Cerebellum最新文献

{"title":"The Spectrum of Peripheral-Vestibular Deficits and Their Change Over Time in CANVAS/RFC1-Related Ataxia Systematic Review and Meta-Analysis of Quantitative Head-Impulse Testing.","authors":"Maja Szymanska Heydel, Felix Heindl, Annette Hartmann, Max Borsche, Andreas Traschütz, Dominik Straumann, Michael Strupp, Alexander Andrea Tarnutzer","doi":"10.1007/s12311-025-01825-y","DOIUrl":"10.1007/s12311-025-01825-y","url":null,"abstract":"<p><p>Cerebellar ataxia, neuropathy, vestibular-areflexia syndrome (CANVAS) has been linked to biallelic intronic repeat-expansions in RFC1. Video-head-impulse testing (vHIT) offers a quantitative assessment of the angular vestibulo-ocular reflex (aVOR) of all three canals. We evaluated patterns of peripheral-vestibular impairment, its change over time and evaluated correlations with other parameters. PubMed/Embase were searched for articles reporting vHIT in patients with CANVAS/RFC1-related ataxia. A multiple linear-regression model was used to analyse relationships between vHIT-gains and clinical parameters (age, disease duration, sex, biallelic RFC1 expansion). A special focus was put on sequential vHIT in individual patients. 23/64 studies met inclusion criteria; additional 13 studies were identified through reference screening. Twenty-five studies reported individual vHIT-gains and demographic data, suitable for quantitative analysis. Substantial aVOR-gain reductions were found for horizontal (0.32 ± 0.02, n = 146 patients), anterior (0.39 ± 0.03, n = 27) and posterior (0.29 ± 0.03, n = 27) canals. Linear regression showed an association between horizontal vHIT-gains (n = 146 patients; range of gain: 0-1.3) and disease duration (range: 0-444 months, coef. =-0.0048, p = 0.031) and male sex (coef. =-0.1604, p < 0.001). A decline in horizontal-canal vHIT-gains at least one side over time was noted in 15/21 patients after a mean follow-up time of 33.4 ± 10.7 months. vHIT is a potential biomarker for monitoring progression of CANVAS/RFC1-related ataxia. The significant association between reduced vHIT-gains and disease duration, and their intra-individual decline over time emphasize that impairment of the aVOR reflects the underlying neurodegenerative disease process. Multi-centre prospective studies are needed for systematic early screening and longitudinal validation as outcome for future targeted therapy trials.</p>","PeriodicalId":50706,"journal":{"name":"Cerebellum","volume":"24 3","pages":"67"},"PeriodicalIF":2.7,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11926034/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143671532","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Validation of the Italian Version of the Scale for the Assessment and Rating of Ataxia (SARA) in Multiple Sclerosis: A Cross-Sectional Study.","authors":"Giovanni Sellitto, Serena D'Aniello, Emanuele Amadio, Francescaroberta Panuccio, Andrea Marini Padovani, Rachele Simeon, Anna Berardi, Giovanni Galeoto, Ilaria Ruotolo","doi":"10.1007/s12311-025-01813-2","DOIUrl":"10.1007/s12311-025-01813-2","url":null,"abstract":"<p><p>Multiple sclerosis (MS) is a chronic neurodegenerative disorder often associated with cerebellar ataxia. Accurate assessment of ataxia is crucial for monitoring disease progression and guiding rehabilitation. The Scale for the Assessment and Rating of Ataxia (SARA) is a clinician-reported outcome measure (ClinRO) designed to evaluate ataxia severity. This study aimed to translate, culturally adapt, and validate the Italian version of SARA in individuals with MS. This study follows a cross-sectional design and was conducted at the Neurorehabilitation Unit of Sapienza University of Rome. The translation followed ISPOR and ISOQOL guidelines to ensure linguistic and cultural equivalence. Psychometric properties evaluation included internal consistency (Cronbach's alpha), test-retest reliability (intraclass correlation coefficient [ICC]), construct validity (correlation with Berg Balance Scale [BBS], Mini-Balance Evaluation Systems Test [Mini-BESTest], and Timed Up and Go [TUG] test), and cross-cultural validity. Seventy-five MS patients (EDSS ≤ 6.5) were recruited. The Italian SARA version demonstrated excellent internal consistency (Cronbach's alpha = 0.855) and test-retest reliability (ICC = 0.993). Strong negative correlations were found with BBS (r = -0.838, p < 0.001) and Mini-BESTest (r = -0.767, p < 0.001), supporting construct validity. Significant differences emerged based on age, employment status, and EDSS scores. The Italian SARA is a valid and reliable tool for assessing ataxia severity in MS. Its strong psychometric properties support its use in clinical and research settings. Future studies should explore its responsiveness to rehabilitation interventions.</p>","PeriodicalId":50706,"journal":{"name":"Cerebellum","volume":"24 3","pages":"66"},"PeriodicalIF":2.7,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11922968/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143665134","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Novel C1A Domain Variant in Protein Kinase Cγ in Spinocerebellar Ataxia Type 14 Decreases Autoinhibition.","authors":"Gayatri Raj Ghosh, Tiffany H Kao, Connolly G Steigerwald, Nora L Chan, Alexandra C Newton, Nicolas J Abreu","doi":"10.1007/s12311-025-01818-x","DOIUrl":"10.1007/s12311-025-01818-x","url":null,"abstract":"<p><p>Spinocerebellar ataxia type 14 (SCA14) is an autosomal dominant neurodegenerative disorder characterized by adult-onset cerebellar ataxia, and occasionally pyramidal signs, cognitive changes, sensory changes, myoclonus, and tremor. SCA14 results from heterozygous gain-of-function pathogenic variants in PRKCG, which encodes protein kinase Cγ. The aim was to elucidate the molecular mechanism of disease in a 60-year-old man with SCA14 due to a novel heterozygous variant in PRKCG c.154T > C p.(C52R). Next-generation sequencing was completed in the proband, targeted variant analysis was conducted in his family, and biochemical functional assays were performed. The C52R variant segregated with disease. Like other C1A domain variants, it had increased basal activity yet was unresponsive to agonist stimulation and was relatively resistant to down-regulation. This expands the genetic landscape of SCA14 and supports the condition as a gain-of-function disease, with variants in the C1A domain having leaky activity yet unresponsiveness to agonist stimulation.</p>","PeriodicalId":50706,"journal":{"name":"Cerebellum","volume":"24 3","pages":"65"},"PeriodicalIF":2.7,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143659618","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neurodevelopmental Outcome in Isolated Vermian Hypoplasia: A Single-Center Retrospective Cohort Study and Literature Review.","authors":"Gianni Cutillo, Marta Zambon, Stefano Faiola, Daniela Casati, Marina Balestriero, Chiara Doneda, Arianna Laoreti, Cecilia Parazzini, Luigina Spaccini, Mariano Lanna, Barbara Scelsa","doi":"10.1007/s12311-025-01819-w","DOIUrl":"https://doi.org/10.1007/s12311-025-01819-w","url":null,"abstract":"<p><p>Vermian hypoplasia (VH) is characterized by reduced cerebellar vermis volume without significant hemispheric involvement. To date, data on long-term neurodevelopmental outcomes in isolated VH cases are limited, complicating prenatal counselling. This is single-center retrospective cohort study analyzing fetuses with posterior fossa abnormalities (PFA) diagnosed between 2010 and 2021. VH cases were confirmed through ultrasonography and fetal MRI, excluding non-isolated anomalies or ischemic/hemorrhagic etiologies. We collected data on Neurodevelopmental outcomes through chart review and structured interviews with the caregiver. We also provided a literature review summarizing prior research on VH outcomes. Out of 45 cases with (PFA), isolated VH was found in 15 children and was confirmed in 7 cases through fetal MRI. Among these patients, median gestational age at diagnosis was 22.5 weeks, with follow-ups extending to a median age of 6 years. Age-appropriate neurodevelopmental outcomes were normal or showed minimal deficits in 6/7 (70%). Literature review highlighted a wide outcome variability, partly due to varying diagnostic criteria and follow-up protocols. Long-term prognosis is influenced by various factors, including genetic testing and environmental support. In isolated VH, outcomes are generally favorable, though mild learning or motor coordination deficits may emerge. Broader normative biometrics and consistent neurodevelopmental evaluations are critical for improved prognostic precision. VH presents diagnostic and prognostic challenges due to variability in outcomes and limited longitudinal data. A multidisciplinary approach, including prenatal imaging, genetic testing, and structured follow-up, is essential for effective family counseling and developmental support. Prospective studies with larger cohorts are warranted to establish clearer guidelines.</p>","PeriodicalId":50706,"journal":{"name":"Cerebellum","volume":"24 3","pages":"64"},"PeriodicalIF":2.7,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143659617","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Tailored Home-Based Training Program Improved Ataxia Severity and Participation in Adults With ARSACS.","authors":"Isabelle Lessard, Cynthia Gagnon, Marjolaine Tremblay, Laura Girard-Côté, Isabelle Côté, Mylène Aubertin-Leheudre, Elise Duchesne","doi":"10.1007/s12311-025-01816-z","DOIUrl":"10.1007/s12311-025-01816-z","url":null,"abstract":"<p><p>Autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS) is a rare degenerative movement disorder impacting balance and mobility. Rehabilitation helps to reduce disease severity and increase the quality of life of people with ARSACS. However, rehabilitation programs require many trips to dedicated facilities, posing a significant challenge for individuals living with ARSACS. This study aimed to develop a home-based training program specific for adults with ARSACS and to document its effects on ataxia severity, balance, mobility, and participation. This non-blinded and non-randomised interventional study used a pre-post design with a control phase. The initial level of training difficulty was tailored to each participant using a standardized assessment tool. Participants trained three times a week for 12 weeks. Outcome measures included the BERG Balance Scale, Ottawa Sitting Scale, 10-meter Walk Test, 30-second Chair Stand Test, 10-Steps Test, LIFE-H, and Scale for the Assessment and Rating of Ataxia. The retrospective acceptability of the program was also assessed using Sekhon's theoretical framework of acceptability. Fourteen participants (eight walkers, 50% men) completed the program (self-reported attendance rate rate: 75-100%) and seven dropped out. All outcome measures remained stable during the control phase. Ataxia severity and participation significantly improved after the 12-week home-based training program. At an individual level, clinical improvements in standing and sitting balance were noted for almost half of the participants, particularly for non-walkers. The eight participants who assisted to the focus group reported that the program was acceptable. This study indicates that tailored home-based training is safe, acceptable, and helps to reduce ataxia severity and participation restriction for adults with ARSACS.</p>","PeriodicalId":50706,"journal":{"name":"Cerebellum","volume":"24 3","pages":"63"},"PeriodicalIF":2.7,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11914335/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143651750","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Tremulous SCA3: The Complex Connection between the Cerebellum and Basal Ganglia.","authors":"Victor Rebelo Procaci, Raphael Pinheiro Camurugy da Hora, Orlando Graziani Povoas Barsottini, José Luiz Pedroso","doi":"10.1007/s12311-025-01817-y","DOIUrl":"https://doi.org/10.1007/s12311-025-01817-y","url":null,"abstract":"","PeriodicalId":50706,"journal":{"name":"Cerebellum","volume":"24 3","pages":"62"},"PeriodicalIF":2.7,"publicationDate":"2025-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143634943","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Polyglutamine Ataxias in Denmark: Incidence and Relative Frequencies of SCA1, 2, 3, 6, 7, 17 and DRPLA in a Nationwide Cohort.","authors":"Rosa Dam Waerling, Jenny Blechingberg, Jesper Kayser, Suzanne Granhøj Lindquist, Tua Vinther-Jensen, Jørgen Erik Nielsen, Morten Duno","doi":"10.1007/s12311-025-01815-0","DOIUrl":"10.1007/s12311-025-01815-0","url":null,"abstract":"<p><p>Polyglutamine ataxias are autosomal dominantly inherited neurodegenerative disorders in which the molecular aetiology is an expanded CAG glutamine-encoding repeat in the causative genes. At present, there is no effective treatment, but there are several ongoing trials addressing polyglutamine disorders increasing the need of knowledge about prevalence and relative frequencies of the different subtypes. To identify all individuals with genetically confirmed polyglutamine ataxia in Denmark, determine frequency of subtypes and estimate the incidences. Retrospective data on all clinical tests performed on polyglutamine ataxias in Denmark during the last 15 years. 215 individuals with alleles in the full penetrant pathogenic range of polyglutamine ataxia genes were identified. The most frequent polyglutamine ataxia in Denmark was SCA6 which accounts for 42% of the identified individuals, followed by SCA2 and SCA3 which both account for approximately 20% each. Incidence rates were calculated. The study reveals the subtype distribution and incidence of polyglutamine ataxias in Denmark, priming the Danish cohort for future clinical trials as developments in the treatment of polyglutamine ataxia advances.</p>","PeriodicalId":50706,"journal":{"name":"Cerebellum","volume":"24 3","pages":"61"},"PeriodicalIF":2.7,"publicationDate":"2025-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11909032/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143631024","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"CAG Repeat Instability and Region-Specific Gene Expression Changes in the SCA12 Brain.","authors":"Shreevidya Parthaje, Meghana Janardhanan, Pradip Paul, Kalyani B Karunakaran, Ashim Paul Deb, Bhagyalakshmi Shankarappa, Pramod Kumar Pal, Anita Mahadevan, Sanjeev Jain, Biju Viswanath, Meera Purushottam","doi":"10.1007/s12311-025-01808-z","DOIUrl":"https://doi.org/10.1007/s12311-025-01808-z","url":null,"abstract":"<p><p>Spinocerebellar ataxia type 12 (SCA12), an autosomal dominant cerebellar ataxia, caused by an expansion of (CAG)_n in the 5' of the PPP2R2B gene on chr5q32, is common in India. The illness often manifests late in life, with diverse neurological and psychiatric symptoms, suggesting involvement of different brain regions. Prominent neuronal loss and atrophy of the cerebellum have been noted earlier. In Huntington's disease (HD), somatic instability associated with the size of the expanded CAG allele in HTT varies across regions of the brain, and influences the nature and severity of symptoms. We estimated CAG repeat size, methylation and gene expression in the PPP2R2B gene across regions in brain tissue from a person with SCA12. We also studied the regional expression of DNA repair pathway and cell cycle genes. Somatic mosaicism, manifested as CAG repeat instability, is detected across brain regions. The cerebellum showed the least somatic instability, and this was coupled with increased methylation, and lower expression, of the PPP2R2B gene. Interestingly, increased expression of DNA maintenance pathway related genes, which might partly explain the lowered DNA instability, was also observed. There was also decreased expression of cell cycle modulators, which could initiate apoptosis, and thus account for neuronal cell death seen in the brain sections. We suggest that drugs that improve DNA repeat stability, could thus be explored as a treatment option for SCA12.</p>","PeriodicalId":50706,"journal":{"name":"Cerebellum","volume":"24 3","pages":"60"},"PeriodicalIF":2.7,"publicationDate":"2025-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143617749","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Autosomal Recessive Ataxias in Northeast Brazil: A Regional Multicenter Case Series.","authors":"Antonio Edvan Camelo-Filho, Rodrigo Fagundes da Rosa, Pedro Lucas Grangeiro Sá Barreto Lima, Gustavo Rodrigues Ferreira Gomes, Paula Camila Alves de Assis Pereira Matos, Deborah Moreira Rangel, Ellen Mourão Soares Lopes, Tamiris Carneiro Mariano, André Luiz Santos Pessoa, Paulo Ribeiro Nóbrega, Pedro Braga-Neto","doi":"10.1007/s12311-025-01814-1","DOIUrl":"https://doi.org/10.1007/s12311-025-01814-1","url":null,"abstract":"<p><p>Hereditary cerebellar ataxias are a diverse group of neurodegenerative disorders characterized by progressive cerebellar dysfunction and possible multisystemic involvement. While significant advancements have been made in understanding autosomal dominant cerebellar ataxias (ADCAs), autosomal recessive cerebellar ataxias (ARCAs) remain less extensively investigated than autosomal dominant ataxias, particularly in regions with high consanguinity. This study aimed to characterize 57 patients with ARCAs in Ceará, northeast Brazil. We analyzed 57 patients diagnosed with ARCAs caused by biallelic variants in ARCA-associated genes. Patients underwent clinical evaluations, including neurological examinations and functional assessments.</p><p><strong>Results: </strong>Friedreich's ataxia (FRDA) was the most prevalent diagnosis, accounting for 12 cases (21%), followed by Ataxia-Telangiectasia (A-T) with (N = 9; 15.8%) and Niemann-Pick Disease Type C (NPC) (N = 9; 15.8%). Metabolic disorders, including Cerebrotendinous Xanthomatosis (N = 6;10.5%) were also common causes. The cohort demonstrated a broad age distribution, with childhood-onset conditions such as A-T predominantly affecting younger patients. In contrast, adult-onset conditions like FRDA and NPC were more common in those aged 18 years and older.</p><p><strong>Discussion: </strong>This study highlights the heterogeneity of ARCAs in a region with high consanguinity, reflecting these disorders' diverse genetic and clinical spectrum.</p><p><strong>Conclusion: </strong>The clinical and genetic characterization of ARCAs presented in this case series emphasizes the importance of early diagnosis, genetic confirmation, and targeted management strategies. Our findings highlight the need for continued research and expanded diagnostic programs, particularly in regions with high consanguinity, to improve patient outcomes and advance therapeutic development.</p>","PeriodicalId":50706,"journal":{"name":"Cerebellum","volume":"24 3","pages":"59"},"PeriodicalIF":2.7,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143606171","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Update on Clinical Physiology and Pathomechanisms for Vestibulo-Autonomic Interplay.","authors":"Sun-Uk Lee, Jeong-Yoon Choi","doi":"10.1007/s12311-025-01811-4","DOIUrl":"https://doi.org/10.1007/s12311-025-01811-4","url":null,"abstract":"<p><p>The vestibulo-autonomic interaction refers to the neural interplay between the vestibular and autonomic systems. In particular, the vestibular system plays an active role in adjusting blood distribution during movement and changes in posture, thereby complementing the baroreflex. This review summarizes recent clinical evidence highlighting the interaction between the vestibular and autonomic systems, including altered vestibular-evoked myogenic potentials in patients with postural orthostatic tachycardia syndrome, orthostatic hypotension, and neurodegenerative disorders. Additionally, the review introduces a model-based explanation of vestibular modulation of the autonomic system via the velocity storage mechanism. Specifically, the model demonstrates how vertigo attacks influence cardiovascular autonomic outflow by altering the estimation of gravity and inertia under pathological conditions.</p>","PeriodicalId":50706,"journal":{"name":"Cerebellum","volume":"24 3","pages":"58"},"PeriodicalIF":2.7,"publicationDate":"2025-03-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143587888","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}