Medical management after subthalamic stimulation in Parkinson’s disease: a phenotype perspective

Abstract Subthalamic nucleus deep brain stimulation (STN DBS) is an established treatment that improves motor fluctuations, dyskinesia, and tremor in Parkinson’s disease (PD). After the surgery, a careful electrode programming strategy and medical management are crucial, because an imbalance between them can compromise the quality of life over time. Clinical management is not straightforward and depends on several perioperative motor and non-motor symptoms. In this study, we review the literature data on acute medical management after STN DBS in PD and propose a clinical algorithm on medical management focused on the patient’s phenotypic profile at the perioperative period. Overall, across the trials, the levodopa equivalent daily dose is reduced by 30 to 50% one year after surgery. In patients taking high doses of dopaminergic drugs or with high risk of impulse control disorders, an initial reduction in dopamine agonists after STN DBS is recommended to avoid the hyperdopaminergic syndrome, particularly hypomania. On the other hand, a rapid reduction of dopaminergic agonists of more than 70% during the first months can lead to dopaminergic agonist withdrawal syndrome, characterized by apathy, pain, and autonomic features. In a subset of patients with severe dyskinesia before surgery, an initial reduction in levodopa seems to be a more reasonable approach. Finally, when the patient’s phenotype before the surgery is the severe parkinsonism (wearing-off) with or without tremor, reduction of the medication after surgery can be more conservative. Individualized medical management following DBS contributes to the ultimate therapy success.

摘要 丘脑底核脑深部电刺激术（Subthalamic nucleus deep brain stimulation, STN DBS）是经证实的成熟治疗手段，可改善帕金森病（Parkinson’s disease, PD）患者的运动波动、异动症与震颤症状。术后，规范的电极程控策略与药物管理至关重要，二者失衡可随时间推移损害患者生活质量。临床管理并非易事，需结合多项围手术期运动与非运动症状综合判定。本研究综述了帕金森病患者丘脑底核脑深部电刺激术后急性期药物管理的相关文献数据，并针对围手术期患者的表型特征，提出了药物管理的临床决策算法。总体而言，现有临床试验结果显示，术后1年患者的左旋多巴等效日剂量（levodopa equivalent daily dose）可降低30%至50%。对于服用高剂量多巴胺能药物或存在较高冲动控制障碍（impulse control disorders）风险的患者，术后初始减量多巴胺能受体激动剂，可避免诱发高多巴胺能综合征（hyperdopaminergic syndrome），尤其是轻躁狂（hypomania）。反之，若在术后最初数月内将多巴胺能受体激动剂快速减量超过70%，则可能引发多巴胺能受体激动剂停药综合征（dopaminergic agonist withdrawal syndrome），临床表现为淡漠、疼痛及自主神经功能异常。对于术前存在严重异动症的部分患者，初始减少左旋多巴用量似乎更为合理。最后，若患者术前表型为伴或不伴震颤的严重帕金森病运动波动（wearing-off），术后药物减量可更为保守。脑深部电刺激术后的个体化药物管理，是保障治疗最终成功的核心要素。