination of lobulus simplex stimulation. In comparison with our anticonvulsant drug studies, these data suggest that cerebellar surface stimulation has a far greater capacity to control excitability and threshold responsiveness of thalamocortical systems. Cerebellar electrode placement and temporal pattern of stimulation appear to be important factors in the production of antiepileptic effects.