The real-life effect of catechol-O-methyltransferase inhibition on non-motor symptoms in levodopa-treated Parkinson's disease: opicapone versus entacapone

Objective: To evaluate the long-term, real-life effects on non-motor symptoms (NMS) of opicapone compared to entacapone in levodopa-treated people with Parkinson's disease (PwP). Methods: A retrospective data analysis, with pre- and post-opicapone initiation data of 17 PwP with motor fluctuations compared to a comparable group of 18 PwP introduced on entacapone. The primary outcome was changes in the NMS Scale (NMSS) total score after 1-year follow-up. Secondary outcomes included changes in the NMSS domains, and Parkinson's Disease Sleep Scale (PDSS) total and item scores after the same time span. Results: Groups were comparable for baseline demographics and Parkinson's-related features (p ≥ 0.314) as well as duration of follow-up (1.33 ± 0.66 years for PwP on opicapone and 1.23 ± 0.49 years for those on entacapone; p = 0.858). PwP who were introduced on opicapone showed no changes in NMSS and PDSS total scores after 1 year (p = 0.605 and p = 0.507, respectively), whereas PwP who were introduced on entacapone showed significant worsening of NMSS and PDSS total scores at follow-up (p = 0.005 and p = 0.001, respectively). In neither group changes in individual NMSS domains from baseline to follow-up were observed (p ≥ 0.288 for entacapone and p ≥ 0.816 for opicapone, respectively). In PwP on entacapone significant worsening was seen in the distressing dreams, hallucinations, and limb numbness items of the PDSS (p ≤ 0.05). Conclusions: Introduction of opicapone in real-life PwP with motor fluctuations seems to stabilise NMS burden and aspects of sleep dysfunction, in contrast to entacapone where there was a worsening of NMS burden and PDSS scores over 1 year follow-up.The views expressed are those of the authors and not necessarily those of the NHS, NIHR or Department of Health. The authors acknowledge the support of the International Parkinson and Movement Disorder Society Non-Motor Parkinson’s disease Study Group, the NIHR London South Clinical Research Network, the NIHR Biomedical Research Centre, and the clinical research team at the Parkinson’s Foundation centre of excellence at King’s College Hospital and King’s College London. This article represents independent collaborative research part funded by the NIHR Biomedical Research Centre at South London and Maudsley NHS Foundation Trust and King’s College London.S

Exploring hyperhidrosis and related thermoregulatory symptoms as a possible clinical identifier for the dysautonomic subtype of Parkinson’s disease

ObjectiveTo identify associated (non-)motor profiles of Parkinson’s disease (PD) patients with hyperhidrosis as a dominant problem.MethodsThis is a cross-sectional, exploratory, analysis of participants enrolled in the Non-motor Longitudinal International Study (NILS; UKCRN No: 10084) at the Parkinson’s Centre at King’s College Hospital (London, UK). Hyperhidrosis scores (yes/no) on question 28 of the Non-Motor Symptom Questionnaire were used to classify patients with normal sweat function (n = 172) and excessive sweating (n = 56) (Analysis 1; n = 228). NMS scale (NMSS) question 30 scores were used to stratify participants based on hyperhidrosis severity (Analysis 2; n = 352) using an arbitrary severity grading: absent score 0 (n = 267), mild 1–4 (n = 49), moderate 5–8 (n = 17), and severe 9–12 (n = 19). NMS burden, as well as PD sleep scale (PDSS) scores were then analysed along with other correlates.ResultsNo differences were observed in baseline demographics between groups in either analysis. Patients with hyperhidrosis exhibited significantly higher total NMSS burden compared to those without (p p p ConclusionsChronic hyperhidrosis appears to be associated with a dysautonomia dominant subtype in PD patients, which is also associated with sleep disorders and a higher rate of dyskinesia (fluctuation-related hyperhidrosis). These data should prompt the concept of hyperhidrosis being used as a simple clinical screening tool to identify PD patients with autonomic symptoms.</div

Utilising accessible and reproducible neurological assessments in clinical studies: Insights from use of the Neurological Impairment Scale in the multi-centre COVID-CNS study

Reproducible and standardised neurological assessment scales are important in quantifying research outcomes. These scales are often performed by non-neurologists and/or non-clinicians and must be robust, quantifiable, reproducible and comparable to a neurologist's assessment. COVID-CNS is a multi-centre study which utilised the Neurological Impairment Scale (NIS) as a core assessment tool in studying neurological outcomes following COVID-19 infection. We investigated the strengths and weaknesses of the NIS when used by non-neurology clinicians and non-clinicians, and compared performance to a structured neurological examination performed by a neurology clinician. Through our findings, we provide practical advice on how non-clinicians can be readily trained in conducting reproducible and standardised neurological assessments in a multi-centre study, as well as illustrating potential pitfalls of these tools

Hypothalamic pathology in Huntington disease

Item does not contain fulltextHuntington's disease (HD), an autosomal dominant hereditary disorder associated with the accumulation of mutant huntingtin, is classically associated with cognitive decline and motor symptoms, notably chorea. However, growing evidence suggests that nonmotor symptoms are equally prevalent and debilitating. Some of these symptoms may be linked to hypothalamic pathology, demonstrated by findings in HD animal models and HD patients showing specific changes in hypothalamic neuropeptidergic populations and their associated functions. At least some of these alterations are likely due to local mutant huntingtin expression and toxicity, while others are likely caused by disturbed hypothalamic circuitry. Common problems include circadian rhythm disorders, including desynchronization of daily hormone excretion patterns, which could be targeted by novel therapeutic interventions, such as timed circadian interventions with light therapy or melatonin. However, translation of these findings from bench-to-bedside is hampered by differences in murine HD models and HD patients, including mutant huntingtin trinucleotide repeat length, which is highly heterogeneous across the various models. In this chapter, we summarize the current knowledge regarding hypothalamic alterations in HD patients and animal models, and the potential for these findings to be translated into clinical practice and management

Parkinson's disease and Covid-19:The effect and use of telemedicine

As a result of the Coronavirus Disease 2019 (Covid-19) pandemic the use of telemedicine and remote assessments for patients has increased exponentially, enabling healthcare professionals to reduce the need for in-person clinical visits and, consequently, reduce the exposure to the Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2). This development has been aided by increased guidance on digital health technologies and cybersecurity measures, as well as reimbursement options within healthcare systems. Having been able to continue to connect with people with Parkinson's Disease (PwP, PD) has been crucial, since many saw their symptoms worsen over the pandemic. Inspite of the success of telemedicine, sometimes even enabling delivery of treatment and research, further validation and a unified framework are necessary to measure the true benefit to both clinical outcomes and health economics. Moreover, the use of telemedicine seems to have been biased towards people from a white background, those with higher education, and reliable internet connections. As such, efforts should be pursued by being inclusive of all PwP, regardless of geographical area and ethnic background. In this chapter, we describe the effect he Covid-19 pandemic has had on the use of telemedicine for care and research in people with PD, the limiting factors for further rollout, and how telemedicine might develop further

Continuous drug delivery aiming continuous dopaminergic stimulation in Parkinson's disease

Continuous dopaminergic stimulation in Parkinson's disease (PD) has several advantages over pulsatile, noncontinuous, stimulation. These therapies currently consist of pump-based and transcutaneous therapies and are based on a more constant delivery of the dopaminergic drug resulting in continuous dopaminergic stimulation and a more stable treatment effect. Several clinical and experimental observations have shown that continuous stimulation of dopaminergic receptors induces fewer complications, such as dyskinesia, compared to pulsatile stimulation. Currently available nonoral pharmacological continuous therapies in PD include the transdermal Rotigotine (RTG) patch, infusion therapies with Apomorphine and Intrajejunal Levodopa (IJLI) and the Rivastigmine patch. Here we aim to provide a concise review of these current therapies and discuss ongoing and future developments of continuous non-oral pharmacological dopaminergic therapies in PD

Advances in the Pharmacological and Non-pharmacological Management of Non-motor Symptoms in Parkinson's Disease:An Update Since 2017

BACKGROUND: Non-motor symptoms (NMS) are an important and ubiquitous determinant of quality of life in Parkinson's disease (PD). However, robust evidence for their treatment is still a major unmet need.OBJECTIVE: This study aimed to provide an updated review on advances in pharmacological, nonpharmacological, and exercise-based interventions for NMS in PD, covering the period since the publication of the MDS Task Force Recommendations.METHODS: We performed a literature search to identify pharmacological, non-pharmacological, and exercise-based interventions for NMS in PD. As there are recent reviews on the subject, we have only included studies from the 1st of January 2017 to the 1st of December 2021 and limited our search to randomised and non-randomised (including open-label) clinical trials.RESULTS: We discuss new strategies to manage NMS based on data that have become available since 2017, for instance, on the treatment of orthostatic hypotension with droxidopa, several dopaminergic treatment options for insomnia, and a range of non-pharmacological and exercise-based interventions for cognitive and neuropsychiatric symptoms, pain, and insomnia and excessive sleepiness.CONCLUSION: Recent evidence suggests that targeted non-pharmacological treatments, as well as some other NMS management options, may have a significant beneficial effect on the quality of life and need to be considered in the pathways of treatment of PD.</p

Blue Light Therapy Glasses in Parkinson's Disease:Patients' Experience

Contains fulltext : 208972.pdf (publisher's version ) (Open Access)Background: Blue light glasses have been introduced as a possible new treatment option to treat sleep disturbances in patients with Parkinson disease (PD). Assessing patient attitudes represents a key step in the road towards formal testing and introduction into clinical practice. Specifically, we aimed to assess how patients experience the use of blue light glasses, aiming to optimise compliance in upcoming clinical trials where these glasses will be tested for efficacy. Methods: We invited 58 PD patients who had used the blue light glasses for at least one week on a daily basis to complete an online survey about their experiences and self-reported impact. For this purpose, the System Usability Scale was used, supplemented with additional questions about (side)effects. A total of 31 patients (53%) replied. Results: 74% of respondents reported subjective improvements in night-time sleep, daytime sleepiness, depressive symptoms, motor functioning, or a combination thereof. The median score for the System Usability Scale (SUS; 0-100 range, higher scores indicating better performance) was 70.0. A total of 26 patients (84%) had an overall positive attitude towards the technique, with patients rating the glasses with an average score of 6.9 +/- 2.0 (SD) out of 10. Except for one patient, all responders would like to continue using the glasses, mostly because they considered it a useful aid. Conclusion: Blue light therapy appears to have a positive effect on sleep, mood, and motor symptoms in PD. PD patients had an overall positive attitude towards blue light glasses as treatment for sleep disorders