Cerebellum最新文献

{"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":"https://doi.org/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":"","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":"","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}

{"title":"The Cerebellar Neuropsychiatric Rating Scale: A New Card in the Deck.","authors":"Stefan Fritze, Roberta Ferrucci, Mario Manto","doi":"10.1007/s12311-025-01802-5","DOIUrl":"10.1007/s12311-025-01802-5","url":null,"abstract":"<p><p>Research on the cerebellum has come a long and impressive way. While traditionally assumed as only engaged in motor control, rediscovery of early literature reports and recent studies also point to the cerebellum´s role in vestibular and cognitive affective functioning at the frontiers of psychiatry. Indeed, damage to the cerebellum often leads to consequences in cognitive affective functioning, including deficits in executive, visuo-spatial and linguistic functioning as well as affect regulation. However, in order to further disseminate these scientific advances and to provide palpable progress to clinicians, smart tools that can be applied in daily clinical practice need to be developed. In particular, rating scales, which remain the most robust clinical method in the assessment of cerebellar patients, need to be developed. Although neuropsychiatric symptoms of cerebellar disease are common, they do not conform to DSM-5 diagnostic categories of psychiatric disorders. The Cerebellar Neuropsychiatric Rating Scale (CNRS), an informant-based questionnaire reported by Daly et al., may fill this gap, allowing clinicians for the first time to capture and quantify neuropsychiatric symptoms that have often been overlooked in ataxias in the past. The CNRS may represent a reliable instrument in ataxias. The scale offers a promising tool for early detection and targeted intervention, fostering interdisciplinary collaboration between neurologists, psychiatrists, and psychologists. Future developments may refine its clinical applicability, expand its use to other neurological disorders, and integrate digital health solutions to enhance real-world assessment and treatment.</p>","PeriodicalId":50706,"journal":{"name":"Cerebellum","volume":"24 2","pages":"57"},"PeriodicalIF":2.7,"publicationDate":"2025-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143544458","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":"The Cerebellar Neuropsychiatric Rating Scale.","authors":"Maureen P Daly, Janet C Sherman, Jeremy D Schmahmann","doi":"10.1007/s12311-025-01799-x","DOIUrl":"10.1007/s12311-025-01799-x","url":null,"abstract":"<p><p>The triad of cerebellar ataxiology is the cerebellar motor, vestibular, and cerebellar cognitive affective / Schmahmann syndrome (CCAS). The CCAS affective component comprises 5 domains: Attentional control, Emotional control, Autism spectrum, Psychosis spectrum, and Social Skill Set, each with hypermetric / overshoot and hypometric / undershoot poles reflecting the dysmetria of thought and universal cerebellar transform theories. There is no validated screening instrument to assess neuropsychiatric impairments in patients with cerebellar disorders. To examine the psychometric properties of our Cerebellar Neuropsychiatric Rating Scale (CNRS) that explores these symptoms and behaviors in patients with cerebellar disorders, 21 adults with ataxia completed the CNRS and other validation measures: the Behavior Rating Inventory of Executive Function-Adult Version Informant Report, Adult Behavior Checklist, Older Adult Behavior Checklist, Neuropsychiatric Inventory Questionnaire. We examined CNRS internal consistency using Cronbach's alpha, assessed item to subscale correlations, studied ceiling and floor effects, and convergent construct validity between CNRS and validity measure subscales. Internal consistency was α > 0.70 for each of the five domains. Subscale structure was generally confirmed: 86% of correlations between CNRS and validity subscales were significant. There were no ceiling effects. Item to subscale correlations indicated adequate reliability for total scale and subdomains. NPI-Q and CNRS scores were correlated, and 86.4% (19/22) of conceptually related subscales were significant. The CNRS is a reliable and valid measure of cerebellar neuropsychiatry. Further development can refine the instrument and shed light on the patient experience of their affective dysregulation and its clinical meaningfulness.</p>","PeriodicalId":50706,"journal":{"name":"Cerebellum","volume":"24 2","pages":"56"},"PeriodicalIF":2.7,"publicationDate":"2025-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143544531","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}