A general clinical overview of the non-motor symptoms in Parkinson's disease: Neuropsychiatric symptoms.

The heterogeneity of non-motor features observed in people with Parkinson's disease (PD) is often dominated by one or more symptoms belonging to the neuropsychiatric spectrum, such as cognitive impairment, psychosis, depression, anxiety, and apathy. Due to their high prevalence in people with PD (PwP) and their occurrence in every stage of the disease, from the prodromal to the advanced stage, it is not surprising that PD can be conceptualised as a complex neuropsychiatric disorder. Despite progress in understanding the pathophysiological mechanisms underlying the neuropsychiatric signs and symptoms in PD, and better identification and diagnosis of these symptoms, effective treatments are still a major unmet need. The impact of these symptoms on the quality of life of PwP and caregivers, as well as their contribution to the overall non-motor symptom burden can be greater than that of motor symptoms and require a personalised, holistic approach. In this chapter, we provide a general clinical overview of the major neuropsychiatric symptoms of PD.

The PD-Ballet study: study protocol for a randomised controlled single-blind hybrid type 2 clinical trial evaluating the effects of ballet dancing on motor and non-motor symptoms in Parkinson's disease.

BACKGROUND: To date, beneficial effects of multimodal exercise programmes on Parkinson's disease (PD) have focused on motor symptoms and little attention has been paid to the potential effects of such programmes on the non-motor symptoms of PD, which are now universally known as one of the key drivers of quality of life and a key unmet need. We aim to explore clinical effectiveness of a ballet-based dance programme in addressing non-motor and motor symptoms of Parkinson's disease across all stages of progression. METHODS: A randomised, single-blind, controlled trial of 160 people with Parkinson's across all motor stages (Participants will be stratified into three groups of motor advancement: Hoehn and Yahr (HY) stages I and II being Mild Group, HY Stage III being Moderate Group and HY Stages IV and V being Severe Group) will be randomly allocated to either an intervention or a control group using an independent randomisation body. The primary outcome is an improvement in non-motor symptoms as measured by the Movement Disorders Society Non-Motor Scale (MDS-NMS). The intervention protocol consists of 12 one-weekly dance sessions led by English National Ballet. Each session is followed by a 'tea and biscuit' social time. Control group follows standard clinical pathway and joins the 'tea and biscuit' to control for any positive effects of social interactions. All participants are assessed at baseline, immediately after completion of the intervention and 3-6 months later to explore any potential longitudinal effects. DISCUSSION: To our knowledge, no adequately powered study has explored the effects of a dance-based intervention on non-motor symptoms of Parkinson's disease, assessing these on both holistic and granular levels. We also aim to stratify participants in accordance with their motor state as assessed by. HY staging to explore specific effects on the symptoms at the initial, moderate and complex stages of the disease. If successful, this trial provides first evidence on clinical effectiveness of a ballet-based dance intervention for symptoms of Parkinson's disease, assessed in a robust, rigorous manner. TRIAL REGISTRATION: NCT04719468.

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.

Covid-19 and Parkinson's disease: Nursing care, vaccination and impact on advanced therapies.

The Coronavirus Disease 2019 (Covid-19) pandemic has created many challenges for the Parkinson's Disease (PD) care service delivery, which has been established over the past decades. The need for rapid adjustments to the new conditions has highlighted the role of technology, which can act as an enabler both in patient-facing aspects of care, such as clinical consultations, as well as in professional development and training. The Parkinson's Disease Nurse Specialists (PNSs) play a vital role in the effective management of people with PD (PwP). Maintaining optimum functionality and availability of device aided therapies is essential in order to ensure patients' quality of life. PwP are particularly recommended to use vaccination as a basic protection from the virus. The long-term consequences of this pandemic on PwP are highly uncertain, and education, support and reassurance of patients and their families may help ease their burden.

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.

Protocol for Rhapsody: a longitudinal observational study examining the feasibility of speech phenotyping for remote assessment of neurodegenerative and psychiatric disorders.

INTRODUCTION: Neurodegenerative and psychiatric disorders (NPDs) confer a huge health burden, which is set to increase as populations age. New, remotely delivered diagnostic assessments that can detect early stage NPDs by profiling speech could enable earlier intervention and fewer missed diagnoses. The feasibility of collecting speech data remotely in those with NPDs should be established. METHODS AND ANALYSIS: The present study will assess the feasibility of obtaining speech data, collected remotely using a smartphone app, from individuals across three NPD cohorts: neurodegenerative cognitive diseases (n=50), other neurodegenerative diseases (n=50) and affective disorders (n=50), in addition to matched controls (n=75). Participants will complete audio-recorded speech tasks and both general and cohort-specific symptom scales. The battery of speech tasks will serve several purposes, such as measuring various elements of executive control (eg, attention and short-term memory), as well as measures of voice quality. Participants will then remotely self-administer speech tasks and follow-up symptom scales over a 4-week period. The primary objective is to assess the feasibility of remote collection of continuous narrative speech across a wide range of NPDs using self-administered speech tasks. Additionally, the study evaluates if acoustic and linguistic patterns can predict diagnostic group, as measured by the sensitivity, specificity, Cohen's kappa and area under the receiver operating characteristic curve of the binary classifiers distinguishing each diagnostic group from each other. Acoustic features analysed include mel-frequency cepstrum coefficients, formant frequencies, intensity and loudness, whereas text-based features such as number of words, noun and pronoun rate and idea density will also be used. ETHICS AND DISSEMINATION: The study received ethical approval from the Health Research Authority and Health and Care Research Wales (REC reference: 21/PR/0070). Results will be disseminated through open access publication in academic journals, relevant conferences and other publicly accessible channels. Results will be made available to participants on request. TRIAL REGISTRATION NUMBER: NCT04939818.

Study protocol: randomised controlled hybrid type 2 trial evaluating the scale-up of two arts interventions for postnatal depression and Parkinson's disease.

INTRODUCTION: Research on the benefits of 'arts' interventions to improve individuals' physical, social and psychological well-being is growing, but evidence on implementation and scale-up into health and social care systems is lacking. This protocol reports the SHAPER-Implement programme (Scale-up of Health-Arts Programmes Effectiveness-Implementation Research), aimed at studying the impact, implementation and scale-up of: Melodies for Mums (M4M), a singing intervention for postnatal depression; and Dance for Parkinson's (PD-Ballet) a dance intervention for Parkinson's disease. We examine how they could be embedded in clinical pathways to ensure their longer-term sustainability. METHODS AND ANALYSIS: A randomised two-arm effectiveness-implementation hybrid type 2 trial design will be used across M4M/PD-Ballet. We will assess the implementation in both study arms (intervention vs control), and the cost-effectiveness of implementation. The design and measures, informed by literature and previous research by the study team, were refined through stakeholder engagement. Participants (400 in M4M; 160 in PD-Ballet) will be recruited to the intervention or control group (2:1 ratio). Further implementation data will be collected from stakeholders involved in referring to, delivering or supporting M4M/PD-Ballet (N=25-30 for each intervention).A mixed-methods approach (surveys and semi-structured interviews) will be employed. 'Acceptability' (measured by the 'Acceptability Intervention Measure') is the primary implementation endpoint for M4M/PD-Ballet. Relationships between clinical and implementation outcomes, implementation strategies (eg, training) and outcomes will be explored using generalised linear mixed models. Qualitative data will assess factors affecting the acceptability, feasibility and appropriateness of M4M/PD-Ballet, implementation strategies and longer-term sustainability. Costs associated with implementation and future scale-up will be estimated. ETHICS AND DISSEMINATION: SHAPER-PND (the M4M trial) and SHAPER-PD (the PD trial) are approved by the West London and GTAC (20/PR/0813) and the HRA and Health and Care Research Wales (REC Reference: 20/WA/0261) Research Ethics Committees. Study findings will be disseminated through scientific peer-reviewed journals and scientific conferences. TRIAL REGISTRATION NUMBERS: Both trials are registered with NIH US National Library of Medicine, ClinicalTrials.gov. The trial registration numbers, URLs of registry records, and dates of registration are: (1) PD-Ballet: URL: NCT04719468 (https://eur03.safelinks.protection. OUTLOOK: com/?url=https%3A%2F%2Fwww.clinicaltrials.gov%2Fct2%2Fshow%2FNCT04719468%3Fterm%3DNCT04719468%26draw%3D2%26rank%3D1&data=04%7C01%7Crachel.davis%40kcl.ac.uk%7C11a7c5142782437919f808d903111449%7C8370cf1416f34c16b83c724071654356%7C0%7C0%7C6375441942616) (date of registration: 22 Jan 2021). (2) Melodies for Mums: NCT04834622 (https://clinicaltrials.gov/ct2/show/NCT04834622?term=shaper-pnd&draw=2&rank=1) (date of registration: 8 Apr 2021).

Does Ethnicity Influence Recruitment into Clinical Trials of Parkinson's Disease?

BACKGROUND: Lack of participation of black and minority ethnic communities (BAME) in registered clinical trials is a concern as data emerging from these studies are used to licence new drugs or other interventions, even though findings made in such selected study populations have limited external validity in the aforesaid ethnic groups. OBJECTIVE: We used Parkinson's disease (PD), the fastest rising neurodegenerative disorder in the world, as an exemplar condition to test our hypothesis that participants from BAME communities are underrepresented in clinical trials. METHODS: A systematic search of clinical trials registered on a Clinicaltrials.gov database which queried for PD with racial distribution data from 2017 to 2021. RESULTS: Out of 266 trials considered, 54 trials were published in peer reviewed journals. Among these, only 23 (42.65%) publications reported data regarding the racial distribution of the participants. Out of these, five studies involved mixed racial participation and two trials included black subjects. CONCLUSION: We found that inclusion of under-represented BAME groups in recently published clinical trials is low, at only 21.57%, and is not even considered in most studies. Out of the reviewed trials, only 5 (21.75%) studies reported detailed demographic categories with black minorities enrolment. This constitutes a severe under-representation when compared to the proportion of Black or African American in the UK population (3%). Results of this study identified the need for better reporting of racial composition in clinical trials. We strongly recommend that future studies should consider ethnicity and other issues around diversity when designing and implementing the clinical trials, not only in the PD field but also beyond.

Evaluation of the effect of bilateral subthalamic nucleus deep brain stimulation on fatigue in Parkinson's Disease as measured by the non-motor symptoms scale.

BACKGROUND: Fatigue is a common and disabling non-motor symptom (NMS) in Parkinson's disease (PD) patients. However, the effect of subthalamic nucleus (STN) deep brain stimulation (DBS) on fatigue has not been widely studied. OBJECTIVE: To determine the effect of STN DBS on fatigue in PD patients, measured by the Non-motor symptoms scale (NMSS). METHODS: Cross-sectional analysis of 50 patients with PD who underwent STN DBS at King's College Hospital and Salford Royal Hospital with fatigue scores (measured by question number 4 from domain 2 (sleep/fatigue) of the NMSS as the primary outcome measure. Secondary outcome measures included the PD Sleep Scale (PDSS), Scales for Outcome in PD (SCOPA)-motor examination, activities of daily living, motor complications, Hoehn and Yahr (HY) stage and changes in Levodopa Equivalent Daily Dose (LEDD). RESULTS: 50 patients with a mean follow-up period of 1.98 ± 1.36 years were studied. Significant improvement in median fatigue scores (4.00 (0.75-9.00) to 1.00 (0.00-4.50); p = .001) was observed. In addition, improvements in question 5 (sleep maintenance and fragmentation; 8.00 (4.00-12.00) to 0.00 (0.00-4.00); p < .001) and in domain 2 total score (sleep/fatigue; 20.00 (8.75-27.25) to 6.00 (0.75-16.00); p < .001) were also significant, together with improvements in NMSS total score, SCOPA scores and HY stage (p ≤ .02). Moreover, LEDD but especially dopamine agonists LEDD was significantly reduced after DBS (310.00 (0.00-480.00) to 150.00 (0.00-300.00); p < .020). CONCLUSIONS: Even though open label and not using a validated fatigue scale, this observational analysis suggest that fatigue improves significantly after STN DBS with persisting benefits at two years follow-up.

Nonmotor symptom burden grading as predictor of cognitive impairment in Parkinson's disease.

BACKGROUND: Identifying predictors of incident cognitive impairment (CI), one of the most problematic long-term outcomes, in Parkinson's disease (PD) is highly relevant for personalized medicine and prognostic counseling. The Nonmotor Symptoms Scale (NMSS) provides a global clinical assessment of a range of NMS, reflecting NMS burden (NMSB), and thus may assist in the identification of an "at-risk" CI group based on overall NMSB cutoff scores. METHODS: To investigate whether specific patterns of PD NMS profiles predict incident CI, we performed a retrospective longitudinal study on a convenience sample of 541 nondemented PD patients taking part in the Nonmotor Longitudinal International Study (NILS) cohort, with Mini-Mental State Examination (MMSE), NMSS, and Scales for Outcomes in PD Motor Scale (SCOPA Motor) scores at baseline and last follow-up (mean 3.2 years) being available. RESULTS: PD patients with incident CI (i.e., MMSE score ≤ 25) at last follow-up (n = 107) had severe overall NMSB level, significantly worse NMSS hallucinations/perceptual problems and higher NMSS attention/memory scores at baseline. Patients with CI also were older and with more advanced disease, but with no differences in disease duration, dopamine replacement therapy, sex, and comorbid depression, anxiety, and sleep disorders. CONCLUSIONS: Our findings suggest that a comprehensive baseline measure of NMS and in particular hallucinations and perceptual problems assessed with a validated single instrument can be used to predict incident CI in PD. This approach provides a simple, holistic strategy to predict future CI in this population.

Scaling-up Health-Arts Programmes: the largest study in the world bringing arts-based mental health interventions into a national health service.

The Scaling-up Health-Arts Programme: Implementation and Effectiveness Research (SHAPER) project is the world's largest hybrid study on the impact of the arts on mental health embedded into a national healthcare system. This programme, funded by the Wellcome Trust, aims to study the impact and the scalability of the arts as an intervention for mental health. The programme will be delivered by a team of clinicians, research scientists, charities, artists, patients and healthcare professionals in the UK's National Health Service (NHS) and the community, spanning academia, the NHS and the charity sector. SHAPER consists of three studies - Melodies for Mums, Dance for Parkinson's, and Stroke Odysseys - which will recruit over 800 participants, deliver the interventions and draw conclusions on their clinical impact, implementation effectiveness and cost-effectiveness. We hope that this work will inspire organisations and commissioners in the NHS and around the world to expand the remit of social prescribing to include evidence-based arts interventions.

Drooling in Parkinson's Disease: Prevalence and Progression from the Non-motor International Longitudinal Study.

Sialorrhoea in Parkinson's disease (PD) is an often neglected yet key non-motor symptom with impact on patient quality of life. However, previous studies have shown a broad range of prevalence figures. To assess prevalence of drooling in PD and its relationship to quality of life, we performed a retrospective analysis of 728 consecutive PD patients who had a baseline and follow-up assessment as part of the Non-motor International Longitudinal Study (NILS), and for whom drooling presence and severity were available, assessed through the Non-Motor Symptoms Scale (NMSS). In addition, we analysed the prevalence of associated dysphagia through self-reported outcomes. Quality of life was assessed through the PDQ-8 scale. Baseline (disease duration 5.6 years) prevalence of drooling was 37.2% (score ≥ 1 NMSS question 19), and after 3.27 ± 1.74 years follow-up, this was 40.1% (p = 0.17). The prevalence of drooling increased with age (p < 0.001). The severity of drooling, however, did not change (p = 0.12). While in 456 patients without drooling at baseline, only 16% (n = 73) had dysphagia (question 20 of the NMSS), in those with drooling this was 34.3% (p < 0.001). At follow-up, the number of patients with dysphagia had increased, 20.4% with no drooling had dysphagia, and 43.6% with drooling had dysphagia. Both at baseline and follow-up, drooling severity was significantly positively associated with quality of life (PDQ-8; r = 0.199; p < 0.001). In moderately advanced PD patients, subjective drooling occurs in over one-third of patients and was significantly associated with decreased quality of life. Dysphagia occurred significantly more often in patients with drooling.

Non-motor correlates of wrist-worn wearable sensor use in Parkinson's disease: an exploratory analysis.

Wearable sensors are becoming increasingly more available in Parkinson's disease and are used to measure motor function. Whether non-motor symptoms (NMS) can also be measured with these wearable sensors remains unclear. We therefore performed a retrospective, exploratory, analysis of 108 patients with a diagnosis of idiopathic Parkinson's disease enroled in the Non-motor Longitudinal International Study (UKCRN No. 10084) at King's College Hospital, London, to determine the association between the range and nature of NMS and an accelerometer-based outcome measure of bradykinesia (BKS) and dyskinesia (DKS). NMS were assessed by the validated NMS Scale, and included, e.g., cognition, mood and sleep, and gastrointestinal, urinary and sexual problems. Multiple linear regression modelling was used to identify NMS associated with BKS and DKS. We found that BKS was associated with domains 6 (gastrointestinal tract; p = 0.006) and 8 (sexual function; p = 0.003) of the NMS scale. DKS was associated with domains 3 (mood/cognition; p = 0.016), 4 (perceptual problems; p = 0.025), 6 (gastrointestinal tract; p = 0.029) and 9 (miscellaneous, p = 0.003). In the separate domains, constipation was significantly associated with BKS. Delusions, dysphagia, hyposmia, weight change and hyperhidrosis were identified as significantly associated with DKS. None of the NMSS domains were associated with disease duration (p ≥ 0.08). In conclusion, measures of BKS and DKS were mainly associated with gastrointestinal problems, independent of disease duration, showing the potential for wearable devices to pick up on these symptoms. These exploratory results deserve further exploration, and more research on this topic in the form of comprehensive large-scale studies is needed.

Caloric vestibular stimulation for the management of motor and non-motor symptoms in parkinson's disease: Intention-to-treat data.

This report provides data related to the safety and effectiveness of repeated time-varying caloric vestibular stimulation (CVS) as a treatment for motor and non-motor features of Parkinson's disease (PD). Forty-six subjects receiving stable anti-Parkinsonian therapy were randomized to active (n = 23) or placebo (n = 23) treatment arms. Subjects self-administered CVS twice-daily over a period of 8 weeks at home via a portable, pre-programmed, solid-state ThermoNeuroModulation (TNM™) device delivering continually-varying thermal waveforms through aluminium ear-probes mounted on a wearable headset. Change scores from baseline to end of treatment and to a 1-month follow-up were determined using standardized clinical measures. The data presented here report sample demographics, detailed safety data and the statistical outcomes from the intention-to-treat and modified intention-to-treat analyses. These data supplement findings of the main per protocol analysis reported in the allied article entitled, 'Caloric Vestibular Stimulation for the Management of Motor and Non-Motor Symptoms in Parkinson's Disease' Wilkinson et al.

Caloric vestibular stimulation for the management of motor and non-motor symptoms in Parkinson's disease.

INTRODUCTION: A recent case study showed that repeated sessions of caloric vestibular stimulation (CVS) relieved motor and non-motor symptoms associated with Parkinson's disease (PD). Here we sought to confirm these results in a prospective, double-blind, randomized, placebo treatment-controlled study. METHODS: 33 PD subjects receiving stable anti-Parkinsonian therapy completed an active (n = 16) or placebo (n = 17) treatment period. Subjects self-administered CVS at home twice-daily via a portable, pre-programmed, solid-state ThermoNeuroModulation (TNM™) device, which delivered continually-varying thermal waveforms through aluminum ear-probes mounted on a wearable headset. Subjects were followed over a 4-week baseline period, 8 weeks of treatment and then at 5- and 24-weeks post-treatment. At each study visit, standardized clinical assessments were conducted during ON-medication states to evaluate changes in motor and non-motor symptoms, activities of daily living, and quality of life ratings. RESULTS: Change scores between baseline and the end of treatment showed that active-arm subjects demonstrated clinically-relevant reductions in motor and non-motor symptoms that were significantly greater than placebo-arm subjects. Active treatment was also associated with improved scores on activities of daily living assessments. Therapeutic gains were still evident 5 weeks after the end of active treatment but had started to recede at 24 weeks follow-up. No serious adverse events were associated with device use, and there was high participant satisfaction and tolerability of treatment. CONCLUSION: The results provide evidence that repeated CVS can provide safe and enduring adjuvant relief for motor and non-motor symptoms associated with PD.

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

OBJECTIVE: To identify associated (non-)motor profiles of Parkinson's disease (PD) patients with hyperhidrosis as a dominant problem. METHODS: This 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. RESULTS: No 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 < 0.001). Secondary analyses revealed higher dyskinesia scores, worse quality of life and PDSS scores, and higher anxiety and depression levels in hyperhidrosis patients (p < 0.001). Tertiary analyses revealed higher NMSS item scores for fatigue, sleep initiation, restless legs, urinary urgency, and unexplained pain (p < 0.001). CONCLUSIONS: Chronic 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.

Slave to the rhythm: Seasonal differences in non-motor symptoms in Parkinson's disease.

INTRODUCTION: Although circadian variation of (motor) symptoms in Parkinson disease (PD) patients has been described, it remains unclear what effect seasonal variation may have on non-motor symptoms (NMS). METHODS: Cross-sectional retrospective study on 372 consecutive PD patients taking part in the Non-motor Longitudinal International Study at King's College Hospital London between November 2011 and July 2018. Patients were divided into three groups based on their date of assessment, using a simplified seasonal model: group 1: November-February (n = 107); group 2: March-15 June (n = 107); and group 3: 16 June-October (n = 158). Primary outcome was a seasonal difference in NMS scale (NMSS) total scores (higher scores reflecting greater disability). We hypothesized that PD patients exhibit circannual NMS burden patterns. RESULTS: All groups were identical concerning disease onset and duration, HY stage, Levodopa equivalent dose, and gender. There was a seasonal difference in NMSS total scores (p = 0.040), with the highest scores (57.1 ±â€¯42.5) in season 1 (winter months) and the lowest (45.1 ±â€¯34.4) in season 3 (summer months) (p = 0.037). Seasonal differences were observed in NMSS domain 1 (cardiovascular symptoms) (p = 0.011), domain 4 (perceptual problems) (p = 0.017) and domain 9 (miscellaneous symptoms) (p = 0.009). A trend was observed for domain 2 (sleep) (p = 0.057). CONCLUSION: NMS in PD fluctuate throughout the year, with worsening of symptoms in the winter months compared to the summer months suggestive of dysfunction of the body's master clock, the suprachiasmatic nuclei. Such variations must be accommodated in daily care to ascertain appropriate changes in medication regimes and in clinical trials for the interpretation of outcomes.

A durable gain in motor and non-motor symptoms of Parkinson's Disease following repeated caloric vestibular stimulation: A single-case study.

OBJECTIVE: To gain 'first-in-man' evidence that repeated caloric vestibular stimulation (CVS), a non-invasive form of neuro-modulation, can induce a lasting and clinically-relevant reduction in Parkinson's Disease (PD) symptoms. METHODS: A 70  yr old male, diagnosed with PD 7 years prior to study enrolment, self-administered CVS at home 2×20 minutes per day for three months using a solid-state portable device. Standardised neuropsychological assessments of motor, cognitive, affective and independent function were carried out prior to stimulation, at the start and end of the sham (month 1) and active (months 2-3) phases, and 5 months post-stimulation. RESULTS: Relative to the pre-stimulation baseline, behavioural improvements that exceeded the minimal detectable change were observed on the EQ5D, Unified Parkinson's Disease Rating Scale, Schwab and England scale, 2 minute walk, Timed up and go, Non-motor symptom assessment scale for PD, Montreal cognitive assessment, Hospital depression scale and Epworth sleepiness scale. The level of change exceeded the threshold for a minimal clinically important difference on all scales for which a threshold has been published. By contrast, little improvement was seen during the sham (i.e., placebo) phase. CONCLUSION: Caloric vestibular stimulation may offer a novel, home-based method of relieving everyday symptoms of PD, and merits further evaluative study.