Cognitive impairment is one of the main features of Huntington's disease and is present across the disease spectrum. As part of the International Parkinson's Disease and Movement Disorder Society‐sponsored project to review all clinical rating scales used in Huntington's disease, a systematic review of the literature was performed to identify cognitive scales used in Huntington's disease and make recommendations for their use. A total of 17 cognitive scales were identified and evaluated. None of the scales met criteria for a “recommended” status. For assessing severity of cognitive dysfunction, the Montreal Cognitive Assessment was “recommended with caveats .” The UHDRS Cognitive Assessment, the UHDRS‐For Advanced Patients cognitive section, the Alzheimer's Disease Assessment Scale‐Cognitive Subscale, the Frontal Assessment Battery, the Mattis Dementia Rating Scale, the Mini‐Mental State Examination, and the Repeatable Battery for the Assessment of Neuropsychological Status were “suggested” for evaluating severity of cognitive impairment. The MoCA was “suggested” as a screening tool for cognitive impairment. The major challenge in the assessment of cognition in Huntington's disease is the lack of a formal definition of dementia and/or mild cognitive impairment in this disease. The committee concluded that there is a need to further validate currently available cognitive scales in Huntington's disease, but that it is premature to recommend the development of new scales. Recently developed Huntington's disease‐specific scales, such as the Huntington's Disease‐Cognitive Assessment Battery, hold promise but require the completion of more comprehensive clinimetric development. © 2017 International Parkinson and Movement Disorder Society

Well-defined and reliable clinical outcome assessments are essential for determining whether a drug provides clinically meaningful treatment benefit for patients. In 2015, FDA convened a workshop, “Assessing Neurocognitive Outcomes in Inborn Errors of Metabolism.” Topics covered included special challenges of clinical studies of inborn errors of metabolism (IEMs) and other rare diseases; complexities of identifying treatment effects in the context of the dynamic processes of child development and disease progression; and the importance of natural history studies. Clinicians, parents/caregivers, and participants from industry, academia, and government discussed factors to consider when developing measures to assess treatment outcomes, as well as tools and methods that may contribute to standardizing measures. Many issues examined are relevant to the broader field of rare diseases in addition to specifics of IEMs.

To explore the optimal cutoff score for initial detection of Alzheimer's Disease (AD) through the Chinese version of Mini-Mental State Examination (CMMSE) in rural areas in China, we conducted a cross-sectional study within the Linxian General Population Nutritional Follow-up study. 16,488 eligible cohort members participated in the survey and 881 completed the CMMSE. Among 881 participants, the median age (Interquartile range) was 69.00 (10.00), 634 (71.92%) were female, 657 (74.57%) were illiterate, 35 (3.97%) had 6 years of education or higher, and 295 (33.48%) were diagnosed with AD. By reducing the CMMSE criteria for illiterate to 16 points, primary school to 19 points, and middle school or higher to 23 points, the efficiency of Chinese version of Mini-Mental State Examination can be significantly improved for initial detection of AD in rural areas in China, especially in those nutrition deficient areas.

The United States Food and Drug Administration (FDA) ensures that patients in the U.S. have access to safe and effective medical devices. The Division of Neurological and Physical Medicine Devices reviews medical technologies that interface with the nervous system. This article addresses how to navigate the FDA's regulatory landscape to successfully bring medical devices to patients.

Objective: To test the hypothesis that chronic treatment of early-stage Huntington disease (HD) with high-dose coenzyme Q10 (CoQ) will slow the progressive functional decline of HD. Methods: We performed a multicenter randomized, double-blind, placebo-controlled trial. Patients with early-stage HD (n = 609) were enrolled at 48 sites in the United States, Canada, and Australia from 2008 to 2012. Patients were randomized to receive either CoQ 2,400 mg/d or matching placebo, then followed for 60 months. The primary outcome variable was the change from baseline to month 60 in Total Functional Capacity score (for patients who survived) combined with time to death (for patients who died) analyzed using a joint-rank analysis approach. Results: An interim analysis for futility revealed a conditional power of <5% for the primary analysis, prompting premature conclusion in July 2014. No statistically significant differences were seen between treatment groups for the primary or secondary outcome measures. CoQ was generally safe and well-tolerated throughout the study. Conclusions: These data do not justify use of CoQ as a treatment to slow functional decline in HD. ClinicalTrials.gov identifier: NCT00608881. Classification of evidence: This article provides Class I evidence that CoQ does not slow the progressive functional decline of patients with HD.

IMPORTANCEIdentifying measures that are associated with the cytosine-adenine-guanine (CAG) expansion in individuals before diagnosis of Huntington disease (HD) has implications for designing clinical trials.OBJECTIVETo identify the earliest features associated with the motor diagnosis of HD in the Prospective Huntington at Risk Observational Study (PHAROS).DESIGN, SETTING, AND PARTICIPANTSA prospective, multicenter, longitudinal cohort study was conducted at 43 US and Canadian Huntington Study Group research sites from July 9, 1999, through December 17, 2009. Participants included 983 unaffected adults at risk for HD who had chosen to remain unaware of their mutation status. Baseline comparability between CAG expansion (≥37 repeats) and nonexpansion (<37 repeats) groups was assessed. All participants and investigators were blinded to individual CAG analysis. A repeated-measures analysis adjusting for age and sex was used to assess the divergence of the linear trend between the expanded and nonexpanded groups. Data were analyzed from April 27, 2010, to September 3, 2013.EXPOSUREHuntington disease mutation status in individuals with CAG expansion vs without CAG expansion.MAIN OUTCOMES AND MEASURESUnified Huntington's Disease Rating Scale motor (score range, 0-124; higher scores indicate greater impairment), cognitive (symbol digits modality is the total number of correct responses in 90 seconds; lower scores indicate greater impairment), behavioral (score range, 0-176; higher scores indicate greater behavioral symptoms), and functional (Total Functional Capacity score range, 0-13; lower scores indicate reduced functional ability) domains were assessed at baseline and every 9 months up to a maximum of 10 years.RESULTSAmong the 983 research participants at risk for HD in the longitudinal cohort, 345 (35.1%) carried the CAG expansion and 638 (64.9%) did not. The mean (SD) duration of follow-up was 5.8 (3.0) years. At baseline, participants with expansions had more impaired motor (3.0 [4.2] vs 1.9 [2.8]; P < .001), cognitive (P < .05 for all measures except Verbal Fluency, P = .52), and behavioral domain scores (9.4 [11.4] vs 6.5 [8.5]; P < .001) but not significantly different measures of functional capacity (12.9 [0.3] vs 13.0 [0.2]; P = .23). With findings reported as mean slope (95% CI), in the longitudinal analyses, participants with CAG expansions showed significant worsening in motor (0.84 [0.73 to 0.95] vs 0.03 [-0.05 to 0.11]), cognitive (-0.54 [-0.67 to -0.40] vs 0.22 [0.12 to 0.32]), and functional (-0.08 [-0.09 to -0.06] vs -0.01 [-0.02 to 0]) measures compared with those without expansion (P < .001 for all); behavioral domain scores did not diverge significantly between groups.CONCLUSIONS AND RELEVANCEUsing these prospectively accrued clinical data, relatively large treatment effects would be required to mount a randomized, placebo-controlled clinical trial involving premanifest HD individuals who carry the CAG expansion.

Selection designs and futility designs offer investigators a way to screen potential therapies in early phase clinical research with fewer patients than would be required for a traditional phase 3 trial for each candidate. There are some avoidable-pitfalls when planning a futility study. The first is that if the sample size is too small, a rather awkward situation can arise. The last pitfall relates to the use of historical control data in the single-arm design. Selection procedures offer an attractive approach to the problem of screening potentially good treatments. There are many different procedures for general ranking and selection goals such as selection from among more than two treatments, selection of best subsets of treatments, and ranking treatments in order of efficacy. Although selection procedures efficiently achieve their goal of selecting best treatments, the desire to 'test something' with an accompanying statement of statistical significance seems irresistible.

Movement DisordersVolume 25, Issue 13 p. 2254-2255 Letter to the Editor Related to Published Articles Reply: An exploration of the burden experienced by spousal caregivers of individuals with Parkinson's disease† Lisa M. Deuel BA, Corresponding Author Lisa M. Deuel BA [email protected] Department of Neurology, University of Rochester, Rochester, New YorkDepartment of Neurology, University of Rochester, Rochester, New YorkSearch for more papers by this authorAmy M. Chesire LCSW-R, MSG, Amy M. Chesire LCSW-R, MSG Department of Neurology, University of Rochester, Rochester, New YorkSearch for more papers by this authorSheelah Eason MSW, Sheelah Eason MSW Lifetime Care, Rochester, New YorkSearch for more papers by this authorPeter G. Como PhD, Peter G. Como PhD United States Food and Drug Administration, Silver Springs, MarylandSearch for more papers by this authorKevin M. Biglan MD, MPH, Kevin M. Biglan MD, MPH Department of Neurology, University of Rochester, Rochester, New YorkSearch for more papers by this author Lisa M. Deuel BA, Corresponding Author Lisa M. Deuel BA [email protected] Department of Neurology, University of Rochester, Rochester, New YorkDepartment of Neurology, University of Rochester, Rochester, New YorkSearch for more papers by this authorAmy M. Chesire LCSW-R, MSG, Amy M. Chesire LCSW-R, MSG Department of Neurology, University of Rochester, Rochester, New YorkSearch for more papers by this authorSheelah Eason MSW, Sheelah Eason MSW Lifetime Care, Rochester, New YorkSearch for more papers by this authorPeter G. Como PhD, Peter G. Como PhD United States Food and Drug Administration, Silver Springs, MarylandSearch for more papers by this authorKevin M. Biglan MD, MPH, Kevin M. Biglan MD, MPH Department of Neurology, University of Rochester, Rochester, New YorkSearch for more papers by this author First published: 27 August 2010 https://doi.org/10.1002/mds.23273Citations: 1 † Potential conflict of interest: Nothing to report. Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onEmailFacebookTwitterLinkedInRedditWechat References 1 Roland KP,Jenkins ME,Johnson AM. An exploration of the burden experienced by spousal caregivers of individuals with Parkinson's Disease. Mov Disord 2010; 25: 189–193. 2 Zarit SH,Reeves KE,Bach-Peterson J. Relatives of the impaired elderly: correlates of feelings of burden. Gerontologist 1980; 20: 649–655. 3 Schrag A,Hovris A,Morley D,Quinn N,Jahanshahi M. Caregiver-burden in Parkinson's Disease is closely associated with psychiatric symptoms, falls, and disability. Parkinsonism Relat Disord 2006; 12: 35–41. 4 Dorsey ER,Deuel LM,Voss TS,Finnigan K,George BP,Eason S,Miller D,Reminick J,Appler A,Polanowicz J,Viti L,Smith S,Joseph A,Biglan KM. Increasing Access to specialty care: a pilot, randomized, controlled trial of telemedicine for Parkinson disease. Mov Disord (in press). Citing Literature Volume25, Issue1315 October 2010Pages 2254-2255 ReferencesRelatedInformation

Coenzyme Q10 (CoQ10), a potential neuroprotective compound, was previously investigated at a dosage of 600 mg/day in Huntington's disease (HD) patients and demonstrated a trend toward slowing disease progression. Higher CoQ10 dosages may prove beneficial. We investigated the tolerability and blood levels associated with 1,200, 2,400, and 3,600 mg/day of CoQ10 in HD and healthy subjects. Twenty‐eight subjects (20 HD, 8 healthy) enrolled in a 20‐week open‐label trial. Subjects started on 1,200 mg/day of CoQ10, increasing every 4 weeks by 1,200 mg to a maximum dosage of 3,600 mg/day. Monthly evaluations included review of adverse events and CoQ10 blood levels. Twenty‐three subjects (82%) achieved the target dosage of 3,600 mg/day. Six subjects (2 healthy, 4 HD) withdrew prematurely (gastrointestinal (GI) symptoms in 3, worsening HD in 2, and 1 because of a fall). All three serious adverse events occurred in a single subject, and were deemed unrelated to CoQ10. The most common adverse events seen were GI symptoms. Mean (± SD) CoQ10 blood levels achieved over the course of the trial were as follows: 1.26 ± 1.27 μg/mL (baseline, n = 28), 5.59 ± 2.24 μg/mL (1,200 mg/day, week 4, n = 26), 6.38 ± 3.25 μg/mL (2,400 mg/day, week 8, n = 25), 7.49 ± 4.09 μg/mL (3,600 mg/day, week 12, n = 23), and 6.78 ± 3.36μg/mL (3,600 mg/day, week 20, n = 20). CoQ10 was well tolerated with over 80% of subjects achieving the target dosage. Dosages of 2,400 mg/day may provide the best balance between tolerability and blood level achieved. Further studies examining the efficacy of 2,400 mg/day are planned. © 2010 Movement Disorder Society.

Little is known about the course of depressive symptoms in Parkinson's disease (PD). We studied the course of clinically significant depressive symptoms using data from two clinical trials that followed 413 early, untreated PD subjects for 12 to 18 months. We measured depressive symptoms with the 15‐item geriatric depression scale (GDS‐15); a score of ≥5 indicates clinically significant depressive symptoms. We used a time‐dependent Cox model to examine the association between demographic variables, PD severity, and medication use on the time to resolution of depressive symptoms. One hundred fourteen of 413 (27.6%) subjects were screened positive for depression during the study, with a median GDS‐15 score of 6, indicating mild symptoms. Within 6 months, 47% of subjects experienced remission of clinically significant depressive symptoms. Subjects with mild depressive symptoms were more likely to develop moderate to severe depressive symptoms (GDS ≥ 10) than those without prior symptoms (relative risk = 6.16). Increasing severity of depressive symptoms, older age, and longer PD duration predicted a lower likelihood of symptom resolution (hazard ratios 0.83–0.92). Mild depressive symptoms have a variable course, with remission and development of more sustained and severe symptoms occurring over time. More severe depressive symptoms may herald a protracted course. © 2009 Movement Disorder Society

In response to recent publicity regarding the potential use of deep brain stimulation (DBS) for reducing tic severity in Tourette's syndrome (TS), the Tourette Syndrome Association convened a group of TS and DBS experts to develop recommendations to guide the early use and potential clinical trials of DBS for TS and other tic disorders. The goals of these recommendations are to ensure that all surgical candidates are (1) fully informed about the risks, benefits, and alternative treatments available; (2) receive a comprehensive evaluation before surgery to ensure that DBS is clearly the appropriate clinical treatment choice; and (3) that early clinical experience will be documented publicly to facilitate rational decision‐making for both clinical care and future clinical trials. © 2006 Movement Disorder Society

Objective: To identify the emerging clinical precursors that indicate the early onset of Huntington disease (HD) in a reliable and gene-specific manner. This information is critical for the development of therapeutic trials aimed at postponing clinical onset in HD gene carriers.Methods: Between July 1999 and January 2004, 1001 adults at 50-50 risk for HD agreed to provide longitudinal clinical data and a blood DNA sample under consent provisions that require their individual clinical and genetic information to never be revealed.Results: The Prospective Huntington At Risk Observational Study (PHAROS) cohort is characterized by a 2:1 predominance of women to men, high educational attainment, and gainful employment. Despite the gender disparity, the demographic, hereditary, and clinical characteristics of the female and male participants were similar. Investigators, who are unaware of individual gene status, characterized the baseline cohort to be highly functional with minimal motor or cognitive impairment; 92.3% of participants were judged to have no or nonspecific motor abnormalities; 6.7%, to have possible or probable motor signs; and only 1.0%, to have unequivocal HD.Conclusion: The baseline characteristics of the PHAROS cohort make it well suited to generate objective and prospective data about gene-specific clinical precursors that can be used as outcomes in controlled trials aimed at postponing the onset of HD.

Patients with Huntington’s disease (HD) experience psychotic symptoms more frequently than the general population. The clinical picture includes a broad spectrum of disorders including poorly systematized paranoia, isolated delusional states, and psychotic states. The challenge to the clinician is to be able to recognize and treat psychotic symptoms in HD patients, who have been diagnosed with this disorder, and also to consider these symptoms as the earliest manifestation of HD in patients, who are at risk. This chapter reviews the literature and clinical experience relating to HD and psychosis and offers a treatment management strategy based on the clinical experience of a multidisciplinary group that was assembled to discuss these issues.

Social Isolation and Psychological Disturbance in Myotonic Dystrophy: PP161 D. Garron;R. Glantz;D. Babcock;P. Como;J. Salloway;S. Daugherty;R. Wright;D. Beck;I. Siegel; Neurology