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Background: Anecdotal evidence suggests paradoxical caffeine overuse in individuals with Huntington's disease (HD). A small retrospective study associated caffeine intake over 190 grams daily to earlier onset of HD symptoms. However, specific data on consumption habits is limited. This study aims to gather pilot data on caffeine use in people with HD, exploring motivations and consequences., Methods: Thirty adults with HD completed a survey on daily caffeine intake, its impact on symptoms, and consumption motivations through multiple-choice and open-ended questions. Descriptive statistics were used to analyze findings and compare them to general population data., Results: Caffeine intake ranged from 0 to 1400.4 mg/day, with a median of 273.2 mg/day and a mean of 382.5 mg/day. Seventy percent of participants with HD consumed more caffeine than the average for their age group in the general population. Additionally, 20% of participants and 38% of family members believed caffeine influenced HD symptoms, primarily anxiety., Discussion: People with HD typically consume more caffeine than the general U.S. population. Contrary to the hypothesis, higher caffeine intake was not associated with significant subjective worsening of HD symptoms. Further research with objective measures and multiple HD centers is necessary to guide screening and counseling on caffeine use in this population., Highlights: Participants with Huntington's disease (HD) had increased caffeine intake compared to the general population, supporting previous anecdotal observations. Anxiety was the most affected HD symptom. Further research using objective measures of symptom burden and including multiple HD centers can help inform screening and counseling regarding caffeine use in this population., Competing Interests: The authors have no competing interests to declare., (Copyright: © 2024 The Author(s).)

Introduction: DAT-SPECT imaging is approved as a diagnostic tool for the evaluation of suspected Parkinsonian syndromes, but the FDA-approved package insert lists 16 potential drugs that may interfere with the image obtained. The clinical impact of these drugs on imaging results has not been established. This study aimed to determine the accuracy of DAT-SPECT imaging in assessing presynaptic dopaminergic denervation in the setting of these drugs., Methods: This is a retrospective chart review of patients at a single center who underwent DAT-SPECT imaging while taking "contraindicated" drugs between December 2012 and December 2022., Results: A total of 1,224 charts were screened, and 153 (12.5%) charts met the inclusion criteria. Bupropion (32%, n = 49) and sertraline (26%, n = 40) were the most common contraindicated drugs. The false-positive rate was 9.2%., Conclusion: This retrospective analysis supports the concern that certain drugs may interfere with DAT-SPECT imaging results, leading to potential false positives. This has implications for how clinicians interpret DAT-SPECT imaging in patients taking these medications and whether they should advise patients to stop these medications before a scan is performed., (© 2024 S. Karger AG, Basel.)

Introduction: Motor and nonmotor Parkinson's disease (PD) symptoms can negatively influence employment, which may contribute to financial hardship. This article explores the association between financial hardship, employment challenges, and quality of life in people with early PD., Methods: We measured financial hardship with a validated summary item (5-point scale, lower score - less hardship) and the Comprehensive Score for Financial Toxicity (0-44, lower score worse toxicity) in a cohort of 60 employed individuals with early PD (<5 years). We used Spearman's Correlations and nonparametric tests to identify associations between financial hardship, demographic characteristics, PD-related factors, employment factors, and quality of life (Neuro-QOL computer adapted measures)., Results: The sample was mostly white (93 %) and male (65 %). The plurality were highly-educated with graduate degrees (42 %). Of the 60 participants, 23 (38 %) reported a little bit and 14 (23 %) reported somewhat or more hardship. Comprehensive financial toxicity (22.0 ± 8.7) was correlated moderately ( ρ  = -0.56) with the single-item summary score. High financial hardship was associated with reduced confidence in job retention ( ρ  = -0.43, p = 0.001) and reduced perceived workplace success ( ρ  = -0.352, p = 0.006). Financial hardship was also associated with poorer quality of life in five Neuro-QOL domains: lower extremity function, satisfaction with social roles and activities, depression, anxiety, and stigma (p < 0.05)., Conclusion: Financial hardship was common and was associated with employment challenges and poor quality of life. Further work should explore the effects of medical and psychosocial interventions to alleviate financial and employment challenges in individuals with early PD., 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., (© 2023 The Authors.)

Background: Most people prefer to die at home. Hospice is the standard in end-of-life care for people with Huntington disease (HD), a neurodegenerative genetic disorder that affects people in middle adulthood. Yet, we have little knowledge regarding the place of death for people with HD. Therefore, the current state of knowledge limits HD clinicians' ability to conduct high-quality goals of care conversations. Objectives: We sought to determine the factors associated with the place of death in people with HD. Design: We obtained cross-sectional data from Enroll-HD and included participants with a positive HD mutation of 36 or more CAG repeats. Results: Out of 16,120 participants in the Enroll-HD study, 536 were reported as deceased. The mean age at death was 60. The leading place of death was home (29%), followed by the hospital (23%). The adjusted odds ratio (aOR) of dying at a skilled nursing facility was significantly lower for those partnered (aOR: 0.48, confidence interval [95% CI]: 0.26-0.86). The aOR for dying on hospice compared to home was increased in a person with some college and above (aOR: 2.40, 95% CI: 1.21-4.75). Conclusions: Our data further suggest that models that predict the place of death for serious illnesses do not appear to generalize to HD. The distribution in the places of death within HD was not uniform. Our findings may assist HD clinicians in communication during goals of care conversations.

Objective: Death anxiety, represented by the HDQLIFE™ Concern with Death and Dying (CwDD) patient-reported outcome (PRO) questionnaire, captures a person's worry about the death and dying process. Previous work suggests that death anxiety remains an unremitting burden throughout all stages of Huntington disease (HD). Although palliative interventions have lessened death anxiety among people with advanced cancer, none has yet to undergo testing in the HD population. An account of how death anxiety is associated with longitudinal changes to aspects of health-related quality of life (HRQoL) would help optimize neuropalliative interventions for people with HD. Methods: HDQLIFE collected PROs concerning physical, mental, social, and cognitive HRQoL domains and clinician-rated assessments from people with HD at baseline and 12 and 24 months. Linear mixed-effects models were created to determine how baseline death anxiety was associated with follow-up changes in HRQoL PROs after controlling for baseline death anxiety and other disease and sociodemographic covariates. Results: Higher baseline HDQLIFE CwDD is associated with 12- and 24-month declines in HDQLIFE Speech Difficulties, neurology quality of life (NeuroQoL) Depression, Suicidality, HDQLIFE Meaning and Purpose, and NeuroQoL Positive Affect and Well-being. Interpretation: Death anxiety may be a risk factor for worsening mental health and speech difficulty. A further prospective study is required to evaluate whether interventions on death anxiety or mental health generally can reduce declines in HRQoL for people with HD over time.

Objective: With Huntington disease (HD), a fatal neurodegenerative disease where the prevalence of suicidal thoughts and behavior (STB) remains elevated as compared to other neurological disorders, it is unknown whether STB and health-related quality of life (HRQoL) affect plans for the end of life or more broadly, advance care planning (ACP). Conversely, it is unknown whether ACP would provoke future changes to STB and HRQoL. Therefore, we sought to evaluate whether STB and HRQoL patient-reported outcomes (PROs) contribute to ACP and whether ACP relates to changes in STB and HRQoL at 24 months., Methods: HD-validated clinician- and patient-assessments (i.e., HRQoL PROs) were obtained at baseline enrollment, 12 and 24 months through our multi-center study (HDQLIFE™) throughout the United States among people with premanifest, early-stage, and late-stage manifest HD. We used linear mixed-effects models to determine the relationships between STB and HRQoL at baseline and HDQLIFE End of Life Planning at follow-up. Separate linear mixed-effects models were used to assess the relationship between HDQLIFE End of Life Planning at baseline, and HRQoL and STB at 12 and 24 months. False discovery rate adjustments were used to account for multiple comparisons., Results: At baseline enrollment, STB and HRQoL were not related to HDQLIFE End of Life Planning at 12 or 24 months. Similarly, at baseline, HDQLIFE End of Life Planning demonstrated no association with STB or HRQoL at 12 or 24 months., Interpretation: STB and HRQoL PROs do not significantly affect patient engagement with ACP. Most importantly, engaging in ACP does not cause untoward effects on HRQoL or STB for this rare neurodegenerative disease where the lifetime prevalence of STB approaches 30%., Competing Interests: L.L.S. receives financial support as a paid consultant from the HDSA, American Film Institute, University of Texas Houston (McGovern School), and Tikvah for Parkinson; he has received research support from the Memorial Sloan Kettering Meaning Centered Psychotherapy (MCP) National Cancer Institute (NCI) R25 Training, and Northwestern Physician Scientist Training program. J.P.T. owns stocks in Procter and Gamble and General Electric, and has received research funding through the University of Michigan with Complexa Inc., Retrophin Inc., and Goldfinch Bio, and the University of Michigan with Vertex Pharmaceuticals and Pfizer Inc. D.B. has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Speaker: Teva Pharmaceuticals, Acorda Therapeutics, Neurocrine Biosciences, Adamas Pharmaceuticals Consulting: Biogen Pharmaceuticals, Amgen Pharmaceuticals, Acadia Pharmaceuticals, Genentech, Inc., GE Healthcare, Gerson Lehrman Group, Guidepoint, L.E.K. C., and has received personal compensation in an editorial capacity for Editor: Annals of Clinical and Translational Neurology. B.M.K. received research grant support from the National Institute of Aging (NIA), National Institute of Nursing Research, and Patient-Centered Outcomes Research Institute; he has received speaker honoraria from the Parkinson's Foundation. H.G.P. receives funding from the NIH (CA197730; AG049666; MH121886; NR018693; CA218313). M.N. has received personal compensation in the range of $5,000–$9,999 for serving as a Consultant for Voyager. M.N. has received personal compensation in the range of $500–$4,999 for serving as a Consultant for Roche. M.N. has received personal compensation in the range of $5,000–$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Roche. M.N. has received personal compensation in the range of $500–$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Uniqure. An immediate family member of M.N. has received stock or an ownership interest from Fresca. The institution of M.N. has received research support from HDSA. The institution of M.N. has received research support from Parkinson Foundation. M.N. has received research support from Parkinson Foundation. The institution of M.N. has received research support from Neuraly. M.N. has received personal compensation in the range of $500–$4,999 for serving as a speaker with American Academy of Neurology (AAN). S.F. has received personal compensation in the range of $500–$4,999 for serving as a Consultant for Oscine Therapeutics. S.F. has received personal compensation in the range of $500–$4,999 for serving as a Consultant for uniQure. S.F. has received personal compensation in the range of $500–$4,999 for serving as a Consultant for MCG Health. The institution of S.F. has received research support from HDSA. The institution of S.F. has received research support from Michael J Fox Foundation. The institution of S.F. has received research support from Roche/Genentech. The institution of Dr. Frank has received research support from CHDI Foundation. The institution of S.F. has received research support from Huntington Study Group (HSG). The institution of S.F. has received research support from Triplet Therapeutics. J{has received research funding from the NIH (NS075321, NS103957, NS107281, NS092865, U10NS077384, NS097437, U54NS116025, U19 NS110456, AG050263, AG-64937, NS097799, NS075527, ES029524, NS109487, R61 AT010753 [NCATS, NINDS, NIA], RO1NS118146, R01AG065214), Department of Defense (W81XWH-217-1-0393), Michael J Fox Foundation, Barnes-Jewish Hospital Foundation (Elliot Stein Family Fund and Parkinson disease research fund), American Parkinson Disease Association (APDA) Advanced Research Center at Washington University, Greater St. Louis Chapter of the APDA, Paula and Rodger Riney Fund, Jo Oertli Fund, HDSA, Murphy Fund, and CHDI; has received honoraria from CHDI, Huntington Disease Study Group, Parkinson Study Group, Beth Israel Hospital (Harvard group), University of Pennsylvania, and Stanford University; is co-director for the Dystonia Coalition, which has received the majority of its support through the NIH (grants NS116025, NS065701 from the NINDS and TR 001456 from the Office of Rare Diseases Research at the NCATS); serves as Director of Medical and Scientific Advisory Committee of the Dystonia Medical Research Foundation, Chair of the Scientific Advisory Committee of the Parkinson Study Group, Chair of the Interim Executive Membership Committee of the HSG, Chair of the Nominating Committee of the HSG; Chair of the Standards Committee of the HSG, member of the Scientific Advisory Board of the APDA, Chair of the Scientific and Publication Committee for ENROLL-HD, and member of the Education Committee of the HSG; and has provided medical legal consultation to Wood, Cooper and Peterson, LLC, and Simmons and Simmons LLP. P.D. reports receiving funding from Vaccinex, Inc., Neurocrine Biosciences Inc., and UniQure, for his role as Site Investigator for clinical trials in Huntington Disease. D.C. reports consultant fees from AbbVie, Bristol Myers Squibb (BMS), Exelixis, Merck, Novartis, and Pfizer; reports licensing fees from FACIT.org; research grants (institutional) from AbbVie, Astellas, Aveo, BMS, GlaxoSmithKline, Merck, Novartis, and Pfizer; and is an officer of FACIT.org. N.E.C. reports research grants from the NIH, the Neilsen Foundation, and CHDI, as well as a contract from Teva Pharmaceuticals. She is also supported by research funding from the Alzheimer's Association, the Food and Drug Administration (FDA), as well as the Department of Health and Human Services—Centers for Medicare and Medicaid Services. She receives honoraria for her role on the CHDI scientific advisory board and is a consultant on the Traumatic Brain Injury (TBI) Congressionally mandated study., (© Leonard L. Sokol et al., 2023; Published by Mary Ann Liebert, Inc.)

Animals often search for food more efficiently with experience. However, the contribution of experience to foraging success under direct competition has rarely been examined. Here we used colonies of an individually foraging desert ant to investigate the value of spatial experience. First, we trained worker groups of equal numbers to solve either a complex or a simple maze. We then tested pairs of both groups against one another in reaching a food reward. This task required solving the same complex maze that one of the groups had been trained in, to determine which group would exploit better the food reward. The worker groups previously trained in the complex mazes reached the food reward faster and more of these workers fed on the food than those trained in simple mazes, but only in the intermediate size group. To determine the relative importance of group size versus spatial experience in exploiting food patches, we then tested smaller trained worker groups against larger untrained ones. The larger groups outcompeted the smaller ones, despite the latter's advantage of spatial experience. The contribution of spatial experience, as found here, appears to be small, and depends on group size: an advantage of a few workers of the untrained group over the trained group negates its benefits., (© 2022 The Authors. Insect Science published by John Wiley & Sons Australia, Ltd on behalf of Institute of Zoology, Chinese Academy of Sciences.)

Purpose of Review: This article provides an overview of the diagnostic and therapeutic approach to a patient with chorea. The phenomenology of chorea is described in addition to other common hyperkinetic movements that may be mistaken for or coexist with chorea. Chorea can be acquired or hereditary. Key historical and clinical features that can aid in determining the etiology are reviewed, and pharmacologic and nonpharmacologic treatment strategies are discussed., Recent Findings: Clinical investigations are under way to target transcription and translation of the mutant huntingtin protein as a potential disease-modifying strategy in Huntington disease (HD). Additional heritable factors have been revealed through genome-wide association studies. Symptom-focused treatments for HD are are being studied, including a third vesicular monoamine transporter-2 (VMAT2) inhibitor for chorea attenuation and drugs to target irritability and cognitive impairment. Increased availability of genetic testing has led to increased awareness of HD mimics (eg, C9orf72 and IgLON5)., Summary: Chorea is a relatively common hyperkinetic disorder with a broad differential. The first step in the approach to a patient with chorea is accurately defining the phenomenology. Once it has been determined that the patient has chorea, the investigation into determining an etiology can begin. Factors such as age of onset, time course, family history, unique clinical features, and imaging and laboratory findings can guide the diagnosis. Treatments for most causes of chorea are purely symptomatic, although it is important to recognize causes that are reversible or have disease-modifying interventions., (Copyright © 2022 American Academy of Neurology.)

Purpose: To compare demographics, self-reported symptom burden, Health-Related Quality of Life (HRQL), and Self-Efficacy for Exercise (SEE) between participants and non-participants of Rock Steady Boxing (RSB), a non-contact boxing program for individuals with Parkinson's disease (PD) that focuses on agility, balance, and speed training., Materials and Methods: Adults with PD who had heard of RSB completed a 20 min, 61-question electronic survey including the Parkinson's Disease Questionnaire-39 (PDQ-39) and the Self-Efficacy for Exercise (SEE) scale. Differences between participants and never-participants were analyzed using chi-squared test, fisher's exact test and Wilcoxon test., Results: Of 2054 individuals enrolled in the survey, 1709 were eligible for analysis. 1333 were current participants, 166 previous-participants, and 210 never-participants. RSB participants were median age 69, 59% male, and 97% Caucasian. The majority of current participants reported that RSB improved their social life (70%), fatigue (63%), fear of falling (62%), depression (60%), and anxiety (59%). Compared to previous and never-participants, current participants had better median PDQ-39 scores (36 and 32 vs 25, p  < 0.01) and SEE scores (43 and 48 vs 54, p  < 0.01)., Conclusions: This is the largest survey of RSB use in PD. RSB participants report improvement in non-motor impairments and have significantly better HRQL and ESE compared to never-participants.IMPLICATIONS FOR REHABILITATIONParkinson's disease (PD) is a slowly progressive neurodegenerative condition that affects motor function and subsequently, quality of life.Exercise is increasingly recognized as an important treatment for motor and non-motor symptoms of PD.Rock Steady Boxing (RSB) is a specific non-contact boxing program for PD that is growing and increasing in popularity, though there is limited data on its effect on PD symptoms and quality of life.

Background: People with Huntington's disease (HD) often become institutionalized and more frequently die away from the home setting. The reasons behind differences in end-of-life care are poorly understood. Less than 5% of people with HD report utilization of palliative care (PC) or hospice services, regardless of the lack of curative therapies for this neurodegenerative disease. It is unknown what factors are associated with in-patient specialty PC consultation in this population and how PC might be related to discharge disposition., Objectives: To determine what HD-specific (e.g., psychosis) and serious illness-specific factors (e.g., resuscitation preferences) are associated with PC encounters in people with HD and explore how PC encounters are associated with discharge disposition., Design: We analyzed factors associated with PC consultation for people with HD using discharge data from the National Inpatient Sample and the Nationwide Inpatient Sample (NIS), Healthcare Cost and Utilization Project (HCUP), Agency for Healthcare Research and Quality. An anonymized, cross-sectional, and stratified sample of 20% of United States hospitalizations from 2007 through 2014 were included using ICD-9 codes., Results: 8521 patients with HD were admitted to the hospital. Of those, 321 (3.8%) received specialty PC. Payer type, (specifically private insurer or other insurer as compared to Medicare), income, (specifically the top quartile as compared to the bottom quartile), mortality risk, D.N.R., aspiration pneumonia, and depression were significantly associated with PC in a multivariate model. Among those who received PC, the odds ratio (OR) of discharge to a facility was 0.43 (95% CI, 0.32-0.58), whereas the OR of discharge to home with services was 2.25 (95% CI 1.57-3.23), even after adjusting for possible confounders., Conclusions: Among patients with HD, economic factors, depression, and serious illness-specific factors were associated with PC, and PC was associated with discharge disposition. These findings have implications for the adaptation of inpatient PC models to meet the needs of persons with HD.

Background: The study provides real-world data on the impact of Huntington's disease (HD) from the perspective of individuals with HD (IHD) and care partners (HD-CP) and contextualizes these results relative to Parkinson's disease (PD) and the general population (GP)., Methods: Cross-sectional survey of IHD and HD-CP in the US (July 2019-August 2019) conducted using the Rare Patient Voice panel. Data for individuals with Parkinson's Disease (IPD), the general population (GP), and respective care partners (PD-CP; GP-CP) came from the 2018 US National Health and Wellness Survey. Outcomes included demographics, mental health, clinical characteristics, and health-related quality of life (HRQoL)., Results: IHD had greater comorbid anxiety (IHD = 51.2%, IPD = 28.8%, GP = 2.0%), and HD-CP had greater comorbid anxiety (HD-CP = 52.5%, PD-CP = 28.6%, GP-CP = 19.6%) and depression (HD-CP = 65.0%, PD-CP = 29.9%, GP-CP = 19.6%), relative to other cohorts ( p < 0.05). Respective of their GP cohorts, IHD exhibited lower HRQoL (EQ-5D: 0.66 ± 0.21 vs. 0.81 ± 0.17) and greater depression (PHQ-9: 11.59 ± 7.20 vs. 5.85 ± 6.71), whereas HD-CP exhibited greater depression only (PHQ-9: 6.84 ± 6.38 vs. 4.15 ± 5.58) ( p < 0.001). No differences were observed between HD/HD-CP and PD/PD-CP cohorts on PHQ-9 or HRQoL., Conclusions: HD has a significant burden on patients and care partners, which is higher than GP. Notably, anxiety and depression were greater among HD vs. PD, despite similar HRQoL.

Objective: Previous work in Huntington's disease (HD) has shown that a sense of meaning and purpose (M&P) is positively associated with positive affect and well-being (PAW); however, it was unknown whether HD-validated patient-reported outcomes (PROs) influence this association and how M&P impacts PROs in the future. Our study was designed to examine if HD-validated PROs moderate the relationship between M&P and PAW and to evaluate if baseline M&P predicts 12- and 24-month changes in HD-validated PROs., Methods: This was a longitudinal, multicenter study to develop several PROs (e.g., specific for the physical, emotional, cognitive, and social domains) for people with HD (HDQLIFE). The sample consisted of 322 people with HD (n = 50 prodromal, n = 171 early-stage manifest, and n = 101 late-stage manifest HD). A single, multivariate linear mixed-effects model was performed with PAW as the outcome predicted by main effects for M&P and several moderators (i.e., an HD-validated PRO) and interactions between M&P and a given PRO. Linear-mixed models were also used to assess if baseline M&P predicted HD-validated PROs at 12 and 24 months., Results: Higher M&P was positively associated with higher PAW regardless of the magnitude of symptom burden, as represented by HD-validated PROs, and independent of disease stage. In our primary analysis, baseline M&P predicted increased PAW and decreased depression, anxiety, anger, emotional/behavioral disruptions, and cognitive decline at 12 and 24 months across all disease stages., Interpretation: These findings parallel those seen in the oncology population and have implications for adapting and developing psychotherapeutic and palliative HD interventions., (© 2021 The Authors. Annals of Clinical and Translational Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association.)

Progressive supranuclear palsy (PSP) and corticobasal syndrome (CBS; the most common phenotype of corticobasal degeneration) are tauopathies with a relentless course, usually starting in the mid-60s and leading to death after an average of 7 years. There is as yet no specific or disease-modifying treatment. Clinical deficits in PSP are numerous, involve the entire neuraxis, and present as several discrete phenotypes. They center on rigidity, bradykinesia, postural instability, gait freezing, supranuclear ocular motor impairment, dysarthria, dysphagia, incontinence, sleep disorders, frontal cognitive dysfunction, and a variety of behavioral changes. CBS presents with prominent and usually asymmetric dystonia, apraxia, myoclonus, pyramidal signs, and cortical sensory loss. The symptoms and deficits of PSP and CBS are amenable to a variety of treatment strategies but most physicians, including many neurologists, are reluctant to care for patients with these conditions because of unfamiliarity with their multiplicity of interacting symptoms and deficits. CurePSP, the organization devoted to support, research, and education for PSP and CBS, created its CurePSP Centers of Care network in North America in 2017 to improve patient access to clinical expertise and develop collaborations. The directors of the 25 centers have created this consensus document outlining best practices in the management of PSP and CBS. They formed a writing committee for each of 12 sub-topics. A 4-member Steering Committee collated and edited the contributions. The result was returned to the entire cohort of authors for further comments, which were considered for incorporation by the Steering Committee. The authors hope that this publication will serve as a convenient guide for all clinicians caring for patients with PSP and CBS and that it will improve care for patients with these devastating but manageable disorders., 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 Bluett, Pantelyat, Litvan, Ali, Apetauerova, Bega, Bloom, Bower, Boxer, Dale, Dhall, Duquette, Fernandez, Fleisher, Grossman, Howell, Kerwin, Leegwater-Kim, Lepage, Ljubenkov, Mancini, McFarland, Moretti, Myrick, Patel, Plummer, Rodriguez-Porcel, Rojas, Sidiropoulos, Sklerov, Sokol, Tuite, VandeVrede, Wilhelm, Wills, Xie and Golbe.)

Images of DaTscan (ioflupane [123I] SPECT) have been used as an adjunct to clinical diagnosis to facilitate the differential diagnosis of neurodegenerative (ND) Parkinsonian Syndrome (PS) vs. non-dopamine deficiency aetiologies of Parkinsonism. Despite several systematic reviews having summarised the evidence on diagnostic accuracy, the impact of imaging results on clinical utility has not been systematically assessed. Our objective was to examine the available evidence on the clinical utility of DaTscan imaging in changing diagnosis and subsequent management of patients with suspected PS. We performed a systematic review of published studies of clinical utility from 2000 to 2019 without language restrictions. A meta-analysis of change in diagnosis and management rates reported from each study was performed using a random-effects model and logit transformation. Sub-group analysis, meta-regression and sensitivity analysis was performed to explore heterogeneity. Twenty studies met the inclusion criteria. Thirteen of these contributed to the meta-analyses including 950 and 779 patients with a reported change in management and change in diagnosis, respectively. The use of DaTscan imaging resulted in a change in management in 54% (95% CI: 47-61%) of patients. Change in diagnosis occurred in 31% (95% CI: 22-42%) of patients. The two pooled analyses were characterised by high levels of heterogeneity. Our systematic review and meta-analysis show that imaging with DaTscan was associated with a change in management in approximately half the patients tested and the diagnosis was modified in one third. Regardless of time from symptom onset to scan results, these changes were consistent. Further research focusing on specific patient subgroups could provide additional evidence on the impact on clinical outcomes.

Background: The American Board of Psychiatry and Neurology and the Accreditation Council for Graduate Medical Education (ACGME) developed Milestones that provide a framework for residents' assessment. However, Milestones do not provide a description for how programs should perform assessments., Objectives: We evaluated graduating residents' status epilepticus (SE) identification and management skills and how they correlate with ACGME Milestones reported for epilepsy and management/treatment by their program's clinical competency committee (CCC)., Methods: We performed a cohort study of graduating neurology residents from 3 academic medical centers in Chicago in 2018. We evaluated residents' skills identifying and managing SE using a simulation-based assessment (26-item checklist). Simulation-based assessment scores were compared to experience (number of SE cases each resident reported identifying and managing during residency), self-confidence in identifying and managing these cases, and their end of residency Milestones assigned by a CCC based on end-of-rotation evaluations., Results: Sixteen of 21 (76%) eligible residents participated in the study. Average SE checklist score was 15.6 of 26 checklist items correct (60%, SD 12.2%). There were no significant correlations between resident checklist performance and experience or self-confidence. The average participant's level of Milestone for epilepsy and management/treatment was high at 4.3 of 5 (SD 0.4) and 4.4 of 5 (SD 0.4), respectively. There were no significant associations between checklist skills performance and level of Milestone assigned., Conclusions: Simulated SE skills performance of graduating neurology residents was poor. Our study suggests that end-of-rotation evaluations alone are inadequate for assigning Milestones for high-stakes clinical skills such as identification and management of SE., Competing Interests: Conflict of interest: The authors declare they have no competing interests.

Symptomatic management of Parkinson's disease (PD) is complex and many symptoms, especially non-motor symptoms, are not effectively addressed with current medications. In the US, cannabis has become more widely available for medical and recreational use, permitting those in the PD community to try alternative means of symptom control. However, little is known about the attitudes towards, and experiences with, cannabis use among those living with PD. To address this shortcoming, we distributed an anonymous survey to 7,607 people with PD in January 2020 and received 1339 responses (17.6%). 1064 complete responses were available for analysis. Respondents represented 49 states with a mean age of 71.2 years (±8.3) and mean PD duration of 7.4 years (±6.2). About a quarter of respondents (24.5%) reported cannabis use within the previous six months. Age and gender were found to be predictors of cannabis use in this sample (Age OR = 0.95, 95% CI 0.93 to 0.97; Male OR = 1.44, 95% CI 1.03 to 2.03). Users reported learning about cannabis use from the internet/news (30.5%) and friends or other people with PD (26.0%). Cannabis users were more likely to report insufficient control of their non-motor symptoms with prescription medications than non-users (p = 0.03). Cannabis was primarily used for PD (63.6%) and was most often used to treat nonmotor symptoms of anxiety (45.5%), pain (44.0%), and sleep disorders (44.0%). However, nearly a quarter of users (23.0%) also reported they had stopped cannabis use in the previous six months, primarily due to a lack of symptom improvement (35.5%). Three quarters of respondents (75.5%) did not use cannabis, primarily because there was a lack of scientific evidence supporting efficacy (59.9%). Our results suggest that the lack of formal guidance or research evidence about cannabis for PD may in part underlie inconsistencies in both use and reported effectiveness.

Burnout has become an increasingly recognized problem in higher medical education and is particularly prevalent within the field of Neurology and its training programs. Many previously reported wellness initiatives in other residencies focused mainly on community/team building. We developed a comprehensive Wellness Curriculum (WC) and established a new role of Resident Wellness Liaison in order to facilitate wellness across the department and training program. Here we present a 6-step outline of our WC which can easily be adapted to the needs of other programs. The steps include creating a Wellness Committee with a Resident Wellness Liaison, identification and optimization of institutional resources, identifying and troubleshooting barriers to wellness, providing education and reflection on wellness, showing appreciation to each other, and assessing the impact of the implemented strategies. In order to measure the impact of our WC and to perform a needs assessment for future directions, we posed questions-grounded in the theory of drivers of burnout and engagement-to our residents (N = 24) at a noon conference in the summer of 2020. Interventions implemented at our institution have been very well received by residents, as evidenced by their comments and feedback. Themes that were highlighted by residents include enjoying flexibility, having a welcoming social support system at work, and being able to find meaning in the day-to-day work. The creation of a comprehensive WC is a feasible and meaningful intervention for addressing resident wellness in a Neurology training program and could be adapted to other programs., Competing Interests: Declaration of conflicting interests:The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2020.)

SRX246 is a vasopressin (AVP) 1a receptor antagonist that crosses the blood-brain barrier. It reduced impulsive aggression, fear, depression and anxiety in animal models, blocked the actions of intranasal AVP on aggression/fear circuits in an experimental medicine fMRI study and demonstrated excellent safety in Phase 1 multiple-ascending dose clinical trials. The present study was a 3-arm, multicenter, randomized, placebo-controlled, double-blind, 12-week, dose escalation study of SRX246 in early symptomatic Huntington's disease (HD) patients with irritability. Our goal was to determine whether SRX246 was safe and well tolerated in these HD patients given its potential use for the treatment of problematic neuropsychiatric symptoms. Participants were randomized to receive placebo or to escalate to 120 mg twice daily or 160 mg twice daily doses of SRX246. Assessments included standard safety tests, the Unified Huntington's Disease Rating Scale (UHDRS), and exploratory measures of problem behaviors. The groups had comparable demographics, features of HD and baseline irritability. Eighty-two out of 106 subjects randomized completed the trial on their assigned dose of drug. One-sided exact-method confidence interval tests were used to reject the null hypothesis of inferior tolerability or safety for each dose group vs. placebo. Apathy and suicidality were not affected by SRX246. Most adverse events in the active arms were considered unlikely to be related to SRX246. The compound was safe and well tolerated in HD patients and can be moved forward as a candidate to treat irritability and aggression., Competing Interests: Funding: National Institute of Neurological Diseases and Stroke SBIR Fast-track award to Azevan Pharmaceuticals, Inc (U44NS090616), NINDS grants supporting the NeuroNext Network (Clinical Coordinating Center U01NS077179; Data Coordinating Center U01NS077352), the CHDI Foundation (grant to NGS) and Azevan Pharmaceuticals, Inc. The STAIR trial was sponsored by Azevan Pharmaceuticals, Inc. and was conducted through the NINDS NeuroNEXT Network (22 sites).

A 37 year-old previously healthy man from Jamaica presented with 2-3 months of progressive trouble ambulating and incontinence. By 1 month prior to arrival he was wheelchair bound and unable to ambulate even with assistance. He started to wear a diaper for bladder and bowel incontinence. He also complained of painless numbness in his legs over the same period of time. His exam is notable for marked weakness and spasticity in his legs, with hyper-reflexia and clonus. He has a sensory level at the level of the umbilicus. An MRI shows a longitudinally extensive T2 signal change throughout the thoracic cord. His cerebrospinal fluid is mildly inflammatory. His HTLV-1 antibody test is reactive., (© 2020 The Authors. Annals of Clinical and Translational Neurology published by Wiley Periodicals, Inc on behalf of American Neurological Association.)

Background: Appropriate and timely treatment of status epilepticus (SE) decreases morbidity and mortality. Therefore, skill-based training in the identification and management of SE is crucial for clinicians., Objective: The objective of the study was to develop and evaluate the impact of a simulation-based mastery learning (SBML) curriculum to train neurology residents on the identification and management of SE., Methods: We used pretest-posttest design with a retention test on SE skills for this study. Neurology residents in the second postgraduate year (PGY-2) were eligible to participate in the SE SBML curriculum. Learners completed a baseline-simulated SE skills assessment (pretest) using a 26-item dichotomous skills checklist. Next, they participated in a didactic session about the identification and management of SE, followed by deliberate skills practice. Subsequently, participants completed another skills assessment (posttest) using the same 26-item checklist. All participants were required to meet or exceed a minimum passing standard (MPS) determined by a panel of 14 SE experts using the Mastery Angoff standard setting method. After meeting the MPS at posttest, participants were reassessed during an unannounced in situ simulation session on the medical wards. We compared pretest with posttest simulated SE skills performance and posttest with reassessment in situ performance., Results: The MPS was set at 88% (23/26) checklist items correct. Sixteen neurology residents participated in the intervention. Participant performance improved from a median of 44.23% (Interquartile range (IQR): 34.62-55.77) at pretest to 94.23% (IQR: 92.13-100) at the posttest after SBML (p < .001). There was no significant difference in scores between the posttest and in situ test up to 8 months later (94.23%; IQR: 92.31-100 vs. 92.31%; IQR: 88.46-96.15; p = .13)., Conclusions: Our SBML curriculum significantly improved residents' SE identification and management skills that were largely retained during an unannounced simulated encounter in the hospital setting., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: Mentorship is critical for achieving success in academic medicine and is also considered one of the core professional competencies for residency training. Despite its importance, there has been a decline in the mentor-mentee relationship, largely due to time constraints and lack of clear guidelines for productive discussions. We provide a mentorship curriculum with an easily adoptable workbook which may serve as a guide for programs seeking more formalized mentorship opportunities., Methods: We created a mentorship curriculum that was divided into 4 quarterly sessions, each with topics to facilitate career guidance and development, and to provide insight into the practical aspects of business of medicine. The mentorship pilot curriculum was implemented during the 2017 to 2018 academic year. Specific questions were provided to stimulate reflection and appropriate discussion between resident mentee and faculty mentor. A post-curriculum survey was distributed to evaluate the effectiveness and satisfaction of the curriculum., Results: A total of 23 residents participated in this pilot project. A majority had not had any formal teaching related to the business aspects of medicine (82%). Upon completion of the curriculum, most residents felt several topics were sufficiently covered, and a majority were satisfied with the course and relationship developed with their mentor (87%)., Conclusions: Our pilot curriculum provides a model to address a knowledge gap in the practical aspects of medicine while simultaneously enhancing residency mentorship. The one-year course was generally well-received by residents and can serve as a model to other academic residency programs with similar challenges and goals., Competing Interests: Declaration of conflicting interests:The author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: AS, DL, and GC have no relevant financial disclosures or competing interest to report. DB serves as a speaker for Teva Pharmaceuticals, Acorda Therapeutics, Neurocrine Biosciences, and Adamas Pharmaceuticals. He has served as a consultant for Gerson Lehrman Group, Guidepoint, GE Healthcare, L.E.K. consulting, Acadia Pharmaceuticals, Genentech Inc, Amneal Pharmaceuticals, Biogen Pharmaceuticals, Ultragenyx Pharmaceuticals, and Acsel Health. He is an associated editor for Annals of Clinical & Translational Neurology., (© The Author(s) 2020.)

Background: Older patients with Huntington's disease (HD) are often thought to have a slower progressing disease course with less behavioral symptoms than younger patients. However, phenotypic differences based on age of onset have not been well characterized in a large HD population. This study will determine the difference in manifestations and disease progression between patients with young, typical, and late onset adult HD at different stages of disease., Methods: Data obtained from Enroll-HD. Adults with manifest HD were included. Age groups were defined as young onset (YO: 20-29 years), typical onset (TO: 30-59 years), and late onset (LO: 60+ years). Subjects were categorized by TFC score, from Stage I (least severe) to Stage V (most severe). Motor, cognitive, and behavioral symptoms were analyzed. Descriptive statistics and Bonferroni p-value correction for pairwise comparison were calculated., Results: 7,311 manifest HD participants were included (612 YO, 5,776 TO, and 923 LO). The average decline in TFC score from baseline to second visit (1.5-2.5 years) was significantly faster for YO (-1.75 points) compared to TO (-1.23 points, p = 0.0105) or LO (-0.97 points, p = 0.0017). Motor deficits were worse for LO participants at early stages of HD, and worse for YO participants at advanced stages. YO and TO participants had greater burden of behavioral symptoms at early stages of disease compared to LO., Discussion: YO is predictive of a faster functional decline for adults with HD when compared to those with TO and LO. Motor and behavioral manifestations differ based on age of onset., Highlights: This study compares HD manifestations while controlling for disease severity, detailing robust phenotypic differences by age of onset alone. These findings have implications for the clinical management of HD symptoms and have the possibility to improve prognostic and treatment precision., Competing Interests: The authors have no competing interests to declare., (Copyright: © 2020 The Author(s).)

Background: Psychosis is considered rare in Huntington's Disease, with an estimated prevalence of 3-11%. However, it has a profound impact on quality of life and disease burden. This study uses the Enroll-HD database to determine the prevalence, onset, and severity of psychosis in Huntington's Disease and to determine demographic and disease characteristics associated with psychosis., Methods: Data were obtained from Enroll-HD. Adults with manifest Huntington's Disease were included. Descriptive statistics were calculated. Simple logistic regression was used to calculate the odds ratio with 95% confidence interval for association with each characteristic., Results: 7,966 manifest Huntington's Disease participants were analyzed, and 12.95% had a history of psychosis. Mean age of psychosis onset (48.34 years, SD 13.26) mirrored Huntington's Disease onset. Family history of psychosis in a first degree relative was documented in 23.6% of participants with psychosis. Variables significantly (p < 0.05) associated with presence of psychosis in manifest HD included lower education level, unemployment, single marital status, depression, decreased verbal fluency score, and decreased total functional capacity & functional assessment score., Discussion: Psychosis in Huntington's Disease is more prevalent than many prior studies have reported. It is associated with several demographic & psychiatric features, decreased cognitive capacity, and worse functional outcomes., Highlights: Psychosis in HD is more prevalent than prior studies have reported. It is associated with a range of demographic and psychiatric variables, worse cognition, and worse functional outcomes suggesting several features that may be used to predict onset of psychosis and improve understanding and management of psychosis in HD., Competing Interests: The authors have no competing interests to declare., (Copyright: © 2020 The Author(s).)

Experience can lead to faster exploitation of food patches through spatial learning or other parallel processes. Past studies have indicated that hungry animals either search more intensively for food or learn better how to detect it. However, fewer studies have examined the contribution of non-spatial information on the presence of food nearby to maze solving, as a parallel process to spatial learning. We exposed Cataglyphis niger ant workers to a food reward and then let them search for food in a maze. The information that food existed nearby, even without spatial information, led to faster maze solving compared to a control group that was not exposed to the food prior to the experiment. Faster solving is probably achieved by a higher number of workers entering the maze, following the information that food is present nearby. In a second experiment, we allowed the ants to make successive searches in the maze, followed by removing them after they had returned to the nest and interacted with their naïve nestmates. This procedure led to a maze-solving time in-between that displayed when removing the workers immediately after they had reached the food and preventing their return to the colony, and that of no removal. The workers that interacted upon returning to the nest might have transferred to naïve workers information, unrelated to spatial learning, that food existed nearby, and driven them to commence searching. Spatial learning, or an increase in the correct movements leading to the food reward relative to those leading to dead-ends, was only evident when the same workers were allowed to search again in the same maze. However, both non-spatial information on the presence of food that elevated search intensity and spatial learning led to faster maze solving., Competing Interests: The authors have declared that no competing interests exist.

Objective: To evaluate the long-term safety and efficacy of deutetrabenazine in patients with tardive dyskinesia (TD)., Method: Patients with TD who completed the 12 week, phase 3, placebo-controlled trials were eligible to enter this open-label, single-arm study. The open-label study consisted of a 6 week dose-escalation phase and a long-term maintenance phase (clinic visits at Weeks 4, 6 and 15, and every 13 weeks until Week 106). Patients began deutetrabenazine at 12 mg/day, titrating up to a dose that was tolerable and provided adequate dyskinesia control, based on investigator judgement, with a maximum allowed dose of 48 mg/day (36 mg/day for patients taking strong cytochrome P450 2D6 (CYP2D6) inhibitors). Safety measures included incidence of adverse events (AEs) and scales used to monitor parkinsonism, akathisia/restlessness, anxiety, depression, suicidality and somnolence/sedation. Efficacy endpoints included the change in Abnormal Involuntary Movement Scale (AIMS) score (items 1 to 7) from baseline and the proportion of patients rated as 'Much Improved' or 'Very Much Improved' on the Clinical Global Impression of Change., Results: A total of 343 patients enrolled in the extension study, and there were 331 patient-years of exposure in this analysis. The exposure-adjusted incidence rates of AEs with long-term treatment were comparable to or lower than those observed in the phase 3 trials. The mean (SE) change in AIMS score was -4.9 (0.4) at Week 54 (n = 146), - 6.3 (0.7) at Week 80 (n = 66) and -5.1 (2.0) at Week 106 (n = 8)., Conclusions: Overall, long-term treatment with deutetrabenazine was efficacious, safe, and well tolerated in patients with TD., Trial Registration Number: NCT02198794., Competing Interests: Competing interests: HHF has received honoraria from Prime Education, Inc, International Parkinson and Movement Disorders Society, Carling Communications, Medscape (speaker in CME events), AbbVie, Biogen, GE Health Care, Inventiv, Kyowa Hakko Kirin, Lundbeck, Merz Pharmaceuticals, Voyager, Sunovion, Pfizer Pharmaceuticals (as a consultant). He has received grant and research support from: AbbVie, Acadia, Teva, Biotie/Acorda Therapeutics, Civitas, Kyowa/Prostrakan, Michael J. Fox Foundation, Movement Disorders Society, NIH/NINDS, Parkinson Study Group, Rhythm, Synosia; he has no owner interest in any pharmaceutical company. He has received royalties from: Demos Publishing (serving as a book author/editor). The Cleveland Clinic has a contract with Teva for his role as a Co-Principal Investigator in SD-809 tardive dyskinesia global studies. He also serves as a member of the publication committee for Acorda Pharmaceuticals but does not receive any personal compensation for this. He receives a stipend from the International Parkinson and Movement Disorders Society for serving as Medical Editor of the MDS Web Site. DS is a former employee of Teva Pharmaceuticals; he has received salary and benefits from Auspex Pharmaceuticals, and has patents pending: US20160346270, US20160287574. MDD is an employee of Teva Pharmaceuticals. SAF has received honoraria from Neurocrine, Lundbeck, Teva, Avanir, UCB, US WorldMeds, Sunovion, Adamas; he has received research support from Ipsen, Medtronic, Auspex, US WorldMeds, Pharm-Olam, Cynapsus Therapeutics/Sunovion, Vaccinex, Solstice, CHDI Foundation, Michael J. Fox Foundation, NIH; he has received royalties from Demos, Blackwell Futura for textbooks, and UpToDate. RAH has served as a consultant for Teva Pharmaceuticals, AbbVie, Inc, Acorda Therapeutics, Adamas Pharmaceuticals, AstraZeneca, Biotie Therapies, Cynapsus Therapeutics, Impax Laboratories, Inc, Lundbeck LLC, Michael J Fox Foundation, Neurocrine Biosciences, Neuropore Therapies, Pfizer Inc, Prexton Therapeutics, US WorldMeds, Guidepoint Global, Gerson Lehrman Group (GLG), LCN Consulting, Putnam Associates, National Parkinson Foundation, eResearch Technology, Inc, Sarepta Therapeutics, Back Bay Life Science, National Institutes of Health, Projects in Knowledge, Vista Research, LifeMax, Peerview Press, ClinicalMind Medical and Therapeutic Communications, Sunovion Pharmaceuticals, Academy for Continued Healthcare Learning, Outcomes Insights, Expert Connect, HealthLogix, Cowen and Company, Pharma Two B, Ltd, RMEI Medical Education for Better Outcomes, ClearView Healthcare Partners, Health Advances, Kyowa Kirin Pharmaceutical Development, Ltd, Quintiles, and Eli Lilly and Company. JJ-S has received research support from Acadia Pharmaceuticals, St. Jude Medical, Biotie, Michael J. Fox Foundation; she has served as a consultant for Teva, St. Jude Medical, Medtronic; she has also received honoraria from Vindico Medical Education. WGO has received research support from Lundbeck, Tremor Research Group, Dystonia Coalition, Restless Leg Syndrome Foundation, Acorda. Speakers’ Bureau: Teva, Lundbeck, UCB, US WorldMeds; he has served as a consultant for Teva, Lundbeck, Acadia. LFJ has received grant support Auspex/Teva, Boehringer Ingelheim, Otsuka, NIH; he has served as a consultant for Roche. SWW has received research support from Teva, Pfizer; he has served as a consultant for Boehringer Ingelheim, Nutria Health. DB has received research support from National Parkinson Foundation; he has served on the speaker’s bureau for Teva Pharmaceuticals and Acadia Pharmaceuticals, Inc; he has served as a consultant for Teva, Cynapsus, Acadia. MSL has served on the speakers’ bureau for Lundbeck, Acadia, and Teva; he has served as a consultant for Teva Neuroscience, US WorldMeds, the Mayo Clinic, Starnes-Davis-Florie, Elite Medical Experts, Spears, Moore, Rebman receives research support from the National Institutes of Health (R01 NS082296, R21 GM118962, U54 TR001456, 5U01 NS090259), Department of Defense (W81XWH-17-1-0062), Michael J. Fox Foundation, Dorothy/Daniel Gerwin Parkinson’s Research Fund, Auspex, Teva, Acorda, US WorldMeds, Axovant and CHDI; and receives royalty payments from Elsevier for editing ‘Animal Models of Movement Disorders’ and ‘Movement Disorders: Genetics and Models.’ DRS has served as a consultant for Eli Lilly, Teva, Lundbeck, and Weston Brain Institute; he has received speaker’s fees from Acadia, Baylor College of Medicine, the Arizona Psychiatric Society, Lundbeck, Teva US World Meds and the Tourette Association of America; he has received research support from Arizona Alzheimer’s Consortium, Axovant, Biotie, Intec, Kyowa, Teva, US WorldMeds, Neurocrine, Michael J. Fox Foundation, and the NIH. KEA has served as a scientific adviser and was the North American study Co-Principal Investigator for LEGATO-HD, Global Principal Investigator for AIM-TD, and Global Co-Principal Investigator for ARM-TD; she was the site Principal Investigator for Pride-HD, First-HD, ARC-HD for Teva; she was the scientific advisor and site Principal Investigator for ENROLL-HD for CHDI Foundation; she was a scientific advisor for Prana and site Principal Investigator for Vaccinex; she served as a consultant for the NeuroNext 105 study for Azevan; she has received salary support from the Griffin Foundation. She has also received honoraria from Vindico Medical Education., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

One neglected aspect of research on foraging behavior is that of the effect of obstacles that increase habitat complexity on foraging efficiency. Here, we explored how long it takes individually foraging desert ant workers (Cataglyphis niger) to reach a food reward in a maze, and examined whether maze complexity affects maze-solving time (the time elapsed till the first worker reached the food reward). The test mazes differed in their complexity level, or the relative number of correct paths leading to the food reward, vs. wrong paths leading to dead-ends. Maze-solving time steeply increased with maze complexity, but was unaffected by colony size, despite the positive correlation between colony size and the number of workers that searched for food. The number of workers observed feeding on the food reward 10 min after its discovery decreased with complexity level but not colony size. We compared our experimental results to three simulation models, applying different search methods, ranked them according to their fit to the data and found the self-avoiding random search to fit the best. We suggest possible reasons for the model deviations from the observational findings. Our data emphasize the necessity to refer to habitat complexity when studying foraging behavior., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Background: There is a lack of published guidelines related to the use of complementary and alternative medicine (CAM) for Huntington's disease (HD). We conducted a review of the literature to summarize the available evidence for various mind-body practices and nutraceuticals., Methods: PubMed and Cochrane Library electronic databases were searched independently from inception to February 2019 by two independent raters. Studies were classified for the level of evidence (Class I, II, III, or IV) according to the American Academy of Neurology (AAN) classification scale., Results: Randomized controlled trials in HD were reviewed for mind-body interventions (dance therapy, music therapy, and exercise), alternative systems (traditional Chinese medicine [TCM]), and nutraceuticals/diet (aminooxyacetic acid [AOAA], coenzyme q10, creatine, cannabinoids, alpha-tocopherol, eicosapentaenoic acid, idebenone, levocarnitine, and triheptanoin). Few studies met AAN Class I or II level of evidence for benefits, and these are highlighted., Discussion: There is a relative paucity of clinical trials examining CAM modalities in HD when compared to other neurodegenerative disorders. Currently, there is no evidence supporting disease modification or symptom improvement with any specific dietary or nutraceutical supplement for HD. Supervised exercise and contemporary dance are safe for people with HD, but more robust studies are warranted to guide specific recommendations for these and other mind-body interventions., Competing Interests: Funding: None. Conflicts of Interest: The authors report no conflicts of interest. Ethics Statement: Not applicable for this category of article.

Wormlions are small fly larvae that dig pits in loose soil to trap their prey. Similar to other trap-building predators, like spiders and antlions, they depend on the habitat structure for successful trap construction and prey catch. We examined whether sites at which wormlions are present differ in sand depth and particle size from nearby sites, at which wormlions are absent. Next, in the laboratory we manipulated both sand depth and type (fine vs. coarse) to determine their joint effect on microhabitat preference, the size of the constructed pit, wormlion movement, and their latency to respond to prey. We expected better performance by wormlions in fine and deep sand, and the sand in wormlions' natural sites to be finer and deeper. However, in only partial agreement with our expectations, wormlion sites featured finer sand but not deeper sand. In the laboratory, wormlions preferred both fine and deep sand, and moved more in shallow and coarse sand, which we interpret as an attempt to relocate away from unfavorable conditions. However, only deep sand led to larger pits being constructed and to a faster response to prey. The preference for fine sand could, therefore, be related to other benefits that sand provides. Finally, body mass was a dominant factor, interacting with the preference for both deep and fine sand: deep over shallow sand was more favored by large wormlions and fine over coarse sand by smaller ones. Our results suggest that several factors should be incorporated when studying microhabitat selection.

Background: An increased risk of suicide in Huntington's disease (HD) patients is well documented, with rates significantly higher than those of the general population as well as other neurodegenerative diseases. However, despite its prevalence, the magnitude of this phenomenon as well as its predictors and etiology are still poorly understood., Methods: We performed the first systematic review of all the studies published between March 1993 and December 2018 which investigated HD patients and gene carriers that reported suicidal ideation, suicide attempt, or suicide as an outcome., Results: This review reveals that some aspects of suicidality in HD are more clearly understood than others. We confirm an increased risk of suicidal ideation, suicide attempt, and suicide for HD patients. We found that suicidal ideation is elevated throughout the course of the disease, and that psychiatric comorbidities are common risk factors with depression being the most prominent., Limitations: Important data are still largely missing, specifically regarding cognitive and neuroanatomical mechanisms and potential effective interventions. Moreover, inconsistencies in terminology, assessment tools, and outcome measures limit the comparability of the research and the conclusions that can be drawn., Conclusions: Incidence of suicidal ideation, suicide attempt, and suicide are higher among those with HD relative to the non-HD population. It is therefore important that suicidal thoughts and behaviors are closely monitored in HD clinics and that clinical trials use standardized scales. Future research should focus on better understanding the etiology of this high suicide risk and on testing the efficacy of potential interventions., (Copyright © 2019. Published by Elsevier B.V.)

Background: Prior Huntington's disease (HD) studies suggest ancillary services improve motor symptoms, cognition, mood, and quality of life but frequency of use and clinicalcharacteristics are unclear., Objective: Describe ancillary service utilization in a cohort of individuals with HD and determine which participant characteristics are associated with ancillary service utilization., Methods: Retrospective cross-sectional analysis of Enroll-HD database. Participants were grouped by therapy: physical and/or occupational (PT/OT), psychotherapy and/or counseling (PC), speech and/or swallowing (ST). We performed bivariate comparisons analysis of demographic and disease characteristics between those with/without each therapy and to analyze one-year mean change in assessment scores., Results: Of 4751 participants, 1537 (32.35%) utilized therapies (11.82% PT/OT, 5.33% PC, 3.01% ST, 1.98% all three, 10.21% two therapies). PT/OT participants had worse motor and functional scores: mean UHDRS motor score (41.17 vs. 38.05, p = 0.002), median total functional capacity score (TFC) (8.00 vs. 9.00, p < 0.001). PC participants had worse mood but better cognitive and functional scores: median depression score (7.00 vs. 2.00, p < 0.001), median MMSE (28.00 vs. 26.00, p < 0.001), median TFC (10.00 vs. 8.00, p < 0.001). ST participants had more dysarthria, and worse cognitive and functional scores: dysarthria (32.2% vs. 20.1% p < 0.001), mean correct Symbol Digit Modality Test (16.79 vs. 23.27, p < 0.001), median TFC (6.00 vs. 9.00, p < 0.001). Over one year, PC participants' depression scores improved compared to untreated (- 1.24 vs. - 0.11, p = 0.040). ST participants' depression scores worsened (1.14 vs. - 0.23, p = 0.044). Mean change in TFC was not significant for any therapies., Conclusions: Only 32% of Enroll-HD site participants received ancillary services. Use correlated with expected clinical characteristics, though impact of use remains unclear.

Background: Huntington's disease (HD) is a progressive neurodegenerative disease characterized by involuntary movements and neuropsychiatric decline. With suicide rates five times higher in patients with HD compared to the general population, there is a need for further research into the management of affective symptoms in these patients. Electroconvulsive therapy (ECT) has been long used as a treatment for severe or medication-refractory mood disorders and catatonia. There are some case studies demonstrating ECT's positive effect on depression and agitation in HD, but the data is limited., Objective: In this single site case series, we review ECT use for four HD patients with medication-refractory depression and/or psychosis to better assess the utility of ECT in this population. We also compile and review the existing literature on the topic., Methods: A single-center retrospective case series was conducted reviewing the indications, outcomes, and regimen of ECT treatments. Literature review was conducted via PubMed., Results: Four patients received ECT treatment during an inpatient hospitalization with three continuing maintenance therapy as an outpatient. All four had improvements in depression, agitation, and suicidal ideation leading to successful hospital discharge. One of the four patients also demonstrated subjective improvement in cognitive and motor symptoms after ECT initiation. Nineteen reported cases were identified through the literature review and are summarized., Conclusions: This case series adds to the existing literature demonstrating the successful use of ECT for psychiatric symptoms in HD. Larger scale studies are warranted to further investigate the specific role and protocol for the use of ECT in the management of refractory depression and psychosis in this population.

Huntington's disease (HD) is a rare neurodegenerative disease associated with disability and loss of patient independence. The caregivers of HD patients are at high risk for burnout. We aimed to identify variables that impact caregiver burden, as measured by the Modified Caregiver Strain Index (MCSI) and the Huntington's disease Quality of Life Battery for Carers Short Form (HD-SF). Total functional capacity and being sole caregiver were significantly associated with higher caregiver burden via MCSI. There was not good correlation between MCSI and HDQoLC-SF. This study highlights the need for more research to effectively identify at-risk caregivers for early intervention.

Background: Previous studies in Parkinson's Disease (PD) have described benefits of dance for motor and non-motor outcomes, yet few studies specifically look at Dance Therapy (DT) as a specific psychotherapeutic model for PD. DT is the psychotherapeutic use of movement to improve physical, emotional, cognitive, and social integration and wellbeing., Objective: 1) Explore the safety and feasibility of a 10-week DT program for PD. 2) Collect pilot data on efficacy of DT., Design/methods: Prospective, randomized-controlled study in subjects with PD. 13 participants randomized 2:1 to DT (n = 9) or support group (n = 4). Assessments were completed 1-2 weeks prior to the first session and after the final session, and included attendance, Hoehn and Yahr Scale (H&Y), Unified Parkinson's Disease Rating Scale (MDS-UPDRS), Montreal Cognitive Assessment, Timed Up and Go, Berg Balance Scale, Beck Depression Inventory, Fatigue Severity Scale, Visual Analog Fatigue Scale, Parkinson's Disease Questionnaire-39, and an exit satisfaction survey., Results: All participants completed the study. The control group was older and had a higher mean baseline MDS-UPDRS III score (27.56 dance vs. 40.75 control) and H&Y score (2.11 dance vs. 2.50 control). 7 of 9 in DT and all control subjects attended at least 70% of classes. All participants in DT enjoyed the classes and most felt they were beneficial. The greatest improvement in motor measures was in MDS-UPDRS III (-4.12 (dance) vs. -1.75 (control)). Non-motor outcomes were explored as well., Conclusions: DT is introduced as an enjoyable mind-body intervention for PD. Further studies powered for efficacy and with groups matched for disease severity are warranted., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Objectives: There are no curative treatments for cervical dystonia (CD), therefore conventional management is aimed at pain relief and muscle relaxation. Many patients with CD use complementary and integrative medicine interventions to manage symptoms, yet there are limited data on the use of acupuncture for CD. The aim of the current study was to determine the feasibility, safety, and efficacy of adjuvant acupuncture. Materials and Methods: A pilot open-label study was conducted on acupuncture treatments as add-on therapy to botulinum-toxin injection sessions (3 months apart) in 5 subjects with chronic idiopathic CD. Six 1-hour acupuncture sessions were administered every other week over the 3-month period between consecutive botulinum-toxin sessions. Data from exploratory efficacy endpoints-including a visual analogue scale for pain, the Clinician Global Impression of Change, the Patient Global Impression of Change, the Toronto Western Spasmodic Torticollis Rating Scale, and the Short Form-36) Health Survey-were collected. Results: Five subjects completed the study with only 1 acupuncture session missed by 1 subject, thereby meeting the study's predetermined adherence goal. All participants reported improvement from acupuncture. Only minor adverse events were reported, with self-resolved discomfort in 1 subject and self-resolved minor bruising in 2 subjects. Conclusions: Acupuncture is feasible and safe as an adjunct treatment for chronic CD, and might be associated with subjective symptomatic benefits., Competing Interests: D.B. has no relevant conflicts to disclose. He has received consultant/speaker fees from Teva Pharmaceuticals, ACADIA Pharmaceuticals, USWorldMeds, Neurocrine Biosciences, and Adamas Pharmaceuticals. No competing financial interests exist for K.P., A.G., F.L., and M.R.

Objective: Compare clinical characteristics and outcomes in cases where DAT-SPECT imaging is used to distinguish Parkinson's disease from Drug-Induced Parkinsonsim., Background: Clinical uncertainty in diagnosing Parkinson's disease is common when patients are on dopamine-blocking medications. DAT-SPECT imaging can improve diagnostic certainty but little data are available on clinical characteristics and outcomes associated with normal and abnormal scan results., Methods: Retrospective chart review of patients seen at a movement disorders center between 2011 and 2017 where DAT-SPECT was ordered to distinguish Parkinson's disease from Drug-induced Parkinsonism. Descriptive statistics were calculated for variables of interest and compared by scan result. Chi-squared analyses was carried out for categorical variables and students' t-tests for continuous values., Results: 51 patients met inclusion criteria with 36 normal scans and 15 abnormal scans. Those with greater than 2 cardinal manifestations (tremor, rigidity, akinesia, postural instability) were more likely to have an abnormal scan (63.89% vs 93.33%, p = 0.04). No other clinical characteristics assessed were associated with scan results. Atypical antipsychotics (aripiprazole 39.21%, olanzapine 31.37%) and mood stabilizers (valproic acid 33.33%, lithium 17.65%) were most commonly associated with suspected Drug-induced Parkinsonism cases. A post-scan change in management occurred in 41.18% of patients. 55.56% of patients with normal scans responded to changes in the offending medication, with 16.66% taking over 3 months to show improvement., Conclusions: Many DAT-SPECT scans at our institution are ordered to distinguish Parkinson's disease from Drug-induced Parkinsonism because clinical characteristics alone are unreliable. DAT-SPECT results lead to changes in management and the outcomes of these changes are consistent with scan results., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Background: Wilson's disease is a genetic disorder in which copper accumulates in the liver, brain, and other tissues. Therapies are limited by efficacy, safety concerns, and multiple daily dosing. Bis-choline tetrathiomolybdate (WTX101) is an oral first-in-class copper-protein-binding molecule that targets hepatic intracellular copper and reduces plasma non-ceruloplasmin-bound copper (NCC) by forming tripartite complexes with albumin and increasing biliary copper excretion. We aimed to assess the efficacy and safety of WTX101 in the initial or early treatment of patients with Wilson's disease., Methods: We did this open-label, phase 2 study at 11 hospitals in the USA and Europe. We enrolled patients (≥18 years) with Wilson's disease who were untreated or had received no more than 24 months of treatment with chelators or zinc, had a Leipzig score of 4 or more, and had NCC concentrations above the lower limit of the normal reference range (≥0·8 μmol/L). Eligible patients received WTX101 monotherapy at a starting dose of 15-60 mg/day on the basis of baseline NCC concentrations for the first 4-8 weeks, with response-guided individualised dosing for the remaining weeks up to week 24. Investigators, other hospital personnel, and patients were aware of the identity of the treatment. The primary endpoint was change in baseline NCC concentrations corrected for copper in tetrathiomolybdate-copper-albumin complexes (NCC corrected ) at 24 weeks, with treatment success defined as achievement or maintenance of normalised NCC corrected (≤2·3 μmol/L [upper limit of normal]) or achievement of at least a 25% reduction in NCC corrected from baseline at 24 weeks. This study is registered with ClinicalTrials.gov, number NCT02273596., Findings: Between Nov 24, 2014, and April 27, 2016, 28 patients were enrolled and received WTX101; 22 (79%) patients completed the study up to week 24. At 24 weeks, 20 (71%, 95% CI 51·3-86·8; p<0·0001) of 28 patients met the criteria for treatment success: 16 (57%) treated with WTX101 either achieved or maintained normalised NCC corrected concentrations and 4 (14%) had at least a 25% reduction from baseline NCC corrected . Mean NCC corrected was reduced by 72% from baseline to week 24 (least squares mean difference -2·4 μmol/L [SE 0·4], 95% CI -3·2 to -1·6; p<0·0001). No cases of paradoxical drug-related neurological worsening were recorded. Liver function was stable in all patients, although reversible increased concentrations of asymptomatic alanine or aspartate aminotransferase, or γ-glutamyltransferase, without increased bilirubin, occurred in 11 (39%) of 28 patients who received at least 30 mg/day. 11 serious adverse events were reported in seven (25%) patients and included psychiatric disorders (six events in four patients), gait disturbance (one event), elevated liver aminotransferases (two events in two patients, one with agranulocytosis), and decline in neurological functioning (one event, likely due to natural disease progression although causality could not be ruled out). The seven serious adverse events categorised as psychiatric disorders and as gait disturbance were assessed as unlikely to be related to the study drug, whereas the remaining four events were possibly or probably related., Interpretation: Our findings indicate that WTX101 might be a promising new therapeutic approach for Wilson's disease, with a unique mode of action. In view of its once-daily dose and favourable safety profile, WTX101 could improve the treatment of patients with this debilitating condition., Funding: Wilson Therapeutics AB., (Copyright © 2017 Elsevier Ltd. All rights reserved.)