Search

Objectives: To provide an update on the effect of sodium-glucose cotransporter 2 (SGLT2) inhibitors on stroke in patients with type 2 diabetes (T2D)., Methods: PubMed, Embase, and Cochrane Library were systematically searched for randomized controlled trials (RCTs) comparing SGLT2 inhibitors versus placebo or other therapies in patients with T2D and reporting stroke endpoint. We computed the risk ratios (RRs) to binary endpoints, with 95 % confidence intervals (CIs)., Results: A total of 71 RCTs and 105,914 patients were included, of whom 62,488 (59 %) were randomized to the SGLT2 inhibitors group. The follow-up ranged from 12 weeks to 4.2 years. There were no significant differences between groups in all types of stroke (RR 0.96; 95 % CI 0.89-1.04), ischemic stroke (RR 0.89; 95 % CI 0.76-1.04), and transient ischemic attack (RR 0.96; 95 % CI 0.79-1.16). Patients on SGLT2 inhibitors experienced lower rates of hemorrhagic stroke (RR 0.62; 95 % CI 0.39-0.98). In the subgroup analysis of the type of drug, sotagliflozin significantly reduced all types of stroke (RR 0.74; 95 % CI 0.56-0.97)., Conclusion: In this meta-analysis of 71 RCTs comprising 105,914 patients with T2D, SGLT2 inhibitors were not associated with a reduced risk of stroke and transient ischemic attack compared to placebo or other therapies; however, there was a trend toward reduced risk of hemorrhagic stroke. Among all SGLT2 inhibitors, sotagliflozin significantly reduced the risk of stroke., Competing Interests: Declaration of competing interest Dr. Sur has served as a consultant for Medtronic; receives research funding as the Evelyn F. McKnight Brain Institute Neurocognitive Scholar and the Florida Stroke Registry COHAN A-2; and serves on the editorial board for Stroke, JACC: Advances, and the Journal of Clinical and Translational Investigation., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Laryngeal dystonia is a potentially disabling task specific dystonia primarily affecting speech. The evaluation and diagnosis of laryngeal dystonia remain challenging, and often require a multi-disciplinary approach, involving collaboration among speech language pathologists, neurologists and laryngologists (1-5). It is crucial to correctly differentiate between the types of laryngeal dystonia due to the distinct therapeutic approaches and responses to botulinum toxin therapy or speech therapy. For educational purposes, we have divided laryngeal dystonia into two main types: adductor and abductor dystonia. In this article, we describe a series of examination techniques that can assist movement disorders neurologists diagnosing this condition, and appropriately differentiating the most common forms of laryngeal dystonia., (© 2024 International Parkinson and Movement Disorder Society.)

Background: Progressive Supranuclear Palsy (PSP) is a sporadic neurodegenerative disease without a clear geographic prevalence. Cohorts studied in the UK and India showed no higher prevalence of atypical parkinsonism in South Asian patients. We describe the ethnic and racial background of PSP patients in the Greater Toronto Area (GTA), Canada., Methods: A prospective observational study of patients with clinically probable PSP evaluated at the dedicated Rossy PSP program. Demographic and clinical data were collected at baseline including PSP phenotype. Results were compared with the latest demographic information from the greater Toronto area., Results: Of the 197 patients screened, 135 had probable PSP and resided within the GTA. The mean age at visit was 71.1 years, disease duration 4.4 years, and disease severity moderate. Compared to our catchment area, there was a higher proportion of patients with a South Asian origin and a lower proportion of patients from East and Southeastern Asia and Africa. A secondary analysis using population census data limited to individuals greater than 65 confirmed the significantly higher representation of South Asians in our clinic but found no differences for other racial and ethnic origins., Conclusion: Evaluation of this Toronto cohort found a greater than expected proportion of affected individuals with South Asian ethnic and racial origin. Despite limitations, our results suggest the possibility of a racial and ethnic predisposition to PSP. Further studies are needed to confirm and to address potential associated risk factors, and genome-environmental interactions., Competing Interests: Declaration of competing interest The authors deny any conflict of interest regarding the data described in this article. BC and DDL have no disclosures related to the content of this manuscript. Dr. Lang has served as an advisor for AbbVie, AFFiRis, Alector, Amylyx, Biogen, BioAdvance, BlueRock, BMS, Denali, Janssen, Jazz, Lilly, Novartis, Paladin, Retrophin, Roche, Sun Pharma, and UCB; received honoraria from Sun Pharma, AbbVie and Sunovion; received grants from Brain Canada, Canadian Institutes of Health Research, Edmond J Safra Philanthropic Foundation, Michael J. Fox Foundation, the Ontario Brain Institute, Parkinson Foundation, Parkinson Canada, and W. Garfield Weston Foundation; received publishing royalties from Elsevier, Saunders, Wiley-Blackwell, Johns Hopkins Press, and Cambridge University Press. Dr. Tartaglia receives funding from NIH, Weston Brain Foundation, and in-kind funding from Roche. She conducts clinical trials for Biogen, Anavex, Janssen, Novo Nordisk, Merck, Green Valley, UCB. Dr Fox has received Clinic support from the Edmond J Safra Foundation for Parkinson Research; Parkinson Foundation and the Toronto Western and General Foundation. Research Funding from Michael J Fox Foundation for Parkinson Research, NIH (Dystonia Coalition); Parkinson Canada. Honoraria from the International Parkinson and Movement Disorder Society. Site PI for Clinical Trials for Alexion, Biotie, Consultancy/Speaker fees from AbbVie, Bial, Ipsen, Sunovion; Paladin and Royalties from Oxford University Press., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Multiple system atrophy is a neurodegenerative disease with α-synuclein pathology predominating in the striatonigral and olivopontocerebellar systems. Mixed pathologies are considered to be of low frequency and mostly comprise primary age-related tauopathy or low levels of Alzheimer's disease-related neuropathologic change. Therefore, the concomitant presence of different misfolded proteins in the same brain region is less likely in multiple system atrophy. During the neuropathological evaluation of 21 consecutive multiple system atrophy cases, we identified four cases exhibiting an unusual discrepancy between high Thal amyloid-β phase and low transentorhinal Braak neurofibrillary tangle stage. We mapped α-synuclein pathology, measured the size and number of glial cytoplasmic inclusions and compared the amyloid-β peptides between multiple system atrophy and Alzheimer's disease. In addition, we performed α-synuclein seeding assay from the affected putamen samples. We performed genetic testing for APOE , MAPT , PSEN1 , PSEN2 and APP . We refer to the four multiple system atrophy cases with discrepancy between amyloid-β and tau pathology as 'amyloid-β-predominant Alzheimer's disease neuropathologic change-multiple system atrophy' to distinguish these from multiple system atrophy with primary age-related tauopathy or multiple system atrophy with typical Alzheimer's disease neuropathologic change. As most multiple system atrophy cases with mixed pathologies reported in the literature, these cases did not show a peculiar clinical or MRI profile. Three amyloid-β-predominant Alzheimer's disease neuropathologic change-multiple system atrophy cases were available for genetic testing, and all carried the APOE ɛ4 allele. The extent and severity of neuronal loss and α-synuclein pathology were not different compared with typical multiple system atrophy cases. Analysis of amyloid-β peptides revealed more premature amyloid-β plaques in amyloid-β-predominant Alzheimer's disease neuropathologic change-multiple system atrophy compared with Alzheimer's disease. α-Synuclein seeding amplification assay showed differences in the kinetics in two cases. This study highlights a rare mixed pathology variant of multiple system atrophy in which there is an anatomical meeting point of amyloid-β and α-synuclein, i.e. the striatum or cerebellum. Since biomarkers are entering clinical practice, these cases will be recognized, and the clinicians have to be informed that the prognosis is not necessarily different than in pure multiple system atrophy cases but that the effect of potential α-synuclein-based therapies might be influenced by the co-presence of amyloid-β in regions where α-synuclein also aggregates. We propose that mixed pathologies should be interpreted not only based on differences in the clinical phenotype but also on whether protein depositions regionally overlap, potentially leading to a different response to α-synuclein-targeted therapies., Competing Interests: G.G.K. holds a shared patent for the 5G4 antibody and received royalty for 5G4 synuclein antibody. Other authors report no competing interests in relation to the work described., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Guarantors of Brain.)

Background: Functional parkinsonism is an important differential diagnosis of Parkinson's disease (PD). Based on anecdotal experience, we hypothesized that arm swing while walking and running could differentiate these two conditions, but this assumption has not been previously explored systematically., Objectives: To examine differences in arm swing while walking and running between patients with PD and functional parkinsonism., Methods: We analyzed blinded video assessments of arm swing and other gait parameters in patients with asymmetrical PD (n = 81) and functional parkinsonism (n = 8) while walking and running. The groups were matched for age, sex and disease duration., Results: In contrast to those with PD, patients with functional parkinsonism (i) were more likely to have a marked asymmetry in arm swing while walking (5/8 vs. 25/81; P = 0.06), (ii) were less likely to improve arm swing while running with full effort (3/8 vs. 72/81; P < 0.001) and (iii) demonstrated normal passive arm swing even when asymmetry of arm swing was marked during running/walking (6/6 vs. 9/33; P = 0.002)., Conclusions: Assessment of arm swing while walking and running and passive arm swing could be important differentiating clinical features between functional parkinsonism and PD., (© 2023 International Parkinson and Movement Disorder Society.)

Background: Impaired glucose and energy metabolism has been suggested as a pathogenic mechanism underlying Parkinson's disease (PD). In recent cohorts, phosphoglycerate kinase 1 activators (PGK1a) have been associated with a lower incidence of PD when compared with other antiprostatic agents that do not activate PGK1., Objective: We aimed to perform a systematic review and meta-analysis comparing the incidence of PD in patients taking PGK1a versus tamsulosin., Methods: We searched PubMed, Embase, and Cochrane Library for studies comparing PGK1a vs. tamsulosin in adults and elderly. The primary outcome was the incidence of PD. We computed hazard ratios (HR) for binary endpoints, with 95% confidence intervals (CIs). Statistical analysis was performed using Review Manager 5.4 and R (version 4.3.1)., Results: A total of 678,433 participants from four cohort studies were included, of whom 287,080 (42.3%) received PGK1a. Mean age ranged from 62 to 74.7 years and nearly all patients were male. Patients taking PGK1a had a lower incidence of PD (PGK1a 1.04% vs. tamsulosin 1.31%; HR 0.80; 95% CI 0.71-0.90; p < 0.01). This result remained consistent in a sensitivity analysis excluding patients of age 60 years old or younger (PGK1a 1.21% vs. tamsulosin 1.42%; HR 0.82; 95% CI 0.71-0.95; p < 0.01)., Conclusions: Glycolysis-enhancing drugs are associated with a lower incidence of PD when compared with tamsulosin in adults and elderly individuals with prostatic disease in use of alpha-blockers. Our findings support the notion of glycolysis as a potential neuroprotective mechanism in PD. Future investigations with randomized controlled trials are needed.

Introduction: Caregivers play an important role in Parkinson's disease (PD) treatment, especially as the disease progresses. As the symptom profile and needs of people with PD (PwP) differ across ethnoracial groups, whether caregiving needs also differ for different ethnoracial groups should be investigated., Methods: Data were obtained from the Parkinson's Foundation funded Parkinson's Outcomes Project for PwP identifying as Hispanic (n = 495), non-Hispanic Asian (n = 170), non-Hispanic Black (n = 162), or non-Hispanic White (n = 7687). Cross-sectional and longitudinal total Multidimensional Caregiver Strain Index (MCSI) and domain-specific scores for caregiving burden were compared across the ethnoracial groups. Effect of demographics and clinical variables, interaction of these variables with ethnoracial groups for caregiver burden was assessed., Results: Care partners of PwP identifying as non-Hispanic Asian experienced the most burden. PwP identifying as non-Hispanic White were oldest, yet their care partners experienced the least burden. Care partners of PwP identifying as non-Hispanic Asian experienced more burden in physical and social domains, care partners of PwP identifying as Hispanic experienced more burden in financial and elder demanding/manipulative domains. Over time, burden increased similarly across the ethnoracial groups. Effect of frequency of falls, hospital admission, neuropsychiatric disorder and social support on burden over time differed across the groups., Conclusion: PwP from different ethnoracial groups can experience different levels of caregiving burden. Predictors for caregiving burden, such as social support and falls can have different impacts based on ethnicity and race. Caregiver needs should also be assessed and culturally competent support should be provided to benefit all affected by PD., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: All authors report data were provided by National Parkinson Foundation. Ece Bayram reports financial support was provided by National Institute on Aging. IL's research is supported by the National Institutes of Health grants: 2R01AG038791-06A, U01NS100610, U01NS80818, R25NS098999; U19 AG063911-1 and 1R21NS114764-01A1; the Michael J Fox Foundation, Parkinson Foundation, Lewy Body Dementia Association, CurePSP, Roche, AbbVie, Biogen, Centogene. EIP-Pharma, Biohaven Pharmaceuticals, Novartis, and United Biopharma SRL, UCB. She is a member of the Scientific Advisory Board for Amydis, but does not receive funds and from the Rossy PSP Program at the University of Toronto. She receives her salary from the University of California San Diego and as Chief Editor of Frontiers in Neurology., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Background: Multiple system atrophy with parkinsonism (MSA-P) is a progressive condition with no effective treatment., Objective: The aim of this study was to describe the safety and efficacy of deep brain stimulation (DBS) of globus pallidus pars interna and externa in a cohort of patients with MSA-P., Methods: Six patients were included. Changes in Movement Disorders Society Unified Parkinson's Disease Rating Scale Part III (MDS-UPDRS III), Parkinson's Disease Questionnaire (PDQ-39) scores, and levodopa equivalent daily dose were compared before and after DBS. Electrode localization and volume tissue activation were calculated., Results: DBS surgery did not result in any major adverse events or intraoperative complications. Overall, no differences in MDS-UPDRS III scores were demonstrated (55.2 ± 17.6 preoperatively compared with 67.3 ± 19.2 at 1 year after surgery), although transient improvement in mobility and dyskinesia was reported in some subjects., Conclusions: Globus pallidus pars interna and externa DBS for patients with MSA-P did not result in major complications, although it did not provide significant clinical benefit as measured by MDS-UPDRS III. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society., (© 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.)

Background and Objectives: Racial and ethnic minorities have been underrepresented in Parkinson disease (PD) research, limiting our understanding of treatments and outcomes across all non-White groups. The goal of this research is to investigate variability in health-related quality of life (HRQoL) and other outcomes in patients with PD across different races and ethnicities., Methods: This was a retrospective, cross-sectional and longitudinal, cohort study of individuals evaluated at PD Centers of Excellence. A multivariable regression analysis adjusted for sex, age, disease duration, Hoehn and Yahr (H&Y) stage, comorbidities, and cognitive score was used to investigate differences between racial and ethnic groups. A multivariable regression with skewed-t errors was performed to assess the individual contribution of each variable to the association of 39-item PD Questionnaire (PDQ-39) with race and ethnicity., Results: A total of 8,514 participants had at least 1 recorded visit. Most of them (90.2%) self-identified as White (n = 7,687), followed by 5.81% Hispanic (n = 495), 2% Asians (n = 170), and 1.9% African American (n = 162). After adjustment, total PDQ-39 scores were significantly higher (worse) in African Americans (28.56), Hispanics (26.62), and Asians (25.43) when compared with those in White patients (22.73, p < 0.001). This difference was also significant in most PDQ-39 subscales. In the longitudinal analysis, the inclusion of cognitive scores significantly decreased the strength of association of the PDQ-39 and race/ethnicity for minority groups. A mediation analysis demonstrated that cognition partially mediated the association between race/ethnicity and PDQ-39 scores (proportion mediated 0.251, p < 0.001)., Discussion: There were differences in PD outcomes across racial and ethnic groups, even after adjustment for sex, disease duration, HY stage, age, and some comorbid conditions. Most notably, there was worse HRQoL among non-White patients when compared with White patients, which was partially explained by cognitive scores. The underlying reason for these differences needs to be a focus of future research., (© 2023 American Academy of Neurology.)

Background: Pain is common in Parkinson's disease (PD), but effective therapies are limited., Objectives: To determine the maximum tolerated dose (MTD) and safety of formulations of delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD) for pain in PD., Methods: In this phase 1b, double-blind, randomized, single-center study, participants were randomized to three formulations of THC/CBD (18:0, 10:10, and 1:20). The MTD, adverse events (AE), and tolerability are described for each formulation., Results: Eight participants were randomized. The MTD was similar among groups (0.8-0.9 mL/daily), and there were no serious AE or study drop-outs. The most common AE were drowsiness and dizziness (three participants). Epworth sleepiness scale scores were higher in the high CBD formulation (1:20)., Conclusions: In patients with pain and PD, mixed formulations of THC/CBD were tolerated with no serious AE. Considering the safety profile, future phase II studies should be considered., (© 2023 International Parkinson and Movement Disorder Society.)

Background and Objectives: Representation of persons from marginalized racial and ethnic groups in Parkinson disease (PD) trials has been low, limiting the generalizability of therapeutic options for individuals with PD. Two large phase 3 randomized clinical trials sponsored by the National Institute of Neurological Disorders and Stroke (NINDS), STEADY-PD III and SURE-PD3, screened participants from overlapping Parkinson Study Group clinical sites under similar eligibility criteria but differed in participation by underrepresented minorities. The goal of this research is to compare recruitment strategies of PD participants belonging to marginalized racial and ethnic groups., Methods: A total of 998 participants with identified race and ethnicity consented to STEADY-PD III and SURE-PD3 from 86 clinical sites. Demographics, clinical trial characteristics, and recruitment strategies were compared. NINDS imposed a minority recruitment mandate on STEADY-PD III but not SURE-PD3., Results: Ten percent of participants who consented to STEADY-PD III self-identified as belonging to marginalized racial and ethnic groups compared to 6.5% in SURE-PD3 (difference = 3.9%, 95% confidence interval [CI] 0.4%-7.5%, p value = 0.034). This difference persisted after screening (10.1% of patients in STEADY-PD III vs 5.4% in SURE-PD 3, difference = 4.7%, 95% CI 0.6%-8.8%, p value = 0.038)., Discussion: Although both trials targeted similar participants, STEADY-PD III was able to consent and recruit a higher percentage of patients from racial and ethnic marginalized groups. Possible reasons include differential incentives for achieving minority recruitment goals., Trial Registration Information: This study used data from The Safety, Tolerability, and Efficacy Assessment of Isradipine for Parkinson Disease (STEADY-PD III; NCT02168842) and the Study of Urate Elevation in Parkinson's Disease (SURE-PD3; NCT02642393)., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.)

Motor symptoms are a core feature of Parkinson's disease (PD) and cause a significant burden on patients' quality of life. Oral levodopa is still the most effective treatment, however, the motor benefits are countered by inherent pharmacologic limitations of the drug. Additionally, with disease progression, chronic levodopa leads to the appearance of motor complications including motor fluctuations and dyskinesia. Furthermore, several motor abnormalities of posture, balance, and gait may become less responsive to levodopa. With these unmet needs and our evolving understanding of the neuroanatomic and pathophysiologic underpinnings of PD, several advances have been made in defining new therapies for motor symptoms. These include newer levodopa formulations and drug delivery systems, refinements in adjunctive medications, and non-dopaminergic treatment strategies. Although some are in early stages of development, these novel treatments potentially widen the available options for the management of motor symptoms allowing clinicians to provide an individually tailored care for PD patients. Here, we review the existing and emerging interventions for PD with focus on newly approved and investigational drugs for motor symptoms, motor fluctuations, dyskinesia, and balance and gait dysfunction., (© 2022. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Background: Periodic limb movements while awake (PLMA) are similar to Periodic limb movements in sleep (PLMS) but occurring during wakefulness and seen in association with restless leg syndrome (RLS)., Objectives: To describe PLMA as a wearing-off phenomenon in Parkinson's Disease (PD)., Methods: We describe four individuals with PD and PLMS, who had associated similar periodic and stereotypic lower extremity movements during wakefulness, thought to be secondary to PLMA, and were highly responsive to dopaminergic treatment., Results: Despite the prevalence of RLS and PLMS in individuals with PD, the presence of similar movements during wakefulness has not been well characterized. The lack of a specific diagnostic criteria poses a significant diagnostic challenge., Conclusions: We describe, for the first time to our knowledge, PLMA as a wearing-off phenomenon in PD. This entity could be classified in the spectrum of "low-dose dyskinesia," as we found that it was highly responsive to dopaminergic treatment., Competing Interests: We did not receive specific funding for this work. We declare that there are no conflicts of interest relevant to this work., (© 2022 International Parkinson and Movement Disorder Society.)

Background: Effective dissemination of scientific results depends on competent peer reviewers. Participating as a reviewer is important for academic advancement, although no formal training in peer review has existed in the movement disorders field., Objectives: To report the design, implementation, and outcomes of a Peer Reviewing Education and Mentoring Program., Methods: We enrolled 10 participants in a 1-year mentored program with didactic training followed by two peer reviews with feedback from a senior mentor. Outcomes measures were an objective skills assessment and subjective questionnaire., Results: Participants were diverse in gender, age, and background. All participants were deemed competent reviewers by their mentors upon completion. Objective skills improved after didactic training and self-assessment increased significantly after program completion (19.5 [12-25] to 29 [25-30], P < 0.001)., Conclusions: This dedicated program helped participants gain competence and confidence in the peer review process. We plan to continue the program while improving educational methods and assessments. © 2022 International Parkinson and Movement Disorder Society., (© 2022 International Parkinson and Movement Disorder Society.)

Competing Interests: There were no funding sources for this paper and no conflicts of interest.

Background: Pallido-nigro-luysian atrophy (PNLA) is a rare neurodegenerative disorder with only a few cases reported to date. Although the clinical picture usually resembles progressive supranuclear palsy, pathological examination reveals more selective atrophy and loss of neurons in the globus pallidus, substantia nigra and subthalamic nucleus., Objectives: To describe the clinical features and pathological findings of a patient with PNLA., Methods: Case report with clinico-pathological discussion., Results: An 83-year-old man presented to our clinic with a vertical supranuclear gaze palsy, parkinsonism, gait impairment and sleep abnormalities suggestive of REM-sleep behavior disorder. Neuropathological examination 5 years after symptom onset revealed subcortical tau proteinopathy compatible with a PNLA pattern. There was also an associated mild degree of limbic/subcortical inflammatory response, Alzheimer's disease-related changes, as well as argyrophilic grain disease., Conclusions: We present a comprehensive clinico-pathological discussion of a patient with PNLA. Besides parkinsonism and vertical supranuclear gaze palsy, the patient also had a sleep disorder, clinically suggestive of REM behavioral disorder, which has not been previously reported in PNLA. We expand the clinical phenotype of this rare condition and provide neuropathological evidence for the associated abnormalities., Competing Interests: Rossy Foundation, Safra Foundation and Porridge for Parkinson's Foundation. The authors declare that there are no conflicts of interest relevant to this work., (© 2021 International Parkinson and Movement Disorder Society.)

Background: Dysphagia is a frequent complication that may increase morbidity and mortality in Parkinson's disease (PD). Nevertheless, there is limited data on its objective impact on healthcare outcomes., Objective: To investigate the outcomes associated with dysphagia in hospitalized patients with PD and associated healthcare costs and utilization., Methods: We performed a retrospective cohort study using the National Inpatient Sample (NIS) data from 2004 to 2014. A multivariable regression analysis was adjusted for demographic, and comorbidity variables to examine the association between dysphagia and associated outcomes. Logistic and negative binomial regressions were used to estimate odds or incidence rate ratios for binary and continuous outcomes, respectively., Results: We identified 334,395 non-elective hospitalizations of individuals with PD, being 21,288 (6.36%) associated with dysphagia. Patients with dysphagia had significantly higher odds of negative outcomes, including aspiration pneumonia (AOR 7.55, 95%CI 7.29-7.82), sepsis (AOR 1.91, 95%CI 1.82-2.01), and mechanical ventilation (AOR 2.00, 95%CI 1.86-2.15). For hospitalizations with a dysphagia code, the length of stay was 44%(95%CI 1.43-1.45) longer and inpatient costs 46%higher (95%CI 1.44-1.47) compared to those without dysphagia. Mortality was also substantially increased in individuals with PD and dysphagia (AOR 1.37, 95%CI 1.29-1.46)., Conclusion: In hospitalized patients with PD, dysphagia was a strong predictor of adverse clinical outcomes, and associated with substantially prolonged length of stay, higher mortality, and care costs. These results highlight the need for interventions focused on early recognition and prevention of dysphagia to avoid complications and lower costs in PD patients.

Background: Deep brain stimulation of the ventral intermediate nucleus (VIM) or caudal zona incerta (cZI) is effective for refractory essential tremor (ET). To refine stereotactic planning for lead placement, we developed a unique individualized anatomy-based planning protocol that targets both the VIM and the cZI in patients with ET., Methods: 33 patients with ET underwent VIM-cZI lead implantation with targeting based on our protocol. Indirect targeting was adjusted based on anatomic landmarks as reference lines bisecting the red nuclei and ipsilateral subthalamus. Outcomes were evaluated through the follow-up of 31.1 ± 18.4 months. Active contact coordinates were obtained from reconstructed electrodes in the Montreal Neurological Institute space using the MATLAB Lead-DBS toolbox., Results: Mean tremor improvement was 79.7% ± 22.4% and remained stable throughout the follow-up period. Active contacts at last postoperative visit had mean Montreal Neurological Institute coordinates of 15.5 ± 1.6 mm lateral to the intercommissural line, 15.3 ± 1.8 mm posterior to the anterior commissure, and 1.4 ± 2.9 mm below the intercommissural plane. No hemorrhagic complications were observed in the analyzed group., Conclusions: Individualized anatomy-based VIM-cZI targeting is feasible and safe and is associated with favorable tremor outcomes., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Introduction: Palliative care in Parkinson's Disease (PD) is an effective intervention to improve quality of life, although historically, access and availability have been very restricted., Methods: We performed a retrospective cohort study using the National Inpatient Sample (NIS) data from 2007 to 2014. Diagnostic codes were used to identify patients with PD and palliative care referral. Trends were calculated and logistic analysis performed to identify predictors of palliative care use., Results: We identified 397,963 hospitalizations from 2007 to 2014 for patients with PD. Of these, 10,639 (2.67%) were referred to palliative care. The rate of consultation increased from 0.85% in 2007 to 4.49% in 2014. For 1 unit in year increase, there was 1.23 time the odds of receiving palliative consultation (OR 1.23, CI 1.21-1.25, p < 0.0001). Hispanics (OR 0.90, CI 0.81-1.01, p = 0.0550), Black (OR 0.90, CI 0.81-1.01, p = 0.0747) and White patients had similar rates of referral after adjustment. Women were less likely to be referred to palliative care (OR 0.90, CI 0.87-0.94, p < 0.0001). Other factors strongly associated with a higher rate of referrals included private insurance when compared to Medicare (OR 2.14, CI 1.89-2.41, p < 0.0001) and higher income (OR 1.41, CI 1.30-1.53, p < 0.0001)., Conclusion: There has been a significant increase in palliative care referrals among hospitalized patients with PD in the US, although the overall rate remains low. After controlling for confounders, racial and ethnic disparities were not found. Women, patients with Medicare/Medicaid, and those with lower income were less likely to be referred to palliative care., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Background: Deep brain stimulation (DBS) is considered standard of care for the treatment of medically refractory Parkinson disease (PD). The placement of brain electrodes is performed using contrast imaging to enhance blood vessel identification during stereotactic planning. We present our experience with a series of patients implanted using noncontrast imaging., Methods: All cases of DBS surgery for PD performed between 2012 and 2018 with noncontrast imaging were retrospectively reviewed. Clinical features, postoperative imaging, and complications were analyzed., Results: A total of 287 deep-seated electrodes were implanted in 152 patients. Leads were placed at the subthalamic nucleus and globus pallidus internus in 258 and 29 hemispheres, respectively. We identified 2 cases of intracranial hemorrhage (0.7%)., Conclusions: DBS lead placement can be performed without the use of intravenous contrast with a postoperative intracranial hemorrhage rate comparable with other reported series., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: Randomized clinical trials (RCTs) in Parkinson's disease (PD) have historically enrolled a low number of underrepresented minorities, lessening the generalizability of therapeutic developments. Although there are racial disparities in PD, little is known regarding neuropsychiatric symptoms and other nonmotor manifestations across all races/ethnicities., Objective: To assess minority participation in PD trials evaluating the treatment of neuropsychiatric symptoms and explore underlying reasons., Methods: We systematically searched PubMed and Embase for RCTs with a primary goal of treating neuropsychiatric symptoms in PD patients from 2000-2019. The pooled prevalence and 95% confidence interval (CI) of being white and enrolled in a clinical trial was calculated using the inverse variance method. I-square was calculated as a measure of heterogeneity and meta-regression was used to evaluate temporal trends., Results: We included 63 RCTs with a total of 7,973 patients. In pooled analysis, 11 (17.5%) RCTs reported race/ethnicity. Of studies reporting this data, 5 African American (0.2%), 16 Hispanics (0.64%), and 539 Asians (21.44%) were enrolled. The pooled prevalence of being white in clinical trials was 98% (CI 0.97-0.98, p < 0.001), with 1,908 patients (75.8%). NIH-funded studies were most likely to report racial data when compared to non-NIH trials (p = 0.032)., Conclusion: This large pooled analysis found a small percentage of RCTs reporting race/ethnicity when evaluating treatment of neuropsychiatric symptoms in PD. There was a disproportionally high number of white patients when compared to African Americans and Hispanics. More studies are needed to investigate this discrepancy and improve rates of & minority enrollment in PD trials.

Introduction : For patients with Parkinson's disease (PD), the treatment of motor and nonmotor fluctuations is tantamount to maintaining quality of life. Subcutaneous apomorphine has been the only commercially available rescue therapy for the treatment of OFF episodes. In December 2018, CVT-301 (Inbrija), an inhaled formulation of levodopa (LD), was approved by the FDA for this indication. Areas covered : In this review, the authors summarize the armamentarium available to address motor fluctuations in PD, including medications in development. The authors discuss the pharmacological properties of CVT-301 as well as its efficacy and safety as reported in phase I, II, and III studies. Expert opinion : More than 20 medications or surgical procedures are available or in development to address motor fluctuations in PD. Deep brain stimulation (DBS) is an invasive but effective intervention at the end of the treatment spectrum. Less invasive therapies are used in combination to ameliorate motor fluctuations. Rescue therapies can help patients taking oral medications who experience delayed onset symptom relief (delayed ON), and unexpected wearing OFF by providing rapid and durable symptoms relief. CVT-301, an inhaled LD formulation, provides a safe and effective delivery mechanism that may be preferred by patients over subcutaneous injections.

Objectives: This study sought to determine whether there is a gender disparity in patients undergoing deep brain stimulation (DBS) surgery for Parkinson's disease (PD) at a single health system, and better understand the reasons for this discrepancy., Materials and Methods: We analyzed data from the University of Miami DBS Database, which included 3251 PD patients, using chi-square, repeated measures ANOVA, and t tests to examine gender differences in the number of patients referred for surgery, reasons for referral, number receiving/not receiving surgery, reasons for not receiving surgery, and postsurgical outcomes., Results: During the study period, 207 PD patients were referred for DBS (75.8% male), and 100 underwent surgery (77.0% male). Of those who did not receive surgery, the most common reasons were need for further medical optimization (26.2%), suboptimal performance on neuropsychological evaluation (22.4%), other reason (20.6%), lost to follow-up (18.7%), or patient preference (12.2%). However, in women one of the most common reasons was patient preference (28.0%), and this was significant compared to men (p < 0.001). Men were more likely to be lost to follow-up (p = 0.046). There was no statistically significant difference in postsurgical outcomes., Conclusions: Despite similar postsurgical improvements, women were less likely to undergo DBS surgery due to their own preference, while men were more likely to be lost to follow-up. These data underscore the need for increased education and awareness of DBS so that all patients with PD who qualify for surgery can benefit from this procedure., (© 2019 International Neuromodulation Society.)

A 24-year-old woman with no significant medical or psychiatric history was brought to the emergency department due to altered mental status and bizarre behaviour. Physical examination was remarkable for decreased speech output and orofacial dyskinesia. Upon further evaluation, electroencephalogram showed extreme delta brush waves and cerebrospinal fluid was positive for anti-NMDA receptor antibodies. Despite aggressive treatment with steroids and immunosuppressive therapy, her dyskinesia was severe enough to cause tooth loss, tongue and lip laceration., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2019. No commercial re-use. See rights and permissions. Published by BMJ.)

Considerable epidemiological and laboratory data have suggested that caffeine, a nonselective adenosine receptor antagonist, may protect against the underlying neurodegeneration of parkinson's disease (PD). Although both caffeine and more specific antagonists of the A2A subtype of adenosine receptor (A2AR) have been found to confer protection in animal models of PD, the dependence of caffeine's neuroprotective effects on the A2AR is not known. To definitively determine its A2AR dependence, the effect of caffeine on 1-methyl-4-phenyl-1,2,3,6 tetra-hydropyridine (MPTP) neurotoxicity was compared in wild-type (WT) and A2AR gene global knockout (A2A KO) mice, as well as in central nervous system (CNS) cell type-specific (conditional) A2AR knockout (cKO) mice that lack the receptor either in postnatal forebrain neurons or in astrocytes. In WT and in heterozygous A2AR KO mice caffeine pretreatment (25mg/kgip) significantly attenuated MPTP-induced depletion of striatal dopamine. By contrast in homozygous A2AR global KO mice caffeine had no effect on MPTP toxicity. In forebrain neuron A2AR cKO mice, caffeine lost its locomotor stimulant effect, whereas its neuroprotective effect was mostly preserved. In astrocytic A2AR cKO mice, both caffeine's locomotor stimulant and protective properties were undiminished. Taken together, these results indicate that neuroprotection by caffeine in the MPTP model of PD relies on the A2AR, although the specific cellular localization of these receptors remains to be determined., (Copyright © 2016 IBRO. All rights reserved.)

Unlabelled: This cross-sectional study involves randomly selected men aged 50 to 99 years and postmenopausal women. Either central fat mass or peripheral fat mass were associated to osteoporosis or osteopenia independently from fat-free body mass and other confounding factors., Introduction: Obesity and osteoporosis are public health problems that probably share common pathophysiological mechanisms. The question if body fat mass, central or peripheral, is protective or harmful for osteoporosis or osteopenia is not completely resolved. This study aims to investigate the association between osteoporosis or osteopenia, and fat body mass (central and peripheral) independently from fat-free body mass, in men aged 50 to 99 years old and postmenopausal women randomly selected in the community., Methods: This is a cross-sectional investigation with a random sample of registered population in Niterói Family Doctor Program (FDP), State of Rio de Janeiro, Brazil. Bone mineral density (BMD) and fat-free mass were assessed by dual X-ray absorptiometry (DXA)., Results: There was statistically significant bivariate association between bone loss with gender, age, skin color, alcohol consumption at risk dose, use of thiazide, fat-free body mass, and fat body mass (central and peripheral). In the multiple analysis of fat-free body mass, central and peripheral fat body mass showed an independent and protective effect on the presence of osteoporosis or osteopenia (p value <0.001)., Conclusion: Since both obesity and osteoporosis are public health problems worldwide, strategies aimed at preventing both conditions should be encouraged during aging.

This is a report on eight non-HIV infected leprosy patients presenting unusual co-infection with other, often neglected, tropical diseases, namely: American tegumentary leishmaniasis (ATL), sporotrichosis, and cryptococcosis. To the best of our knowledge, there have been very few ATL-leprosy co-infection reports in the literature to date and only one previous description of the coexistence of leprosy-cryptococcosis and leprosy-sporotricosis.

Introduction: The consolidation of nephrology as a medical specialty is relatively new and its denomination does not intuitively reflects its true scope., Objective: To assess the degree of knowledge from a population sample regarding the term "nephrology"., Methods: We carried out a cross-sectional study in Niterói, RJ, with adult passerby individuals answering to the question "Do you know what nephrology is?". The variables recorded included: gender, age, skin-color, residence, income, educational level and kidney-disease history in the family. p values < 0.05 were considered significant., Results: Of the 564 individuals asked, 504 were willing to answer. Of those who refused, 64% were males, 58% caucasians--from whom 85% were aged > 30 years. The mean age among participants was 39 (22-56) years, 49% were males and 56% caucasians. Twenty-eight percent of the interviewees knew the term "nephrology". Their knowledge came from school (39%) and family (30%). Those who knew about the term "nephrology" were older (42 ± 17 vs. 39 ± 17 years, p < 0.05), had higher income (R$ 4,522 vs. R$ 2,934, p < 0.05) and higher education (27% vs. 12% with complete higher education, p < 0.001). They were predominantly caucasians (64% vs. 53%, p = 0.001), and had a higher rate of renal disease in the family (55% vs. 36%, p < 0.001). In the multivariate analysis, associations were maintained for age (OR 1.02; 95% CI 1.00 to 1.03, p = 0.004); higher education (OR 10.60, 95% CI, 4.20 to 26.86, p < 0.001) and kidney disease in the family (OR 2.2, 95% CI, 1.40 to 3.41, p < 0.001)., Conclusions: Only 28% knew the term "nephrology", illustrating the specialty's low penetration. We must strive to popularize this field of medicine aiming at better educating the population concerning the prevention and care of kidney diseases.