Cerebellum最新文献

{"title":"Cerebellar Oscillatory Patterns in Essential Tremor: Modulatory Effects of VIM-DBS.","authors":"Taylor J Bosch, Christopher Groth, Arturo I Espinoza, Vishal Bharmauria, Oliver Flouty, Arun Singh","doi":"10.1007/s12311-025-01787-1","DOIUrl":"10.1007/s12311-025-01787-1","url":null,"abstract":"<p><p>Essential tremor (ET) is a common movement disorder, and while ventral intermediate nucleus deep brain stimulation (VIM-DBS) is a well-established treatment, its precise mechanisms or modulatory effects, particularly in relation to cerebellar oscillations, remain unclear. In this study, we hypothesized that VIM-DBS would modulate cerebellar oscillatory activity across both resting and motor task conditions, reflecting its impact on cerebello-thalamic pathways. Ten patients diagnosed with ET participated in this study. We examined the effects of VIM-DBS on mid-cerebellar oscillations during resting-state and lower-limb pedaling motor tasks. Frequency analysis was conducted on the resting-state signal and time-frequency analysis was performed on motor task-related signals. We explored the modulatory effects of VIM-DBS on oscillatory activity across delta, theta, alpha, beta, and gamma frequency bands. We found that ON VIM-DBS increased mid-cerebellar relative theta power during resting-state conditions, with no significant changes in other frequency bands. During a pedaling motor task, VIM-DBS led to significant reductions in theta, alpha, and gamma power, highlighting the frequency-specific effects of stimulation. VIM-DBS also increased peak acceleration of leg movements during the pedaling task. Furthermore, VIM-DBS selectively increased mid-frontal relative theta and beta power as well as mid-occipital relative theta power during resting condition, suggesting localized mid-cerebellar modulation. Moreover, similarity analyses between mid-cerebellar and nearby mid-occipital signals revealed differences in coherence, phase coherence, and cross-spectrum phase coherence. Overall, these results support the role of VIM-DBS in modulating mid-cerebellar oscillations in ET and provide new insights into the neural mechanisms underlying DBS efficacy.</p>","PeriodicalId":50706,"journal":{"name":"Cerebellum","volume":"24 2","pages":"40"},"PeriodicalIF":2.7,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11787153/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143076468","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":"Cerebellar Development and the Burden of Prematurity.","authors":"Tobias Muehlbacher, Jeroen Dudink, Sylke J Steggerda","doi":"10.1007/s12311-025-01790-6","DOIUrl":"10.1007/s12311-025-01790-6","url":null,"abstract":"<p><p>The role of the cerebellum in the neurodevelopmental outcomes of preterm infants has often been neglected. However, accumulating evidence indicates that normal cerebellar development is disrupted by prematurity-associated complications causing cerebellar injury and by prematurity itself. This hampers not only the normal development of motor skills and gait, but also cognitive, language, and behavioral development, collectively referred to as \"developmental cognitive affective syndrome.\" In this comprehensive narrative review, we provide the results of an extensive literature search in PubMed and Embase to summarize recent evidence on altered cerebellar development in premature infants, focusing on neuroimaging findings, its causative factors and its impact on long-term neurodevelopmental outcomes.</p>","PeriodicalId":50706,"journal":{"name":"Cerebellum","volume":"24 2","pages":"39"},"PeriodicalIF":2.7,"publicationDate":"2025-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11782465/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143069432","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":"Emerging Deep Brain Stimulation Targets in the Cerebellum for Tremor.","authors":"Ludy C Shih","doi":"10.1007/s12311-025-01789-z","DOIUrl":"10.1007/s12311-025-01789-z","url":null,"abstract":"<p><p>Deep brain stimulation (DBS) for essential tremor is remarkably effective, leading to over 80% reduction in standardized tremor ratings. However, for certain types of tremor, such as those accompanied by ataxia or dystonia, conventional DBS targets have shown poor efficacy. Various rationales for using cerebellar DBS stimulation to treat tremor have been advanced, but the varied approaches leave many questions unanswered: which anatomic target, stimulation settings, and indications seem most promising for this emerging approach. This article reviews the clinical experience published to date and explores some of the pre-clinical and human physiology data that might support a role for further systematic investigation of cerebellar DBS for clinical use. Four tremor disorders to date have been targeted with cerebellar DBS in humans: essential tremor, post-stroke tremor, dystonic tremor, and tremor associated with degenerative cerebellar ataxias, like spinocerebellar ataxia type 3. The dentate nucleus is the most frequently chosen target, but key stereotactic and imaging details are missing from many of the case reports. Interestingly, consensus on laterality has not been definitively established as there are conflicting models of the hypothesized mechanism of action of DBS of the dentate nuclei, and conflicting reports of benefit on the tremor ipsilateral to and contralateral toto the affected limb. Several points are highlighted, including the prediction from in vivo preclinical physiology studies and interventional studies, the remaining uncertainty regarding the preferred laterality of targets, and the lack of clear prioritization of tremor etiologies to be targeted in future rigorously designed interventional studies (e.g., preferably repeated n-of-1 or sham-controlled studies involving more than one patient).</p>","PeriodicalId":50706,"journal":{"name":"Cerebellum","volume":"24 2","pages":"38"},"PeriodicalIF":2.7,"publicationDate":"2025-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143048173","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":"Assessment of Peripheral Neuropathy Using Current Perception Threshold Measurement in Patients with Spinocerebellar Ataxia Type 3.","authors":"Xia-Hua Liu, Wei Lin, Hao-Ling Xu, Mao-Lin Cui, Zhuo-Ying Huang, Ying Li, Nan-Nan Zhang, Ning Wang, Zhi-Yong Wang, Shi-Rui Gan","doi":"10.1007/s12311-024-01769-9","DOIUrl":"10.1007/s12311-024-01769-9","url":null,"abstract":"<p><p>Peripheral neuropathy (PN) identified as a significant contributor to disability in Spinocerebellar ataxia type 3 (SCA3) patients. This study seeks to assess the utility of current perception threshold (CPT) measurements in evaluating PN in individuals with SCA3 and aims to identify factors influencing CPT values in SCA3 and ascertain whether these values correlate with the severity of ataxia. Ninety-four patients diagnosed with SCA3 and 44 healthy controls were recruited for this investigation. All participants were performed standard CPT assessments. Comparative analysis was conducted on CPT variables between the groups. Multivariable linear regression models were employed to identify potential risk factors influencing CPT values, and to investigate the association between CPT values and the severity of ataxia in SCA3. The case group exhibited significantly higher values across all CPT variables compared to the control group (P < 0.01). Peripheral neuropathy was prevalent among SCA3 patients, with lower limb nerves demonstrating greater susceptibility than upper limb nerves. Increasing age (β = 1.813, P = 0.012) and heightened ataxia severity (β = 3.763, P = 0.013) as predictors of poorer CPT values. Gender also emerged as a predictor of CPT values. Furthermore, CPT values (β = 0.003, P = 0.013) and disease duration (β = 0.118, P < 0.001) were associated with more severe ataxia. Our findings suggest that the CPT test holds promise for assessing peripheral neuropathy in SCA3 patients and that CPT values may serve as indicators of disease severity in this population.</p>","PeriodicalId":50706,"journal":{"name":"Cerebellum","volume":"24 2","pages":"37"},"PeriodicalIF":2.7,"publicationDate":"2025-01-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143043289","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 in the Age of Omics: An Overview of the Transcriptomic Landscape of Essential Tremor.","authors":"Farah Aboasali, Charles-Etienne Castonguay, Miranda Medeiros, Patrick A Dion, Guy A Rouleau","doi":"10.1007/s12311-025-01793-3","DOIUrl":"10.1007/s12311-025-01793-3","url":null,"abstract":"<p><p>Essential Tremor (ET) is the most common movement disorder and has a worldwide prevalence of 1%, including 5% of the population over 65 years old. It is characterized by an active, postural or kinetic tremor, primarily affecting the upper limbs, and is diagnosed based on clinical characteristics. The pathological mechanisms of ET, however, are mostly unknown. Moreover, despite its high heritability, genetic studies of ET genetics have yielded mixed results. Transcriptomics is a field that has the potential to reveal valuable insights about the processes and pathogenesis of ET thus providing an avenue for the development of more effective therapies. With the emergence of techniques such as single-cell and single-nucleus RNA sequencing (scRNA-seq and snRNA-seq), molecular and cellular events can now be more closely examined, providing valuable insights into potential causal mechanisms. In this review, we review the growing literature on transcriptomic studies in ET, aiming to identify biological pathways involved and explore possible avenues for further ET research. We emphasized the convergence on shared of biological pathways across several studies, specifically axonal guidance and calcium signaling. These findings posit multiple hypotheses linking both pathways through the regulation of axonal and synaptic plasticity. We conclude that increasing the sample size is vital to uncover the subtleties of ET clinical and pathological heterogeneity. Additionally, integrating Multiomics approaches should provide a comprehensive understanding of the disease's pathophysiology.</p>","PeriodicalId":50706,"journal":{"name":"Cerebellum","volume":"24 2","pages":"35"},"PeriodicalIF":2.7,"publicationDate":"2025-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143034654","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":"Whole Blood DNA Methylation Analysis Reveals Epigenetic Changes Associated with ARSACS.","authors":"Giulia De Riso, Valentina Naef, Devid Damiani, Stefano Doccini, Filippo M Santorelli, Daniele Galatolo","doi":"10.1007/s12311-025-01791-5","DOIUrl":"10.1007/s12311-025-01791-5","url":null,"abstract":"<p><p>Autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS) is a rare inherited condition described worldwide and characterized by a wide spectrum of heterogeneity in terms of genotype and phenotype. How sacsin loss leads to neurodegeneration is still unclear, and current knowledge indicates that sacsin is involved in multiple functional mechanisms. We hence hypothesized the existence of epigenetic factors, in particular alterations in methylation patterns, that could contribute to ARSACS pathogenesis and explain the pleiotropic effects of SACS further than pathogenic mutations. To investigate this issue, we recruited eight patients affected by ARSACS, four characterized by early onset of the disease and four with late onset. We performed Whole Genome Bisulfite Sequencing using DNA from peripheral blood to define the methylome of patients and compared them with a control group. Our analysis showed that patients with ARSACS exhibit an altered methylation pattern and that the observed differences exist also among affected individuals with different age of onset. Our study provides valuable insights for employing epigenetic biomarkers to assess the severity and progression of this disorder and propels further investigations into the role of epigenetic processes in ARSACS pathogenesis.</p>","PeriodicalId":50706,"journal":{"name":"Cerebellum","volume":"24 2","pages":"36"},"PeriodicalIF":2.7,"publicationDate":"2025-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143061428","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":"Spontaneous Nystagmus Violating the Alexander's Law: Neural Substrates and Mechanisms.","authors":"Jae-Hwan Choi, Eun Hye Oh, Hyun Sung Kim, Ji-Yun Park, Suk-Min Lee, Seo Young Choi, Hyo Jung Kim, Jeong-Yoon Choi, Ji-Soo Kim, Jorge Otero-Millan, Kwang-Dong Choi","doi":"10.1007/s12311-025-01788-0","DOIUrl":"10.1007/s12311-025-01788-0","url":null,"abstract":"<p><p>Alexander's law states that spontaneous nystagmus increases when looking in the direction of fast-phase and decreases during gaze in slow-phase direction. Disobedience to Alexander's law is occasionally observed in central nystagmus, but the underlying neural circuit mechanisms are poorly understood. In a retrospective analysis of 2,652 patients with posterior circulations stroke, we found a violation of Alexander's law in one or both directions of lateral gaze in 17 patients with lesions of unilateral lateral medulla affecting the vestibular nucleus. Patients with vestibular neuritis served as a control. When Alexander's law is violated, the time constant (Tc) was larger than that in the controls (median [interquartile range, IQR]: 14.4s [6.4-38.9] vs 9.0s [IQR 5.5-12.6], p = 0.036) while the Tc did not differ between the groups when Alexander' law is obeyed (9.6s [3.6-16.1] vs 9.0s [5.5-12.6], p = 0.924). To test the study hypothesis that an unstable neural integrator may generate nystagmus violating Alexander's law, we utilized the gaze-holding neural integrator model incorporating brainstem leaky neural integrator and negative velocity feedback loop via the cerebellum. The lesion-induced changes included false rotational cue, primarily attributed to central vestibular imbalance, and unstable neural integrator, examined in two ways: hyperexcitable brainstem neural integrator and paradoxical excitatory effect of Purkinje cells. With normal integrator function, the false rotational cue generated nystagmus consistent with Alexander's law. However, both types of unstable neural integrators tested produced nystagmus that violated Alexander's law. We propose that when the neural integrator is unstable with lesions in the brainstem neural integrator itself or the neural synapse between Purkinje cells and the brainstem vestibular nucleus, nystagmus violates Alexander's law. The spontaneous nystagmus violating Alexander's law may be the useful clue for identifying central vestibular syndrome.</p>","PeriodicalId":50706,"journal":{"name":"Cerebellum","volume":"24 2","pages":"34"},"PeriodicalIF":2.7,"publicationDate":"2025-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143015519","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":"Causally Mapping the Cerebellum in Children and Young Adults: from Motor to Cognition.","authors":"Marina Veyrie, Bertrand Beffara, Nathalie Richard, Carmine Mottolese, Alexandru Szathmari, Federico Di Rocco, Cécile Faure Conter, Pierre Leblond, Michel Desmurget, Irene Cristofori, Pierre-Aurélien Beuriat","doi":"10.1007/s12311-024-01778-8","DOIUrl":"10.1007/s12311-024-01778-8","url":null,"abstract":"<p><p>While the cerebellum's role in orchestrating motor execution and routines is well established, its functional role in supporting cognition is less clear. Previous studies claim that motricity and cognition are mapped in different areas of the cerebellar cortex, with an anterior/posterior dichotomy. However, most of the studies supporting this claim either use correlational methods (neuroimaging) or are lesion studies that did not consider central covariates (such as age, gender, treatment presence, and deep nuclei impairment) known to influence motor and cognitive recoveries in patients. Here, we used voxel-based lesion-symptom mapping (VLSM) on children and young adults having undergone cerebellar tumor resection. This approach allows to control for these covariates and evaluate causal relationships between brain anatomy and behavioral performances to disentangle the anatomic substrate of motor and cognitive functions. VLSM analyses showed that both motor and cognitive impairments were greater in children and young adults with lesions of the posterior cerebellum. These results highlight distinct and overlapping structural correlates of motor and cognitive performance in the cerebellum and are consistent with structural and functional hypotheses of integration of the cerebellum in motor and cognitive functions.</p>","PeriodicalId":50706,"journal":{"name":"Cerebellum","volume":"24 2","pages":"31"},"PeriodicalIF":2.7,"publicationDate":"2025-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11735598/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143015509","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":"ATXN10 Gene Expansions in Mexican Patients with Ataxia Without Epilepsy.","authors":"Aurelio Jara-Prado, Eukeni Arias-Capistran, Jorge Guerrero-Camacho, Adriana Ochoa-Morales, Marie Catherine Boll, David Dávila-Ortíz de Montellano, Astrid Rasmussen, Tetsuo Ashizawa, Juan Fernandez-Ruiz, Petra Yescas-Gómez, Miguel Ángel Ramírez-García","doi":"10.1007/s12311-024-01784-w","DOIUrl":"10.1007/s12311-024-01784-w","url":null,"abstract":"<p><p>Spinocerebellar ataxia type 10 (SCA10) is an autosomal dominant (AD) neurodegenerative disorder prevalent in the Americas, particularly in Mexico. Clinical manifestations include progressive ataxia and epilepsy. However, it can exhibit wide phenotypic variability and even reduced penetrance. Because the diagnostic overlaps with other ataxias, molecular diagnosis is essential. This cross-sectional study conducted a retrospective review and analysis of 183 DNA samples from a laboratory registry of patients with ataxia who were suspected of having AD ataxia (n = 86; negative for ATXN1, ATXN2, ATXN3, ATXN7, TBP, and ATN1 genes) or sporadic ataxia (n = 97). Triplet repeat-primed PCR (TP-PCR) was performed to identify ATXN10 gene expansions. 19.6% (n = 36) of the samples showed ATXN10 expansions, with a higher proportion of hereditary AD cases (30.2%; n = 26) compared to sporadic cases (10.3%; n = 10). Clinical information was available in only 23 registries, with manifestations predominantly including cerebellar signs, but notably not epilepsy. The frequency of SCA10 in our country underlines the need to change the diagnostic suspicion, as the absence of epilepsy challenges previous diagnostic assumptions. As this is a study from a laboratory registry, we are aware of certain limitations.</p>","PeriodicalId":50706,"journal":{"name":"Cerebellum","volume":"24 2","pages":"33"},"PeriodicalIF":2.7,"publicationDate":"2025-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143055930","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":"Delayed Progression of Ataxia with a Static Cerebellar Lesion- Consider SCA27B.","authors":"Tsz Hang Wong, Jamie Manuputty, Tom van Seeters, Erik-Jan Kamsteeg, Bart van de Warrenburg","doi":"10.1007/s12311-025-01786-2","DOIUrl":"10.1007/s12311-025-01786-2","url":null,"abstract":"<p><p>Repeat expansions in the fibroblast growth factor 14 gene (FGF14), associated with spinocerebellar ataxia type 27B (SCA27B), have emerged as a prevalent cause of previously unexplained late-onset cerebellar ataxia. Here, we present a patient with residual symptom of gait ataxia after complicated meningioma surgery, who presented with progressive symptoms of oculomotor disturbances, speech difficulties, vertigo and worsening of gait imbalance, twelve years post-resection. Neuroimaging revealed a surgical resection cavity in the dorsolateral side of the left cerebellar hemisphere, accompanied by gliosis in left cerebellar hemisphere extending into the vermis, extensive non-specific supratentorial periventricular white matter abnormalities, and mild atrophy of the cerebellar vermis. Initially, her symptoms were attributed to re-emergence of her cerebellar symptoms related to the static cerebellar lesion, and due to a failure of compensatory mechanisms with aging. However, the progressive nature of her cerebellar symptoms and the emergence of novel downbeat nystagmus prompted genetic testing for FGF14 repeat expansion, confirming SCA27B as a significant contributor to her delayed, progressive cerebellar symptoms. This case highlights the significance of considering SCA27B in the differential diagnosis of delayed progressive cerebellar ataxia with oculomotor abnormalities in the presence of a static cerebellar lesion.</p>","PeriodicalId":50706,"journal":{"name":"Cerebellum","volume":"24 2","pages":"32"},"PeriodicalIF":2.7,"publicationDate":"2025-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11739311/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143055944","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}