Dag Nyholm

Background: Deep brain stimulation (DBS) for essential tremor (ET) is commonly evaluated using tremor scales, which capture only snapshot of symptoms and miss daily variability. Wearable sensors enable objective monitoring and may offer complementary information to support clinical decisions. Objectives: To investigate whether continuous wearable monitoring provides additional information to traditional analysis in ET. Methods: Forty‐five patients with ET undergoing DBS were assessed preoperatively and 9–12 months postoperatively using TETRAS scale, the EQ‐5D‐3L, and the Personal KinetiGraph (PKG) which quantified percentage time with tremor (PTT). Pre‐ and postoperative measures were compared and correlated. Results: DBS significantly improved outcomes: median TETRAS scores decreased by 55% and PKG PTT by 59%. Individual responses varied, and TETRAS and PTT showed week correlation, indicating that instruments capture different aspects of the disorder. Conclusions: Combining clinical scales with wearable monitoring complements traditional assessments by capturing daily tremor fluctuations and supporting optimized DBS management.

Enhancing levodopa efficacy through peripheral COMT inhibition and using continuous infusion are both established strategies for managing motor fluctuations. Both approaches aim to improve the pharmacokinetics of levodopa in order to maintain a steady delivery of levodopa to the brain, avoid the deep troughs in levodopa plasma concentrations associated with oral levodopa delivery, and thereby reduce OFF time. In this review, we describe the pharmacologic rationale for combining COMT inhibition with entacapone and continuous dopaminergic delivery that led to the development of levodopa/entacapone/carbidopa intestinal gel (LECIG). Entacapone is a peripheral COMT inhibitor, that effectively reduces the metabolism of levodopa to 3-O-methyldopa and increases the amount of levodopa that can be transported into the brain. However, entacapone has a short half-life and poor oral bioavailability that necessitates frequent dosing for optimal efficacy. Continuous infusion of entacapone allows for improved bioavailability from direct delivery to the duodenum/jejunum. As such, lower overall levodopa doses can be given to achieve therapeutically effective concentrations. Accumulating real-world evidence with LECIG supports its use in managing motor fluctuations in patients whose control is becoming suboptimal with oral approaches. We provide an overview of the growing evidence base for its risk-benefit profile in patients with motor fluctuations.

Introduction The Swedish Parkinson’s Disease (PD) Registry provides rich data on cost and quality of life for patients receiving device-aided therapies (DATs) for Parkinson’s disease in Sweden. This study sought to use this real-world evidence to determine the cost-effectiveness profile of specific DATs in Sweden. Methods We developed a state transition (Markov) model to represent disease progression over time and used published clinical data to represent short- and long-term disease outcomes. We used data from the Swedish PD Registry to assign costs and quality of life measures (utilities) to each health state and modelled total costs and outcomes over a 20-year time horizon. The four treatment groups modelled were: best medical therapy, deep brain stimulation, levodopa-carbidopa intestinal gel, and continuous subcutaneous apomorphine infusion. We calculated results from both payer and societal perspectives. Results The most cost-effective intervention was deep brain stimulation (DBS), which dominated all other interventions. Sensitivity analysis indicated that the key drivers of uncertainty were the transition probabilities between successive Hoehn and Yahr stages on each treatment. Results were consistent from both payer and societal perspectives. Conclusion DBS is a cost-effective use of resources in Sweden. However, uncertainty remains regarding long-term symptom control as well as quality of life within specific health states for all device-aided therapies, and further data are needed to fully validate the model projections and provide more insight into areas of future research.

Background: Levodopa‐induced dyskinesia (LID) in Parkinson's disease (PD) is associated with ‘false neurotransmitter’ release of dopamine from serotonin (5‐HT) neurons. NLX‐112 is a first‐in‐class, highly selective 5‐HT_1A receptor agonist which counteracts LIDs in experimental PD models.Objectives: The primary objective was to evaluate the safety and tolerability of NLX‐112 compared with placebo in people with PD. The secondary objective was to assess the preliminary efficacy of NLX‐112 in reducing LID and its effects on PD symptoms.Methods: Participants received NLX‐112 or placebo (2:1 ratio) alongside stable Parkinson's medications, with 22 participants completing the study. Dosing was up‐titrated over 28 days to 2 mg/day (1 mg twice daily), stabilized for 14 days (to day 42), and down‐titrated for 14 days. Efficacy was measured using the Unified Dyskinesia Rating Scale (UDysRS), Unified Parkinson's Disease Rating Scale (UPDRS), and Clinical Global Impression of Change (CGI‐C) following a levodopa challenge (150% of usual dose).Results: Adverse events (AEs) were mainly central nervous system (CNS)‐related and mostly occurred during up‐titration, with no serious AEs in the NLX‐112 group. There were no treatment‐induced clinically significant changes in vital signs, electrocardiogram, or laboratory parameters. NLX‐112 reduced LID from baseline levels: at day 42, UDysRS total score decreased by 6.3 points, whereas placebo group changes were not significant (−2.4). NLX‐112 also reduced parkinsonism from baseline values: UPDRS Part 3 scores decreased by 3.7 points, whereas placebo group changes were non‐significant (+0.1). In CGI‐C assessment, the NLX‐112 group showed greater improvement than the placebo group (53% vs. 29%).Conclusion: These results support further clinical investigation of NLX‐112 for treatment of PD LID. © 2025 Neurolixis SAS. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Background: Levodopa–entacapone–carbidopa intestinal gel (LECIG) was introduced on the Swedish market in 2019. The therapy is aimed at patients with Parkinson's disease (PD) with fluctuations and dyskinesias. Long‐term efficacy and safety data are lacking.Objective: To investigate the efficacy, tolerability, and safety of LECIG in regular clinical practice for Parkinson's disease in Sweden.Methods: Real‐world data were collected from the Swedish registry for Parkinson's disease (ParkReg) for all patients reported to receive LECIG during the period from 2019 until 31 August 2022.Results: A total of 150 patients were identified. Sixty‐one (41%) of 150 patients were females. At the start of treatment, the median age was 73 years (range: 43–86). The median duration since motor symptoms onset was 17 years (IQR: 9). Fifty (33%) of 150 patients switched from another device‐assisted therapy, mostly LCIG (39 patients).Reported complications were mainly related to PEG‐J tube and stoma (30%). Twenty (13.3%) of 150 patients discontinued LECIG and 11 (7.3%) patients died while on LECIG.The Parkinson KinetiGraph scores for bradykinesia, dyskinesia, fluctuations, tremor, and immobility for 53 patients during LECIG showed good therapy control. The median (IQR) p‐Hcy during LECIG was 12 (4.6) μmol/L (n = 44). The median (IQR) PDQ‐8 summary index during LECIG was 31 (17) (n = 52). The median (IQR) EQ5D during LECIG was 0.62 (0.32) (n = 41).Conclusions: Data from ParkReg covering 150 patients over 3 years show LECIG to be an effective and safe device‐aided therapy for advanced PD. However, the long‐term efficacy and tolerability of LECIG need to be further investigated.

Background: Levodopa‐entacapone‐carbidopa intestinal gel (LECIG) infusion was introduced to the Swedish market in 2019 for Parkinson's disease (PD) with motor fluctuations. Long‐term data are lacking.Objectives: To study long‐term data on LECIG treatment.Methods: A retrospective analysis of the first 24 patients receiving LECIG in Sweden from 2019 to 2023.Results: Five of 24 (21%) patients discontinued LECIG because of side effects, mostly diarrhea. Eight of the 24 (33%) patients died while receiving LECIG. Eleven of 24 (46%) patients were still on LECIG. Median (range) for disease and treatment duration was 19 (9–30) and 3.6 (3.1–4.0) years, respectively, whereas health‐related quality of life scales showed median (interquartile range; n) Parkinson's Disease Questionnaire 8‐item summary index scores of 38 (4; n = 7), EuroQol 5D scores of 0.59 (0.17; n = 7), and EQ‐5D visual analogue scale scores of 65 (10; n = 7).Conclusions: LECIG infusion is a viable treatment option for PD patients with motor fluctuations, for up to 4 years in our cohort.

Background: It has been suggested that carbidopa at high blood concentrations may counter the therapeutic effect of levodopa in Parkinson's disease by entering the brain and blocking central levodopa conversion to dopamine. We previously demonstrated equivalent plasma levodopa concentration in patients with Parkinson's disease during 16 h of (1) intravenous carbidopa/levodopa (DIZ101) infusion, (2) subcutaneous carbidopa/levodopa (DIZ102) infusion or (3) intestinal carbidopa/levodopa gel infusion. Plasma levels of carbidopa were however approximately four times higher with DIZ101 and DIZ102 than with LCIG, and higher than those usually observed with oral levodopa/carbidopa.Objectives: To investigate if high carbidopa blood concentrations obtained with parenteral levodopa/carbidopa (ratio 8:1) counter the effect of levodopa on motor symptoms.Methods: Eighteen patients with advanced Parkinson's disease were administered DIZ101, DIZ102, and intestinal levodopa/carbidopa gel for 16 h on different days in randomized order. Video recordings of a subset of the motor examination in the Unified Parkinson's Disease Rating Scale (UPDRS) were evaluated by raters blinded for treatment and time. Motor function was also measured using a wrist‐worn device monitoring bradykinesia, dyskinesia, and tremor (Parkinson KinetiGraph).Results: There was no tendency for poorer levodopa effect with DIZ101 or DIZ102 as compared to LCIG.Conclusion: Although DIZ101 or DIZ102 causes approximately four times higher plasma carbidopa levels than LCIG, patients responded equally well to all treatments. The results do not indicate that high plasma carbidopa levels hamper the motor efficacy of levodopa.

Improvement of activity and participation for the disabled and chronically ill is an important aim of rehabilitation. Cervical dystonia is a neurological movement disorder characterized by involuntary contractions of the neck muscles. Until now, research has identified factors contributing to disability rather than factors which may make it easier to be active and participate in the community. Explore and describe perceived experiences of activity and participation in daily life as experienced by persons with cervical dystonia. Sixteen informants participated in this semi-structured interview study. Inductive qualitative content analysis was performed to understand and interpret experiences shared by the informants. Results from the analysis generated two themes "An active life" and "A challenging life" and six sub-themes: Using helpful coping strategies, Accepting a new life situation, Adhering to BT treatment, Facing the negative impact of stress, Experiencing a negative self-image and Suffering from pain and fatigue. Our results support the importance of actions using a rehabilitation approach that consider both motor and non-motor symptoms. Future studies should compare the effects of physiotherapy taking into account wishes and challenges in patients' everyday life versus traditional physiotherapy addressing mostly the motor disorder.