Rehabilitation for Functional Dystonia: Cases and Review of the Literature.

BACKGROUND: Functional dystonia (FD) is a common subtype of functional movement disorder. FD can be readily diagnosed based on positive signs and is potentially treatable with rehabilitation. Despite this, clinical outcomes remain variable and a gold standard approach to treatment is lacking. CASES: Here we present four cases of axial and limb functional dystonia who were treated with integrated rehabilitation and improved. The therapy approach and clinical outcomes are described, including videos. LITERATURE REVIEW: A literature review evaluated the published treatment strategies for the treatment of functional dystonia. Out of 338 articles, 25 were eligible for review and included mainly case reports and case series. Most patients received more than one treatment modality. Non-invasive therapies, commonly physiotherapy and psychological approaches were mostly associated with positive outcomes. Multiple treatments commonly used in dystonia were used, including botulinum toxin injections, pharmacotherapy and surgery, leading to variable outcomes. CONCLUSION: Therapy should be personalized to the clinical presentation. In challenging cases, initiation of a multidisciplinary approach may provide benefit regardless of etiology. Pharmacotherapy should be used judiciously, and surgical therapy should be avoided.

If Art Were a Drug: Implications for Parkinson's Disease.

Parkinson's disease (PD) is a chronic and complex neurodegenerative disorder. Conventional pharmacological or surgical therapies alone are often insufficient at adequately alleviating disability. Moreover, there is an increasing shift toward person-centered care, emphasizing the concept of "living well". In this context, arts-based interventions offer great promise, functioning as platforms for creative expression that could provide novel mechanisms to promote quality of life. Here we present a qualitative review of arts-based interventions for PD, including music, dance, drama, visual arts, and creative writing. For each, we discuss their applications to PD, proposed mechanisms, evidence from prior studies, and upcoming research. We also provide examples of community-based projects. Studies to date have had relatively small sample sizes, but their findings suggest that arts-based interventions have the potential to reduce motor and non-motor symptoms. They may also empower people with PD and thereby address issues of self-esteem, foster personal problem-solving, and augment holistic well-being. However, there is a paucity of research determining optimal dosage and symptom-specific benefits of these therapies. If art were a drug, we would have to perform appropriately powered studies to provide these data before incorporating it into routine patient care. We therefore call for further research with properly designed studies to offer more rigorous and evidence-based support for what we intuitively think is a highly promising approach to support individuals living with PD. Given the possible positive impact on people's lives, arts-based approaches merit further development and, if proven to be effective, systematic inclusion within integrated management plans.

Prevention and treatment of traumatic brain injury-related delirium: a systematic review.

BACKGROUND: Our systematic review examines the effectiveness and safety of non-pharmacologic and pharmacologic interventions in preventing or treating traumatic brain injury (TBI)-related delirium in acute care. METHODS: We searched four electronic databases (MEDLINE, EMBASE, CENTRAL/CDSR, and PsycINFO) to identify randomized controlled trials (RCTs), quasi-experimental, and observational studies. Eligible studies included adults with TBI, at least one comparator group, delirium as an outcome and took place in acute care. Two reviewers independently completed all study screening, data abstraction, and risk of bias assessment using the Cochrane risk of bias 2 tool for RCTs or risk of bias in non-randomized studies-of interventions tool for observational studies. We implemented the PROGRESS-Plus framework to describe social determinants of health (SDoH) reporting. RESULTS: We identified 20,022 citations, reviewed 301 in full text, and included eight studies in the descriptive synthesis. The mean age of study participants ranged from 32 to 62 years. 12.5% of included studies reported SDoH. Included studies had moderate-to-high risk of bias. Studies compared reorientation programs and an intervention bundle to usual care, but these interventions were not better than usual care in treating TBI-related delirium. Individual studies found that rosuvastatin and aripiprazole were more efficacious than placebo, and dexmedetomidine was more efficacious than propofol and haloperidol for preventing TBI-related delirium. No studies reported safety as the primary outcome. CONCLUSIONS: We identified efficacious pharmacologic interventions for preventing TBI-related delirium, but these studies were at moderate-to-high risk of bias, which limits our confidence in these findings. Future studies should incorporate safety outcomes, and a diverse study population, including older adults.

Infratentorial brain injury and death by neurologic criteria in Canada: a narrative review.

There are two anatomic formulations of death by neurologic criteria accepted worldwide: whole-brain death and brainstem death. As part of the Canadian Death Definition and Determination Project, we convened an expert working group and performed a narrative review of the literature. Infratentorial brain injury (IBI) with an unconfounded clinical assessment consistent with death by neurologic criteria represents a nonrecoverable injury. The clinical determination of death cannot distinguish between IBI and whole-brain cessation of function. Current clinical, functional, and neuroimaging assessments cannot reliably confirm the complete and permanent destruction of the brainstem. No patient with isolated brainstem death has been reported to recover consciousness and all patients have died. Studies suggest a significant majority of isolated brainstem death will evolve into whole-brain death, influenced by time/duration of somatic support and impacted by ventricular drainage and/or posterior fossa decompressive craniectomy. Acknowledging variability in intensive care unit (ICU) physician opinion on this matter, a majority of Canadian ICU physicians would perform ancillary testing for death determination by neurologic criteria in the context of IBI. There is currently no reliable ancillary test to confirm complete destruction of the brainstem; ancillary testing currently includes evaluation of both infratentorial and supratentorial flow. Acknowledging international variability in this regard, the existing evidence reviewed does not provide sufficient confidence that the clinical exam in IBI represents a complete and permanent destruction of the reticular activating system and thus the capacity for consciousness. On this basis, IBI consistent with clinical signs of death by neurologic criteria without significant supratentorial involvement does not fulfill criteria for death in Canada and ancillary testing is required.

RéSUMé: Il existe deux formulations anatomiques du décès selon des critères neurologiques acceptés dans le monde entier : la mort du cerveau entier et la mort du tronc cérébral. Dans le cadre du Projet canadien de définition et de détermination du décès, nous avons réuni un groupe de travail composé d'experts et réalisé un compte rendu narratif de la littérature. Une lésion cérébrale infratentorielle (LCI) avec une évaluation clinique sans facteur confondant et compatible avec un décès selon des critères neurologiques représente une atteinte irrécupérable. La détermination clinique du décès ne permet pas de faire la distinction entre une LCI et l'arrêt de la fonction dans le cerveau entier. Les évaluations cliniques, fonctionnelles et de neuroimagerie actuelles ne peuvent pas confirmer de manière fiable la destruction complète et permanente du tronc cérébral. La récupération de la conscience n'a jamais été signalée chez aucun patient présentant une mort isolée du tronc cérébral, et tous les patients sont décédés. Des études suggèrent qu'une majorité significative des morts isolées du tronc cérébral évolueront vers la mort cérébrale entière, étant influencées par le temps et la durée de l'assistance somatique et impactées par le drainage ventriculaire et/ou la craniectomie décompressive de la fosse postérieure. Compte tenu de la variabilité des opinions des médecins intensivistes à ce sujet, la majorité des médecins intensivistes canadiens réaliseraient des examens auxiliaires pour déterminer le décès selon des critères neurologiques dans le contexte d'une LCI. Il n'existe actuellement aucun examen auxiliaire fiable pour confirmer la destruction complète du tronc cérébral; les examens auxiliaires comprennent actuellement l'évaluation de la circulation infratentorielle et supratentorielle. Reconnaissant la variabilité internationale à cet égard, les données probantes existantes passées en revue ne sont pas suffisamment fiables pour affirmer que l'examen clinique en cas de LCI représente une destruction complète et permanente du système d'activation réticulaire et donc de la capacité de conscience. En se fondant sur cette base, une LCI compatible avec les signes cliniques d'un décès selon des critères neurologiques sans atteinte supratentorielle significative ne répond pas aux critères de décès au Canada et un examen auxiliaire est requis.

The reticular activating system: a narrative review of discovery, evolving understanding, and relevance to current formulations of brain death.

A series of landmark experiments conducted throughout the 20th century progressively localized the regions involved in consciousness to the reticular activating system (RAS) and its ascending projections. The first description of the RAS emerged in 1949 through seminal experiments performed by Moruzzi and Magoun in feline brainstems; additional experiments in the 1950s revealed connections between the RAS and the thalamus and neocortical structures. This knowledge has allowed for the explanation of disorders of consciousness with exquisite anatomic precision. The clinical relevance of the RAS is further apparent in modern definitions of brain death/death by neurologic criteria (BD/DNC), which require demonstration of the complete and permanent loss of capacity for consciousness as one of their core criteria. BD/DNC is currently understood across jurisdictions in terms of "whole brain" and "brainstem" formulations. Although their clinical examination between formulations is indistinguishable, policies for BD/DNC declaration may differ in the rare scenario of patients with isolated infratentorial brain injuries, in which ancillary testing is advised in the whole brain formulation but not the brainstem formulation. Canadian guidelines acknowledge that the distinction between whole brain and brainstem formulations is unclear with respect to clinical implications for patients with isolated infratentorial injuries. This has led to variability in Canadian clinicians' use of ancillary testing when the mechanism of BD/DNC is suspected to be an isolated infratentorial injury. The present narrative review highlights these concepts and explores implications for determination of BD/DNC in Canada, with specific emphasis on the RAS and its relevance to both formulations.

RéSUMé: Une série d'expériences marquantes menées tout au long du 20e siècle a progressivement permis de localiser les régions impliquées dans la conscience dans le système d'activation réticulaire (SAR) et ses projections ascendantes. La première description du SAR a vu le jour en 1949 grâce à des expériences fondatrices réalisées par Moruzzi et Magoun dans des troncs cérébraux félins; d'autres expériences menées au cours des années 1950 ont révélé des liens entre le SAR et le thalamus et les structures néocorticales. Ces connaissances ont permis d'expliquer les troubles de la conscience avec une précision anatomique extraordinaire. La pertinence clinique du SAR est encore plus évidente dans les définitions modernes de la mort cérébrale / du décès déterminé par des critères neurologiques (MC/DCN), qui exigent la démonstration de la perte complète et permanente de la capacité de conscience comme l'un de ses critères de base. La mort cérébrale est actuellement comprise partout en termes de formulations de « cerveau entier ¼ et de « tronc cérébral ¼. Bien que l'examen clinique ne fasse pas de distinction entre ces formulations, les politiques de déclaration de MC/DCN peuvent différer dans le rare cas de patients présentant des lésions cérébrales infratentorielles isolées, pour lesquels des examens auxiliaires sont conseillés lorsqu'on parle de cerveau entier mais pas lorsqu'on utilise la formulation de tronc cérébral. Les lignes directrices canadiennes reconnaissent que la distinction entre les termes de cerveau entier et de tronc cérébral n'est pas claire en ce qui concerne leurs implications cliniques pour les patients présentant des lésions infratentorielles isolées. Cela a entraîné une variabilité dans l'utilisation des examens auxiliaires par les cliniciens canadiens lorsqu'ils soupçonnent que le mécanisme de MC/DCN consiste en une lésion infratentorielle isolée. Ce compte rendu narratif met en lumière ces concepts et explore les implications pour la détermination de la MC/DCN au Canada, en mettant une emphase spécifique sur le SAR et sa pertinence pour les deux formulations.

Exposure to Phosphoglycerate Kinase 1 Activators and Incidence of Parkinson's Disease.

BACKGROUND: Preclinical and epidemiological data suggest that phosphoglycerate kinase 1 activators could have neuroprotective properties and prevent PD. OBJECTIVES: The objective of this study was to compare the association between increased use of phosphoglycerate kinase 1 activators and increased use of tamsulosin with PD incidence. METHODS: Our retrospective cohort study included men older than age 66 years newly exposed to phosphoglycerate kinase 1 activators or tamsulosin and compared their PD incidence, using health care administrative data of Ontario, Canada. RESULTS: Among 265,745 men, each additional year of cumulative use of phosphoglycerate kinase 1 activators or tamsulosin was associated with 6% and 8% reduction, respectively, in the hazard of PD incidence. These hazards were not significantly different (P = 0.2094). A secondary analysis with the observation window starting after 6 months and 1 and 2 years showed similar results. CONCLUSIONS: Increasing exposure to phosphoglycerate kinase 1 activators and tamsulosin were both associated with small reductions in PD incidence. These results support further investigation of phosphoglycerate kinase 1 activators and tamsulosin for possible PD disease-modifying properties. © 2021 International Parkinson and Movement Disorder Society.

Modification to Neurology Residency Training: The Toronto Neurology COVID-19 Pandemic Experience.

We describe the University of Toronto Adult Neurology Residency Program's early experiences with and response to the coronavirus disease 2019 pandemic, including modifications to the provision of neurologic care while upholding neurology education and safety. All academic and many patient-related activities were virtualized. This maintained physical distancing while creating a city-wide videoconference-based teaching curriculum, expanding the learning opportunities to trainees at all academic sites. Furthermore, we propose a novel split-team model to promote resident safety through physical distancing of teams and to establish a capacity to rapidly adapt to redeployment, service needs, and trainee illness. Finally, we developed a unique protected code stroke framework to safeguard staff and trainees during hyperacute stroke assessments in this pandemic. Our shared experiences highlight considerations for contingency planning, maintenance of education, sustainability of team members, and promotion of safe neurologic care. These interventions serve to promote trainee safety, wellness, and resiliency.

Innovation in resident education - Description of the Neurology International Residents Videoconference and Exchange (NIRVE) program.

There is considerable heterogeneity in residency education around the world. The Neurology International Residents Videoconference and Exchange (NIRVE) program aims to deliver neurology educational content to residents across different resource settings and countries through a monthly videoconferencing platform. Its purpose is to fill gaps in didactic teaching, increase exposure to a variety of cases including various practices and delivery of neurology in multiple countries, as well as integrate global health content into neurology education. NIRVE also facilitates resident exchanges among participating sites. In this descriptive article, we report NIRVE's structure and its cumulative productivity. Since its creation, NIRVE has held more than 90 videoconference rounds and has connected 16 sites in North America, South America, Europe, Asia and Africa. We describe challenges encountered since the inception of the program eleven years ago. NIRVE also fosters a culture of long-term international connection and collaboration. During global disease outbreaks, such as the current COVID-19 pandemic, videoconference rounds serve as a sustainable alternative means to deliver education. Future goals include increasing the number of sites involved, including a focus on Africa and Asia, and fostering resident-led advocacy projects.

Searching for autoimmune encephalitis: Beware of normal CSF.

OBJECTIVE: To determine the prevalence of cerebrospinal fluid (CSF) markers associated with inflammation (i.e., elevated white blood cell count, protein concentration, and CSF-specific oligoclonal bands) in patients with early active autoimmune encephalitis (AE). METHODS: CSF characteristics, including WBC count, protein concentration, and oligoclonal banding, were analyzed in patients diagnosed with AE at two tertiary care centers. RESULTS: Ninety-five patients were included in the study. CSF white blood cell counts and protein levels were within normal limits for 27% (CI95%: 19-37) of patients with AE. When results of oligoclonal banding were added, 14% (CI95%: 6-16) of patients with AE had "normal" CSF. The median CSF white blood cell count was 8 cells/mm3 (range: 0-544) and the median CSF protein concentration was 0.42 g/L (range: 0.15-3.92). CONCLUSIONS: White blood cell counts and protein levels were within normal limits in the CSF of a substantial proportion of patients with early active AE. Inclusion of CSF oligoclonal banding identified a higher proportion of patients with an inflammatory CSF profile, especially when CSF was sampled early in the disease process.

Obstructive sleep apnea, CPAP therapy and Parkinson's disease motor function: A longitudinal study.

INTRODUCTION: We aimed to assess, in patients with Parkinson's disease (PD), the association between obstructive sleep apnea (OSA), progression of motor dysfunction and the effect of OSA treatment. METHODS: Data were analysed from a prospective cohort study of idiopathic PD patients from a movement disorders clinic. Patients found to have OSA on polysomnography (apnea-hypopnea index [AHI] ≥15 events/h, OSA+) were offered treatment using continuous positive airway pressure (CPAP). CPAP+ was defined as an average ≥ 2 h/night use at each follow-up. Motor symptoms were assessed using the motor section of the Movement Disorder Society Unified Parkinson's Disease Rating Scale (mUPDRS) and the Timed-Up-And-Go (TUG). Follow-up times were 3, 6 and 12 months. Mixed models were constructed, adjusting for age, sex, body mass index, levodopa equivalent dose and comorbidities. RESULTS: We studied 67 individuals (61.2% male) of mean age 64.7 years (SD = 10.1). Baseline mUPDRS was higher in OSA+ compared to OSA- (24.5 [13.6] vs. 16.2 [7.2], p < 0.001). Motor dysfunction increased at comparable rates in OSA- and OSA+CPAP-. However, in OSA+CPAP+, mUPDRS change was significantly lower compared to OSA- (ß = -0.01 vs. 0.61, p = 0.03; p = 0.12 vs. OSA+CPAP- [ß = 0.39]) and TUG change was lower compared to OSA+CPAP- (ß = -0.01 vs. 0.13, p = 0.002; p = 0.05 vs. OSA- [ß = 0.02]). CONCLUSIONS: In this PD cohort, OSA was associated with higher baseline mUPDRS. In those with OSA, CPAP use was associated with stabilization of motor function (mUPDRS and TUG) over 12 months. These observations support further research to clarify the role of OSA in PD pathophysiology and motor dysfunction.

Overview of Sleep and Circadian Rhythm Disorders in Parkinson Disease.

Sleep disorders are common among PD patients and affect quality of life. They are often under-recognized and under-treated. Mechanisms of sleep disorders in PD remain relatively poorly understood. Improved awareness of common sleep problems in PD. Tailored treatment and evidence for efficacy are lacking. The purpose of this review is to provide an overview and update on the most common sleep disorders in PD. We review specific features of the most common sleep disorders in PD, including insomnia, excessive daytime sleepiness, sleep-disordered breathing, restless legs syndrome, circadian rhythm disorders and REM sleep behavior disorders.

Deep brain stimulation: potential for neuroprotection.

Over the last two decades there has been an exponential rise in the number of patients receiving deep brain stimulation (DBS) to manage debilitating neurological symptoms in conditions such as Parkinson's disease, essential tremor, and dystonia. Novel applications of DBS continue to emerge including treatment of various psychiatric conditions (e.g. obsessive-compulsive disorder, major depression) and cognitive disorders such as Alzheimer's disease. Despite widening therapeutic applications, our understanding of the mechanisms underlying DBS remains limited. In addition to modulation of local and network-wide neuronal activity, growing evidence suggests that DBS may also have important neuroprotective effects in the brain by limiting synaptic dysfunction and neuronal loss in neurodegenerative disorders. In this review, we consider evidence from preclinical and clinical studies of DBS in Parkinson's disease, Alzheimer's disease, and epilepsy that suggest chronic stimulation has the potential to mitigate neuronal loss and disease progression.

Change in Cognition and Other Non-Motor Symptoms With Obstructive Sleep Apnea Treatment in Parkinson Disease.

STUDY OBJECTIVES: Parkinson disease (PD) non-motor symptoms are associated with sleep disorders and impair quality of life. Our objective was to assess the effect of obstructive sleep apnea (OSA) treatment using continuous positive airway pressure (CPAP) on PD non-motor symptoms. METHODS: In this prospective observational study, 67 patients with idiopathic PD underwent polysomnography. Those with moderate-severe OSA were offered CPAP therapy. Subjects were divided into those without OSA (OSA-), and those with OSA (OSA+). Analyses were conducted for 6 and 12 months' follow-up data. At 6 months, those who had used CPAP at home for at least 1 month were considered CPAP users (OSA+CPAP+), whereas those who did not try it, or declined further treatment following a short trial were considered non-users (OSA+CPAP-). For the 12-month analysis, only those still actively using CPAP at 12 months were included in the OSA+CPAP+ group. Non-motor symptom measurements were: Epworth Sleepiness Scale, Montreal Cognitive Assessment (MoCA), Unified Parkinson's Disease Rating Scale part 1 (UPDRS1), Parkinson's Disease Sleep Scale (PDSS), Fatigue Severity Scale, Apathy Scale, Beck Depression Inventory, and Hospital Anxiety and Depression Scale (HADS). RESULTS: Sixty-five participants were re-assessed at least once. At 6 months, 30 participants were categorized as OSA+CPAP+, 11 OSA+CPAP-, and 18 OSA-. At 12 months, 21 were categorized as OSA+CPAP+, 21 OSA+CPAP-, and 17 OSA-. The UPDRS1 and PDSS improved from baseline in OSA+CPAP+ at 6 months (-2.7, standard deviation [SD] 4.0, P = .001, and 7.9, SD 19.0, P = .03, respectively) and 12 months (-4.1, SD 5.4, P = .002, and 11.4, SD 24.4, P = .04, respectively), but not in other groups. The MoCA and HADS-A improved in OSA+CPAP+ at 12 months (1.7, SD 3.5, P = .04, and -2.1, SD 3.8, P = .02, respectively). The MoCA improved in those with low baseline MoCA and those with REM sleep behavior disorder. Mean CPAP use in users at 12 months was 3 hours 36 minutes per night. CONCLUSIONS: CPAP treatment of OSA in PD is associated with improved overall non-motor symptoms, sleep quality, anxiety, and global cognitive function over a 12-month period.

SLEEP AND CIRCADIAN RHYTHM DISORDERS IN PARKINSON'S DISEASE.

PURPOSE OF REVIEW: Sleep disorders are among the most challenging non-motor features of Parkinson's disease (PD) and significantly affect quality of life. Research in this field has gained recent interest among clinicians and scientists and is rapidly evolving. This review is dedicated to sleep and circadian dysfunction associated with PD. RECENT FINDINGS: Most primary sleep disorders may co-exist with PD; majority of these disorders have unique features when expressed in the PD population. SUMMARY: We discuss the specific considerations related to the common sleep problems in Parkinson's disease including insomnia, rapid eye movement sleep behavior disorder, restless legs syndrome, sleep disordered breathing, excessive daytime sleepiness and circadian rhythm disorders. Within each of these sleep disorders, we present updated definitions, epidemiology, etiology, diagnosis, clinical implications and management. Furthermore, areas of potential interest for further research are outlined.

Reduced cognitive function in patients with Parkinson disease and obstructive sleep apnea.

OBJECTIVE: To assess the association between obstructive sleep apnea (OSA) and nonmotor symptoms (NMS), including cognitive dysfunction, in patients with Parkinson disease (PD). METHODS: Patients with idiopathic PD, recruited from a movement disorder clinic, underwent overnight polysomnography. OSA was defined as an apnea-hypopnea index (AHI) ≥15/h. PD severity was assessed using the Hoehn & Yahr (H&Y) scale and the Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS). NMS were assessed using the Montreal Cognitive Assessment (MoCA), Epworth Sleepiness Scale (ESS), Fatigue Severity Scale, Apathy Scale, Beck Depression Inventory, Hospital Depression and Anxiety Scale, and PD sleep Scale. RESULTS: Sixty-seven patients (61.2% male), mean age 64.4 (SD 9.9) years and motor MDS-UPDRS 21.9 (12.6) using levodopa equivalent dose (LED) 752.4 (714.6) mg/d, were studied. OSA occurred in 47 patients (61.6%, mean AHI 27.1/h, SD 20.2/h), and NMS in 57 patients (85%). ESS and MoCA were associated with the AHI (ESS ß = 0.0670, p = 0.031; MoCA ß = -0.0520, p = 0.043, adjusted for age, sex, body mass index, LED, and H&Y). ESS was associated with respiratory arousals (ß = 0.1015, p = 0.011) and intermittent hypoxemia (ß = 0.1470, p = 0.006). MoCA was negatively associated with respiratory arousals (ß = -0.0596, p = 0.049) but not intermittent hypoxemia. CONCLUSIONS: OSA is associated with sleepiness and cognitive dysfunction in PD, suggesting that OSA may be a reversible contributor to these NMS. Further studies will be required to evaluate whether OSA treatment can improve excessive sleepiness and cognitive dysfunction in PD.

Obstructive sleep apnea in Parkinson's disease patients: effect of Sinemet CR taken at bedtime.

PURPOSE: Obstructive sleep apnea (OSA) results from upper airway (UA) obstruction. In Parkinson's disease (PD), levodopa improves UA obstruction during wakefulness. We hypothesized that bedtime controlled-release levodopa (Sinemet CR) is associated with less severe OSA (lower apnea-hypopnea index [AHI]) in PD patients. METHODS: Idiopathic PD subjects underwent nocturnal polysomnography (PSG) and were divided into those taking bedtime Sinemet CR (SinCR+) and those not taking Sinemet CR (SinCR-). Outcomes were compared between groups for PSG recordings analyzed in whole and split at their mid-point with each half analyzed separately, using linear regression. RESULTS: Fifty-seven subjects were studied, eight SinCR+, and 49 SinCR-. They were 65 % male, aged 64.4 ± 10.3 years (mean ± SD), with body mass index 27.26 ± 3.98 kg/m(2). The whole night AHI was 15.6 ± 13.3 and 29.1 ± 20.8 in SinCR+ and SinCR-, respectively (p = 0.07 unadjusted, p = 0.11 adjusted for confounders). A similar trend was observed in the first half of the night. In the second half, the SinCR+ group had significantly lower AHI (beta = -18.8; p = 0.01 adjusted) and respiratory arousal index (beta = -14.2; p = 0.02 adjusted) than the SinCR- group. CONCLUSIONS: Bedtime Sinemet CR appears to reduce OSA in PD patients. There were no significant differences between groups in the first half of the night likely because of residual effects of short-acting levodopa in both groups, while Sinemet CR had residual effect in the second half. These results possibly provide an alternative to help manage OSA and improve sleep quality in PD patients.

Diagnosis of Obstructive Sleep Apnea in Parkinson's Disease Patients: Is Unattended Portable Monitoring a Suitable Tool?

Purpose. Obstructive sleep apnea (OSA) is frequent in Parkinson's disease (PD) and may contribute to nonmotor symptoms. Polysomnography (PSG) is the gold standard for OSA diagnosis. Unattended portable monitoring (PM) may improve access to diagnosis but has not been studied in PD. We assessed feasibility and diagnostic accuracy in PD. Methods. Selected PD patients without known OSA underwent home PM and laboratory PSG. The quality of PM signals (n = 28) was compared with matched controls. PM accuracy was calculated compared with PSG for standard apnea hypopnea index (AHI) thresholds. Results. Technical failure rate was 27.0% and airflow signal quality was lower than in controls. Sensitivity of PM was 84.0%, 36.4%, and 50.0% for AHI cut-offs of 5/h, 15/h, and 30/h, respectively, using the same cut-offs on PM. Specificity was 66.7%, 83.3%, and 100%, respectively. PM underestimated the AHI with a mean bias of 12.4/h. Discrepancy between PM and PSG was greater in those with more motor dysfunction. Conclusion. PM was adequate to "rule in" moderate or severe OSA in PD patients, but the failure rate was relatively high and signal quality poorer than in controls. PM overall underestimated the severity of OSA in PD patients, especially those with greater motor dysfunction.

USP8 regulates mitophagy by removing K6-linked ubiquitin conjugates from parkin.

Mutations in the Park2 gene, encoding the E3 ubiquitin-ligase parkin, are responsible for a familial form of Parkinson's disease (PD). Parkin-mediated ubiquitination is critical for the efficient elimination of depolarized dysfunctional mitochondria by autophagy (mitophagy). As damaged mitochondria are a major source of toxic reactive oxygen species within the cell, this pathway is believed to be highly relevant to the pathogenesis of PD. Little is known about how parkin-mediated ubiquitination is regulated during mitophagy or about the nature of the ubiquitin conjugates involved. We report here that USP8/UBPY, a deubiquitinating enzyme not previously implicated in mitochondrial quality control, is critical for parkin-mediated mitophagy. USP8 preferentially removes non-canonical K6-linked ubiquitin chains from parkin, a process required for the efficient recruitment of parkin to depolarized mitochondria and for their subsequent elimination by mitophagy. This work uncovers a novel role for USP8-mediated deubiquitination of K6-linked ubiquitin conjugates from parkin in mitochondrial quality control.