Johana Escudero-Cabarcas, Wilmar Pineda-Alhucema, Martha Martinez-Banfi, Johan E Acosta-López, Martha L Cervantes-Henriquez, Elsy Mejía-Segura, Giomar Jiménez-Figueroa, Cristian Sánchez-Barros, Pedro J Puentes-Rozo, Luz M Noguera-Machacón, Mostapha Ahmad, Moisés de la Hoz, Jorge I Vélez, Mauricio Arcos-Burgos, David A Pineda, Manuel Sánchez
{"title":"Theory of Mind in Huntington's Disease: A Systematic Review of 20 Years of Research.","authors":"Johana Escudero-Cabarcas, Wilmar Pineda-Alhucema, Martha Martinez-Banfi, Johan E Acosta-López, Martha L Cervantes-Henriquez, Elsy Mejía-Segura, Giomar Jiménez-Figueroa, Cristian Sánchez-Barros, Pedro J Puentes-Rozo, Luz M Noguera-Machacón, Mostapha Ahmad, Moisés de la Hoz, Jorge I Vélez, Mauricio Arcos-Burgos, David A Pineda, Manuel Sánchez","doi":"10.3233/JHD-230594","DOIUrl":"10.3233/JHD-230594","url":null,"abstract":"<p><strong>Background: </strong>People with Huntington's disease (HD) exhibit neurocognitive alterations throughout the disease, including deficits in social cognitive processes such as Theory of Mind (ToM).</p><p><strong>Objective: </strong>The aim is to identify methodologies and ToM instruments employed in HD, alongside relevant findings, within the scientific literature of the past two decades.</p><p><strong>Methods: </strong>We conducted a comprehensive search for relevant papers in the SCOPUS, PubMed, APA-PsyArticles, Web of Science, Redalyc, and SciELO databases. In the selection process, we specifically focused on studies that included individuals with a confirmed genetic status of HD and investigated ToM functioning in patients with and without motor symptoms. The systematic review followed the PRISMA protocol.</p><p><strong>Results: </strong>A total of 27 papers were selected for this systematic review, covering the period from 2003 to 2023. The findings consistently indicate that ToM is globally affected in patients with manifest motor symptoms. In individuals without motor symptoms, impairments are focused on the affective dimensions of ToM.</p><p><strong>Conclusions: </strong>Based on our analysis, affective ToM could be considered a potential biomarker for HD. Therefore, it is recommended that ToM assessment be included as part of neuropsychological evaluation protocols in clinical settings. Suchinclusion could aid in the identification of early stages of the disease and provide new opportunities for treatment, particularly with emerging drugs like antisense oligomers. The Prospero registration number for this review is CRD42020209769.</p>","PeriodicalId":16042,"journal":{"name":"Journal of Huntington's disease","volume":" ","pages":"15-31"},"PeriodicalIF":2.1,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140189701","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Carlos Estevez-Fraga, Sarah J Tabrizi, Edward J Wild
{"title":"Huntington's Disease Clinical Trials Corner: March 2024.","authors":"Carlos Estevez-Fraga, Sarah J Tabrizi, Edward J Wild","doi":"10.3233/JHD-240017","DOIUrl":"10.3233/JHD-240017","url":null,"abstract":"<p><p>In this edition of the Huntington's Disease Clinical Trials Update, we expand on the ongoing program from VICO Therapeutics and on the recently terminated VIBRANT-HD clinical trials. We also discuss updates from uniQure's AMT-130 program and PTC therapeutics' trial of PTC518 and list all currently registered and ongoing clinical trials in Huntington's disease.</p>","PeriodicalId":16042,"journal":{"name":"Journal of Huntington's disease","volume":" ","pages":"1-14"},"PeriodicalIF":3.1,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11091610/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140136910","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Cristina Sampaio, Sandra K Kostyk, Sarah J Tabrizi, Anne E Rosser
{"title":"Refining the Language of Huntington's Disease Progression with the Huntington's Disease Integrated Staging System (HD-ISS).","authors":"Cristina Sampaio, Sandra K Kostyk, Sarah J Tabrizi, Anne E Rosser","doi":"10.3233/JHD-240043","DOIUrl":"10.3233/JHD-240043","url":null,"abstract":"","PeriodicalId":16042,"journal":{"name":"Journal of Huntington's disease","volume":"13 2","pages":"115-118"},"PeriodicalIF":2.1,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11307057/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141537924","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Muhammad Arham Bin Kashif, Samar Mahmood, Tahrim Saqib, Syeda Tahira Waheed, Piresh Kumar, Aima Javaid, Muhammad Asjad Riaz, Urooj Fatima, Zain Ali Nadeem, Shahbaz Ali Nasir, Afrah Hassan
{"title":"Huntington's Disease-Related Mortality Patterns: A Two-Decade Analysis of Mortality Trends in the United States, from 1999-2019.","authors":"Muhammad Arham Bin Kashif, Samar Mahmood, Tahrim Saqib, Syeda Tahira Waheed, Piresh Kumar, Aima Javaid, Muhammad Asjad Riaz, Urooj Fatima, Zain Ali Nadeem, Shahbaz Ali Nasir, Afrah Hassan","doi":"10.3233/JHD-240037","DOIUrl":"10.3233/JHD-240037","url":null,"abstract":"<p><strong>Background: </strong>Huntington's disease (HD) is an autosomal dominant, progressive neurodegenerative disorder debilitating mainly in adults.</p><p><strong>Objective: </strong>This study aimed to assess the trends in HD-related mortality regarding various demographic factors.</p><p><strong>Methods: </strong>Death certificates from the CDC WONDER were studied from 1999 to 2019, for HD-related mortality in adults aged 25 + years. Age-adjusted Mortality Rate (AAMR) per 100,000 persons and Annual Percentage Change (APC) were calculated and stratified by year, age groups, gender, race/ethnicity, state, census region, urbanization, and place of death.</p><p><strong>Results: </strong>Between 1999 to 2019, 22,595 deaths occurred in adults due to HD. The AAMR increased from 0.43 to 0.54 during this period (APC = 0.50; 95% CI: 0.18 to 0.84). Old adults (65-85 + years) had the highest overall AAMR, followed by middle-aged adults (45-64 years) and young adults (25-44 years) (AAMR old: 1.01 vs. AAMR middle-age: 0.68 vs. AAMR young: 0.16). Men had slightly greater overall AAMRs than women (AAMR men: 0.54 vs. AAMR women: 0.48). When stratified by race, non-Hispanic (NH) Whites had significantly higher mortality rates than NH African Americans (AAMR NH White: 0.61 vs. NH African American: 0.35), while the AAMR were lowest in Hispanic/Latino (0.28). The AAMRs also showed variation by region (overall AAMR: Midwest: 0.63, Northeast: 0.47, West: 0.48, South: 0.46), and non-metropolitan areas had higher HD-related AAMR (0.66) than metropolitan areas (0.47).</p><p><strong>Conclusions: </strong>HD-related mortality in US adults has increased since 1999. Reflecting on the variations in trends observed, new strategies are required to optimize the quality of care in long-term care facilities.</p>","PeriodicalId":16042,"journal":{"name":"Journal of Huntington's disease","volume":" ","pages":"329-338"},"PeriodicalIF":2.1,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142108103","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Magnetic Resonance Imaging to Detect Structural Brain Changes in Huntington's Disease: A Review of Data from Mouse Models.","authors":"Jenna Hanrahan, Drew P Locke, Lindsay S Cahill","doi":"10.3233/JHD-240045","DOIUrl":"10.3233/JHD-240045","url":null,"abstract":"<p><p>Structural magnetic resonance imaging (MRI) is a powerful tool to visualize 3D neuroanatomy and assess pathology and disease progression in neurodegenerative disorders such as Huntington's disease (HD). The development of mouse models of HD that reproduce many of the psychiatric, motor and cognitive impairments observed in human HD has improved our understanding of the disease and provided opportunities for testing novel therapies. Similar to the clinical scenario, MRI of mouse models of HD demonstrates onset and progression of brain pathology. Here, we provided an overview of the articles that used structural MRI in mouse models of HD to date, highlighting the differences between studies and models and describing gaps in the current state of knowledge and recommendations for future studies.</p>","PeriodicalId":16042,"journal":{"name":"Journal of Huntington's disease","volume":" ","pages":"279-299"},"PeriodicalIF":2.1,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11494634/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142108104","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Renee R Handley, Suzanne J Reid, Zoe Burch, Jessie C Jacobsen, Tammy Gillis, Kevin Correia, Skye R Rudiger, Clive J McLaughlin, C Simon Bawden, Marcy E MacDonald, Vanessa C Wheeler, Russell G Snell
{"title":"Somatic CAG Repeat Stability in a Transgenic Sheep Model of Huntington's Disease.","authors":"Renee R Handley, Suzanne J Reid, Zoe Burch, Jessie C Jacobsen, Tammy Gillis, Kevin Correia, Skye R Rudiger, Clive J McLaughlin, C Simon Bawden, Marcy E MacDonald, Vanessa C Wheeler, Russell G Snell","doi":"10.3233/JHD-231516","DOIUrl":"10.3233/JHD-231516","url":null,"abstract":"<p><p>Somatic instability of the huntingtin (HTT) CAG repeat mutation modifies age-at-onset of Huntington's disease (HD). Understanding the mechanism and pathogenic consequences of instability may reveal therapeutic targets. Using small-pool PCR we analyzed CAG instability in the OVT73 sheep model which expresses a full-length human cDNA HTT transgene. Analyses of five- and ten-year old sheep revealed the transgene (CAG)69 repeat was remarkably stable in liver, striatum, and other brain tissues. As OVT73 sheep at ten years old have minimal cell death and behavioral changes, our findings support instability of the HTT expanded-CAG repeat as being required for the progression of HD.</p>","PeriodicalId":16042,"journal":{"name":"Journal of Huntington's disease","volume":" ","pages":"33-40"},"PeriodicalIF":3.1,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11091634/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139940058","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Hannah S Bakels, Stephanie Feleus, Mar Rodríguez-Girondo, Monique Losekoot, Emilia K Bijlsma, Raymund A C Roos, Susanne T de Bot
{"title":"Prevalence of Juvenile-Onset and Pediatric Huntington's Disease and Their Availability and Ability to Participate in Trials: A Dutch Population and Enroll-HD Observational Study.","authors":"Hannah S Bakels, Stephanie Feleus, Mar Rodríguez-Girondo, Monique Losekoot, Emilia K Bijlsma, Raymund A C Roos, Susanne T de Bot","doi":"10.3233/JHD-240034","DOIUrl":"10.3233/JHD-240034","url":null,"abstract":"<p><strong>Background: </strong>Juvenile-onset Huntington's disease (JHD) represents 1-5% of Huntington's disease (HD) patients, with onset before the age of 21. Pediatric HD (PHD) relates to a proportion of JHD patients that is still under 18 years of age. So far, both populations have been excluded from interventional trials.</p><p><strong>Objective: </strong>Describe the prevalence and incidence of JHD and PHD in the Netherlands and explore their ability to participate in interventional trials.</p><p><strong>Methods: </strong>The prevalence and incidence of PHD and JHD patients in the Netherlands were analyzed. In addition, we explored proportions of JHD patients diagnosed at pediatric versus adult age, their diagnostic delay, and functional and modelled (CAP100) disease stage in JHD and adult-onset HD patients at diagnosis.</p><p><strong>Results: </strong>The prevalence of JHD and PHD relative to the total manifest HD population in January 2024 was between 0.84-1.25% and 0.09-0.14% respectively. The mean incidence of JHD patients being diagnosed was between 0.85-1.28 per 1000 patient years and of PHD 0.14 per 1.000.000 under-aged person years. 55% of JHD cases received a clinical diagnosis on adult age. At diagnosis, the majority of JHD patients was functionally compromised and adolescent-onset JHD patients were significantly less independent compared to adult-onset HD patients.</p><p><strong>Conclusions: </strong>In the Netherlands, the epidemiology of JHD and PHD is lower than previously suggested. More than half of JHD cases are not eligible for trials in the PHD population. Furthermore, higher functional dependency in JHD patients influences their ability to participate in trials. Lastly, certain UHDRS functional assessments and the CAP100 score do not seem appropriate for this particular group.</p>","PeriodicalId":16042,"journal":{"name":"Journal of Huntington's disease","volume":" ","pages":"357-368"},"PeriodicalIF":2.1,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11492014/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141909822","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Andressa da Silva van der Laan, Vanderci Borges, Roberta Arb Saba, Henrique Ballalai Ferraz
{"title":"Economic Burden of Huntington's Disease: Analysis from a Brazilian Tertiary Care Perspective.","authors":"Andressa da Silva van der Laan, Vanderci Borges, Roberta Arb Saba, Henrique Ballalai Ferraz","doi":"10.3233/JHD-240025","DOIUrl":"10.3233/JHD-240025","url":null,"abstract":"<p><strong>Background: </strong>Huntington's disease (HD) exerts significant impacts on individuals and families worldwide. Nevertheless, data on its economic burden in Brazil are scarce, revealing a critical gap in understanding the associated healthcare costs.</p><p><strong>Objective: </strong>This study was conducted at a tertiary neurology outpatient clinic in Brazil with the aim of assessing annual healthcare service utilization and associated costs for HD patients.</p><p><strong>Methods: </strong>We conducted a cross-sectional observational study involving 34 HD patients. A structured questionnaire was applied to collect data on direct medical costs (outpatient services, medications), non-medical direct costs (complementary therapies, mobility aids, home adaptations), and indirect costs (lost productivity, caregiver costs, government benefits) over one year.</p><p><strong>Results: </strong>Significant economic impacts were observed, with average annual direct medical costs of $4686.82 per HD patient. Non-medical direct and indirect costs increased the financial burden, highlighting extensive resource utilization beyond healthcare services. Thirty-three out of 34 HD patients were unemployed or retired, and 16 relied on government benefits, reflecting broader socioeconomic implications. Despite the dataset's limitations, it provides crucial insights into the economic impact of HD on patients and the Brazilian public health system.</p><p><strong>Conclusions: </strong>The findings underscore the urgent need for a more comprehensive evaluation of the costs to inform governmental policies related to HD. Future research is needed to expand the data pool and develop a nuanced understanding of the economic burdens of HD to help formulate effective healthcare strategies for patients.</p>","PeriodicalId":16042,"journal":{"name":"Journal of Huntington's disease","volume":" ","pages":"349-356"},"PeriodicalIF":2.1,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141992338","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Annabelle Coleman, Mackenzie T Langan, Gaurav Verma, Harry Knights, Aaron Sturrock, Blair R Leavitt, Sarah J Tabrizi, Rachael I Scahill, Nicola Z Hobbs
{"title":"Assessment of Perivascular Space Morphometry Across the White Matter in Huntington's Disease Using MRI.","authors":"Annabelle Coleman, Mackenzie T Langan, Gaurav Verma, Harry Knights, Aaron Sturrock, Blair R Leavitt, Sarah J Tabrizi, Rachael I Scahill, Nicola Z Hobbs","doi":"10.3233/JHD-231508","DOIUrl":"10.3233/JHD-231508","url":null,"abstract":"<p><strong>Background: </strong>Perivascular spaces (PVS) are fluid-filled cavities surrounding small cerebral blood vessels. There are limited reports of enlarged PVS across the grey matter in manifest Huntington's disease (HD). Little is known about how PVS morphometry in the white matter may contribute to HD. Enlarged PVS have the potential to both contribute to HD pathology and affect the distribution and success of intraparenchymal and intrathecally administered huntingtin-lowering therapies.</p><p><strong>Objective: </strong>To investigate PVS morphometry in the global white matter across the spectrum of HD. Relationships between PVS morphometry and disease burden and severity measures were examined.</p><p><strong>Methods: </strong>White matter PVS were segmented on 3T T2 W MRI brain scans of 33 healthy controls, 30 premanifest HD (pre-HD), and 32 early manifest HD (early-HD) participants from the Vancouver site of the TRACK-HD study. PVS count and total PVS volume were measured.</p><p><strong>Results: </strong>PVS total count slightly increased in pre-HD (p = 0.004), and early-HD groups (p = 0.005), compared to healthy controls. PVS volume, as a percentage of white matter volume, increased subtly in pre-HD compared to healthy controls (p = 0.044), but not in early-HD. No associations between PVS measures and HD disease burden or severity were found.</p><p><strong>Conclusions: </strong>This study reveals relatively preserved PVS morphometry across the global white matter of pre-HD and early-HD. Subtle morphometric abnormalities are implied but require confirmation in a larger cohort. However, in conjunction with previous publications, further investigation of PVS in HD and its potential impact on future treatments, with a focus on subcortical grey matter, is warranted.</p>","PeriodicalId":16042,"journal":{"name":"Journal of Huntington's disease","volume":" ","pages":"91-101"},"PeriodicalIF":2.1,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140189700","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Carsten Saft, Julia Jessen, Rainer Hoffmann, Carsten Lukas, Sabine Skodda
{"title":"Speech Biomarkers in Huntington's Disease: A Longitudinal Follow-Up Study in Premanifest Mutation Carriers.","authors":"Carsten Saft, Julia Jessen, Rainer Hoffmann, Carsten Lukas, Sabine Skodda","doi":"10.3233/JHD-240021","DOIUrl":"10.3233/JHD-240021","url":null,"abstract":"<p><p>Speech alterations have been reported in manifest Huntington's disease (HD) and premanifest mutation carriers (preHD). The aim of our study was to explore these alterations in preHD and whether they can be used as biomarkers. 13 preHD mutation carriers performed reading task, sustained phonation task and syllable repetition tasks at baseline and after 21 months, as well as clinical examination and MRI. Syllable repetition capacity and self-chosen velocity of single syllable repetition differed significantly between time points. There were no changes in clinical ratings or MRI volumetry. Measurements of speech might be sensitive tools for monitoring subclinical changes in preHD.</p>","PeriodicalId":16042,"journal":{"name":"Journal of Huntington's disease","volume":" ","pages":"369-373"},"PeriodicalIF":2.1,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141600249","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}