Cerebellum最新文献

{"title":"Crossed Cerebellar Diaschisis in a Patient with MELAS Syndrome: A Case Report.","authors":"Ivana Karla Franić, Andreja Bujan Kovač, Branko Malojčić","doi":"10.1007/s12311-025-01847-6","DOIUrl":"https://doi.org/10.1007/s12311-025-01847-6","url":null,"abstract":"<p><p>Mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes (MELAS) is a rare genetic disorder from a spectrum of mitochondrial diseases. Most commonly it presents with stroke-like symptoms, seizures, encephalopathy and myopathy. As it affects predominantly metabolically active organs, it can cause cardiomyopathy, diabetes mellitus, etc. We report a case of a young male patient with genetically proven MELAS who had a history of periodical generalized tonic-clonic seizures and then developed recurrent transient paresthesia of the right extremities, speech disturbance and apraxia. During work-up, an MRI done after a generalized tonic-clonic seizure showed hypoperfusion and edema in right cerebellar hemisphere caused by the contralateral cerebral acute ischemic lesion in left insular cortex which produced initial symptoms. This interesting finding is called crossed cerebellar diaschisis (CCD). CCD is a rare entity which refers to a decrease in metabolism, perfusion, and overall function in a cerebellar hemisphere because of a contralateral cerebral lesion. The disturbance of the function in an area distant from the location of initial brain lesion is possible because the two areas are connected via fiber tracts. This pathology most commonly occurs after ischemic stroke but also after seizures, supratentorial tumors, encephalitis etc. Our patient continued to have recurrent occasional transient paresthesia of the right extremities, but the follow-up MRI showed complete regression of hyperintensities in the left cerebral cortex and edema in right cerebellar hemisphere. In this paper we report co-existence of a rare neuroradiological finding such as CCD, in patient with rare cerebrovascular disease.</p>","PeriodicalId":50706,"journal":{"name":"Cerebellum","volume":"24 4","pages":"90"},"PeriodicalIF":2.7,"publicationDate":"2025-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144020200","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":"Clinical Characteristics of Spinocerebellar Ataxia Type 3 in Uruguay.","authors":"Nicolás Sommaruga, Nicolás Labaure, Andrea Zamora, Santiago Giménez, Gonzalo Pérez-Hornos, Cristina Vázquez","doi":"10.1007/s12311-025-01839-6","DOIUrl":"https://doi.org/10.1007/s12311-025-01839-6","url":null,"abstract":"<p><p>Spinocerebellar ataxias (SCAs) are autosomal dominant genetic disorders characterized by progressive cerebellar degeneration and phenotypic variability. MJD/SCA3, the most prevalent form around the world and in Latin America, is also likely the most common hereditary ataxia in Uruguay. Despite its relevance, Uruguay lacks comprehensive epidemiological studies, and molecular diagnostics remain inaccessible in public health systems. This review provides a phenotypic description on genetically confirmed patients with MJD/SCA3 as a first step towards generating knowledge on this matter in our country. A retrospective review of 37 Uruguayan patients with suspected SCA was conducted. Sixteen patients with confirmed molecular diagnosis of MJD/SCA3 were included on this review. Data collected encompassed demographic information, genetic testing results, clinical manifestations, and imaging findings. Patients were evaluated at the Ataxias Polyclinic, Hospital de Clínicas, between 2019 and 2024 by the authors. Statistical analyses were performed using SPSS version 29.0. The mean age of symptom onset was 41.75 years, with gait ataxia as the initial symptom in 87.5% of cases. Clinical findings included appendicular ataxia (100%), dysarthria (90%), and oculomotor alterations (90%), with diverse deep sensitivity impairment in 62.5%. Genetic testing revealed an average of 72.9 CAG repeats in the ATXN3 gene. Cerebellar atrophy was observed in 75% of patients with MRI. Most had a diagnostic delay of 6.5 years and an autosomal dominant family history. Findings align with international descriptions of MJD/SCA3 while highlighting regional characteristics, including a potential genetic link with southern Brazil. The absence of dysautonomia, typically prevalent in MJD/SCA3, suggests underdiagnosis or insufficient evaluation. This study underscores the need for systematic clinical and molecular evaluations in Uruguay and serves as a foundation to understand hereditary ataxias at a national level. Further research is essential for improving diagnosis and management of this complex pathology.</p>","PeriodicalId":50706,"journal":{"name":"Cerebellum","volume":"24 4","pages":"89"},"PeriodicalIF":2.7,"publicationDate":"2025-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144027399","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":"New Perspectives on Non-Invasive Cerebellar Stimulation for Social and Affective Functions in Children and Adolescents.","authors":"Ludovica Pasca, Romina Romaniello, Renato Borgatti, Andrea Ciricugno","doi":"10.1007/s12311-025-01844-9","DOIUrl":"https://doi.org/10.1007/s12311-025-01844-9","url":null,"abstract":"<p><p>Cerebellar dysfunction affects socio-affective abilities beyond motor control. Recent studies suggest that non-invasive cerebellar neurostimulation can modulate social cognition networks, offering potential therapeutic benefits for children with autism, ADHD, and mood disorders. However, its application in pediatrics remains largely unexplored. This review summarizes emerging pediatric research on cerebellar transcranial magnetic stimulation (TMS) and transcranial direct current stimulation (tDCS). We discuss their mechanisms, potential benefits, and safety considerations, highlighting preliminary findings that suggest feasibility and effectiveness. Ethical concerns and technical challenges related to pediatric neuroanatomy and stimulation parameters are also addressed. While early results are promising, further clinical trials and neurophysiological studies are essential to optimize protocols and confirm long-term efficacy. Advancing our understanding of cerebellar involvement in socio-affective functions could lead to innovative rehabilitation strategies for neurodevelopmental disorders.</p>","PeriodicalId":50706,"journal":{"name":"Cerebellum","volume":"24 4","pages":"88"},"PeriodicalIF":2.7,"publicationDate":"2025-04-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12033187/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144023656","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":"Mapping Anatomical Landmarks of the Cerebellum Central Core: Enhancing Precision in Surgical Interventions for Cerebellar Lesions.","authors":"Luis Gustavo Biondi-Soares, Richard Gonzalo Párraga, Rene Alejandro Apaza-Tintaya, Lucca B Palavani, Veronica Alzate-Carvajal, Felipe Salvagni, Alexander Feliciano Vilcahuaman Paitán, Gabriel Ataide Monção, Luis Ángel Canache Jiménez, Raphael Wuo-Silva, Feres Chaddad-Neto","doi":"10.1007/s12311-025-01841-y","DOIUrl":"https://doi.org/10.1007/s12311-025-01841-y","url":null,"abstract":"<p><p>Similar to the cerebrum, the cerebellum exhibits a central neuronal core region enveloped by a network of white fibers, identified as the central nucleus. The dentate nucleus and the extension of its fibers into the superior cerebellar peduncle play a key role. Understanding this anatomical and functional concept would improve the accuracy of surgical interventions for cerebellar infiltrative lesions. Twenty-two formalin-fixed and frozen human cerebellar and brainstems were stored at -16º C for two weeks, according to the Klingler protocol. Dissection was performed to identify the cerebellar central nucleus and its structures. Images were captured, analyzed, and processed for the distribution of landmarks in each dissection phase. We defined the cerebellar landmarks proximal to the central nucleus. The anatomical division into planes: Superoinferior; we found the superior border of the amygdala and the MCP. Superior: the anterior portion of the horizontal fissure, the MCP, and the origin of the V cranial nerve. Anteroposterior plane: the cerebello-mesencephalic fissure and the postclival fissure. In the medio-lateral plane, we identify the cerebellar vermis's PCS and lateral border. Laterally, the fibers of the MCP and the lateral aspect of the tonsil. The biventral lobule may obscure this landmark, and we consider it an alternative landmark. This study provides reliable anatomical landmarks of the cerebellum, which describe the central cerebellar nucleus. Establishing these landmarks favors three-dimensional knowledge and helps avoid associated neurological damage in this crucial structure.</p>","PeriodicalId":50706,"journal":{"name":"Cerebellum","volume":"24 4","pages":"87"},"PeriodicalIF":2.7,"publicationDate":"2025-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144020279","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":"Spinocerebellar Ataxia Type 10 (SCA 10) in Brazil.","authors":"Hélio A Ghizoni Teive, Léo Coutinho, Carlos Henrique F Camargo","doi":"10.1007/s12311-025-01838-7","DOIUrl":"https://doi.org/10.1007/s12311-025-01838-7","url":null,"abstract":"<p><p>Spinocerebellar ataxia type 10 (SCA10) is an autosomal dominant inherited ataxia caused by the expansion of ATTCT pentanucleotide repeats in intron 9 of the ATXN10 gene. This rare form of SCA has predominantly been observed in individuals of Indigenous American and East Asian descent. Notably, in Mexico and the southern Brazilian states of Paraná and Santa Catarina, SCA10 is identified as the second most prevalent type of spinocerebellar ataxia. Initially, the phenotype described in Mexico featured a combination of cerebellar ataxia and epilepsy-a presentation also observed in other Latin American and Asian countries, as well as some Brazilian states. However, in Paraná and Santa Catarina, the predominant manifestation of SCA10 is pure cerebellar ataxia, which is distinguished from the presentations seen in other regions.</p>","PeriodicalId":50706,"journal":{"name":"Cerebellum","volume":"24 4","pages":"86"},"PeriodicalIF":2.7,"publicationDate":"2025-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144037972","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 Rare Case of Lhermitte Duclos Disease Associated with Somatic PTEN and Germline SUFU Variants.","authors":"Özge Güngör, Aslı Ece Solmaz, Emin Karaca, Taner Akalın, Elif Bolat, Haluk Akın","doi":"10.1007/s12311-025-01835-w","DOIUrl":"https://doi.org/10.1007/s12311-025-01835-w","url":null,"abstract":"<p><p>Lhermitte-Duclos disease (LDD) is a rare dysplastic gangliocytoma of the cerebellum, typically manifesting as a hamartomatous lesion in the posterior fossa. Currently, LDD has been only linked to PTEN pathogenic variants, with the PI3K/AKT/mTOR pathway acting as the primary signaling cascade responsible for its pathogenesis. We present a case of LDD in which a novel germline heterozygous splice site variant (c.183-2 A > G) in the SUFU gene and a somatic heterozygous missense variant (c.389 G > A) in the PTEN gene, identified from tumor tissue were detected by targeted next-generation sequencing (NGS). SUFU, a tumor suppressor gene, primarily inhibits the hedgehog (Hh) signaling pathway and furthermore influences the AKT/mTOR pathway. Pathogenic variants in SUFU have been linked to medulloblastoma, and their potential role in LDD remains under investigation. Given that both conditions involve granule cell progenitors and are influenced by impaired Hh signaling, they may share a similar developmental path. This is the first research indicating that SUFU may play a role in the etiology of LDD, despite SUFU variants being associated with several central nervous system malignancies. The SUFU variant was shown to disrupt splicing via Sanger sequencing and gel electrophoresis of RNA extracted from blood. Analysis of DNA from tumor tissue using the TWIST Exome 2.0 Panel revealed de novo pathogenic SUFU (c.183-2 A > G) and PTEN (c.389G > A) variants. This paper establishes an initial link between LDD and germline SUFU along with somatic PTEN variants identified from tumor tissue, providing novel insights into the molecular pathogenesis of this rare condition.</p>","PeriodicalId":50706,"journal":{"name":"Cerebellum","volume":"24 3","pages":"85"},"PeriodicalIF":2.7,"publicationDate":"2025-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144055689","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":"Spinocerebellar Ataxia 44 Caused by a Novel GRM1 Variant: Reviewing the Contrasting Pathogenic Mechanisms Underlying Two GRM1-Associated Hereditary Ataxias.","authors":"Shih-Chun Lan, Yung-Yee Chang, Tsu-Kung Lin, Min-Yu Lan","doi":"10.1007/s12311-025-01837-8","DOIUrl":"10.1007/s12311-025-01837-8","url":null,"abstract":"<p><p>GRM1 encodes type 1 metabotropic glutamate receptor (mGluR1). Its pathogenic variants are associated with the rare autosomal recessive cerebellar ataxia 13 (SCAR13) due to loss of mGluR1 function, and the even rarer spinocerebellar ataxia 44 (SCA44) due to a gain-of-function molecular basis. We report a new case of SCA44 caused by a novel and de novo GRM1 variant c.2303 C > T (p.Thr768Ile), which was considered \"likely pathogenic\" by the American College of Medical Genetic criteria (PS2, PM2, PP3). This variant was predicted to lead to a stability effect on mGluR1 in the evaluation with DynaMut2, like the other known SCA44 GRM1 variants and in contrast to lower stability or destabilizing effects for SCAR13 missense variants. The affected residue Thr768 was located close to the binding pockets of allosteric modulators and within the highly conserved cholesterol recognition association/interaction consensus motif. Collectively, this novel GRM1 variant caused SCA44 by increasing the constitutive activity of mGluR1. Our findings underscore the distinct molecular mechanisms of mGluR1 aberration for the two GRM1-associated hereditary ataxias, and provide a mechanism-relevant prospect in the pharmacological therapies for restoring mGluR1 function.</p>","PeriodicalId":50706,"journal":{"name":"Cerebellum","volume":"24 3","pages":"84"},"PeriodicalIF":2.7,"publicationDate":"2025-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143812841","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":"Hereditary Ataxias in Argentina.","authors":"Malco Rossi, Marcelo Merello","doi":"10.1007/s12311-025-01834-x","DOIUrl":"10.1007/s12311-025-01834-x","url":null,"abstract":"<p><p>Hereditary or genetic ataxias are hundreds of disorders characterized by large phenotypic, genetic, and epidemiological heterogeneity. In Argentina, 35 genetic ataxias have been identified, with SCA1 (ATX-ATXN1), SCA2 (ATX-ATXN2), SCA3 (ATX-ATXN3), and Friedreich ataxia (ATX-FXN) as the most prevalent causes, reflecting the epidemiology of most Western European countries, the main origin of immigration to the country. Genetic diagnostic studies of ataxia cohorts in Argentina have found high rates of undiagnosed patients, ranging from 65 to 82%. Deep phenotyping, comprehensive genetic testing, and knowledge of the prevalence of different genetic ataxias are essential for an accurate diagnostic and treatment approach in clinical practice. This narrative review proposes a targeted, tiered genetic diagnostic approach for undiagnosed patients based on the Argentinian epidemiological and healthcare system data. Future national efforts should support comprehensive screening studies on ataxia cohorts, including testing for repeat expansions in RFC1 and FGF14 genes. In addition, establishing a trial-ready patient registry for genetic ataxias, enhancing networking with international clinical and research initiatives, and developing specialized centers for interdisciplinary care of genetic ataxia patients are recommended.</p>","PeriodicalId":50706,"journal":{"name":"Cerebellum","volume":"24 3","pages":"82"},"PeriodicalIF":2.7,"publicationDate":"2025-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143812788","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":"Novel KIF1A Variant in a Patient with Cerebellar Atrophy and Ataxia: A Case Report.","authors":"Sema Akkus, Ayuko A Iverson, Winona Tse","doi":"10.1007/s12311-025-01836-9","DOIUrl":"10.1007/s12311-025-01836-9","url":null,"abstract":"<p><p>Pathogenic variants in KIF1A are associated with a spectrum of neurological disorders collectively known as KIF1A-associated neurological disorders (KAND). We present the case of a 57-year-old female with lifelong dysarthria, gait instability, and progressive ataxia, diagnosed with cerebellar ataxia in her late 40s. Brain MRI revealed diffuse cerebellar atrophy. Genetic testing identified a novel heterozygous KIF1A (NM_004321.6) variant, c.1788_1790delinsACG (p.His596_Pro597delinsGlnArg), which is absent from population databases and predicted to be deleterious by multiple in silico tools. Unlike most pathogenic KIF1A variants that cluster within the motor domain, this variant lies outside this region. In silico structural modeling suggests this substitution likely affects local protein architecture through two concurrent changes: the substitution of histidine 596 with glutamine represents a modest change to the local biochemical environment, while the replacement of the conformationally restrictive proline 597 with arginine removes the characteristic cyclic structure that constrains the peptide backbone. Family history was notable for cerebellar atrophy in the mother and similar neurological symptoms in the maternal brother, suggesting possible autosomal dominant inheritance. The identification of this novel KIF1A variant outside the motor domain expands our understanding of KAND's genetic basis and suggests that non-motor domain variants may be associated with slowly progressive neurological symptoms.</p>","PeriodicalId":50706,"journal":{"name":"Cerebellum","volume":"24 3","pages":"83"},"PeriodicalIF":2.7,"publicationDate":"2025-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143812837","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":"Homozygous CAG Repeat Expansion in Spinocerebellar Ataxia Type 6: Longitudinal Analysis of Vestibulo-Ocular Reflex Findings.","authors":"Jae-Myung Kim, Tai-Seung Nam, Jae-Hwan Choi, Seung-Han Lee","doi":"10.1007/s12311-025-01833-y","DOIUrl":"10.1007/s12311-025-01833-y","url":null,"abstract":"<p><p>Spinocerebellar ataxia type 6 (SCA6) homozygotes are known to have an earlier onset and faster disease progression than heterozygotes. Although several studies have reported more severe clinical manifestations in SCA6 homozygotes, longitudinal, quantitative assessments remain lacking. A 55-year-old female presented with intermittent positional dizziness/vertigo and gradually progressive gait disturbance. She denied a family history of similar symptoms. Neuro-ophthalmologic evaluations revealed spontaneous downbeat nystagmus, horizontal gaze-holding deficits and hypermetric saccades with preserved saccadic velocity. Bedside horizontal head impulses showed a perverted response. Video head impulse test (HIT) showed normal VOR gain in all six semicircular canals and bithermal caloric test was also normal. Brain magnetic resonance imaging (MRI) showed diffuse and prominent, pure cerebellar atrophy. Genetic testing for SCA using Sanger sequencing confirmed the expanded repeats for SCA6 with homozygous abnormal allele 20 repeats. During the 8-year follow-up, bedside HIT turned positive on both sides and accordingly decreased VOR gains with abnormal catch-up saccades in both horizontal canals (HCs) were detected during video HITs, while bithermal caloric test revealed canal paresis only on the right side. Follow-up brain MRI demonstrated more prominent diffuse cerebellar atrophy and indicated mild brainstem atrophy as well. Vestibular performance in SCA6 is characterized by frequent high-frequency angular VOR impairments, predominantly affecting the horizontal and posterior canals, while low-frequency responses remain variable. Neuro-otologic deterioration during follow-up in our patient may be partly attributed to involvement of the brainstem VOR pathway including the medial vestibular nuclei, in contrast to SCA6 heterozygotes who typically exhibit pure cerebellar involvement.</p>","PeriodicalId":50706,"journal":{"name":"Cerebellum","volume":"24 3","pages":"81"},"PeriodicalIF":2.7,"publicationDate":"2025-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143796807","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}