Cerebellum最新文献

{"title":"PHARC (Polyneuropathy, Hearing Loss, Ataxia, Retinitis Pigmentosa and Cataract) - A Case Report and Clinical-Focused Literature Review.","authors":"Sergio Roberto Pereira da Silva, Renata Montes Garcia Barbosa, Patricia Pontes Cruz, Lunielle da Cruz Caldeira, Daniel de Queiroz Omote, João Cláudio da Costa Urbano, Matheus Augusto Araújo Castro, Jacy Bezerra Parmera, Fernando Magri, Fernando Kok, Fernando Freua","doi":"10.1007/s12311-025-01860-9","DOIUrl":"https://doi.org/10.1007/s12311-025-01860-9","url":null,"abstract":"<p><p>Polyneuropathy, hearing loss, ataxia, retinitis pigmentosa, and cataract (PHARC) is a rare condition caused by mutations in ABHD12. We present the first documented case of PHARC in a Brazilian patient. Describe the clinical and genetic aspects of patients diagnosed with PHARC through a literature review. A literature review was conducted in February 2024 using Pubmed/Medline database. We also report a 37-year-old Brazilian woman diagnosed with PHARC. Between 38 patients diagnosed with this condition, the majority were male (74.35%) and the median age was 35.7 years. The most common symptom reported was ataxia (79.4%). The main finding of Brain MRI was cerebellar atrophy, and demyelinating polyneuropathy was the commonest finding in electroneuromyography, both were found in 28.2% of patients. PHARC syndrome is a rare autosomal recessive condition that is increasingly reported in the literature. Refsum disease and Usher syndrome are the main differential diagnosis. A multidisciplinary approach and follow-up are crucial for accurate diagnosis and treatment.</p>","PeriodicalId":50706,"journal":{"name":"Cerebellum","volume":"24 4","pages":"120"},"PeriodicalIF":2.7,"publicationDate":"2025-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144327601","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":"Characteristics of Adverse Events and Clinical Risks of Omaveloxolone Based on FAERS Data.","authors":"Hua Liu, Dandan Fan, Hong Tao, Zhu Shen, Kun Yao","doi":"10.1007/s12311-025-01873-4","DOIUrl":"https://doi.org/10.1007/s12311-025-01873-4","url":null,"abstract":"<p><p>Omaveloxolone, the first approved therapeutic agent for Friedreich ataxia (FRDA), currently has limited real-world safety data available. This study aims to evaluate post-marketing adverse events (AEs) associated with its clinical use by analyzing data from the FDA Adverse Event Reporting System (FAERS). We collected all adverse reaction reports associated with omaveloxolone from the first quarter of 2023 (Q1 2023) to the fourth quarter of 2024 (Q4 2024) in the FAERS database and performed signal detection using four distinct pharmacovigilance methods: the Reporting Odds Ratio (ROR), Proportional Reporting Ratio (PRR), Bayesian Confidence Propagation Neural Network (BCPNN), and Empirical Bayesian Geometric Mean (EBGM). A total of 9,326,057 AE reports were collected, among which 820 reports were associated with omaveloxolone. All AEs were categorized into 25 System Organ Classes (SOCs) and 67 positive Preferred Terms (PTs). Investigations represented the most frequently reported SOC, followed by gastrointestinal disorders and general disorders and administration site conditions. Hepatic enzyme increased emerged as the most prominent adverse event, demonstrating both high reporting frequency and strong signal intensity, primarily manifesting as elevated ALT and AST levels. Other commonly reported AEs included fatigue, nausea, headache, and blood cholesterol increased. The study also identified several novel potential AEs, such as urinary tract infection, diabetes mellitus, urine odour abnormal, atrial flutter, and urosepsis. Although some of these AEs were reported in relatively low frequencies, their clinical severity and elevated signal strengths suggest that omaveloxolone may potentially affect patients' urinary and endocrine systems, warranting particular attention during clinical administration. In conclusion, while omaveloxolone demonstrates multifaceted benefits in improving neurological function in patients with FRDA, its clinical application necessitates comprehensive evaluation of potential risks, and the development of safe and rational therapeutic strategies is crucial for optimizing treatment outcomes.</p>","PeriodicalId":50706,"journal":{"name":"Cerebellum","volume":"24 4","pages":"119"},"PeriodicalIF":2.7,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144327599","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":"Tremor and Ataxia in Paraneoplastic Anti-Diacylglycerol Lipase Alpha (DAGLA) Cerebellitis.","authors":"José Fidel Baizabal-Carvallo, Raquel Ruiz-García, Laura Naranjo, Francesc Graus","doi":"10.1007/s12311-025-01875-2","DOIUrl":"https://doi.org/10.1007/s12311-025-01875-2","url":null,"abstract":"<p><p>Antibodies directed against the enzyme diacylglycerol lipase alpha (DAGLA) have been recently discovered to cause a severe autoimmune cerebellar syndrome. We report a patient with DAGLA antibodies with prominent tremor and ataxia occurring in the context of a malignant melanoma, indicating that these antibodies may also occur in paraneoplastic cerebellar degeneration.</p>","PeriodicalId":50706,"journal":{"name":"Cerebellum","volume":"24 4","pages":"118"},"PeriodicalIF":2.7,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144327602","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":"Isolated Bilateral Cerebellar Dysfunction as the Initial Manifestation of HIV Infection: A Diagnostic Challenge, Case Report, and Literature Review.","authors":"Ritwick Mondal, Shramana Deb, Ananya Sengupta, Subhadeep Banerjee, Nirmalya Ray, Mona Tiwari, Jayanta Roy, Julián Benito-León","doi":"10.1007/s12311-025-01861-8","DOIUrl":"10.1007/s12311-025-01861-8","url":null,"abstract":"","PeriodicalId":50706,"journal":{"name":"Cerebellum","volume":"24 4","pages":"117"},"PeriodicalIF":2.7,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12177021/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144327600","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":"Approach to Oculomotor Apraxia: A Syndromic Approach to Genetic Causes.","authors":"Mehri Salari, Kamran Rezaei, Mahsa Haghighatzadeh, Maryam Mirabedini, Masoud Etemadifar","doi":"10.1007/s12311-025-01869-0","DOIUrl":"https://doi.org/10.1007/s12311-025-01869-0","url":null,"abstract":"<p><strong>Background: </strong>Oculomotor apraxia (OMA), the clinical manifestation of impaired voluntary initiation of saccadic eye movements, has long been associated with several disorders and genetic mutations in the literature.</p><p><strong>Objectives: </strong>The present study aims to review all the disorders and genetic mutations associated with OMA reported in the literature.</p><p><strong>Methods: </strong>PubMed, MEDLINE, Scopus, EMBASE, and Web of Science databases were systematically searched for related keywords, and related publications from January 2000 to January 2024 were reviewed.</p><p><strong>Results: </strong>All the disorders and genetic mutations presented with OMA in the literature were reported. Clinical manifestations of the congenital disorders- particularly members of autosomal recessive cerebellar ataxias- including Joubert syndrome, ataxia with oculomotor apraxia, ataxia-telangiectasia, and other disorders were discussed, Additionally, the pathophysiology of the genetic mutations in the anatomical pathway of OMA is discussed in this paper.</p><p><strong>Conclusions: </strong>Most of the cases with OMA present this sign early in their disease course; thus, evaluating the possible differential diagnoses can guide clinicians to a more accurate diagnosis. Understanding the spectrum of disorders and clinical manifestations with OMA also provides valuable insights into further clinic-pathological and genetic evaluations of this clinical manifestation.</p>","PeriodicalId":50706,"journal":{"name":"Cerebellum","volume":"24 4","pages":"116"},"PeriodicalIF":2.7,"publicationDate":"2025-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144318608","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":"Cerebellar control over inter-regional excitatory/inhibitory dynamics discriminates execution from observation of an action.","authors":"Roberta Maria Lorenzi, Gökçe Korkmaz, Adnan A S Alahmadi, Anita Monteverdi, Letizia Casiraghi, Egidio D'Angelo, Fulvia Palesi, Claudia A M Gandini Wheeler-Kingshott","doi":"10.1007/s12311-025-01863-6","DOIUrl":"10.1007/s12311-025-01863-6","url":null,"abstract":"<p><p>The motor learning theory anticipates that cerebro-cerebellar loops perform sensorimotor prediction, thereby regulating motor control during action execution (AE) and observation (AO), but the causal interaction between the cerebellum and cerebral cortex remains unclear. Therefore, our aim was to understand what triggers neuronal activity between brain areas engaged in a visuo-motor task that involves cortico-cerebellar interactions, organised in loops. We used Dynamic Causal Modelling (DCM) to study functional MRI (fMRI) data obtained in healthy participants during a squeeze-ball task in either execution or observation conditions. In both cases, active regions included bilateral primary visual cortex (V1), left primary motor cortex (M1), supplementary motor and premotor cortex (SMAPMC), cingulate cortex (CC), superior parietal lobule (SPL), and right cerebellum (CRBL). Networks supporting executing or observing an action showed the same effective connectivity, with pathways between regions wired in closed loops. However, the cerebellar communication towards the cerebral cortex switched from excitatory in execution to inhibitory in observation. Moreover, when executing the action signal modulation was non-linear from SMAPMC to CRBL and within the CRBL self-connection, supporting that the CRBL elaborates motor plans received from SMAPMC. Thus, the need for motor planning and the presence of a sensorimotor feedback in action execution discriminate the modality of forward control operated by the CRBL. Interestingly, this study also showed that the CRBL differentially controls the excitatory/inhibitory dynamics of inter-regional effective connectivity, depending on its functional engagement. These findings are fundamental for understanding brain dynamics in health and disease and for designing artificial sensorimotor controllers.</p>","PeriodicalId":50706,"journal":{"name":"Cerebellum","volume":"24 4","pages":"115"},"PeriodicalIF":2.7,"publicationDate":"2025-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12170755/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144310771","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":"Characterization of Upper Limb Motor Dysfunctions in Spinocerebellar Ataxia 38: Kinematic Analysis of the \"Hand-to-Mouth\" Task.","authors":"Massimiliano Pau, Micaela Porta, Paolo Tacconi, Angela Sanna","doi":"10.1007/s12311-025-01874-3","DOIUrl":"https://doi.org/10.1007/s12311-025-01874-3","url":null,"abstract":"<p><p>Individuals affected by spinocerebellar ataxia 38 (SCA 38) progressively lose the ability to efficiently perform important activities of daily living involving the use of upper limbs, like personal care and feeding. However, it is important to note that data on the extent of upper limb motor dysfunction in SCAs are generally limited, and specifically, no information is currently available for SCA38-particularly in the context of performing functional tasks. To partly fill this gap, in this study we analyze the kinematic features of the Hand-to-Mouth task in 7 individuals with SCA 38 and an equally sized group matched for age and sex using an optical motion capture system, by analyzing performance, stability and smoothness parameters based on the 3D hand trajectory. The results show that, in comparison with unaffected individuals, those with SCA 38 required longer time to complete the task, especially during the going phase towards the mouth, perform more adjustment in proximity of the target and their movement results more fragmented and less smooth. Such findings provide new and relevant insights regarding the upper limb residual functions under 'real-life' conditions in SCA 38, and represent a complementary tool to the usual clinical assessment to support better monitoring the disease progression as well as the design of specific tailored therapeutic interventions.</p>","PeriodicalId":50706,"journal":{"name":"Cerebellum","volume":"24 4","pages":"114"},"PeriodicalIF":2.7,"publicationDate":"2025-06-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144295268","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":"Projections from Regions of the Cerebellar Nuclei Receiving Jaw Muscle Proprioceptive Signals to Trigeminal Motoneurons and Their Premotoneurons in the Rat Pons and Medulla.","authors":"Fumihiko Sato, Yumi Tsutsumi, Ayaka Oka, Takahiro Furuta, Jaerin Sohn, Yuki Oi, Mai Amano, Akiko Morita, Katsuro Uchino, Takafumi Kato, Yong Chul Bae, Yoshihisa Tachibana, Barry J Sessle, Atsushi Yoshida","doi":"10.1007/s12311-025-01862-7","DOIUrl":"10.1007/s12311-025-01862-7","url":null,"abstract":"<p><p>The cerebellum plays a crucial role in sensorimotor control through cerebellofugal projections from the cerebellar nuclei. However, little is known about the cerebellofugal projection features involved in jaw sensorimotor control, although the dorsolateral parts of the interposed cerebellar nucleus (IntDL) and medial cerebellar nucleus (MedDL) do receive proprioceptive signals bilaterally from rat jaw-closing muscle spindles (JCMSs). This study aimed to detail the cerebellofugal projection features involved in jaw sensorimotor control. Anterograde tracer was injected into regions of the rat IntDL and MedDL receiving JCMS proprioceptive inputs (i.e., jcms-IntDL and jcms-MedDL). Axon terminals arising from the jcms-IntDL were labeled bilaterally with an ipsilateral predominance in several pontomedullary regions, although very few terminals were labeled in the dorsolateral and ventromedial divisions (5dl and 5vm) of the trigeminal motor nucleus. In contrast, terminals from the jcms-MedDL were labeled bilaterally with a contralateral predominance in several pontomedullary regions and a few terminals were labeled in the contralateral 5dl and 5vm. Thus, the projections from the jcms-IntDL and jcms-MedDL were well segregated. Subsequent retrograde tracer injections into the pontomedullary regions demonstrated that amongst the entire cerebellar nuclei the nucleofugal projections principally arose from the IntDL and MedDL. Additionally, many premotoneurons for the 5dl or 5vm were widely labeled in the pontomedullary regions where many axons from the jcms-IntDL or jcms-MedDL terminated. The various connections involving the jcms-IntDL and jcms-MedDL may play a crucial role in jaw sensorimotor control, mainly through indirect cerebellofugal pathways to the 5dl and 5vm via their premotoneurons.</p>","PeriodicalId":50706,"journal":{"name":"Cerebellum","volume":"24 4","pages":"113"},"PeriodicalIF":2.7,"publicationDate":"2025-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12162381/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144287022","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":"Phenotypic Diversity in Stress-induced Childhood-Onset Neurodegeneration with Variable Ataxia and Seizures: Novel Associations with Parkinsonism, Icthyosis and Cataract.","authors":"Jayakumari Nandana, Alfiya Fasaludeen, Adarsh Anil Kumar, Asish Vijayaraghavan, Sruthi S Nair, Ajith Cherian, Ramshekhar N Menon, Soumya Sundaram","doi":"10.1007/s12311-025-01866-3","DOIUrl":"https://doi.org/10.1007/s12311-025-01866-3","url":null,"abstract":"<p><p>Stress-induced childhood-onset neurodegeneration with variable ataxia and seizures (CONDSIAS) is an exceptionally rare autosomal recessive neurodegenerative disorder. It is caused by biallelic inactivating variants in the ADP-ribosyl-serine hydrolase (ADPRS) gene that encodes for the enzyme ADP-ribosyl hydrolase3 (ARH3) involved in DNA repair. A distinctive feature of this condition is the exacerbation of clinical symptoms triggered by physical or emotional stress, as well as febrile illnesses. In this report, we describe three unrelated patients diagnosed with CONDSIAS, each having variable clinical phenotypes and responses to treatment. Patient 1 is a 26-year-old female with language delay, intellectual disability, and infrequent seizures in childhood. She later developed parkinsonism, truncal dystonia, ataxia, peripheral neuropathy, and neuropsychiatric symptoms in her second decade. Patient 2, an 8-year-old boy born to consanguineous parents, presented with infection-triggered episodic ataxia and ichthyosis. His elder sibling had suffered from progressive ataxia and succumbed to sudden death at the age of 8. Patient 3 is a 6-year-old girl who presented with progressive ataxia, myoclonus, oculomotor apraxia, and upward gaze palsy. Both patients 2 and 3 responded favourably to treatment with high-dose vitamin supplementation, while patient 1 showed stable disease progression without specific therapeutic intervention, suggesting spontaneous stabilization of her condition. Extra-neurological manifestations included ichthyosis in patients 1 and 2 and cataracts in patient 1. These three cases illustrate the heterogeneity in clinical presentation and prognosis of CONDSIAS, highlighting the occurrence of predominant extrapyramidal features and systemic involvement, thereby expanding the phenotypic spectrum beyond the typical manifestations of ataxia and seizures.</p>","PeriodicalId":50706,"journal":{"name":"Cerebellum","volume":"24 4","pages":"112"},"PeriodicalIF":2.7,"publicationDate":"2025-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144259290","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":"Comprehensive Characterisation of the RFC1 Repeat in an Australian Cohort.","authors":"Kayli C Davies, Haloom Rafehi, Liam G Fearnley, Penny Snell, Greta Gillies, Tess A Field, Gábor M Halmágyi, Kishore R Kumar, Kate Pope, Renee Smyth, Susan E Tomlinson, Stephen Tisch, Chi-Chang Tang, Shaun R D Watson, Thomas Wellings, Kathy H C Wu, David J Szmulewicz, Martin B Delatycki, Melanie Bahlo, Paul J Lockhart","doi":"10.1007/s12311-025-01867-2","DOIUrl":"https://doi.org/10.1007/s12311-025-01867-2","url":null,"abstract":"<p><p>RFC1-related disease, which includes cerebellar ataxia, neuropathy, and vestibular areflexia syndrome (CANVAS), is a late-onset neurodegenerative disorder primarily caused by biallelic AAGGG_(n) repeat expansions (RE) in RFC1. The RFC1 locus is highly polymorphic, with multiple pathogenic and non-pathogenic repeat motifs identified. This study aimed to characterise the structure of the RFC1 repeat and determine the pathogenic allele frequency in an Australian cohort. Using a combination of PCR and next generation sequencing techniques, we provide a comprehensive characterisation of the RFC1 repeat locus in an Australian cohort of 232 individuals with adult-onset ataxia and 269 healthy controls. Biallelic pathogenic RFC1 variants were identified in 34.1% of affected individuals. The overwhelming majority (93.7%) have biallelic AAGGG_(n) RE, although other pathogenic alleles, including ACAGG_(n), AAAGG_(>500) and the Māori AAAGG_(10-25)AAGGG_(n)AAAGG_(4-6) configuration were detected in some affected individuals. We also demonstrate the utility of targeted long-read sequencing in resolving complex alleles. The carrier frequency of the pathogenic AAGGG_(n) expansion was approximately 1 in 16 in controls, highlighting the potential for pseudodominant inheritance and the likelihood that RFC1-related disease is underdiagnosed. We further demonstrate the significant RFC1 repeat heterogeneity, identifying 16 distinct motifs, complex repeat structures, and at least six motifs with an allele frequency > 1%. The frequency of RFC1-related disease in individuals with adult-onset cerebellar ataxia and the high carrier frequency of pathogenic RFC1 alleles in the Australian population underscores the need for improved diagnostic strategies. Our findings indicate RFC1 RE are a major cause of late-onset cerebellar ataxia and sensory neuropathy in Australia and provide further insights into RFC1 repeat diversity.</p>","PeriodicalId":50706,"journal":{"name":"Cerebellum","volume":"24 4","pages":"111"},"PeriodicalIF":2.7,"publicationDate":"2025-06-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144250589","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}