Li Xin-Yao, Yang Ying-Mai, Li Li-Bo, Zhang Meng-Yu, Huang Yang-Yu, Wang Jie, Wang Lin, Wan Xin-Hua
Department of Neurology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, China.
Front Neurol. 2021 May 12;12:644910. doi: 10.3389/fneur.2021.644910. eCollection 2021.
Dopa-responsive dystonia (DRD) is a movement disorder that is highly clinically and genetically heterogeneous. Our study summarizes clinical characteristics and long-term outcomes in patients with dopa-responsive dystonia with the aim of obtaining further knowledge on this disorder. Patients who met DRD genetic diagnostic criteria through whole-exome sequencing and took levodopa for over 3 years were included in our study. Detailed information was collected on these patients, including family history, age at onset, age and dosage at starting levodopa, current medication and dosage, levodopa duration, diurnal fluctuation, and other clinical features. The Burke-Fahn-Marsden Dystonia Rating Scale-Motor (BFMDRS-M) score was used to evaluate patients' dystonia and variation after levodopa. According to the long-term outcomes, patients were further graded as good (dystonia improved by more than 50% after levodopa, and no further motor symptoms appeared) and poor (dystonia improved by <50% after levodopa, or new motor symptoms appeared). A total of 20 DRD patients were included (11 with variants, 9 with variants). During long-term levodopa treatment, three patients with variants (3/20, 15%) developed motor symptoms, including body jerks and paroxysmal symptoms, and responded well to increasing levodopa doses. The patient with homozygous mutation c.1481C>T/p. Thr494Met harbored more serious symptoms and poor response to levodopa and showed decreased cardiac uptake in MIBG. Most DRD patients showed satisfactory treatment outcomes after long-term levodopa, whereas few patients with variants presented motor symptoms, which is considered to be related to dopamine insufficiency. For patients with motor symptoms after long-term levodopa, increasing the dose slowly might be helpful to relieve symptoms.
多巴反应性肌张力障碍（DRD）是一种运动障碍性疾病，在临床和遗传方面具有高度异质性。我们的研究总结了多巴反应性肌张力障碍患者的临床特征和长期预后，旨在进一步了解这种疾病。通过全外显子测序符合DRD基因诊断标准且服用左旋多巴超过3年的患者纳入我们的研究。收集了这些患者的详细信息，包括家族史、发病年龄、开始服用左旋多巴的年龄和剂量、当前用药及剂量、左旋多巴治疗时长、日间波动情况以及其他临床特征。采用伯克-法恩-马斯登肌张力障碍评定量表-运动部分（BFMDRS-M）评分来评估患者的肌张力障碍及左旋多巴治疗后的变化。根据长期预后情况，将患者进一步分为良好（左旋多巴治疗后肌张力障碍改善超过50%，且未出现进一步的运动症状）和不良（左旋多巴治疗后肌张力障碍改善不足50%，或出现新的运动症状）。共纳入20例DRD患者（11例携带 变异，9例携带 变异）。在长期左旋多巴治疗期间，3例携带 变异的患者（3/20，15%）出现了运动症状，包括身体抽搐和阵发性症状，增加左旋多巴剂量后反应良好。纯合突变c.1481C>T/p.Thr494Met的患者症状更严重，对左旋多巴反应不佳，且MIBG心肌摄取降低。大多数DRD患者长期使用左旋多巴后治疗效果满意，而少数携带 变异的患者出现运动症状，这被认为与多巴胺不足有关。对于长期左旋多巴治疗后出现运动症状的患者，缓慢增加剂量可能有助于缓解症状。
