Epidural Electrical Stimulation for Stroke Rehabilitation: Results of the Prospective, Multicenter, Randomized, Single-Blinded Everest Trial
Epidural Electrical Stimulation for Stroke Rehabilitation: Results of the Prospective, Multicenter, Randomized, Single-Blinded Everest Trial
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DOI：
10.1177/1545968315575613
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发表时间：
2016-02-01
影响因子：
4.2
通讯作者：
Venkatesan, Lalit
中科院分区：
文献类型：
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作者：
Levy, Robert M.;Harvey, Richard L.;Venkatesan, Lalit
背景资料。这项前瞻性、单盲、多中心研究评价了硬膜外运动皮质电刺激(EECS)改善中重度偏瘫缺血性中风患者上肢运动功能的安全性和有效性。方法：研究方法。卒中后4个月的患者被随机分为研究组(n=104)和对照组(n=60)。研究患者(n=94)植入了垂直于初级运动皮质的硬膜外6触点导线和脉冲发生器。两组患者均接受6周的康复治疗，但在康复期间给予受试者EECS。主要疗效终点(PE)定义为康复4周后上肢Fugl-Meyer量表(UEFM)和手臂运动能力测试(AMAT)至少提高4.5分和0.21分。分别于康复后1、4、12、24周进行随访评估。安全性是通过监测从登记到康复结束之间发生的不良事件(AEs)来评估的。结果。初次意向治疗分析显示，4周时两组间无差异，分别有32%和29%的研究组和对照组患者达到PE标准(P=0.36)。重复测量二次分析显示，治疗组的平均UEFM或AMAT评分没有显著差异。然而，事后比较显示，在康复后24周，研究患者(39%)比对照组(15%)维持或实现PE的比例更大(P=0.003)。与对照组相比，研究组在康复后24周的平均AMAT评分也有显著提高(P<；0.05)。事后分析还显示，在刺激测试中引发运动阈值的受试者中，69%(n=13)在4周时达到PE，在4周、12周和24周的评估中，这一亚组的平均UEFM和AMAT得分也显著高于对照组(P<；.05)。头痛(19%)、疼痛(13%)、肿胀(7%)和感染(7%)是最常见的植入物相关不良反应。总体而言，在9名研究组患者中，共有11例严重不良反应(7例与手术有关，4例与麻醉有关)。结论。对慢性卒中患者上肢运动康复中EECS疗效的初步分析在康复后4周为阴性。在每次康复治疗前进行的运动阈值评估中，在刺激诱导上肢运动的患者中观察到了更好的治疗反应。治疗后比较显示，24周时治疗效果存在差异，与研究组相比，对照组的综合主要结果指标显著下降。这些结果有可能为未来的慢性卒中康复试验设计提供参考。
Background. This prospective, single-blinded, multicenter study assessed the safety and efficacy of electrical epidural motor cortex stimulation (EECS) in improving upper limb motor function of ischemic stroke patients with moderate to moderately severe hemiparesis. Methods. Patients 4 months poststroke were randomized 2:1 to an investigational (n = 104) or control (n = 60) group, respectively. Investigational patients were implanted (n = 94) with an epidural 6-contact lead perpendicular to the primary motor cortex and a pulse generator. Both groups underwent 6 weeks of rehabilitation, but EECS was delivered to investigational patients during rehabilitation. The primary efficacy endpoint (PE) was defined as attaining a minimum improvement of 4.5 points in the upper extremity Fugl-Meyer (UEFM) scale as well as 0.21 points in the Arm Motor Ability Test (AMAT) 4 weeks postrehabilitation. Follow-up assessments were performed 1, 4, 12, and 24 weeks postrehabilitation. Safety was evaluated by monitoring adverse events (AEs) that occurred between enrollment and the end of rehabilitation. Results. Primary intent-to-treat analysis showed no group differences at 4 weeks, with PE being met by 32% and 29% of investigational and control patients, respectively (P = .36). Repeated-measures secondary analyses revealed no significant treatment group differences in mean UEFM or AMAT scores. However, post hoc comparisons showed that a greater proportion of investigational (39%) than control (15%) patients maintained or achieved PE (P = .003) at 24 weeks postrehabilitation. Investigational group mean AMAT scores also improved significantly (P < .05) when compared to the control group at 24 weeks postrehabilitation. Post hoc analyses also showed that 69% (n = 9/13) of the investigational patients who elicited movement thresholds during stimulation testing met PE at 4 weeks, and mean UEFM and AMAT scores was also significantly higher (P < .05) in this subgroup at the 4-, 12-, and 24-week assessments when compared to the control group. Headache (19%), pain (13%), swelling (7%), and infection (7%) were the most commonly observed implant procedure-related AEs. Overall, there were 11 serious AEs in 9 investigational group patients (7 procedure related, 4 anesthesia related). Conclusions. The primary analysis pertaining to efficacy of EECS during upper limb motor rehabilitation in chronic stroke patients was negative at 4 weeks postrehabilitation. A better treatment response was observed in a subset of patients eliciting stimulation induced upper limb movements during motor threshold assessments performed prior to each rehabilitation session. Post hoc comparisons indicated treatment effect differences at 24 weeks, with the control group showing significant decline in the combined primary outcome measure relative to the investigational group. These results have the potential to inform future chronic stroke rehabilitation trial design.