Levodopa / Opicapone As a Complement to STN-DBS in Clinical Practice. A Retrospective Single-centre Analysis

Overview

Journal eNeurologicalSci

Specialty Neurology

Date 2024 Oct 21

PMID 39429501

Authors

Moritz A Loeffler

Philipp Klocke

Idil Cebi

Alireza Gharabaghi

Daniel Weiss

Affiliations

Soon will be listed here.

Abstract

Objective: 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.

Methods: 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).

Results: 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.

Conclusion: 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.

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