Synergistic clinical outcome assessments for cervical dystonia

肌张力障碍总体上是一种罕见的神经系统疾病。颈部肌张力障碍（CD），有时称为 “痉挛性斜颈”是肌张力障碍的最常见形式之一。CD的特点是部分 颈部肌肉组织失去自主控制，产生异常姿势和/或运动， 头部以头部震颤的形式出现。除了这些明显的运动异常，这种障碍也是 与非运动症状相关，包括疼痛、疲劳、焦虑和抑郁。治疗 CD的选择是次优的。许多口服药物已经尝试过，但它们的疗效是最小的， 受到剂量依赖性不良副作用的限制。肉毒杆菌神经毒素（BoNT）注射重复每 3-4月是首选的治疗方法。虽然BoNT对许多患者非常有效， 由于各种原因，约1/3的患者停止BoNT治疗， 约1/3的患者对治疗效果不满意。 由于治疗选择是次优的，因此积极努力寻找更好的策略， 治疗CD，正如ClinicalTrials.gov上列出的数十项积极试验所证明的那样。 用于测量运动异常的常见临床结局评估-多伦多西部 痉挛性斜颈评定量表（TWSTRS）-不包括头部震颤。此外，与大多数 临床评定量表，TWSTRS本质上是一种主观评估，因此存在以下问题： 评分者间变异性。这降低了我们在临床试验中检测治疗效果的能力。 以技术为基础的客观措施有可能规避这种可变性。 计算机视觉技术的进步使得能够测量头部取向/旋转 从传统视频记录中的二维面部图像。我们的长期目标之一 该小组将利用这些进展开发软件，可以捕捉和量化电机 多种类型的局灶性肌张力障碍的异常。我们称这个系统为计算 运动客观评分器（CMOR）。在这个专门针对CD的项目中，我们的目标是1）评估 CMOR对异常头位和头震颤严重程度的聚合效度 和2）确定CMOR对与干预相关的严重程度变化的敏感性。到 为了实现这些目标，我们将从视频记录中对运动症状进行CMOR分析， 100例CD患者入组单独的肌张力障碍联盟项目，以评价疗效的变异性 的BONT。该项目还将以患者为中心的结果的形式获取患者报告， 关于CD的两个运动特征和患者对变化的总体印象的具体问题 （PGIC）对每种BoNT治疗的响应。总的来说，这些结果将提供重要的信息 关于CMOR的有效性和定量基础的样本量估计，为未来的临床试验在CD。

The dystonias overall are a rare neurologic disorder. Cervical dystonia (CD), sometimes called “spasmodic torticollis”, is one of the most common forms of dystonia. CD is characterized by the partial loss of voluntary control of the neck musculature producing abnormal postures and/or movements of the head in the form of head tremor. In addition to these overt motor abnormalities, the disorder is also associated with non-motor symptoms including pain, fatigue, anxiety, and depression. Treatment options for CD are suboptimal. Many oral medications have been tried but their efficacy is minimal and limited by dose-dependent adverse side effects. Botulinum neurotoxin (BoNT) injections repeated every 3-4 months are the primary treatment of choice. Although BoNT is highly efficacious for many patients, for a variety of reasons about 1/3 of patients discontinue BoNT treatment, and of those who continue treatment about 1/3 are unsatisfied with the response. Because treatment options are suboptimal, there is an active effort to find better strategies for treating CD, as evidenced by dozens of active trials listed on ClinicalTrials.gov. However, the most common clinical outcome assessment used to measure motor abnormalities – the Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) – does not capture head tremor. Also, as with most clinical rating scales, the TWSTRS is an intrinsically subjective assessment and therefore suffers from inter-rater variability. This reduces our power to detect treatment effects in clinical trials. Technology-based objective measures have the potential to circumvent this variability. Advances in computer vision technology have enabled the measurement of head orientation/rotation from 2-D images of the face in conventional video recordings. One of the long-term objectives of our group is to leverage these advances to develop software that can capture and quantify motor abnormalities across multiple types of focal dystonia. We are calling this system the Computational Motor Objective Rater (CMOR). In this project specifically targeting CD, our aims are 1) to evaluate CMOR’s convergent validity with patient reports of severity of abnormal head posture and head tremor and 2) to determine CMOR’s sensitivity to changes in severity associated with interventions. To accomplish these aims, we will conduct CMOR analyses of motor symptoms from video recordings of 100 CD patients enrolled in a separate Dystonia Coalition project to evaluate the variability of efficacy of BoNT. That project will also acquire patient reports in the form of a patient centered outcome with specific questions about the two motor features of CD and the patient’s global impression of change (PGIC) in response to each BoNT treatment. Collectively the results will provide important information about CMOR’s validity and a quantitative basis for sample size estimates for future clinical trials in CD.