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Purpose of Review: The most common four neurodegenerative atypical parkinsonian disorders (APDs) are progressive supranuclear palsy (PSP), multiple system atrophy (MSA), corticobasal syndrome (CBS), and dementia with Lewy bodies (DLB). Their formal diagnostic criteria often require subspecialty experience to implement as designed and all require excluding competing diagnoses without clearly specifying how to do that. Validated diagnostic criteria are not available at all for many of the other common APDs, including normal pressure hydrocephalus (NPH), vascular parkinsonism (VP), or drug-induced parkinsonism (DIP). APDs also include conditions of structural, genetic, vascular, toxic/metabolic, infectious, and autoimmune origin. Their differential diagnosis can be challenging early in the course, if the presentation is atypical, or if a rare or non-neurodegenerative condition is present. This review equips community general neurologists to make an early provisional diagnosis before, or in place of, referral to a tertiary center. Early diagnosis would allay diagnostic uncertainty, allow prompt symptomatic management, provide disease-specific information and support resources, avoid further pointless testing and treatments, and create the possibility of trial referral., Recent Findings: We address 64 APDs using one over-arching flow diagram and a series of detailed tables. Most instances of APDs can be diagnosed with a careful history and neurological exam, along with a non-contrast brain MRI. Additional diagnostic tests are rarely needed but are delineated where applicable. Our diagnostic algorithm encourages referral to a tertiary center whenever the general neurologist feels it would be in the patient's best interest. Our algorithm emphasizes that the diagnosis of APDs is an iterative process, refined with the appearance of new diagnostic features, availability of new technology, and advances in scientific understanding of the disorders. Clinicians' proposals for all diagnostic tests for the APDs, including repeat visits, should be discussed with patients and their families to ensure that the potential information to be gained aligns with their larger clinical goals., Summary: We designed this differential diagnostic algorithm for the APDs to enhance general neurologists' diagnostic skills and confidence and to help them address the less common or more ambiguous cases., Competing Interests: M.K. Bruno: no relevant conflict of interest. She does have research funding from Michael J. Fox Foundation; R. Dhall: no relevant conflict of interest. He has received financial support from the following within the last year: Amneal pharmaceuticals, Sage Therapeutics, Neuroderm, Cerevel Therapeutics, Neurocrine, Neuraly, Alexion, Sun Pharma, Praxis Precision Medicines, Parkinson's Foundation, Aeon Biopharma, Abbvie, Pharma Two B, NIH Parent Grant #UL1TR003107 TRI Pilot Grant “Research Benefitting Rural Populations”. Dr. Dhall has received consulting revenues from Mitsubishi Tanabe Pharma America and Best Doctors. Dr. Dhall reports stock ownership (all at <$10,000) in medically related fields for Armata Pharmaceuticals, Compass Pathways, Biogen Idec, Atea Pharmaceuticals, Gilead Sciences, Imara, Inc, and SQZ Biotech; L.S. Honig: consulted for Biogen Eisai, Genentech/Roche, Medscape, and Prevail/Lilly. L.S. Honig has received research funding from Abbvie, Acumen, Alector, Biogen, Bristol-Myer Squibb, Cognition, Eisai, Genentech/Roche, Janssen/Johnson & Johnson, Eli Lilly, Transposon, UCB, and Vaccinex; Z. Mari: no relevant conflict of interest. He is immediate past Chair of the Movement Disorder Society's Telemedicine Study Group, Director of the Cleveland Clinic Lou Ruvo Center for Brain Health Parkinson's Foundation Center of Excellence, Chair of Parkinson Study Group's Motor Features WG, Associate Editor of Parkinsonism & Related Disorders, president-elect for the Clark County Medical Society, which he also is a Trustee; Z. Mari serves on the IAPRD's Congress Site Selection Committee and Website Committee, and the PPMI's Wearable Devices Task Force. Z. Mari has been recipient of institutional grant support from the NIH, PF, MJFF, Biogen, Eli Lilly, AbbVie, Cerevel, and Praxis Precision Medicines; is cofounder and CMO of Neuraly, Inc, and Z NeuroSciences LLC; is shareholder of D&D PharmaTech, NeuroReserve, Neunos Inc, and Sensory Cloud; and has received honoraria for consulting and advisory board service from GB Sciences, GKC, Bial, Supernus, AbbVie, ACADIA, Sunovion. N.R. McFarland: received research support from the NIH-NINDS, Michael J. Fox Foundation, and Parkinson Foundation. He receives royalties from UpToDate and serves on advisory committee for ONO Pharmaceutical. L. Montaser-Kouhsari received consultant fees from Darmyian, Trinity Life Sciences, Guidepoint, and Techspert, has received research support from the NIH (NINDS), and has received Talk honorarium from Cleveland Clinic. A.M. Wills: no relevant conflict of interest. She does have consulting agreements with Genentech, Amylyx, and Ono pharmaceuticals and have research funding from the NIH, Parkinson's Foundation, and CurePSP. L.I. Golbe: consults for AI Therapeutics, Amylyx, Apellis, Aprinoia, Ferrer, IQVIA, Mitochon, Mitsubishi Tanabe, P3Lab, Roche, Switch, UCB and Woolsey. He serves on advisory boards for Amylyx, CurePSP, Roche, Rossy Centre and Springer. He receives royalties from Rutgers University Press, licensing fees from Rutgers University and travel expenses from CurePSP. The rest of the authors report no relevant conflicts of interest. Full disclosure form information provided by the authors is available with the full text of this article at Neurology.org/cp., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.)

Competing Interests: Declaration of competing interest Dr. Rosenthal: Dr. Rosenthal receives research funding support from the NINDS, the Daniel B. and Florence E. Green Family Foundation, the Macks Family Foundation, and the National Ataxia Foundation. She receives additional programmatic support from the Gordon and Marilyn Macklin Foundation. She receives salary support for her role as the site Principal Investigator for research studies with Biohaven Pharmaceuticals and Pfizer and for serving on the Clinical Events Committee for a research study with Functional Neuromodulation. She also serves on the steering committees for the Parkinson Study Group's research study with both UCB and Bial Pharmaceuticals. Dr. Rosenthal also served on an advisory board for Reata pharmaceuticals and Biohaven Pharmaceuticals. Dr. Phillips: Dr. Phillips has no conflicts of interest to declare. Dr. Mari: Dr. Mari is a paid consultant for GB Sciences, AbbVie, and Ipsen. He is a speaker for AbbVie, Supernus, and Acadia. He holds shares in Sensory Cloud, NeuroReserve, GB Sciences, Neunos, D&D PharmaTech. He is a co-founder and CMO of Neuraly, Inc. and Z NeuroSciences, LLC.

Spatial normalization-the process of mapping subject brain images to an average template brain-has evolved over the last 20+ years into a reliable method that facilitates the comparison of brain imaging results across patients, centers & modalities. While overall successful, sometimes, this automatic process yields suboptimal results, especially when dealing with brains with extensive neurodegeneration and atrophy patterns, or when high accuracy in specific regions is needed. Here we introduce WarpDrive, a novel tool for manual refinements of image alignment after automated registration. We show that the tool applied in a cohort of patients with Alzheimer's disease who underwent deep brain stimulation surgery helps create more accurate representations of the data as well as meaningful models to explain patient outcomes. The tool is built to handle any type of 3D imaging data, also allowing refinements in high-resolution imaging, including histology and multiple modalities to precisely aggregate multiple data sources together., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: A.H. reports a relationship with Boston Scientific Corporation that includes: speaking and lecture fees. L.A. reports a relationship with Boston Scientific Corporation that includes: consulting or advisory. L.A. reports a relationship with Medtronic that includes: consulting or advisory. K.F. reports a relationship with Medtronic that includes: consulting or advisory. K.F. reports a relationship with Boston Scientific Corporation that includes: consulting or advisory. K.F. reports a relationship with Abbott that includes: funding grants. K.F. reports a relationship with Functional Neuromodulation that includes: funding grants. D.W. reports a relationship with Functional Neuromodulation that includes: funding grants. D.W. reports a relationship with Avid Lily that includes: funding grants. D.W. reports a relationship with Merck that includes: funding grants. D.W. reports a relationship with Jannsen that includes: consulting or advisory. D.W. reports a relationship with GE Healthcare that includes: consulting or advisory. D.W. reports a relationship with Biogen that includes: consulting or advisory. D.W. reports a relationship with Neuronix that includes: consulting or advisory. S.S. reports a relationship with Elsai that includes: consulting or advisory. S.S. reports a relationship with Lilly that includes: consulting or advisory. S.S. reports a relationship with Roche that includes: consulting or advisory. S.S. reports a relationship with Novartis that includes: consulting or advisory. S.S. reports a relationship with Biogen that includes: consulting or advisory. G.S. reports a relationship with NIH that includes: funding grants. M.S. reports a relationship with Allergan that includes: consulting or advisory. M.S. reports a relationship with Biogen that includes: consulting or advisory. M.S. reports a relationship with Roche that includes: consulting or advisory. M.S. reports a relationship with Cortexyme that includes: consulting or advisory. M.S. reports a relationship with Bracket that includes: consulting or advisory. M.S. reports a relationship with Brain Health Inc that includes: consulting or advisory. M.S. reports a relationship with uMethod Health that includes: consulting or advisory. C.L. reports a relationship with Functional Neuromodulation that includes: funding grants. C.L. reports a relationship with Avanir that includes: funding grants. C.L. reports a relationship with Eli Lily that includes: funding grants. C.L. reports a relationship with NFL Benefits Office that includes: funding grants. M.O. reports a relationship with NIH that includes: funding grants. M.O. reports a relationship with Tourette Association of America Grant that includes: funding grants. M.O. reports a relationship with Parkinson's Alliance that includes: funding grants. M.O. reports a relationship with Smallwood Foundation that includes: funding grants. M.O. reports a relationship with Parkinson's Foundation Medical Director that includes: consulting or advisory. M.O. reports a relationship with Books4Patients that includes: consulting or advisory. M.O. reports a relationship with American Academy of Neurology that includes: consulting or advisory. M.O. reports a relationship with Peerview that includes: consulting or advisory. M.O. reports a relationship with WebMD Medscape that includes: consulting or advisory. M.O. reports a relationship with Mededicus that includes: consulting or advisory. M.O. reports a relationship with Movement Disorders Society that includes: consulting or advisory. M.O. reports a relationship with Taylor and Francis that includes: consulting or advisory. M.O. reports a relationship with Demos that includes: consulting or advisory. M.O. reports a relationship with Robert Rose that includes: consulting or advisory. M.O. reports a relationship with Medtronic that includes: non-financial support. A.L. reports a relationship with Medtronic that includes: funding grants. A.L. reports a relationship with Functional Neuromodulation that includes: funding grants. A.L. reports a relationship with Medtronic that includes: consulting or advisory. A.L. reports a relationship with St. Jude that includes: consulting or advisory. A.L. reports a relationship with Boston Scientific that includes: consulting or advisory. A.L. has patent #US Patent 8346,365 licensed to Functional Neuromodulation., (Copyright © 2023. Published by Elsevier B.V.)

Background: Mild memory impairment, termed amnestic mild cognitive impairment (aMCI), is associated with rapid progression towards dementia in Parkinson's disease (PD). Studies have shown hyperactivation of hippocampal DG/CA3 subfields during an episodic memory task as a biomarker of aMCI related to Alzheimer's disease. This project investigates the feasibility of a trial to establish the efficacy of a repurposed antiepileptic drug, levetiracetam, in low doses as a putative treatment to target DG/CA3 hyperactivation and improve episodic memory deficits in aMCI in PD. Based on previous work, it is hypothesized that levetiracetam will normalize DG/CA3 overactivation in PD-aMCI participants and improve memory performance., Methods: Twenty-eight PD-aMCI participants, 28 PD participants without memory impairment (PD-nMI), and 28 healthy controls will be recruited. PD-aMCI participants will undertake a 12-week randomized, placebo-controlled, double-blind cross-over trial with a 14-day treatment of 125 mg levetiracetam or placebo twice daily, separated by a 4-week washout period. After each treatment period, participants will complete an episodic memory task designed to tax hippocampal subregion-specific function during high-resolution functional magnetic resonance imaging (fMRI). PD-nMI and healthy controls will undergo the fMRI protocol only, to compare baseline DG/CA3 subfield activity., Results: Episodic memory task performance and functional activation in the DG/CA3 subfield during the fMRI task will be primary outcome measures. Global cognition, PD severity, and adverse events will be measured as secondary outcomes. Recruitment, eligibility, and study completion rates will be explored as feasibility outcomes., Conclusions: This study, the first of its kind, will establish hippocampal subregion functional impairment and proof of concept of levetiracetam as an early therapeutic option to reduce dementia risk in PD., Trial Registration: ClinicalTrials.gov, NCT04643327 . Registered on 25 November 2020., (© 2023. The Author(s).)

Parkinson's disease (PD) is a progressive neurodegenerative disorder that leads to numerous impairments in motor function that compromise the ability to perform activities of daily living. Practical and effective adjunct therapies are needed to complement current treatment approaches in PD. Transcranial direct current stimulation applied to the cerebellum (c-tDCS) can increase motor skill in young and older adults. Because the cerebellum is involved in PD pathology, c-tDCS application during motor practice could potentially enhance motor skill in PD. The primary purpose was to examine the influence of c-tDCS on motor skill acquisition in a complex, visuomotor isometric precision grip task (PGT) in PD in the OFF-medication state. The secondary purpose was to determine the influence of c-tDCS on transfer of motor skill in PD. The study utilized a double-blind, SHAM-controlled, within-subjects design. A total of 16 participants completed a c-tDCS condition and a SHAM condition in two experimental sessions separated by a 7-day washout period. Each session involved practice of the PGT concurrent with either c-tDCS or SHAM. Additionally, motor transfer tasks were quantified before and after the practice and stimulation period. The force error in the PGT was not significantly different between the c-tDCS and SHAM conditions. Similarly, transfer task performance was not significantly different between the c-tDCS and SHAM conditions. These findings indicate that a single session of c-tDCS does not elicit acute improvements in motor skill acquisition or transfer in hand and arm tasks in PD while participants are off medications.

Objective: To investigate the subjective phenomenon and the neural underpinnings of tics compared with voluntary movements in patients with tic disorders., Methods: We recorded electroencephalographic and electromyographic data while subjects completed a Libet clock paradigm. Patients and healthy volunteers reported the times of W (willing to move) and M (movement occurrence) while performing voluntary movements. This was repeated only for the patients for the tics., Results: In the patients, W and M times preceding voluntary movements and tics did not significantly differ from voluntary movements of healthy volunteers. The Bereitschaftspotentials in the patients were similar to healthy volunteers. Tics were only assessable for 7 patients due to artifacts. Two subjects did not show Bereitschaftspotentials, and they reported the lowest levels of tic voluntariness. 5 subjects did not show beta band event-related desynchronization before tics., Conclusions: For patients, the sense of volition for tics is similar to that of their voluntary movements which is similar to normal. Patients showed dissociations between the Bereitschaftspotential and beta desynchronization for tics, with 5/7 showing normal Bereitschaftspotentials and 2/7 showing desynchronization. The absence of desynchronization may suggest attempts to suppress tics., Significance: This physiology shows a difference for most tics compared with normal movements., (Published by Elsevier B.V.)

Background and Purpose: Resting-state functional MRI (rs-fMRI) studies in Parkinson's disease (PD) patients with freezing of gait (FOG) have implicated dysfunctional connectivity over multiple resting-state networks (RSNs). While these findings provided network-specific insights and information related to the aberrant or altered regional functional connectivity (FC), whether these alterations have any effect on topological reorganization in PD-FOG patients is incompletely understood. Understanding the higher order functional organization, which could be derived from the "hub" and the "rich-club" organization of the functional networks, could be crucial to identifying the distinct and unique pattern of the network connectivity associated with PD-FOG., Methods: In this study, we use rs-fMRI data and graph theoretical approaches to explore the reorganization of RSN topology in PD-FOG when compared to those without FOG. We also compared the higher order functional organization derived using the hub and rich-club measures in the FC networks of these PD-FOG patients to understand whether there is a topological reorganization of these hubs in PD-FOG., Results: We found that the PD-FOG patients showed a noticeable reorganization of hub regions. Regions that are part of the prefrontal cortex, primary somatosensory, motor, and visuomotor coordination areas were some of the regions exhibiting altered hub measures in PD-FOG patients. We also found a significantly altered feeder and local connectivity in PD-FOG., Conclusions: Overall, our findings demonstrate a widespread topological reorganization and disrupted higher order functional network topology in PD-FOG that may further assist in improving our understanding of functional network disturbances associated with PD-FOG., (© 2023 The Authors. Journal of Neuroimaging published by Wiley Periodicals LLC on behalf of American Society of Neuroimaging.)

Deep brain stimulation (DBS) to the fornix is an investigational treatment for patients with mild Alzheimer's Disease. Outcomes from randomized clinical trials have shown that cognitive function improved in some patients but deteriorated in others. This could be explained by variance in electrode placement leading to differential engagement of neural circuits. To investigate this, we performed a post-hoc analysis on a multi-center cohort of 46 patients with DBS to the fornix (NCT00658125, NCT01608061). Using normative structural and functional connectivity data, we found that stimulation of the circuit of Papez and stria terminalis robustly associated with cognitive improvement (R = 0.53, p < 0.001). On a local level, the optimal stimulation site resided at the direct interface between these structures (R = 0.48, p < 0.001). Finally, modulating specific distributed brain networks related to memory accounted for optimal outcomes (R = 0.48, p < 0.001). Findings were robust to multiple cross-validation designs and may define an optimal network target that could refine DBS surgery and programming., (© 2022. The Author(s).)

Anxiety that occurs in association with on-off dopamine medication fluctuations is a major cause of distress, dysfunction, and lower quality of life in people with Parkinson's disease (PD). However, the association between anxiety and on-off fluctuations is poorly understood and it is difficult to predict which patients will suffer from this atypical form of anxiety. To understand whether fluctuating anxiety in PD exists as part of an endophenotype that is associated with other signs or symptoms, we prospectively assessed the change in anxiety and a battery of clinical variables when transitioning from the off-dopamine medication state to the on state in 200 people with PD. We performed latent profile analysis with observed variables as latent profile indicators measuring the on-off-state difference in anxiety, depression, motor function, daily functioning, and the wearing off questionnaire 19 item scale (WOQ-19) in order to model unobserved (i.e., latent) profiles. A two-class model produced the best fit. The majority of participants, 69%, were categorized as having a 'typical on-off response' compared to a second profile constituting 31% of the sample who experienced a worsening in anxiety in the off state that was three times that of other participants. This profile referred to as "anxious fluctuators" had a Hamilton Anxiety Rating Scale change between the off and on medication state of 10.22(32.85) compared to 3.27 (7.62), higher depression scores, greater disability and was less likely to improve on select WOQ-19 items when in the on-state. Anxious fluctuators were more likely to be male and have a family history of anxiety disorder. Given the adverse impact of this profile we believe it may be important to distinguish patients with a typical on-off response from those with this more problematic course of fluctuations., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Background: The impacts of multicomponent school water, sanitation, and hygiene (WaSH) interventions on children's health are unclear. We conducted a cluster-randomized controlled trial to test the effects of a school WaSH intervention on children's malnutrition, dehydration, health literacy (HL), and handwashing (HW) in Metro Manila, Philippines., Methods: The trial lasted from June 2017 to March 2018 and included children, in grades 5, 6, 7, and 10, from 15 schools. At baseline 756 children were enrolled. Seventy-eight children in two clusters were purposively assigned to the control group (CG); 13 clusters were randomly assigned to one of three intervention groups: low-intensity health education (LIHE; two schools, n = 116 children), medium-intensity health education (MIHE; seven schools, n = 356 children), and high-intensity health education (HIHE; four schools, n = 206 children). The intervention consisted of health education (HE), WaSH policy workshops, provision of hygiene supplies, and WaSH facilities repairs. Outcomes were: height-for-age and body mass index-for-age Z scores (HAZ, BAZ); stunting, undernutrition, overnutrition, dehydration prevalence; HL and HW scores. We used anthropometry to measure children's physical growth, urine test strips to measure dehydration, questionnaires to measure HL, and observation to measure HW practice. The same measurements were used during baseline and endline. We used multilevel mixed-effects logistic and linear regression models to assess intervention effects., Results: None of the interventions reduced undernutrition prevalence or improved HAZ, BAZ, or overall HL scores. Low-intensity HE reduced stunting (adjusted odds ratio [aOR] 0.95; 95% CI 0.93 to 0.96), while low- (aOR 0.57; 95% CI 0.34 to 0.96) and high-intensity HE (aOR 0.63; 95% CI 0.42 to 0.93) reduced overnutrition. Medium- (adjusted incidence rate ratio [aIRR] 0.02; 95% CI 0.01 to 0.04) and high-intensity HE (aIRR 0.01; 95% CI 0.00 to 0.16) reduced severe dehydration. Medium- (aOR 3.18; 95% CI 1.34 to 7.55) and high-intensity HE (aOR 3.89; 95% CI 3.74 to 4.05) increased observed HW after using the toilet/urinal., Conclusion: Increasing the intensity of HE reduced prevalence of stunting, overnutrition, and severe dehydration and increased prevalence of observed HW. Data may be relevant for school WaSH interventions in the Global South. Interventions may have been more effective if adherence was higher, exposure to interventions longer, parents/caregivers were more involved, or household WaSH was addressed., Trial Registration Number: DRKS00021623., (© 2022. The Author(s).)

Introduction: Parkinson's disease (PD) frequently causes communication difficulties due to various voice impairments and there are few treatment options for vocal/communication complaints. We assessed the effects of weekly group singing on PD patients' objective vocal and motoric function, cognition, mood, self-efficacy, and quality of life., Methods: Thirty-two participants were randomly assigned to either a singing group or a facilitated discussion group weekly over 12 weeks. After 12 weeks, participants crossed over for an additional 12 weeks. Evaluations were performed at baseline and every six weeks for 30 weeks. Objective voice measures included volume/loudness (decibels), held vowel duration, jitter, shimmer, and harmonic-to-noise ratio. Additional outcome measures included patient-centered quality of life, voice-related quality of life, MDS-UPDRS, Montreal Cognitive Assessment, and questionnaires assessing depression, self-efficacy, and overall well-being., Results: Twenty-six participants (16 M/10F; Hoehn & Yahr stage 2.3 (range 2-3); and age 68.6 (55-89)) completed the study. Across participants in both groups (intention-to-treat analyses), there was significant improvement from baseline in average loudness on the Cookie Theft picture description at 24 weeks (end of interventions), corresponding with improved minimal reading volumes at 24 weeks and 30 weeks (end of study). Similarly, there were improvements in minimal loudness on Rainbow passage reading at 24 and 30 weeks. There were improvements observed in the Emotional Well-Being (mean delta -12.7 points, p = 0.037) and Body Discomfort (mean delta -18.6 points, p = 0.001) domains of the PDQ-39 from baseline to week 24 in the overall cohort and greater improvement in the Communication domain for Group S than Group D after 12 weeks of singing (delta -12.9 points, p = 0.016). Baseline differences between the participant groups (age, gender, Hoehn & Yahr stage, and several voice loudness measures) and observed improvements during the weekly discussion group period limited our ability to attribute all of the above results specifically to singing (per-protocol analyses). No significant changes in other assessed outcome measures were found., Conclusions: Weekly group singing may improve some aspects of conversational voice volume and quality of life in PD. Some improvements were sustained at least six weeks after interventions ended. Further investigations of the mechanism of benefit and randomized controlled studies (without crossover) to assess the longitudinal effects of singing in PD are necessary., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2022 Ankur Butala et al.)

Introduction: Freezing of gait (FOG) is a highly disabling symptom in Parkinson's Disease (PD) with varying degree of benefits from oral dopaminergic medications and several subtypes that present with different medication states (e.g., off FOG, on FOG, pseudo-on FOG, supra-on FOG). Levodopa-Carbidopa Intestinal Gel (LCIG) greately reduces the variability of cerebral dopamine replacement inherent to oral therapies by continuous levodopa intestinal infusion. While LCIG may be superior to oral therapy in its ability to treat motor fluctuations and minimize off-time, there is no consensus regarding the overall effectiveness of LCIG specifically for the treatment of FOG in PD patients., Methods: A systematic literature review was conducted to understand the efficacy of LCIG to treat FOG in PD patients. A PubMed search was conducted using the search query "Intestinal AND (Levodopa OR L-dopa) AND Freezing of Gait AND Parkinson." Additional eligibility criteria included articles written in English and currently published journal articles. Articles were excluded if they did not have a clinical design or if they did not yield reportable data on FOG., Results: The literature search yielded 16 articles, of which 10 articles were included. Of the 10 studies included, there were 3 retrospective studies, 6 case reports or case series, and 1 open-label study. (n = 449 patients total and 318 FOG patients). Nine of the 10 studies concluded that LCIG has a favorable effect on FOG, though the metrics to evaluate benefits of LCIG on FOG varied among the articles., Conclusion: LCIG may be an effective treatment for PD patients suffering from FOG including those with poor response to oral medication, likely because of its ability to maintain steadier dopamine levels. Further research is necessary on LCIG as a therapy for refractory FOG, with particular attention to the different subtypes of FOG., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2022 Published by Elsevier Ltd.)

Cerebellar transcranial direct current stimulation (c-tDCS) enhances motor skill acquisition and motor learning in young and old adults. Since the cerebellum is involved in the pathophysiology of Parkinson's disease (PD), c-tDCS may represent an intervention with potential to improve motor learning in PD. The primary purpose was to determine the influence of long-term application of c-tDCS on motor learning in PD. The secondary purpose was to examine the influence of long-term application of c-tDCS on transfer of motor learning in PD. The study was a randomized, double-blind, SHAM-controlled, between-subjects design. Twenty-one participants with PD were allocated to either a tDCS group or a SHAM stimulation group. Participants completed 9 practice sessions over a 2-week period that involved extensive practice of an isometric pinch grip task (PGT) and a rapid arm movement task (AMT). These practice tasks were performed over a 25-min period concurrent with either anodal c-tDCS or SHAM stimulation. A set of transfer tasks that included clinical rating scales, manual dexterity tests, and lower extremity assessments were quantified in Test sessions at Baseline, 1, 14, and 28 days after the end of practice (EOP). There were no significant differences between the c-tDCS and SHAM groups as indicated by performance changes in the practice and transfer tasks from Baseline to the 3 EOP Tests. The findings indicate that long-term application of c-tDCS does not improve motor learning or transfer of motor learning to a greater extent than practice alone in PD., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

The field of neurology has experienced a dramatic push towards providing care via telemedicine approaches, triggered by the COVID-19 pandemic. The remote monitoring of movement disorders, including tremor, provides a set of challenges compared to gold-standard in-clinic assessments, but also opens opportunities to assess patients' symptoms in a setting where it most matters, such as patients' homes, and during their daily life activities. A successful remote interaction with patients experiencing tremor is dependent on a seamless teleneurology interaction allowing for a high-quality medical history and physical examination. In addition to the clinical evaluation, tremor may be characterized and quantified remotely using transducer-based methods, which may be applying devices containing sensors to objectively and precisely capture tremor movements. This review aims to provide (Zheng et al., 2017 [1]) a practice-oriented overview of telemedicine basics, when it comes to the assessment of tremor, Powers et al. (2021) [2] an update of the most notable techniques and devices, and (Mari, 2021 [3]) an outlook into future opportunities and challenges, as well as and next steps towards seamless remote care of patient with tremor. In conclusion, teleneurology, propelled by the COVID-19 pandemic, has evolved into to a widely established method of physician-patient interaction, aided by technological advancement of remote assessment tools of tremor. However, as the technological, regulatory and reimbursement environment is increasingly adapting to serve the needs of telemedicine, the methods presented for remote measurement of tremor using devices are still largely experimental and largely limited to the research setting. This article is part of the Special Issue "Tremor" edited by Daniel D. Truong, Mark Hallett, and Aasef Shaikh., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Introduction: Outcomes after deep brain stimulation (DBS) therapy are dependent on good surgical placement in the target nucleus and optimized stimulation parameters through multiple programming sessions. This often requires frequent travel to a specialized DBS center, which presents a challenge for those with limited access. Recently, the FDA approved a remote tele-programming solution for DBS. To determine if remote tele-programming of DBS systems is beneficial and useful for Parkinson's Disease (PD) patients, Parkinson's Foundation hosted a survey in collaboration with Abbott Labs., Methods: The survey was conducted to assess the need for telemedicine among PD patients with DBS and the usability of the telehealth interface for DBS teleprogramming. The survey included two validated instruments: The Effective Accessibility and Accommodation survey (EAA) and the Telehealth Usability Questionnaire (TUQ)., Results: 47 patients completed the EAA and 41 completed the TUQ. Results from the EAA revealed more than a third of PD patients cannot easily get to a clinic for various reasons, and more than a quarter reported difficulty contacting their clinic for advice. Results from the TUQ revealed overall satisfaction with the DBS remote programming telehealth interface and care provided. The majority of respondents reported that remote tele-programming visits are similar in quality to in-person visits., Conclusion: This study provides support for the use of telehealth and tele-programming for DBS management in PD patients. The ability to use remote technologies for care will increase access to DBS and mitigate the disparities that currently prevent access to care., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

In the last half-century, Parkinson's disease (PD) has played a historical role in demonstrating our ability to translate preclinical scientific advances in pathology and pharmacology into highly effective clinical therapies. Yet, as highly efficacious symptomatic treatments were successfully developed and adopted in clinical practice, PD remained a progressive disease without a cure. In contrast with the success story of symptomatic therapies, the lack of translation of disease-modifying interventions effective in preclinical models into clinical success has continued to accumulate failures in the past two decades. The ability to stop, prevent or mitigate progression in PD remains the "holy grail" in PD science at the present time. The large number of high-quality disease modification clinical trials in the past two decades with its lessons learned, as well as the growing knowledge of PD molecular pathology should enable us to have a deeper understanding of the reasons for past failures and what we need to do to reach better outcomes. Periodic reviews and mini-reviews of the unsolved disease modification conundrum in PD are important, considering how this field is rapidly evolving along with our views and understanding of the possible explanations., Competing Interests: The authors were the Chair (TM) and Co-Chair (ZM) of the PSG’s “Motor Features Working Group” and in that capacity advise a variety of sponsors on clinical trial design related matters. ZM has received consulting fees from Global Kinetics Corporation, served as Medical Chief Officer for Neuraly, Inc., and holds shares of nQ Medical Inc., GB Sciences, and D&D Pharmatech, Inc. TM reports speaker honorarium from Abbvie, and International Parkinson and Movement Disorder Society; consultancies from CHDI Foundation/Management, Sunovion, Valeo Pharma, Roche, nQ Medical and Merz; advisory board from Abbvie; Biogen, Sunovion, Medtronic, and research funding from EU Joint Programme—Neurodegenerative Disease Research, uOBMRI, Roche, Ontario Research Fund, CIHR, MJFF, Parkinson Canada, PDF/PSG, LesLois Foundation, PSI Foundation, Parkinson Research Consortium and Brain Canada., (Copyright © 2022 Mari and Mestre.)

The Lewy Body Dementia Association (LBDA) held a virtual event, the LBDA Biofluid/Tissue Biomarker Symposium, on January 25, 2021, to present advances in biomarkers for Lewy body dementia (LBD), which includes dementia with Lewy bodies (DLBs) and Parkinson's disease dementia (PDD). The meeting featured eight internationally known scientists from Europe and the United States and attracted over 200 scientists and physicians from academic centers, the National Institutes of Health, and the pharmaceutical industry. Methods for confirming and quantifying the presence of Lewy body and Alzheimer's pathology and novel biomarkers were discussed., Competing Interests: TB has conducted consultation for a peripheral synuclein assay and speakers honorarium from Roche Diagnostics. RL is employed full time by Amprion, serves on Amprion's Board, and is a shareholder. CT research is supported by the European Commission (Marie Curie International Training Network, grant agreement No 860197 (MIRIADE), and JPND), Health Holland, the Dutch Research Council (ZonMW), Alzheimer Drug Discovery Foundation, the Selfridges Group Foundation, Alzheimer Netherlands, Alzheimer Association. CT is the recipient of ABOARD, which is a public-private partnership receiving funding from ZonMW (#73305095007) and Health Holland, Topsector Life Sciences & Health (PPP allowance; #LSHM20106). More than 30 partners participate in ABOARD. ABOARD also receives funding from Edwin Bouw Fonds and Gieskes Strijbisfonds. IV is appointed on a research grant by Alzheimer Nederland (NL 17004). CT has a collaboration contract with ADx Neurosciences, Quanterix, and Eli Lilly, who performed contract research or received grants from AC Immune, Axon Neurosciences, Biogen, Brainstorm Therapeutics, Celgene, EIP Pharma, Eisai, PeopleBio, Roche, Toyama, Vivoryon. CT serves on editorial boards of Medidact Neurologie/Springer, Alzheimer Research and Therapy, Neurology: Neuroimmunology and Neuroinflammation, and is editor of a Neuromethods book by Springer. HZ has served at scientific advisory boards and/or as a consultant for Abbvie, Alector, Eisai, Denali, Roche Diagnostics, Wave, Samumed, Siemens Healthineers, Pinteon Therapeutics, Nervgen, AZTherapies, CogRx, and Red Abbey Labs has given lectures in symposia sponsored by Cellectricon, Fujirebio, Alzecure and Biogen, and is a co-founder of Brain Biomarker Solutions in Gothenburg AB (BBS), which is a part of the GU Ventures Incubator Program (all outside submitted work). CMo is an inventor of several US and International Georgetown University patents to use tyrosine kinase inhibitors (TKis) for the treatment of neurodegenerative diseases. CMo is a co-founder and shareholder and receives consulting fees from KeifeRx LLC. CMo receives consulting fees from Neumentum LLC, SUn Pharmaceuticals Research Industry, and SkyBIo. CMo received NIH NIA funding, Alzheimer's Association, and Sun Pharmaceuticals Research Industry Funding to study TKis in neurodegeneration, including LBD. KP has received consulting fees from Curasen and is funded by grants from the NIH, Michael J Fox Foundation for Parkinson's Research, LBDA, and Alzheimer's Drug Discovery Foundation, and has received funding from Sanofi US Services, Inc. to perform clinical trials. MS declares ownership interest (Stock or stock options): Brain Health Inc, NeuroTau, Optimal Cognitive Health Company, uMethod Health, Versanum, Athira, Cognoptix and consulting work for Alzheon, Biogen, Cortexyme, Roche Genentech, Stage 2 Innovations/Renew Research, Acadia, T3D, Eisai, KeifeRx. MS also declares royalties: HarperCollins, Humanix and speakers bureau: Health and Wellness Partners. LR receives grant funding from the NINDS, Michael J. Fox Foundation, Parkinson's Foundation, and National Ataxia Foundation. She has also served on advisory boards for Uniqure and other pharmaceutical companies through the Parkinson's Study Group. MJA receives research support from the NIA (R01AG068128, P30AG047266), the Florida Department of Health (Grant 20A08), and as the local PI of a Lewy Body Dementia Association Research Center of Excellence. MJA serves on the data safety monitoring boards (DSMBs) for ACTC/ATRI and ADCS. MJA receives royalties from the publication of the book Parkinson's Disease: Improving Patient Care. MJA serves on the level of evidence editorial board for Neurology and related publications (uncompensated). JGG declares grants/research—Acadia, Michael J. Fox Foundation, Parkinson's Foundation, Consultant—Worldwide Med, Honoraria—American Academy of Neurology, Davis Phinney Foundation, International Parkinson and Movement Disorders Society, Medscape, Parkinson's Foundation, Other: Lewy Body Dementia Association Research Center of Excellence. ZM received institutional grant support from NIH, MJFF, LBDA, Parkinson's Foundation, Eli Lilly, NeuroDerm, Cerevel Therapeutics and personal consulting honoraria from Global Kinetics Corporation, GB Sciences, ACADIA, PSG, Elsevier, Kyowa Kirin, AbbVie, and Supernus. 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 Association, CurePSP, Roche, Abbvie, Biogen, Centogene. EIP-Pharma, Biohaven Pharmaceuticals, Novartis, Brain Neurotherapy Bio, and United Biopharma SRL—UCB. IL was a member of the Scientific Advisory Board of Lundbeck and is a Scientific Advisor for Amydis and Rossy Center for the Progressive Supranuclear Palsy University of Toronto. IL receives her salary from the University of California San Diego and as Chief Editor of Frontiers in Neurology. JL receives grant funding from the NIH/NIA/NINDS (P30AG072959/P30AG062428/U01NS100610), LBDA, GE Healthcare and serves as a consultant for Eisai Pharmaceuticals. RW serves on the data safety monitoring boards for Alexion, Bukwang, and Sarepta Pharmaceuticals and the Scientific Platform Steering Committee for Adams Pharmaceuticals. RW serves as a consultant for Lundbeck, Acadia, Teva, Abbvie, Alexion, Adamas, Prime, Bukwang, Sarepta, Syneos, Techspert, Guidepoint and also for R01R01NS117547 with Principal Investigator, Virendra Mishra. AL has received research support from the Dutch Research Council (ZonMW), Alzheimer Netherlands, Dioraphte Foundation, AL has given lectures in symposia sponsored by GE. CG is a scientific consultant and has stock in CND Life Sciences. SG has served on Advisory Boards of Jannsen, Acadia, and Sanofi, has received consulting fees from EIP Pharma, and has received funding from the NIH, the DOD CDMRP, the Michael J. Fox Foundation, the FFFPRI, and the Lewy Body Dementia Association. BB has served as an investigator for clinical trials sponsored by Alector, EIP Pharma, and Biogen. He serves on the Scientific Advisory Board of the Tau Consortium. He receives institutional research support from the NIH, the Lewy Body Dementia Association Research Centers of Excellence Program, the Mayo Clinic Dorothy and Harry T. Mangurian Jr. Lewy Body Dementia Program, the Little Family Foundation, and the Ted Turner and Family Foundation. AP serves on the Scientific Advisory Board of MedRhythms, Inc. and receives research support from the Lewy Body Dementia Association (as Co-Director of the Johns Hopkins LBDA Research Center of Excellence) and NIH/NINDS/NIA (U01NS102035; K23AG059891). DG receives research support from NIA (AG062429), the State of California, and the Michael J. Fox Foundation, which is a paid consultant for Biogen, Roche, Esai, Cognition Therapeutics, Fujirebio, Amprion, Generian, and Editor of Alzheimer's Research & Therapy. DH is supported by The Michael J. Fox Foundation (MJFF-010556), NIH-NINDS 1K23NS105944-01A1, the American Parkinson's Disease Association Center for Advanced Research (Emory University), and the Lewy Body Dementia Association Research Center of Excellence (Emory University). JF is on the editorial board of the American Academy of Neurology's Brain and Life magazine (uncompensated), Lewy Body Dementia Association Scientific Affairs Committee (uncompensated), and has received honoraria from Parkinson's Foundation. JF receives grant funding from the NIH/NIA/NINDS (K23NS097615, 5P30AG064200-02), CurePSP, and Parkinson's Foundation. KD-R receives research funding from the NIH (P30 AG066509) and LBDA Research Center of Excellence; has served on a Biogen advisory board; receives speakers honoraria from MedBridge. LS receives research support from NIH/NIA U19 AG024904, ADNI3 grant; NIH/NIA P30 AG010124, UPENN ADCC grant; and the Michael J. Fox Foundation for Parkinson's Research. He is a consultant for Biogen and Roche Diagnostics and is on the speaker's bureaus for Biogen and Fujirebio. DI receives research funding from NIH (R01-NS109260, P01-AG066597, U19-AG062418, U01-NS100610), Penn Institute on Aging and is the co-PI of the Penn LBDA Research Centers of Excellence. He is a member of the scientific advisory board of Denali Therapeutics. LH is a paid consultant for Biogen, Cortexyme, Eisai, Medscape, and Prevail. LH receives grant support from NIA, NINDS, LBDA, Acumen, Alector, Avanir, Eisai, Genentech/Roche, Janssen/Johnson & Johnson, NovoNordisk, Transposon, UCB, and Vaccinex. JD receives research funding from NIH, the Department of Veterans Affairs, the Michael J. Fox Foundation and Innervace, Inc. He is also the co-PI of the Penn LBDA Research Center of Excellence. IL is the Editor in Chief of the journal but she was not involved in the process of referee selection, peer review or the acceptance decision. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Scott, Arnold, Beach, Gibbons, Kanthasamy, Lebovitz, Lemstra, Shaw, Teunissen, Zetterberg, Taylor, Graham, Boeve, Gomperts, Graff-Radford, Moussa, Poston, Rosenthal, Sabbagh, Walsh, Weber, Armstrong, Bang, Bozoki, Domoto-Reilly, Duda, Fleisher, Galasko, Galvin, Goldman, Holden, Honig, Huddleston, Leverenz, Litvan, Manning, Marder, Pantelyat, Pelak, Scharre, Sha, Shill, Mari, Quinn and Irwin.)

Inequalities in mental healthcare and lack of social support during the COVID-19 pandemic have lowered quality of life and increased overall burden of disease in people with Parkinson's (PWP). Although the pandemic has brought attention to these inequalities, they are long standing and will persist unless addressed. Lack of awareness of mental health issues is a major barrier and even when recognized disparities based on race, gender, and socioeconomic factors limit access to already scarce resources. Stigma regarding mental illness is highly prevalent and is a major barrier even when adequate care exists. Limited access to mental healthcare during the pandemic and in general increases the burden on caregivers and families. Historically, initiatives to improve mental healthcare for PWP focused on interventions designed for specialty and academic centers generally located in large metropolitan areas, which has created unintended geographic disparities in access. In order to address these issues this point of view suggests a community-based wellness model to extend the reach of mental healthcare resources for PWP., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Background: The initial COVID-19 pandemic shutdown led to the canceling of elective surgeries throughout most of the USA and Canada., Objective: This survey was carried out on behalf of the Parkinson Study Group (PSG) to understand the impact of the shutdown on deep brain stimulation (DBS) practices in North America., Methods: A survey was distributed through RedCap® to the members of the PSG Functional Neurosurgical Working Group. Only one member from each site was asked to respond to the survey. Responses were collected from May 15 to June 6, 2020., Results: Twenty-three sites participated; 19 (83%) sites were from the USA and 4 (17%) from Canada. Twenty-one sites were academic medical centers. COVID-19 associated DBS restrictions were in place from 4 to 16 weeks. One-third of sites halted preoperative evaluations, while two-thirds of the sites offered limited preoperative evaluations. Institutional policy was the main contributor for the reported practice changes, with 87% of the sites additionally reporting patient-driven surgical delays secondary to pandemic concerns. Pre-post DBS associated management changes affected preoperative assessments 96%; electrode placement 87%; new implantable pulse generator (IPG) placement 83%; IPG replacement 65%; immediate postoperative DBS programming 74%; and routine DBS programming 91%., Conclusion: The COVID-19 pandemic related shutdown resulted in DBS practice changes in almost all North American sites who responded to this large survey. Information learned could inform development of future contingency plans to reduce patient delays in care under similar circumstances., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Because of its involvement in a wide variety of cardiovascular, metabolic and behavioural functions, the hypothalamus constitutes a potential target for neuromodulation in a number of treatment-refractory conditions. The precise neural substrates and circuitry subserving these responses, however, are poorly characterized to date. We sought to retrospectively explore the acute sequelae of hypothalamic region deep brain stimulation and characterize their neuroanatomical correlates. To this end we studied-at multiple international centres-58 patients (mean age: 68.5 ± 7.9 years, 26 females) suffering from mild Alzheimer's disease who underwent stimulation of the fornix region between 2007 and 2019. We catalogued the diverse spectrum of acutely induced clinical responses during electrical stimulation and interrogated their neural substrates using volume of tissue activated modelling, voxel-wise mapping, and supervised machine learning techniques. In total 627 acute clinical responses to stimulation-including tachycardia, hypertension, flushing, sweating, warmth, coldness, nausea, phosphenes, and fear-were recorded and catalogued across patients using standard descriptive methods. The most common manifestations during hypothalamic region stimulation were tachycardia (30.9%) and warmth (24.6%) followed by flushing (9.1%) and hypertension (6.9%). Voxel-wise mapping identified distinct, locally separable clusters for all sequelae that could be mapped to specific hypothalamic and extrahypothalamic grey and white matter structures. K-nearest neighbour classification further validated the clinico-anatomical correlates emphasizing the functional importance of identified neural substrates with area under the receiving operating characteristic curves between 0.67 and 0.91. Overall, we were able to localize acute effects of hypothalamic region stimulation to distinct tracts and nuclei within the hypothalamus and the wider diencephalon providing clinico-anatomical insights that may help to guide future neuromodulation work., (© The Author(s) (2021). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: The use of telemedicine has increased to address the ongoing healthcare needs of patients with movement disorders. Objective: We aimed to describe the technical and basic security features of the most popular telemedicine videoconferencing software. Methods: We conducted a systematic review of articles/websites about "Telemedicine," "Cybersecurity," and "Videoconferencing software." Technical capabilities and basic security features were determined for each videoconferencing software. Results: Twenty-six videoconferencing software programs were reviewed, 13 (50.0%) were specifically designed for general healthcare, and 6/26 (23.0%) were compliant with European and US regulations. Overall technical and security information were found in 5/26 software (19.2%), including Microsoft Teams, Google Hangout, Coviu, Doxy.me, and Thera platforms. Conclusions: Detailed information about technical capabilities and data security of videoconferencing tools is not easily and openly retrievable. Our data serves as a guide for practitioners seeking to understand what features should be examined when choosing software and what options are available., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Cubo, Arnaiz-Rodriguez, Arnaiz-González, Díez-Pastor, Spindler, Cardozo, Garcia-Bustillo, Mari and Bloem.)

Importance: Urate elevation, despite associations with crystallopathic, cardiovascular, and metabolic disorders, has been pursued as a potential disease-modifying strategy for Parkinson disease (PD) based on convergent biological, epidemiological, and clinical data., Objective: To determine whether sustained urate-elevating treatment with the urate precursor inosine slows early PD progression., Design, Participants, and Setting: Randomized, double-blind, placebo-controlled, phase 3 trial of oral inosine treatment in early PD. A total of 587 individuals consented, and 298 with PD not yet requiring dopaminergic medication, striatal dopamine transporter deficiency, and serum urate below the population median concentration (<5.8 mg/dL) were randomized between August 2016 and December 2017 at 58 US sites, and were followed up through June 2019., Interventions: Inosine, dosed by blinded titration to increase serum urate concentrations to 7.1-8.0 mg/dL (n = 149) or matching placebo (n = 149) for up to 2 years., Main Outcomes and Measures: The primary outcome was rate of change in the Movement Disorder Society Unified Parkinson Disease Rating Scale (MDS-UPDRS; parts I-III) total score (range, 0-236; higher scores indicate greater disability; minimum clinically important difference of 6.3 points) prior to dopaminergic drug therapy initiation. Secondary outcomes included serum urate to measure target engagement, adverse events to measure safety, and 29 efficacy measures of disability, quality of life, cognition, mood, autonomic function, and striatal dopamine transporter binding as a biomarker of neuronal integrity., Results: Based on a prespecified interim futility analysis, the study closed early, with 273 (92%) of the randomized participants (49% women; mean age, 63 years) completing the study. Clinical progression rates were not significantly different between participants randomized to inosine (MDS-UPDRS score, 11.1 [95% CI, 9.7-12.6] points per year) and placebo (MDS-UPDRS score, 9.9 [95% CI, 8.4-11.3] points per year; difference, 1.26 [95% CI, -0.59 to 3.11] points per year; P = .18). Sustained elevation of serum urate by 2.03 mg/dL (from a baseline level of 4.6 mg/dL; 44% increase) occurred in the inosine group vs a 0.01-mg/dL change in serum urate in the placebo group (difference, 2.02 mg/dL [95% CI, 1.85-2.19 mg/dL]; P<.001). There were no significant differences for secondary efficacy outcomes including dopamine transporter binding loss. Participants randomized to inosine, compared with placebo, experienced fewer serious adverse events (7.4 vs 13.1 per 100 patient-years) but more kidney stones (7.0 vs 1.4 stones per 100 patient-years)., Conclusions and Relevance: Among patients recently diagnosed as having PD, treatment with inosine, compared with placebo, did not result in a significant difference in the rate of clinical disease progression. The findings do not support the use of inosine as a treatment for early PD., Trial Registration: ClinicalTrials.gov Identifier: NCT02642393.

The present review asks whether magnetic resonance imaging (MRI) studies are able to define neural correlates of episodic memory within the hippocampus in Parkinson's disease (PD). Systematic searches were performed in PubMed, Web of Science, Medline, CINAHL, and EMBASE using search terms related to structural and functional MRI (fMRI), the hippocampus, episodic memory, and PD. Risk of bias was assessed for each study using the Newtown-Ottawa Scale. Thirty-nine studies met inclusion criteria; eight fMRI, seven diffusion MRI (dMRI), and 24 structural MRI (14 exploring whole hippocampus and 10 exploring hippocampal subfields). Critical analysis of the literature revealed mixed evidence from functional and dMRI, but stronger evidence from sMRI of the hippocampus as a biomarker for episodic memory impairment in PD. Hippocampal subfield studies most often implicated CA1, CA3/4, and subiculum volume in episodic memory and cognitive decline in PD. Despite differences in imaging methodology, study design, and sample characteristics, MRI studies have helped elucidate an important neural correlate of episodic memory impairment in PD with both clinical and theoretical implications. Natural progression of this work encourages future research on hippocampal subfield function as a potential biomarker of, or therapeutic target for, episodic memory dysfunction in PD., (© 2021 Wiley Periodicals LLC.)

Objective: The mechanisms and neuronal networks associated with anxiety in Parkinson's disease (PD) are incompletely understood. One of the best tools for investigating both component function and neuronal networks associated with psychiatric symptoms is functional MRI (fMRI). Unlike structural scans, functional scans, whether task-based or resting-state, are more likely to be clinically relevant and sensitive to changes related to treatment. The investigators provide a comprehensive review of and present results for imaging studies of anxiety in PD., Methods: A systematic review of the literature on fMRI and anxiety in PD was conducted, and the quality of all included studies was simultaneously assessed. Eighteen studies were included: 15 studies assessed anxiety directly, and three evaluated emotional processing. Imaging methodology and behavioral assessments varied across studies, preventing direct comparison of results in most cases., Results: There was a convergence in findings across methods, implicating involvement of the amygdala, caudate, and putamen in association with anxiety in PD. For both task-based activation and resting-state connectivity, dopamine medication status was associated with differences in activation and behavioral function., Conclusions: Although there is little consensus in the current fMRI literature studying anxiety in PD, these results suggest an overlap between structures classically involved in the brain's fear circuit (particularly the amygdala) and the alterations in the nigro-striatal system (e.g., the caudate and putamen and on-off dopamine findings) related to PD and its dopaminergic treatments.

Background: The pathological hallmarks of Parkinson's disease include intraneuronal Lewy bodies, neuronal loss, and gliosis. We aim to correlate Parkinson's disease neuropsychiatric symptoms, (e.g., depression, psychosis, and anxiety) with the severity of neuropathology in the substantia nigra and locus coeruleus., Methods: The brains of 175 participants with a primary pathologic diagnosis of Parkinson's disease were analyzed semi-quantitatively to ascertain the burden of neuronal loss and gliosis and Lewy body pathology within the locus coeruleus and substantia nigra. Participants' history of anxiety, depression, and psychosis were determined using a chart-extracted medical history or record of formal psychiatric evaluation., Results: Of the sample, 56% (n = 98), 50% (n = 88), and 31.25% (n = 55) of subjects had a diagnosis of psychosis, depression, and anxiety, respectively. Psychosis (χ 2  = 7.1, p = 0.008, df = 1) and depression (χ 2  = 7.2, p = 0.007, df = 1) were associated with severe neuronal loss and gliosis in the substantia nigra but not in the locus coeruleus. No association was observed between anxiety and neuronal loss and gliosis in either region. No neuropsychiatric symptoms were associated with Lewy body score. After controlling for disease duration and dementia, psychosis (odds ratio [OR]: 3.1, 95% confidence interval [CI]: 1.5-6.4, χ 2  = 9.4, p = 0.012, df = 1) and depression (OR: 2.6, 95% CI: 1.3-5.0, χ 2  = 7.9, p = 0.005, df = 1) remained associated with severe neuronal loss and gliosis in the substantia nigra., Conclusion: These results suggest that psychosis and depression in Parkinson's disease are associated with the underlying neurodegenerative process and demonstrate that cell loss and gliosis may be a better marker of neuropsychiatric symptoms than Lewy body pathology., (Copyright © 2020 American Association for Geriatric Psychiatry. Published by Elsevier Inc. All rights reserved.)

The use of telemedicine in the management of chronic neurological conditions including movement disorders has expanded over time. In addition to enabling remote access to specialized care, telemedicine has also been shown to reduce caregiver burden and to improve patient satisfaction. With the COVID-19 pandemic, implementation of telehealth for patients with movement disorders, particularly those with more severe mobility issues, has increased rapidly. Although telemedicine care has been shown to be effective for patients with various movement disorders, its utilization for patients with device aided therapies such as deep brain stimulation (DBS) is limited due to challenges related to adjusting these devices remotely and to the lack of consensus recommendations for using telemedicine in this patient population. Thus, guidelines for telemedicine and DBS will assist clinicians on the appropriate implementation of telemedicine to provide care to DBS patients. Optimizing the use of telemedicine for DBS will expand this type of therapy to remote locations with limited access to programming expertise, and also reduce the need for patient travel. Telemedicine is particularly important during the ongoing pandemic due to infection risk and limited access to clinic visits. In this article we review the currently available and emerging strategies for telemedicine and remote care for DBS. We then outline common principles and recommendations for telemedicine care in patients with DBS, review patient selection and best practices. Finally, we briefly discuss the current state of reimbursement for DBS telemedicine visits., (Copyright © 2021. Published by Elsevier Ltd.)

Purpose of Review: According to the amyloid cascade hypothesis, removing amyloid beta (Aβ) should cure Alzheimer's disease (AD). In the past three decades, many agents have been tested to try to lower Aβ production, prevent Aβ aggregation, and dissolve Aβ deposits. However, the paucity in definitive preventative or curative properties of these agents in clinical trials has resulted in more avant-garde approaches to therapeutic investigations. Immunotherapy has become an area of focus for research on disease-modifying therapies for neurodegenerative diseases. In this review, we highlight the current clinical development landscape of monoclonal antibody (mAb) therapies that target Aβ plaque formation and removal in AD., Recent Findings: Multiple potential disease-modifying therapeutics for AD are in active development. Targeting Aβ with mAbs has the potential to treat various stages of AD: prodromal, prodromal to mild, mild, and mild to moderate. Monoclonal antibodies discussed here include aducanumab, lecanemab, solanezumab, crenezumab, donanemab, and gantenerumab. The final decision by the FDA regarding the approval of aducanumab will offer valuable insight into the trajectory of drug development for mAbs in AD and other neurodegenerative diseases. Future directions for improving the treatment of AD will include more inquiry into the efficacy of mAbs as disease-modifying agents that specifically target Aβ peptides and/or multimers. In addition, a more robust trial design for AD immunotherapy agents should improve outcomes such that objective measures of clinical efficacy will eventually lead to higher chances of drug approval.

Introduction: Dementia with Lewy bodies (DLB) is characterized by the toxic accumulation of α-synuclein protein inside neural cells; this results in neurodegeneration which is clinically accompanied by behavioral and psychological changes. DLB shares features with Parkinson's disease (PD) and Parkinson's disease dementia (PDD), but also overlaps neurochemically and pathologically with Alzheimer's disease. Symptomatic treatments for LBD differ in their effectiveness while disease-modifying and curative approaches are much needed. Areas covered: We explore emerging therapeutics for DLB through the lens of repurposing approved drugs and survey their potential for disease modifying actions in DLB. Given the complexity of DLB with multiple pathologies, potential therapeutic targets that could affect Lewy body pathology, or metabolism or neurotransmitters or immunomodulation were surveyed. We queried PubMed and ClinicalTrials.gov searches 2017-2020. Expert opinion: DLB is not simply aredux ofAD or PD; hence, treatments should not be exclusively duplicative ofAD or PD directed treatments. This opens amyriad of possibilities for therapeutic approaches that are disease specific or repurposed.

Introduction: Traditionally, medical care and research in Parkinson's disease (PD) have been conducted with in-person encounters. The recent COVID-19 pandemic has profoundly impacted the delivery of in-person clinical care and clinical research. We conducted an online survey of active clinician members of the Parkinson Study Group (PSG) to evaluate the adoption of various non-face-to-face methods in clinical practice and research in PD during the COVID-19 pandemic., Methods: We conducted a survey using the open-access online SurveyMonkey tool (http://www.surveymonkey.com). The survey had 27 items and was designed to elucidate clinical/research care before and during the COVID-19 pandemic. The survey was sent to 414 active PSG members with weekly reminders and it remained accessible for 30 days from May 2020., Results: We received 142 responses, of which 133 (93.7%) provided demographic data. The clinical use of virtual visits via synchronous video conferencing increased from 39.5% pre-COVID-19 to 94.6% during the COVID-19 pandemic. Lack of access for patients (68.2%) and patient resistance (51.4%) were the top barriers for its use. Approximately 70% respondents stated that 75-100% of their research activities were suspended during the COVID-19 pandemic. Many sites had to fill out protocol deviations (38.2%), protocol exceptions (25.5%) or change their research profile due to layoffs (16.8%). The overall use of video conferencing increased from 30.3% to 64.1%., Conclusion: The current results suggest a need for flexibility in conducting office visits and clinical trials in PD patients. Technology has the potential to enhance patient care and convenience, when in-person visits can be challenging., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Introduction: Deep brain stimulation (DBS) has become a standard treatment option for select patients with Parkinson's disease (PD). The selection process and surgical procedures employed have, to date, not been standardized., Methods: A comprehensive 58-question web-based survey was developed with a focus on DBS referral practices and peri-operative management. The survey was distributed to the Parkinson's Foundation Centers of Excellence, members of the International Parkinson's Disease and Movement Disorders Society, and the Parkinson Study Group (Functional Neurosurgery Working Group) between December 2015 and May 2016., Results: There were 207 individual respondents (20% response rate) drawn from 59 countries and 6 continents, of whom 64% received formal training in DBS. Thirteen percent of centers reported that DBS could proceed despite a confidence level of < 50% for PD diagnosis. A case-based approach to DBS candidacy was applied in 51.3% of centers without a cut-off for levodopa-responsiveness. Surprisingly, 33% of centers regularly used imaging for diagnostic confirmation of idiopathic PD. Thirty-one percent of centers reported that neuropsychological evaluation did not affect DBS target selection. Approximately half of the respondents reported determination of DBS candidacy based on a multidisciplinary committee evaluation and 1/3 rd reported that a committee was used for target selection. Eight percent of respondents felt that psychosocial factors should not impact DBS candidacy nor site selection. Involvement of allied health professionals in the preoperative process was sparse. There was high variability in preoperative education about DBS outcome expectations. Approximately half of the respondents did not utilize a "default brain target," though STN was used more commonly than GPi. Specific DBS procedure techniques applied, as well as follow-up timelines, were highly variable., Conclusion: Results revealed high variability on the best approaches for DBS candidate selection, brain target selection, procedure type, and postoperative practices. Cognitive and mood assessments were underutilized. There was low reliance on multidisciplinary teams or psychosocial factors to impact the decision-making process. There were small but significant differences in practice across global regions, especially regarding multidisciplinary teams. The wide variability of responses across multiple facets of DBS care highlights the need for prospective studies to inform evidence-based guidelines., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Mahajan, Butala, Okun, Mari and Mills.)

Objective: To assess the clinical manifestations and predictors of different types of tremors in individuals with different types of isolated dystonia., Methods: Clinical manifestations of tremor were assessed in a multicenter, international cross-sectional, cohort study of 2,362 individuals with all types of isolated dystonia (focal, segmental, multifocal, and generalized) recruited through the Dystonia Coalition., Results: Methodical and standardized assessments of all participants in this cohort revealed the overall prevalence of any type of tremor was 53.3%. The prevalence of dystonic tremor varied from 36.9% to 48.4%, depending on criteria used to define it. To identify the factors associated with tremors in dystonia, the data were analyzed by generalized linear modeling and cluster analyses. Generalized linear modeling indicated 2 of the strongest factors associated with tremor included body region affected by dystonia and recruitment center. Tremor was also associated with severity of dystonia and duration of dystonia, but not with sex or race. The cluster analysis distinguished 8 subgroups within the whole cohort; defined largely by body region with dystonia, and secondarily by other clinical characteristics., Conclusion: The large number of cases evaluated by an international team of movement disorder experts facilitated the dissection of several important factors that influence the apparent prevalence and phenomenology of tremor in dystonia. These results are valuable for understanding the many differences reported in prior studies, and for guiding future studies of the nosology of tremor and dystonia., (© 2020 American Academy of Neurology.)

Neurological disorders significantly impact the world's economy due to their often chronic and life-threatening nature afflicting individuals which, in turn, creates a global disease burden. The Group of Twenty (G20) member nations, which represent the largest economies globally, should come together to formulate a plan on how to overcome this burden. The Neuroscience-20 (N20) initiative of the Society for Brain Mapping and Therapeutics (SBMT) is at the vanguard of this global collaboration to comprehensively raise awareness about brain, spine, and mental disorders worldwide. This paper aims to provide a comprehensive review of the various brain initiatives worldwide and highlight the need for cooperation and recommend ways to bring down costs associated with the discovery and treatment of neurological disorders. Our systematic search revealed that the cost of neurological and psychiatric disorders to the world economy by 2030 is roughly $16T. The cost to the economy of the United States is $1.5T annually and growing given the impact of COVID-19. We also discovered there is a shortfall of effective collaboration between nations and a lack of resources in developing countries. Current statistical analyses on the cost of neurological disorders to the world economy strongly suggest that there is a great need for investment in neurotechnology and innovation or fast-tracking therapeutics and diagnostics to curb these costs. During the current COVID-19 pandemic, SBMT, through this paper, intends to showcase the importance of worldwide collaborations to reduce the population's economic and health burden, specifically regarding neurological/brain, spine, and mental disorders.

Diarrhea, soil-transmitted helminth infection and malnutrition are leading causes of child mortality in low- and middle-income countries (LMICs). To reduce the prevalence of these diseases, effective interventions for adequate water, sanitation, and hygiene (WaSH) should be implemented. This paper describes the design of a cluster-randomized controlled trial that will compare the efficacy of four school-based WaSH interventions for improving children's health literacy, handwashing, and nutrition. Interventions consisted of (1) WaSH policy reinforcement; (2) low-, medium-, or high-volume health education; (3) hygiene supplies; and (4) WaSH facilities (e.g., toilets, urinals, handwashing basins) improvements. We randomly allocated school clusters from the intervention arm to one of four groups to compare with schools from the control arm. Primary outcomes were: children's health literacy, physical growth, nutrition status, and handwashing prevalence. Secondary outcomes were: children's self-reported health status and history of extreme hunger, satisfaction with WaSH facilities, and school restrooms' WaSH adequacy. We will measure differences in pre- and post-intervention outcomes and compare these differences between control and intervention arms. This research protocol can be a blueprint for future school-based WaSH intervention studies to be conducted in LMICs. Study protocols were approved by the ethics committees of the University of Bonn, Germany, and the University of the Philippines Manila. This trial was retroactively registered, ID number: DRKS00021623.

Freezing of gait (FoG) is a disabling symptom characterized as a brief inability to step or by short steps, which occurs when initiating gait or while turning, affecting over half the population with advanced Parkinson's disease (PD). Several non-competing hypotheses have been proposed to explain the pathophysiology and mechanism behind FoG. Yet, due to the complexity of FoG and the lack of a complete understanding of its mechanism, no clear consensus has been reached on the best treatment options. Moreover, most studies that aim to explore neural biomarkers of FoG have been limited to semi-static or imagined paradigms. One of the biggest unmet needs in the field is the identification of reliable biomarkers that can be construed from real walking scenarios to guide better treatments and validate medical and therapeutic interventions. Advances in neural electrophysiology exploration, including EEG and DBS, will allow for pathophysiology research on more real-to-life scenarios for better FoG biomarker identification and validation. The major aim of this review is to highlight the most up-to-date studies that explain the mechanisms underlying FoG through electrophysiology explorations. The latest methodological approaches used in the neurophysiological study of FoG are summarized, and potential future research directions are discussed., (Copyright © 2020 Marquez, Hasan, Siddiquee, Luca, Mishra, Mari and Bai.)

There remains a significant mismatch between the complexity and variability of symptoms and disabilities in Parkinson's disease (PD), and the capabilities of existing validated assessment tools to objectively measure and monitor them. However, with the advances of circuit and sensor technologies, it is now possible to apply the concept of digital phenotyping to PD, providing a moment-by-moment quantification of individual patient phenotypes using personal digital devices, such as smartphones. Such technology holds considerable potential if a patient-centered multidisciplinary team is able to select digital outcomes that are not only clinically relevant, but also provide measurement-based care results that support individual patient clinical decision making. However, it is likely to be a long road, requiring large collaborative efforts to undertake a number of essential steps before full integration and synchronization of these outcomes into patient management platforms that can deliver individualized data to patients, caregivers, and treating neurologists. In the meantime, both neurologists and patients can empower themselves with digital technologies, working as a team to define the ways that new technologies can be most powerfully employed in PD management. Once digital phenotyping becomes feasible and widely adopted in PD communities, it is likely to expand our understanding of individual PD patients' lives and priorities, leading to targeted treatments and better outcomes for PD patients and their families., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Schizophrenic patients often do not have the sense that they direct their own movements or author their own thoughts (passivity phenomena). As willing must precede movement to be causal and thus generate the sense of agency, it is possible that the timing between the senses of willing and movement is shortened in schizophrenia. We tested the subjective perception of this time interval in patients with schizophrenia using a method based on Libet's paradigm, in which subjects specify a time W - the time of willing a movement - and a time M - the time that movement occurred. Patients with schizophrenia and healthy volunteers made voluntary movements at times of their own choice while looking at a fast-rotating clock on a computer screen and reported when their movements were willed and made. We recorded surface electromyography to determine the time of actual movement, and electroencephalography to record brain potentials associated with movement. Results showed a significantly reduced interval between the reported M and W in patients with respect to the healthy volunteers ( p < 0.05). Specifically, patients did not report a significant difference in the timing of W at 19 ms prior to movement onset and M at 7.4 ms prior to movement onset ( p > 0.05), while the control group experienced a time W at 100 ms prior to movement onset and this differed significantly from their time M at 19 ms prior to movement onset ( p < 0.01). These results suggest that patients with schizophrenia do have an altered timing of awareness of action - or an impaired judgment of the sequence of events - and that this might be etiologic in the development of the abnormal sense of agency., (Copyright © 2020 Pirio Richardson, Triggiani, Matsuhashi, Voon, Peckham, Nahab, Mari and Hallett.)

Transcranial direct current stimulation of the cerebellum (c-tDCS) improves motor performance in young and old adults. Based on the cerebellar involvement in Parkinson's disease (PD), c-tDCS could have potential to improve motor function in PD. The purpose was to determine the effects of c-tDCS on motor performance in PD while participants were on medications. The study was a randomized, double-blind, SHAM-controlled, between-subjects design. Twenty-two participants with PD were allocated to either a c-tDCS group or a SHAM group. All participants completed one experimental session and performed two motor tasks with their most affected hand in a Baseline condition (no stimulation) and an Experimental condition. The motor tasks were a visuomotor isometric precision grip task (PGT) and a rapid arm movement task (AMT). The primary dependent variables were force error and endpoint error in the PGT and AMT, respectively. There were no significant differences in force error or endpoint error in the Experimental condition between the c-tDCS and SHAM groups. These results indicate that an acute application of c-tDCS does not enhance motor performance in hand and arm tasks in PD. Longer-term c-tDCS application over multiple days may be needed to enhance motor function in PD.

Background: The COVID-19 pandemic restricted usual healthcare management for movement-disorders patients, with a consequent upsurge in telemedicine to bridge the gap., Objective: To assess global telemedicine usage in the context of the pandemic., Methods: The Movement Disorder Society (MDS) Telemedicine Study Group surveyed telemedicine experts from 40 countries across all continents in March-April 2020. Four domains of telemedicine were assessed: legal regulations, reimbursement, clinical use, and barriers; comparing emerging responses to the pandemic versus the baseline scenario., Results: All forms of telemedicine for movement disorders increased globally, irrespective of country income categorization, as an immediate response to the pandemic. This was aided by widespread availability of technology and updated government regulations. However, privacy concerns, lack of reimbursement, limited access, and lack of telemedicine training were barriers highlighted worldwide., Conclusions: Questions remain about the longevity and extent of changes in regulations and reimbursement regarding telemedicine in the aftermath of the pandemic. © 2020 International Parkinson and Movement Disorder Society., (© 2020 International Parkinson and Movement Disorder Society.)

[This corrects the article DOI: 10.1038/s41531-019-0102-8.]., (© The Author(s) 2020.)

Objective: To investigate the topographic arrangement and strength of whole-brain white matter (WM) structural connectivity in patients with early-stage drug-naive Parkinson disease (PD)., Methods: We employed a model-free data-driven approach for computing whole-brain WM topologic arrangement and connectivity strength between brain regions by utilizing diffusion MRI of 70 participants with early-stage drug-naive PD and 41 healthy controls. Subsequently, we generated a novel group-specific WM anatomical network by minimizing variance in anatomical connectivity of each group. Global WM connectivity strength and network measures were computed on this group-specific WM anatomical network and were compared between the groups. We tested correlations of these network measures with clinical measures in PD to assess their pathophysiologic relevance., Results: PD-relevant cortical and subcortical regions were identified in the novel PD-specific WM anatomical network. Impaired modular organization accompanied by a correlation of network measures with multiple clinical variables in early PD were revealed. Furthermore, disease duration was negatively correlated with global connectivity strength of the PD-specific WM anatomical network., Conclusion: By minimizing variance in anatomical connectivity, this study found the presence of a novel WM structural connectome in early PD that correlated with clinical symptoms, despite the lack of a priori analytic assumptions. This included the novel finding of increased structural connectivity between known PD-relevant brain regions. The current study provides a framework for further investigation of WM structural changes underlying the clinical and pathologic heterogeneity of PD., (© 2019 American Academy of Neurology.)

Anxiety is a severe problem for at least one-third of people living with Parkinson's disease (PD). Anxiety appears to have a greater adverse impact on quality of life than motor impairment. Despite its high prevalence and impact on daily life, anxiety is often undiagnosed and untreated. To better address anxiety in PD, future research must improve knowledge about the mechanism of anxiety in PD and address the lack of empirical evidence from clinical trials. In response to these challenges, the Parkinson's Foundation sponsored an expert meeting on anxiety on June 13th and 14th 2018. This paper summarizes the findings from that meeting informed by a review of the existing literature and discussions among patients, caregivers, and an international, clinician-scientist, expert panel working group. The goal is to provide recommendations to improve our understanding and treatment of anxiety in PD., Competing Interests: Competing interestsThe authors declare no competing interests., (© The Author(s) 2019.)

Objective: To determine the minimal clinically important change (MCIC) on Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) scores using data from Cervical Dystonia Patient Registry for Observation of OnabotulinumtoxinA Efficacy (CD PROBE), which captured real-world practices and outcomes., Methods: Changes in the baseline TWSTRS scores (point and percentage changes) were compared to changes in the Patient and Clinician Global Impression of Change (PGIC and CGIC) ratings. Using logistic regression, the discrimination of the model was determined., Results: Among the 479 patients who completed all TWSTRS assessments, the mean TWSTRS Total score significantly decreased from baseline (39.2) to the final visit (27.1) (P < .0001). TWSTRS Total score point changes that compared with PGIC assessments "very much improved," "much improved" or better, and "minimally improved" or better were -11, -9, and -8, respectively, and were similar to previously published changes (ie, a decrease of ≥10 points). TWSTRS Total score data met indicators of good cutoffs for discrimination of the model including ≥70% percentage of outcomes correctly classified when compared with PGIC ratings. The TWSTRS Total score mapped to PGIC and CGIC ratings better than any TWSTRS subscale score., Conclusions: The MCIC for improvement was ≥8 points based on mean TWSTRS Total scores in patients with cervical dystonia when compared against the patient-based evaluation of benefit (PGIC)., (Copyright © 2019 The Authors. Published by Elsevier B.V. All rights reserved.)