Loeffler Moritz A, Klocke Philipp, Cebi Idil, Gharabaghi Alireza, Weiss Daniel
Centre for Neurology, Department of Neurodegenerative Diseases, University of Tübingen, Hoppe-Seyler-Str. 3, 72076 Tübingen, Germany.
Hertie-Institute for Clinical Brain Research, University of Tübingen, Otfried-Müller-Straße 27, 72076 Tübingen, Germany.
eNeurologicalSci. 2024 Sep 28;37:100530. doi: 10.1016/j.ensci.2024.100530. eCollection 2024 Dec.
Deep brain stimulation of the subthalamic nucleus (STN-DBS) is a well-established treatment option in Parkinson's disease with motor and non-motor fluctuations allowing for postoperative reduction of dopaminergic medication. However, evidence is scarce on optimal medication adjustments following STN-DBS implantation. Opicapone allows for long-lasting inhibition of the catechol--methyltransferase (COMT) thereby enabling more constant dopaminergic stimulation compared to levodopa alone. However, especially COMT inhibitors are regularly discontinued after STN-DBS surgery. In this single-centre retrospective analysis, we aimed to analyse the clinical phenotype of patients selected for opicapone treatment following STN-DBS implantation and to define clinical determinants of patients requiring more intense dopamine-stabilising strategies after STN-DBS implantation.
A patient cohort treated with STN-DBS + levodopa + opicapone ( = 16) was compared to an age-matched control cohort without opicapone treatment at baseline before and ≥ 5 months post-surgery. As main outcomes we assessed the MDS-UPDRS III and IV scores and reduction of the cumulative dopaminergic medication quantified by the levodopa equivalent dosages (LED).
Whilst the MDS-UPDRS III (median [min - max]) in patients with STN-DBS as well as anatomical electrode positions did not differ significantly between the opicapone 20 [4-40] and control cohort 14 [1-44], the patients selected for opicapone treatment showed a significantly higher degree of dyskinesias already preoperatively as reflected by a UPDRS-IV A subscore of 2 [0-4] compared to controls 0 [0-4]. Postoperatively, the opicapone cohort showed stronger motor fluctuations MDS-UPDRS IV 6 [0-14] compared to the controls 0 [0-10], albeit without statistical significance. Moreover, the opicapone cohort showed significantly less reduction of dopaminergic medication (-36.4 % vs. -46.2 % in the control cohort) following STN-DBS implantation independent from the intake of dopamine agonists.
These results indicate a clinical phenotype characterised by more motor fluctuations requiring a more stable dopamine replacement therapy to address the patients' disease biology. In these cases, levodopa + COMT inhibition by opicapone represents a therapeutic approach but determination of the potential clinical benefit requires further prospective studies.
丘脑底核深部脑刺激术（STN-DBS）是帕金森病运动和非运动波动的一种成熟治疗选择，可在术后减少多巴胺能药物的使用。然而，关于STN-DBS植入术后最佳药物调整的证据很少。奥匹卡朋可长期抑制儿茶酚-O-甲基转移酶（COMT），从而与单独使用左旋多巴相比能实现更持续的多巴胺能刺激。然而，尤其是COMT抑制剂在STN-DBS手术后经常停用。在这项单中心回顾性分析中，我们旨在分析STN-DBS植入术后选择接受奥匹卡朋治疗的患者的临床表型，并确定STN-DBS植入术后需要更强化多巴胺稳定策略的患者的临床决定因素。
将一组接受STN-DBS + 左旋多巴 + 奥匹卡朋治疗的患者（n = 16）与一个年龄匹配的对照组进行比较，对照组在术前基线以及术后≥5个月时未接受奥匹卡朋治疗。作为主要结局，我们评估了MDS-UPDRS III和IV评分以及通过左旋多巴等效剂量（LED）量化的累积多巴胺能药物的减少情况。
虽然接受STN-DBS治疗以及解剖电极位置的患者中，奥匹卡朋组的MDS-UPDRS III（中位数[最小值 - 最大值]）为20 [4 - 40]，对照组为14 [1 - 44]，差异无统计学意义，但选择接受奥匹卡朋治疗的患者术前异动症程度明显更高，这体现在UPDRS-IV A子评分为2 [0 - 4]，而对照组为0 [0 - 4]。术后，奥匹卡朋组的运动波动比对照组更明显，MDS-UPDRS IV为6 [0 - 14]，而对照组为0 [0 - 10]，尽管无统计学意义。此外，奥匹卡朋组在STN-DBS植入术后多巴胺能药物的减少明显较少（-36.4% vs. 对照组的-46.2%），与多巴胺激动剂的摄入无关。
这些结果表明一种临床表型，其特征为运动波动更多，需要更稳定的多巴胺替代疗法来应对患者的疾病生物学特性。在这些情况下，左旋多巴 + 奥匹卡朋抑制COMT代表一种治疗方法，但确定其潜在临床益处需要进一步的前瞻性研究。
