LANCET NEUROL：苍白球刺激治疗原发性肌张力障碍

　　原发性肌张力障碍的严重型很难用药物控制。一个多中心对照研究证实了苍白球神经刺激对原发性全身性或局灶性肌张力患者的安全性和有效性。德国科尔的Christian-Albrechts大学神经科的Jens Volkmann博士等人对这项研究的研究对象延长随访时间5年发现：延长随访时间的结果依然支持苍白球刺激治疗严重原发性肌张力障碍的安全性和有效性，可推荐作为药物治疗效果不佳的严重全身性或局灶性肌张力障碍患者的一线治疗。相关论文发表在Lancet Neurology杂志2012年12月刊上。

　　在原先的研究中，40位患者被随机分入假的神经刺激组或内囊苍白球神经刺激组，治疗3个月，随后6个月所有的患者都进行真的神经刺激。有38位患者同意在神经刺激后进行每年随访。随访内容包括肌张力障碍严重程度、疼痛、残疾和生活质量。延长的5年随访研究的主要的终点事件为第3年和第5年随访时肌张力障碍严重程度的改变，通过Burke—Fahn—Marsden肌张力评级量表（BFMDRS）运动评分的开放标签评级与术前基线和治疗后6个月随访时进行比较。根据意向治疗为基础分析主要终点。

　　将意向性治疗分析纳入了原来研究中的所有患者，结果显示：相较基线，在第3年和第5年随访时肌张力障碍严重程度获得改善，治疗后6个月为20.8 分 (SD：17.1%~47.9%；n=40)，治疗后3年为26.5分(19.7%～61.1%；n=31) ；在术后5年为25·1分 (21.3%～57.8%；n=32)。治疗后6个月到治疗后3年获得显著改善5.7分 （SD：8.4%～34%)，改善效果持续到第5年随访。这种新发不良事件在治疗后6个月到治疗后5年这段期间出现。构音障碍和肌张力障碍暂时加重是最常见的非严重不良反应事件。21件不良反应事件评级为严重，基本都是纯设备相关的。一位患者在治疗6个月的随访后不久的抑郁期试图自杀。所有的严重不良反应事件均治愈，不留永久性后遗症。

　　该研究发现：根据术后随访3年和5年的结果，苍白球神经刺激仍然是严重原发性肌张力障碍的患者安全有效的治疗选择。这项长期观察研究的结果支持了苍白球神经电刺激作为药物治疗效果不佳的局灶性后全身性肌张力障碍患者的一线治疗方案。　

Pallidal deep brain stimulation in patients with primary generalised or segmental dystonia: 5-year follow-up of a randomised trial

Background

Severe forms of primary dystonia are difficult to manage medically. We assessed the safety and efficacy of pallidal neurostimulation in patients with primary generalised or segmental dystonia prospectively followed up for 5 years in a controlled multicentre trial.

Methods

In the parent trial, 40 patients were randomly assigned to either sham neurostimulation or neurostimulation of the internal globus pallidus for a period of 3 months and thereafter all patients completed 6 months of active neurostimulation. 38 patients agreed to be followed up annually after the activation of neurostimulation, including assessments of dystonia severity, pain, disability, and quality of life. The primary endpoint of the 5-year follow-up study extension was the change in dystonia severity at 3 years and 5 years as assessed by open-label ratings of the Burke—Fahn—Marsden dystonia rating scale (BFMDRS) motor score compared with the preoperative baseline and the 6-month visit. The primary endpoint was analysed on an intention-to-treat basis. The original trial is registered with ClinicalTrials.gov (NCT00142259).

Findings

An intention-to-treat analysis including all patients from the parent trial showed significant improvements in dystonia severity at 3 years and 5 years compared with baseline, which corresponded to −20·8 points (SD 17·1; −47·9%; n=40) at 6 months; −26·5 points (19·7; −61·1%; n=31) at 3 years; and −25·1 points (21·3; −57·8%; n=32). The improvement from 6 months to 3 years (—5·7 points [SD 8·4]; −34%) was significant and sustained at the 5-year follow-up (—4·3 [10·4]). 49 new adverse events occurred between 6 months and 5 years. Dysarthria and transient worsening of dystonia were the most common non-serious adverse events. 21 adverse events were rated serious and were almost exclusively device related. One patient attempted suicide shortly after the 6-month visit during a depressive episode. All serious adverse events resolved without permanent sequelae.

Interpretation

3 years and 5 years after surgery, pallidal neurostimulation continues to be an effective and relatively safe treatment option for patients with severe idiopathic dystonia. This long-term observation provides further evidence in favour of pallidal neurostimulation as a first-line treatment for patients with medically intractable, segmental, or generalised dystonia.