Background: To compare drug regimens across clinical trials in Parkinson's disease (PD) conversion formulae between antiparkinsonian drugs have been developed. These are reported in relation to levodopa as the benchmark drug in PD pharmacotherapy as ‘levodopa equivalent dose’ (LED). Currently, the LED conversion formulae proposed in 2010 by Tomlinson et al. based on a systematic review are predominantly used. However, new drugs with established and novel mechanisms of action and novel formulations of longstanding drugs have been developed since 2010. Therefore, consensus proposals for updated LED conversion formulae are needed.Objectives: To update LED conversion formulae based on a systematic review.Methods: The MEDLINE, CENTRAL, and Embase databases were searched from January 2010 to July 2021. Additionally, in a standardized process according to the GRADE grid method, consensus proposals were issued for drugs with scarce data on levodopa dose equivalency.Results: The systematic database search yielded 3076 articles of which 682 were eligible for inclusion in the systematic review. Based on these data and the standardized consensus process, we present proposals for LED conversion formulae for a wide range of drugs that are currently available for the pharmacotherapy of PD or are expected to be introduced soon.Conclusions: The LED conversion formulae issued in this Position Paper will serve as a research tool to compare the equivalence of antiparkinsonian medication across PD study cohorts and facilitate research on the clinical efficacy of pharmacological and surgical treatments as well as other non‐pharmacological interventions in PD. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Deep brain stimulation of the subthalamic nucleus improves non-motor symptoms in Parkinson’s disease, but with considerable inter-individual variability. Petry-Schmelzer et al. show that neurostimulation in specific subregions of the subthalamic nucleus has differential effects on mood/apathy, attention/memory and sleep-related outcomes. Neurostimulation could thus be tailored to patients’ individual non-motor profiles.

Objective: Subthalamic nucleus deep brain stimulation (STN‐DBS) in Parkinson's disease (PD) not only stimulates focal target structures but also affects distributed brain networks. The impact this network modulation has on non‐motor DBS effects is not well‐characterized. By focusing on the affective domain, we systematically investigate the impact of electrode placement and associated structural connectivity on changes in depressive symptoms following STN‐DBS, which have been reported to improve, worsen, or remain unchanged.Methods: Depressive symptoms before and after STN‐DBS surgery were documented in 116 patients with PD from 3 DBS centers (Berlin, Queensland, and Cologne). Based on individual electrode reconstructions, the volumes of tissue activated (VTAs) were estimated and combined with normative connectome data to identify structural connections passing through VTAs. Berlin and Queensland cohorts formed a training and cross‐validation dataset used to identify structural connectivity explaining change in depressive symptoms. The Cologne data served as the test‐set for which depressive symptom change was predicted.Results: Structural connectivity was linked to depressive symptom change under STN‐DBS. An optimal connectivity map trained on the Berlin cohort could predict changes in depressive symptoms in Queensland patients and vice versa. Furthermore, the joint training‐set map predicted changes in depressive symptoms in the independent test‐set. Worsening of depressive symptoms was associated with left prefrontal connectivity.Interpretation: Fibers connecting the electrode with left prefrontal areas were associated with worsening of depressive symptoms. Our results suggest that for the left STN‐DBS lead, placement impacting fibers to left prefrontal areas should be avoided to maximize improvement of depressive symptoms. ANN NEUROL 2020;87:962–975

To investigate the relation between deep brain stimulation (DBS) of the posterior-subthalamic-area (PSA) and the ventral-intermediate-nucleus (VIM) and the distance to the dentatorubrothalamic tract (DRTT) in essential tremor (ET). Tremor rating scale (TRS) hemi-scores were analyzed in 13 ET patients, stimulated in both the VIM and the PSA in a randomized, crossover trial. Distances of PSA and VIM contacts to population-based DRTTs were calculated. The relationships between distance to DRTT and stimulation amplitude, as well as DBS efficiency (TRS improvement per amplitude) were investigated. PSA contacts were closer to the DRTT (p = 0.019) and led to a greater improvement in TRS hemi-scores (p = 0.005) than VIM contacts. Proximity to the DRTT was related to lower amplitudes (p < 0.001) and higher DBS efficiency (p = 0.017). Differences in tremor outcome and stimulation parameters between contacts in the PSA and the VIM can be explained by their different distance to the DRTT.