Samotus Olivia, Lee Jack, Jog Mandar
Department of Clinical Neurological Sciences, London Health Sciences Centre - Lawson Health Research Institute, London, ON, Canada.
Department of Clinical Neurological Sciences, London Health Sciences Centre - Lawson Health Research Institute, 339 Windermere Road, A10-026, London, ON N6A 5A5, Canada.
Ther Adv Neurol Disord. 2020 Sep 23;13:1756286420954083. doi: 10.1177/1756286420954083. eCollection 2020.
Inadequate efficacy and significant side effect profile makes pharmacological treatment of Parkinson's disease (PD) tremor challenging. Personalized dosing of botulinum toxin type A (BoNT-A) using tremor analysis has shown efficacy and safety for treating upper limb tremor. This study incorporated a novel, standardized treatment algorithm for determining injection pattern and BoNT-A dosing, customizable by the physician, in PD patients with disabling tremor in one or both arms.
This open-label study included 47 PD participants (25 "De-novo" and 22 "L-dopa") who received 4 serial BoNT-A treatments with follow-ups at 6 weeks post-treatment over 42 weeks. The treatment algorithm utilized kinematic tremor analysis of each participant's whole arm tremor and determined the physician's injection pattern of BoNT-A. Endpoints included changes in angular tremor amplitude, Fahn-Tolosa-Marin (FTM C) tremor scale, Movement Disorder Society-Unified Parkinson's disease rating scale (MDS-UPDRS) tremor-related score, tremor-related quality of life questionnaire, Likert ratings of perceived weakness, and maximal grip strength.
BoNT-A significantly ( < 0.05) improved tremor amplitude (41.6%), quality of life (23.0%), UPDRS tremor score (29.6%), and arm function (FTM C; 24.6%) for both treatment cohorts from weeks 6 to 42. Maximum grip strength was reduced between 7.4% and 23.0% at follow-up visits and did not impact activities of daily living. Efficacy was obtained with first injection and remained without adjustment over two serial injection in 45% of participants.
This is the first study to use a fully standardized treatment algorithm for personalization of BoNT-A injection patterns for disabling PD tremor over serial treatments. A sustained alleviation of tremor severity and improved arm function and quality of life fulfills an important unmet need for the treatment of PD tremor. This study demonstrated that BoNT-A can be administered as a monotherapy in tremor-dominant PD or as an add-on therapy for refractory PD tremor.
帕金森病（PD）震颤的药物治疗面临疗效不足和显著副作用的挑战。使用震颤分析对A型肉毒毒素（BoNT-A）进行个体化给药已显示出治疗上肢震颤的有效性和安全性。本研究纳入了一种新颖的标准化治疗算法，用于确定注射模式和BoNT-A剂量，医生可根据需要进行定制，用于治疗一臂或双臂有致残性震颤的PD患者。
这项开放标签研究纳入了47名PD参与者（25名“初治”和22名“左旋多巴治疗”），他们接受了4次连续的BoNT-A治疗，并在42周内于治疗后6周进行随访。该治疗算法利用对每个参与者全臂震颤的运动学震颤分析，并确定医生的BoNT-A注射模式。终点指标包括角震颤幅度的变化、法恩-托洛萨-马林（FTM C）震颤量表、运动障碍协会统一帕金森病评定量表（MDS-UPDRS）震颤相关评分、震颤相关生活质量问卷、感知无力的李克特评分以及最大握力。
从第6周到第42周，BoNT-A显著（<0.05）改善了两个治疗队列的震颤幅度（41.6%）、生活质量（23.0%）、UPDRS震颤评分（29.6%）和手臂功能（FTM C；24.6%）。随访时最大握力降低了7.4%至23.0%，但不影响日常生活活动。45%的参与者在首次注射时即获得疗效，且在两次连续注射中无需调整。
这是第一项使用完全标准化治疗算法对连续治疗中致残性PD震颤的BoNT-A注射模式进行个体化的研究。震颤严重程度的持续缓解以及手臂功能和生活质量的改善满足了治疗PD震颤的一项重要未满足需求。本研究表明，BoNT-A可作为震颤为主型PD的单一疗法或难治性PD震颤的附加疗法给药。
