随机对照试验：聚焦超声丘脑切开术治疗原发性震颤

A Randomized Trial of Focused Ultrasound Thalamotomy for Essential Tremor.

机构信息

From the University of Virginia Health Sciences Center, Charlottesville (W.J.E., B.B.S., D.H., R.F.D.); Toronto Western Hospital (N.L., A.M.L.) and Sunnybrook Health Sciences Centre (M.S., K.H.), Toronto; Methodist Neurological Institute, Houston (W.G.O.); Stanford University School of Medicine, Stanford, CA (P.G., C.H.H., K.B.P.); Yonsei University College of Medicine, Seoul, South Korea (Y.G.K., W.L., J.W.C.); Swedish Neuroscience Institute, Seattle (R.G., J.W., S.R., R.C.); University of Maryland School of Medicine, Baltimore (H.M.E., P.S.F., D.G.); University of Miami School of Medicine, Nicklaus Children's Hospital, Miami (T.S.T.); Brigham and Women's Hospital, Boston (M.T.H., G.R.C.); and Shin-yurigaoka General Hospital, Kawasaki (T.Y.), and Tokyo Women's Medical University, Tokyo (K.A., T.T.) - both in Japan.

出版信息

N Engl J Med. 2016 Aug 25;375(8):730-9. doi: 10.1056/NEJMoa1600159.

DOI:10.1056/NEJMoa1600159

PMID:27557301

Abstract

BACKGROUND

Uncontrolled pilot studies have suggested the efficacy of focused ultrasound thalamotomy with magnetic resonance imaging (MRI) guidance for the treatment of essential tremor.

METHODS

We enrolled patients with moderate-to-severe essential tremor that had not responded to at least two trials of medical therapy and randomly assigned them in a 3:1 ratio to undergo unilateral focused ultrasound thalamotomy or a sham procedure. The Clinical Rating Scale for Tremor and the Quality of Life in Essential Tremor Questionnaire were administered at baseline and at 1, 3, 6, and 12 months. Tremor assessments were videotaped and rated by an independent group of neurologists who were unaware of the treatment assignments. The primary outcome was the between-group difference in the change from baseline to 3 months in hand tremor, rated on a 32-point scale (with higher scores indicating more severe tremor). After 3 months, patients in the sham-procedure group could cross over to active treatment (the open-label extension cohort).

RESULTS

Seventy-six patients were included in the analysis. Hand-tremor scores improved more after focused ultrasound thalamotomy (from 18.1 points at baseline to 9.6 at 3 months) than after the sham procedure (from 16.0 to 15.8 points); the between-group difference in the mean change was 8.3 points (95% confidence interval [CI], 5.9 to 10.7; P<0.001). The improvement in the thalamotomy group was maintained at 12 months (change from baseline, 7.2 points; 95% CI, 6.1 to 8.3). Secondary outcome measures assessing disability and quality of life also improved with active treatment (the blinded thalamotomy cohort)as compared with the sham procedure (P<0.001 for both comparisons). Adverse events in the thalamotomy group included gait disturbance in 36% of patients and paresthesias or numbness in 38%; these adverse events persisted at 12 months in 9% and 14% of patients, respectively.

CONCLUSIONS

MRI-guided focused ultrasound thalamotomy reduced hand tremor in patients with essential tremor. Side effects included sensory and gait disturbances. (Funded by InSightec and others; ClinicalTrials.gov number, NCT01827904.).

摘要

背景

未经控制的初步研究表明，在磁共振成像（MRI）引导下进行的聚焦超声丘脑切开术对原发性震颤的治疗具有疗效。

方法

我们招募了患有中重度原发性震颤且至少两种药物治疗试验均无效的患者，并将他们以 3:1 的比例随机分配至单侧聚焦超声丘脑切开术或假手术组。在基线和 1、3、6 和 12 个月时，使用震颤临床评分量表和原发性震颤生活质量问卷对患者进行评估。震颤评估通过一个独立的、不了解治疗分组的神经病学家小组进行视频记录和评分。主要结局是在 3 个月时，手震颤从基线变化的组间差异，采用 32 分制评分（分数越高表示震颤越严重）。3 个月后，假手术组的患者可交叉至接受积极治疗（开放标签扩展队列）。

结果

76 例患者纳入分析。与假手术组（从基线的 16.0 分改善至 15.8 分）相比，聚焦超声丘脑切开术后手震颤评分改善更明显（从基线的 18.1 分改善至 9.6 分）；组间平均变化差异为 8.3 分（95%置信区间[CI]：5.9 至 10.7；P＜0.001）。丘脑切开术组在 12 个月时的改善仍持续（从基线的变化为 7.2 分；95%CI：6.1 至 8.3）。与假手术相比，评估残疾和生活质量的次要结局指标也随着积极治疗而改善（两种比较均 P＜0.001）。丘脑切开术组的不良事件包括 36%的患者出现步态障碍和 38%的患者出现感觉异常或麻木；这些不良事件在 12 个月时分别有 9%和 14%的患者持续存在。