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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.

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.

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.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.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- (β = -0.01 vs. 0.61, p = 0.03; p = 0.12 vs. OSA+CPAP- [β = 0.39]) and TUG change was lower compared to OSA+CPAP- (β = -0.01 vs. 0.13, p = 0.002; p = 0.05 vs. OSA- [β = 0.02]).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.

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.

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.

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.

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. 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. 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/m2. 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. 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.

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.

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. Most primary sleep disorders may co-exist with PD; the majority of these disorders have unique features when expressed in the PD population. 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.

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.