9 research outputs found

    Exploring the levodopa-paradox of freezing of gait in dopaminergic medication-naïve Parkinson’s disease populations

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    Abstract The relationship between dopaminergic treatment and freezing of gait (FOG) in Parkinson’s disease (PD) is complex: levodopa is the most effective symptomatic treatment for FOG, but long-term pulsatile levodopa treatment has also been linked to an increase in the occurrence of FOG. This concept, however, continues to be debated. Here, we compared the occurrence of FOG between a levodopa-naive PD cohort and a levodopa-treated cohort. Forty-nine treatment-naive patients and 150 levodopa-treated patients were included. The time since first motor symptoms was at least 5 years. Disease severity was assessed using the MDS-UPDRS part III. Occurrence of FOG was assessed subjectively (new freezing-of-gait-questionnaire) and objectively (rapid turns test and Timed Up-and-Go test). The presence of FOG was compared between the levodopa-treated and levodopa-naive groups using a chi-square test of homogeneity. We also performed a binomial Firth logistic regression with disease duration, disease severity, country of inclusion, location of measurement, and executive function as covariates. Subjective FOG was more common in the levodopa-treated cohort (n = 41, 27%) compared to the levodopa-naive cohort (n = 2, 4%, p < 0.001). The association between FOG and levodopa treatment remained after adjustment for covariates (OR = 6.04, 95%Cl [1.60, 33.44], p = 0.006). Objectively verified FOG was more common in the levodopa-treated cohort (n = 21, 14%) compared to the levodopa-naive cohort (n = 1, 2%, p = 0.02). We found an association between long-term pulsatile levodopa treatment and an increased occurrence of FOG. Future studies should further explore the role of nonphysiological stimulation of dopamine receptors in generating FOG, as a basis for possible prevention studies

    A Pragmatic Review on Spinal Cord Stimulation Therapy for Parkinson\u27s Disease Gait Related Disorders: Gaps and Controversies

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    \ua9 2024 International Parkinson and Movement Disorder Society.Background: Parkinson\u27s Disease (PD) is a progressive neurological disorder that results in potentially debilitating mobility deficits. Recently, spinal cord stimulation (SCS) has been proposed as a novel therapy for PD gait disorders. The highest levels of evidence remain limited for SCS. Objectives: In this systematic review and narrative synthesis, the literature was searched using combinations of key phrases indicating spinal cord stimulation and PD. Methods: We included pre-clinical studies and all published clinical trials, case reports, conference abstracts as well as protocols for ongoing clinical trials. Additionally, we included trials of SCS applied to atypical parkinsonism. Results: A total of 45 human studies and trials met the inclusion criteria. Based on the narrative synthesis, a number of knowledge gaps and future avenues of potential research were identified. This review demonstrated that evidence for SCS is currently not sufficient to recommend it as an evidence-based therapy for PD related gait disorders. There remain challenges and significant barriers to widespread implementation, including issues regarding patient selection, effective outcome selection, stimulation location and mode, and in programming parameter optimization. Results of early randomized controlled trials are currently pending. SCS is prone to placebo, lessebo and nocebo as well as blinding effects which may impact interpretation of outcomes, particularly when studies are underpowered. Conclusion: Therapies such as SCS may build on current evidence and be shown to improve specific gait features in PD. Early negative trials should be interpreted with caution, as more evidence will be required to develop effective methodologies in order to drive clinical outcomes
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