On the Use of Fixed‐Intensity Functional Electrical Stimulation for Attenuating Essential Tremor

A great proportion of essential tremor (ET) patients have not so far been able to receive functional benefits from traditional therapies. In this regard, the use of functional electrical stimulation (FES) has been proposed for reducing tremor amplitude by stimulating muscles in antiphase with respect to the trembling motion. Although some studies have reported success in terms of tremor attenuation, drawbacks still exist that prevent the method from being used in real‐life applications. In this article, we explore an alternative approach: a strategy based on the hypothesis that FES‐induced constant muscle contraction may provide functional benefit for tremor patients. To evaluate the proposed strategy, experiments were conducted in which stimulation was intermittently turned on and off while the subjects performed a static motor task. The results of the proposed experimental protocol indicate that tremor attenuation using this strategy is feasible, as consistent tremor attenuation levels were obtained in eight out of 10 ET patients. Nonetheless, tremor reduction was not instantaneous for all successful trials, indicating that prior training with FES may improve the overall response. Furthermore, although simpler assistive devices may potentially be designed based on this technique, some experimental difficulties still exist, which suggests that further studies are necessary.     

Surgical Strategy for Directional Deep Brain Stimulation

Deep brain stimulation (DBS) is a well-established treatment for drug-resistant involuntary movements. However, the conventional quadripole cylindrical lead creates electrical fields in all directions, and the resulting spread to adjacent eloquent structures may induce unintended effects. Novel directional leads have therefore been designed to allow directional stimulation (DS). Directional leads have the advantage of widening the therapeutic window (TW), compensating for slight misplacement of the lead and requiring less electrical power to provide the same effect as a cylindrical lead. Conversely, the increase in the number of contacts from four to eight and the addition of directional elements has made stimulation programming more complex. For these reasons, new treatment strategies are required to allow effective directional DBS. During lead implantation, the directional segment should be placed in a “sweet spot,” and the orientation of the directional segment is important for programming. Trial-and-error testing of a large number of contacts is unnecessary, and efficient and systematic execution of the programmed procedure is desirable. Recent improvements in imaging technologies have enabled image-guided programming. In the future, optimal stimulations are expected to be programmed by directional recording of local field potentials.     

Intraoperative Test Stimulation with a Modified Implantable Pulse Generator in Deep Brain Stimulation

A modified implantable pulse generator (MIPG) for intraoperative test stimulation in chronic deep brain stimulation is described. The MIPG can be used for bipolar stimulation with quadripolar electrodes. The device is programmed and controlled with a standard console programmer. It can also be used for postoperative test stimulation with externalized electrodes. In our experience, the MIPG has several advantages as compared to the screener that is usually used.     

Effect of thalamic deep brain stimulation on lower urinary tract function

OBJECTIVE: The precise mechanisms underlying cerebral regulation of lower urinary tract function are still poorly understood. In patients with disabling essential tremor (ET) refractory to pharmacotherapy, thalamic deep brain stimulation (DBS) is an effective treatment for tremor control. Here, we evaluated the effect of thalamic DBS on urodynamic parameters in patients with ET. PATIENTS AND METHODS: We investigated seven patients (two females, five males) with ET 15-85 mo after implantation of DBS leads into the ventral intermediate nucleus of the thalamus. We compared urodynamic parameters during thalamic DBS (ON state) and 30 min after turning the stimulator off (OFF state). RESULTS: In the ON compared with the OFF state, there was a significant decrease in bladder volume at first desire to void (median, 218 ml vs. 365 ml, p=0.031), at strong desire to void (median, 305 ml vs. 435 ml, p=0.031), and at maximum cystometric capacity (median, 345 ml vs. 460 ml, p=0.016). No significant differences between the ON and OFF state were detected for changes in detrusor pressure during filling cystometry, bladder compliance, maximum detrusor pressure, detrusor pressure at maximum flow rate, maximum flow rate, voided volume, and postvoid residual. CONCLUSIONS: Thalamic deep brain stimulation resulted in an earlier desire to void and decreased bladder capacity, suggesting a regulatory role of the thalamus in lower urinary tract function. Therefore, the thalamus may be a promising target for the development of new therapies for lower urinary tract dysfunction.     

The Present Indication and Future of Deep Brain Stimulation

The use of electrical stimulation to treat pain in human disease dates back to ancient Rome or Greece. Modern deep brain stimulation (DBS) was initially applied for pain treatment in the 1960s, and was later used to treat movement disorders in the 1990s. After recognition of DBS as a therapy for central nervous system (CNS) circuit disorders, DBS use showed drastic increase in terms of adaptability to disease and the patient’s population. More than 100,000 patients have received DBS therapy worldwide. The established indications for DBS are Parkinson’s disease, tremor, and dystonia, whereas global indications of DBS expanded to other neuronal diseases or disorders such as neuropathic pain, epilepsy, and tinnitus. DBS is also experimentally used to manage cognitive disorders and psychiatric diseases such as major depression, obsessive-compulsive disorder (OCD), Tourette’s syndrome, and eating disorders. The importance of ethics and conflicts surrounding the regulation and freedom of choice associated with the application of DBS therapy for new diseases or disorders is increasing. These debates are centered on the use of DBS to treat new diseases and disorders as well as its potential to enhance ability in normal healthy individuals. Here we present three issues that need to be addressed in the future: (1) elucidation of the mechanisms of DBS, (2) development of new DBS methods, and (3) miniaturization of the DBS system. With the use of DBS, functional neurosurgery entered into the new era that man can manage and control the brain circuit to treat intractable neuronal diseases and disorders.     

The Effectiveness of the Stereotactic Burr Hole Technique for Deep Brain Stimulation

Deep brain stimulation (DBS) is performed by burr hole surgery. In microelectrode recording by multi-channel parallel probe, because all microelectrodes do not always fit in the burr hole, additional drilling to enlarge the hole is occasionally required, which is time consuming and more invasive. We report a stereotactic burr hole technique to avoid additional drilling, and the efficacy of this novel technique compared with the conventional procedure. Ten patients (20 burr holes) that received DBS were retrospectively analyzed (5 in the conventional burr hole group and 5 in the stereotactic burr hole group). In the stereotactic burr hole technique, the combination of the instrument stop slide of a Leksell frame and the Midas Rex perforator with a 14-mm perforator bit was attached to the instrument carrier slide of the arc in order to trephine under stereoguidance. The efficacy of this technique was assessed by the number of additional drillings. Factors associated with additional drilling were investigated including the angle and skull thickness around the entry points. Four of the 10 burr holes required additional drilling in the conventional burr hole group, whereas no additional drilling was required in the stereotactic burr hole group (p = 0.043). The thicknesses in the additional drilling group were 10.9 ± 0.9 mm compared to 9.1 ± 1.2 mm (p = 0.029) in the non-additional drilling group. There were no differences in the angles between the two groups. The stereotactic burr hole technique contributes to safe and exact DBS, particularly in patients with thick skulls.     

Deep Brain Stimulation for Refractory Tourette Syndrome: Electrode Position and Clinical Outcome

The efficacy of deep brain stimulation (DBS) for refractory Tourette syndrome (TS) is accepted, but whether the efficacy of DBS treatment in the Japanese population is equivalent to those reported internationally and whether adverse effects are comparable are not yet known. This study evaluated the clinical practice and outcome of DBS for TS in a Japanese institution. This study included 25 consecutive patients with refractory TS treated with thalamic centromedian-parafascicular nucleus DBS. The severity of tics was evaluated with the Yale Global Tic Severity Scale (YGTSS) before surgery, at 1 year after surgery, and at the last follow-up of 3 years or more after surgery. The occurrence of adverse events, active contact locations, and stimulation conditions were also evaluated. YGTSS tic severity score decreased by average 45.2% at 1 year, and by 56.6% at the last follow-up. The reduction was significant for all aspects of the scores including motor tics, phonic tics, and impairment. The mean coordinates of active contacts were 7.62 mm lateral to the midline, 3.28 mm posterior to the midcommissural point, and 3.41 mm above anterior commissure–posterior commissure plane. Efficacy and stimulation conditions were equivalent to international reports. The stimulation-induced side effects included dysarthria (32.0%) and paresthesia (12.0%). Device infection occurred in three patients (12.0%) as a surgical complication. The DBS device was removed because of infection in two patients. DBS is an effective treatment for refractory TS, although careful indication is necessary because of the surgical risks and unknown long-term outcome.     

Deep brain stimulation in the subthalamic area is more effective than nucleus ventralis intermedius stimulation for bilateral intention tremor

Summary Background. The ventro-lateral thalamus is the stereotactic target of choice for severe intention tremor. Nevertheless, the optimal target area has remained controversial, and targeting of the subthalamic area has been suggested to be superior. Patients and methods. Eleven patients with disabling intention tremor of different etiology (essential tremor (n = 8), multiple sclerosis (n = 2) and one with, spinocerebellar ataxia) were implanted bilaterally with DBS electrodes targeted to the ventro-lateral thalamus using micro-recording and micro-stimulation. Among five tracks explored in parallel optimal tracks were chosen for permanent electrode implantation. Postoperative tremor suppression elicited by individual electrode contacts was quantified using a lateralised tremor rating scale at least 3 months (in most patients >1 year) after implantation. The position of electrode contacts was determined retrospectively from stereotactic X-ray exams and by correlation of pre- and postoperative MRI. Results. In all patients, DBS suppressed intention tremor markedly. On average, tremor on the left and right side of the body was improved by 68% (±19; standard deviation) and 73% (±21), respectively. In most patients, distal electrode contacts located in the subthalamic area proved to be more effective than proximal contacts in the ventro-lateral thalamus. In stereotactic coordinates, the optimal site was located 12.7 mm (±1.4; mean ± standard deviation) lateral, 7.0 (±1.6) mm posterior, and 1.5 (±2.0) mm ventral to the mid-commissural point. In general, the best contacts could be selected for permanent stimulation. Nevertheless, in some instances, more proximal contacts had to be chosen because of adverse effects (paraesthesiae, dysarthria, gait ataxia) which were more pronounced with bilateral stimulation resulting in slightly less tremor suppression on the left and right side of body (63 ± 18 and 68 ± 19%, respectively). Conclusion. Direct comparison of different stimulation sites in individual patients revealed that DBS in the subthalamic area is more effective in suppressing pharmacoresistant intention tremor than the ventro-lateral thalamus proper. Anatomical structures possibly involved in tremor suppression include cerebello-thalamic projections, the prelemniscal radiation, and the zona incerta.     

微电极导向立体定向手术治疗帕金森病应用

目的 评价微电极导向立体定向脑内核团毁损术和脑深部电刺激(Deep brain stimulation，DBS)治疗帕金森病的临床疗效。方法 1999年4月～2003年3月采用微电极导向立体定向毁损手术治疗帕金森病510例(毁损手术组)和DBS治疗帕金森病30例(电刺激组)。毁损手术组中行单侧苍白球腹后部毁损术(Posteroventral pallidotomy，PVP)385例，丘脑腹中间核(Ventral intermedius，Vim)毁损术9l例，行同期同侧PVP和Vim毁损术12例，同期双侧PVP8例，分期双侧PVP10例，分期一侧PVP、另一侧Vim毁损术4例。电刺激组中，刺激靶点为丘脑底核(Subthalamic nucleus，STN)29例和Viml例，其中单侧18例，双侧12例。结果 毁损手术组术后UPDRS运动评分，在“关”状态下，症状改善率为47．3％，在“开”状态下症状改善率38．7％。开一关症状和异动症均消失。220例随访平均11．6月，其中显效130例(59．1％)，改善75例(34．1％)，无效15例(6．8％)。电刺激组术后在“关”状态下UPDRS运动评分改善率45．2％。在“开”状态下改善率25．7％，30例随访平均10．3月，其中18例于1月内调整参数后再无调整参数，12例术后需再次调整参数。结论 对伴震颤的帕金森病苍白球损毁术较丘脑损毁术更有效。脑深部电刺激能有效控制病人的运动症状。     

Deep brain stimulation devices: a brief technical history and review

Deep brain stimulation (DBS)—a broadly accepted therapeutic modality with tens of thousands of patients currently implanted—is the application of implantable electrical stimulation devices to treat neurological disorders. Approved indications include involuntary movement disorders; investigational applications include epilepsy, selected psychiatric disorders, and other conditions. DBS differs fundamentally from functional electrical stimulation and sensory prosthetics in that DBS therapies do not substitute for or replace injured tissues, organs, or body functions. DBS—targeted to particular brain nuclei or pathways that are specific for the disorder under treatment—influences brain function and behavioral output in ways that can relieve symptoms and improve the overall functioning of the patient. We will briefly review the history and present status of DBS from a technical and device-oriented perspective, with an eye toward future advances.     

Application of Deep Brain Stimulation for Treatment-resistant Obsessive Compulsive Disorder: Current Status and Future Perspectives in Japan

As in many Western countries, deep brain stimulation (DBS) is already being used daily in Japan to clinically treat neurological diseases such as Parkinson’s disease, essential tremor, and dystonia. Additionally, in both Europe and the United States, numerous case reports as well as multicenter randomized controlled trials have examined its use for treatment-refractory mental illnesses such as obsessive compulsive disorder (OCD) and major depressive disorder. Based on a number of the reports, the European Union (EU) and the USA Food and Drug Administration (FDA) granted limited approval of DBS for treatment-resistant OCD in 2009. Furthermore, a systematic review and meta-analysis in 2015 showed that DBS therapy for patients with treatment-resistant OCD had efficacy and was safe. Unlike the EU and the USA, DBS is not used to treat OCD or other psychiatric disorders in Japan, even though people with treatment-resistant OCD and their physicians and families urgently need additional treatments. This situation results from the “Resolution of total denial for psychosurgery,” which the Japanese Society of Psychiatry and Neurology adopted in 1975. We believe that the appropriateness of using DBS for treating psychiatric disorders including OCD should be considered after thorough discussion and consideration based on accurate and objective understanding. Currently, the field of psychiatry in Japan seems to lack scientific consideration as well as scientific understanding in this area. Under these circumstances, we hope that this review article will help psychiatrists and other relevant parties in Japan to gain an accurate and scientific understanding of DBS.     

双侧丘脑底核脑深部刺激治疗帕金森病

目的 探讨双侧脑深部刺激(Deep brain stimulation，DBS)系统治疗帕金森病(Parkinson’s disease，PD)的手术方法和效果。方法 对13例具有双侧症状的帕金森病进行同期双侧丘脑底核双通道DBS治疗。术中采用磁共振扫描结合微电极记录技术进行靶点定位。术后用UPDRS运动评分评价刺激效果。结果 13例PD术后随访3月—3年，平均6．3月。脉冲发生器开启时，在“关”状态下，UPDRS运动评分症状平均改善率62．3％，其中对左旋多巴类药物反应敏感改善率达75．5％；在“开”状态下，UPDRS运动评分症状改善率24．2％。未发现任何并发症。结论 双侧丘脑底核脑深部刺激治疗可明显改善PD患运动功能。