Cerebellum最新文献

{"title":"Cerebellar Ataxia, Neuropathy, and Vestibular Areflexia as a Presentation of a Novel DNMT1 Mutation.","authors":"Jake Sossamon, Patrick O'Connell, David P W Rastall","doi":"10.1007/s12311-024-01780-0","DOIUrl":"10.1007/s12311-024-01780-0","url":null,"abstract":"<p><p>A 50-year-old woman with a 20-year history of gait instability presented with new-onset vertigo and oscillopsia. Examination revealed bilateral vestibular loss, cerebellar ataxia, sensory neuropathy, a \"yes-yes\" head tremor, nystagmus and a family history of a similar syndrome. Genetic testing for cerebellar ataxia with neuropathy and bilateral vestibular areflexia syndrome (RFC1) was negative, but whole exome sequencing identified a novel mutation in the DNA methyltransferase 1 (DNMT1) gene, broadening the differential diagnosis for this phenotype. Management was focused on symptomatic treatment and genetic counseling. This case highlights the importance of considering DNMT1 mutations in patients with a similar clinical presentation.</p>","PeriodicalId":50706,"journal":{"name":"Cerebellum","volume":"24 1","pages":"25"},"PeriodicalIF":2.7,"publicationDate":"2025-01-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142928747","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":"ARSACS: Clinical Features, Pathophysiology and iPS-Derived Models.","authors":"Ikhlass Haj Salem, Mathieu Blais, Valeria M Zuluaga-Sánchez, Laurence Rouleau, Esther B E Becker, Nicolas Dupré","doi":"10.1007/s12311-024-01777-9","DOIUrl":"10.1007/s12311-024-01777-9","url":null,"abstract":"<p><p>Autosomal-recessive spastic ataxia of Charlevoix-Saguenay (ARSACS) is an early-onset neurodegenerative disease caused by mutations in the SACS gene. The first two mutations were identified in French Canadian populations 20 years ago. The disease is now known as one of the most frequent recessive ataxias worldwide. Prominent features include cerebellar ataxia, pyramidal spasticity, and neuropathy. Neuropathological findings revealed cerebellar atrophy of the superior cerebellar vermis and the anterior vermis associated with Purkinje cell death, pyramidal degeneration, cortical atrophy, loss of motor neurons, and demyelinating neuropathy. No effective therapy is available for ARSACS patients but, in the last two decades, there have been significant advances in our understanding of the disease. New approaches in ARSACS, such as the reprogramming of induced pluripotent stem cells derived from patients, open exciting perspectives of discoveries. Several research questions are now emerging. Here, we review the clinical features of ARSACS as well as the cerebellar aspects of the disease, with an emphasis on recent fields of investigation.</p>","PeriodicalId":50706,"journal":{"name":"Cerebellum","volume":"24 1","pages":"24"},"PeriodicalIF":2.7,"publicationDate":"2025-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142928743","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 Cognitive Event-Related Potential Components and N170 Source Analysis in Patients with Acute Cerebellar Infarction.","authors":"Qirong Ling, Xiaodong Yuan, Ya Ou, Jing Wang, Liqin Duan, Lingyun Cao, Pingshu Zhang","doi":"10.1007/s12311-024-01776-w","DOIUrl":"10.1007/s12311-024-01776-w","url":null,"abstract":"<p><p>This study aims to evaluate cognitive impairments in patients with acute cerebellar infarction using event-related potentials (ERP) and electrophysiological source imaging (ESI). Thirty patients with acute cerebellar infarction and 32 healthy volunteers were selected. Cognitive potentials were recorded and measured using a visual Oddball paradigm. Source analysis of the N170 component was performed using standardized low-resolution brain electromagnetic tomography (sLORETA) to compare the standardized current density distribution between the two groups under different stimuli. For inverted and upright face stimuli, the amplitudes of N170, VPP, and N300 in the patient group were significantly lower than those in the control group (p < 0.05). For upright house stimuli, the VPP amplitude in the patient group was also lower than that in the control group (p < 0.05). Source analysis revealed that the brain regions with significant differences between the acute cerebellar infarction group and the control group included the temporal and parietal lobes. Specifically, activation in the precuneus was reduced during inverted face stimuli; activation in the middle temporal gyrus was reduced during upright face stimuli; and activation in the middle temporal gyrus and fusiform gyrus was increased during both inverted and upright house stimuli. Patients with acute cerebellar infarction exhibit abnormal P100, N170/VPP, and N300 amplitudes. Source analysis of the N170 component revealed altered activation in the middle and inferior temporal gyri, fusiform gyrus, middle occipital gyrus, and precuneus, which play a role in selective cognitive impairments following cerebellar infarction.</p>","PeriodicalId":50706,"journal":{"name":"Cerebellum","volume":"24 1","pages":"23"},"PeriodicalIF":2.7,"publicationDate":"2025-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142923799","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 Transcranial AC Stimulation Produces a Frequency-Dependent Bimodal Cerebellar Output Pattern.","authors":"Devry Mourra, Angela M Cavalieri, Madison M Casey, Mesut Sahin, Eric J Lang","doi":"10.1007/s12311-024-01756-0","DOIUrl":"10.1007/s12311-024-01756-0","url":null,"abstract":"<p><p>Cerebellar transcranial alternating current stimulation (ctACS) has the potential to be an appealing, non-invasive treatment option for psychiatric and neurological disorders. However, realization of this potential has been limited by gaps in our knowledge of how ctACS affects cerebellar output on single cell and population levels. Previously, we showed that AC stimulation applied to the cerebellar surface produced a strong, frequency-dependent modulation of Purkinje cell (PC) and cerebellar nuclear (CN) cell activity. Here, to approximate more closely the ctACS conditions, we investigated how AC stimulation applied to the external skull surface overlying crus 1 altered PC and CN activity in anesthetized adult female Sprague-Dawley rats. PC and CN activity showed a frequency-dependent modulation in response to ctACS at frequencies ranging from 0.5 to 80 Hz. A unimodal response was seen for most PCs across all frequencies, whereas most CN cells transitioned to bimodal patterns as stimulus frequency increased. The frequency-dependence of the phases of the local minima of the CN cell modulation were consistent with CN cells being driven synaptically by PC activity. Furthermore, comparison of responses with ipsilateral and contralateral placement of the stimulus electrode with respect to the recording site showed that the strength and pattern of the entrainment depended on the stimulus electrode location, suggesting that ctACS electrode placement could be used to target specific cerebellar output channels. In sum, the results show that transcranial stimulation of the cerebellar cortex can modulate cerebellar output, which has potential implications for its use in treating neurological and psychiatric disorders.</p>","PeriodicalId":50706,"journal":{"name":"Cerebellum","volume":"24 1","pages":"21"},"PeriodicalIF":2.7,"publicationDate":"2025-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142916227","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":"How and where Effectively Apply Cerebellum Stimulation: The frequency-dependent Modulation of Cerebellar Output by Transcranial Alternating Current Stimulation.","authors":"Vincenzo Romano, Mario Manto","doi":"10.1007/s12311-024-01772-0","DOIUrl":"10.1007/s12311-024-01772-0","url":null,"abstract":"<p><p>As brain-machine interfaces (BMI) are growingly used in clinical settings, understanding how to apply brain stimulation is increasingly important. Despite the emergence of optogenetic techniques, ethical and medical concerns suggest that interventions that are safe and non-invasive, such as Transcranial Alternating Current Stimulation (tACS), are more likely to be employed in human in the near future. Consequently, the question of how and where to apply current stimulation is becoming increasingly important for the efficient neuromodulation of both neurological and psychiatric disorders. In this edition of The Cerebellum, Mourra et al. demonstrate how ctACS influences cerebellar output at both single-cell and population levels by stimulating Crus I in rats. As the neuron generating this output serves as a crucial convergence and divergence center in the nervous system, it can be leveraged as a strategic hub to target multiple brain structures and influence various behaviors. Accordingly, the discovery that neurons in this relatively deep brain region can be indirectly entrained through Purkinje neuron activation and optimal frequency around 80 Hz could be highly relevant for future medical interventions. In light of these findings, high-γ-tACS might be more effective in humans compared to the more commonly used low-γ (50 Hz) or θ-tACS (5 Hz). This could enhance the chance of cerebellar tACS being utilized in clinical settings and BMI.</p>","PeriodicalId":50706,"journal":{"name":"Cerebellum","volume":"24 1","pages":"22"},"PeriodicalIF":2.7,"publicationDate":"2025-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142916229","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 Japanese Family with a Novel Pathogenic Variant in KIF1A Presenting with Spastic Paraparesis, Cerebellar Ataxia, and Intellectual Disability.","authors":"Akihiko Mitsutake, Mizuho Kawai, Kenta Orimo, Takashi Matsukawa, Hiroyuki Ishiura, Jun Mitsui, Hideki Nakajima, Hiroyuki Murai, Shoji Tsuji, Jun Goto, Nobue K Iwata","doi":"10.1007/s12311-024-01782-y","DOIUrl":"10.1007/s12311-024-01782-y","url":null,"abstract":"<p><p>Variants in KIF1A are associated with hereditary spastic paraplegia (SPG30), which can manifest in both pure and complex forms. We describe a Japanese family with a novel KIF1A variant presenting with a complex form of SPG30. Patient 1, a 69-year-old woman, experienced progressive gait disturbance due to spastic paraparesis and cerebellar atrophy, and intellectual disability. Patient 2, the daughter of Patient 1, exhibited similar symptoms with more severe dysarthria. Patients 1 and 2 shared a heterozygous c.173 C > G (p.Ser58Trp) variant in the motor domain of KIF1A (NM_001244008.2), which is classified as likely pathogenic. This family highlights the role of autosomal dominant inheritance in a complex form of SPG30, expanding the understanding of its genetic basis and clinical presentation.</p>","PeriodicalId":50706,"journal":{"name":"Cerebellum","volume":"24 1","pages":"20"},"PeriodicalIF":2.7,"publicationDate":"2024-12-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142900174","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":"Unravelling Heterogeneity: A Rare PNPT1 Variant in Childhood-Onset Spinocerebellar Ataxia with Sensorineural Hearing Loss.","authors":"Lakshmi Madhuri Nallapaneni, Anish Mehta, Prabhudev Hiremath, R Pradeep, Mahendra Javali, Purushotham T Acharya","doi":"10.1007/s12311-024-01779-7","DOIUrl":"10.1007/s12311-024-01779-7","url":null,"abstract":"<p><p>Spinocerebellar ataxias (SCAs) are a diverse and heterogeneous group of inherited neurodegenerative disorders marked by progressive ataxia and cerebellar degeneration. This case report details an 11-year-old Indian boy with childhood-onset ataxia and severe sensorineural hearing loss, a rarely reported concomitance in pediatric neurology. Genetic analysis identified a unique heterozygous 3' splice site variant in the PNPT1 gene (c.2014-3 C > G) of pathogenic significance, confirming the diagnosis of SCA25. This case highlights the phenotypic and genotypic heterogeneity of PNPT1 gene-related SCA25 and suggests an autosomal dominant inheritance pattern with low penetrance. It underscores the need for functional studies to further validate the splice variant reported herein and emphasizes the importance of a high index of suspicion for genetic analysis and genetic counselling in children with concurrent hearing loss and progressive ataxia, even in the absence of a clear autosomal dominant inheritance pattern.</p>","PeriodicalId":50706,"journal":{"name":"Cerebellum","volume":"24 1","pages":"19"},"PeriodicalIF":2.7,"publicationDate":"2024-12-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142900175","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":"Detection of Crossed Cerebellar Diaschisis in Intractable Epilepsy Using Integrated ¹⁸F-FDG PET/MR Imaging.","authors":"Yaqin Hou, Jie Hu, Jingjuan Wang, Chenyang Yao, Zhenming Wang, Jie Lu","doi":"10.1007/s12311-024-01759-x","DOIUrl":"10.1007/s12311-024-01759-x","url":null,"abstract":"<p><p>Crossed cerebellar diaschisis(CCD) involves reduced metabolism and blood flow in the cerebellar hemisphere contralateral to a supratentorial lesion. ASL is a valuable tool for quantifying regional cerebral blood flow. This study assesses ASL-MRI's ability to detect CCD in epilepsy using integrated ¹⁸F-FDG PET/MRI and compares ASL with PET images in evaluating CCD. 74 patients with drug-refractory epilepsy who underwent integrated ¹⁸F-FDG PET/MRI pre-surgery and CT/MRI post-surgery was analysed. Regions of interest were outlined on MRI images and simultaneously transferred to PET and ASL images. CCD detection was evaluated visually and semi-quantitatively using the absolute asymmetry index (AIabs). Out of 74 patients, PET detected CCD in 24 (32.43%) and ASL in 18 (24.32%), with no significant difference between them (P = 0.274). Based on the PET results, the ROC curve for ASL's diagnostic accuracy for CCD showed an area under the curve of 0.69 (P = 0.008), an accuracy of 75.68%, a sensitivity of 50%, a specificity of 88%, a positive predictive value (PPV) of 66.67%, and a negative predictive value (NPV) of 78.57%. Four CCD types were identified: both PET and ASL positive (16.22%), PET positive and ASL negative (16.22%), ASL positive and PET negative (8.10%), and both negative (59.46%). AIabs correlation was positive between PET and ASL in the epileptic zone (r = 0.658, P < 0.001) and cerebellum (r = 0.407, P < 0.001). In ASL CCD-positive cases, AIabs showed a negative correlation between the epileptic zone and cerebellum (r=-0.581, P = 0.011), while in both PET and ASL CCD-positive cases, AIabs correlation was positive (r = 0.670, P = 0.017). ASL can be used as a method for evaluating CCD, and when combined with FDG-PET, it can further enhance its diagnostic accuracy for CCD. In CCD-positive cases, a notable discrepancy was observed: no correlation in PET images but a correlation in ASL images between the supratentorial epileptic zone and contralateral cerebellar hemisphere, indicating CCD might be linked to regional cerebral blood flow changes.</p>","PeriodicalId":50706,"journal":{"name":"Cerebellum","volume":"24 1","pages":"18"},"PeriodicalIF":2.7,"publicationDate":"2024-12-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142873367","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":"Uneven Distribution of Purkinje Cell Injury in the Cerebellar Vermis of Term Neonates with Hypoxic-Ischemic Encephalopathy.","authors":"Kim V Annink, Ilona C E van Leeuwen, Nina A Smeets, Lianne A J Peeters, Niek E van der Aa, Thomas Alderliesten, Floris Groenendaal, Reint K Jellema, Cora H A Nijboer, Peter G J Nikkels, Martin Lammens, Manon J N L Benders, Freek E Hoebeek, Jeroen Dudink","doi":"10.1007/s12311-024-01765-z","DOIUrl":"10.1007/s12311-024-01765-z","url":null,"abstract":"<p><p>In term neonates with hypoxic-ischemic encephalopathy (HIE), cerebellar injury is becoming more and more acknowledged. Animal studies demonstrated that Purkinje cells (PCs) are especially vulnerable for hypoxic-ischemic injury. In neonates, however, the extent and pattern of PC injury has not been investigated. The aim of this study was to characterize the morphology and distribution of PCs in the cerebellar vermis of term born neonates with HIE. Twenty-two term born neonates with severe HIE, several of which received therapeutic hypothermia, who underwent post-mortem autopsy of the brain including cerebellar vermis within three to five days after birth were included. Haematoxylin & Eosin (H&E) stained sections of the vermis were used to determine total PC count and morphology (normal, abnormal or non-classified) at the bases and crowns of the folia and of the lobules in both the anterior and posterior lobes. Differences in PC count and PC morphology between the anterior and posterior lobe and between the bases and crowns were compared. The total number of PCs was significantly higher at the crowns compared to the bases (p < 0.001) irrespective of the precise location. Besides, PCs at the bases more often had an abnormal morphology. Also, a significant difference between the injury in the anterior and posterior lobe was observed, notably at specific microscopic locations with more abnormal PCs in the posterior lobe. The number of PCs scored as abnormal was increased in the bases compared to the crowns, which might resemble supratentorial ulegyria.</p>","PeriodicalId":50706,"journal":{"name":"Cerebellum","volume":"24 1","pages":"17"},"PeriodicalIF":2.7,"publicationDate":"2024-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142856579","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":"Balance Performance in Aged Mice is Dependent on Unipolar Brush Cells.","authors":"Gabrielle Kizeev, Isabelle Witteveen, Timothy Balmer","doi":"10.1007/s12311-024-01767-x","DOIUrl":"10.1007/s12311-024-01767-x","url":null,"abstract":"<p><p>The vestibular processing regions of the cerebellum integrate vestibular information with other sensory modalities and motor signals to regulate balance, gaze stability, and spatial orientation. A class of excitatory glutamatergic interneurons known as unipolar brush cells (UBCs) are highly concentrated within the granule cell layer of these regions. UBCs receive vestibular signals directly from primary vestibular afferents and indirectly from mossy fibers. Each UBC excites numerous granule cells and could contribute to computations necessary for balance-related motor function. Prior research has implicated UBCs in motor function, but their influence on balance performance remains unclear, especially in aged mice that have age-related impairment. Here we tested whether UBCs contribute to motor coordination and balance by disrupting their activity with chemogenetics in aged and young mice. Age-related balance deficits were apparent in mice > 6 months old. Disrupting the activity of a subpopulation of UBCs caused aged mice to fall off a balance beam more frequently and altered swimming behaviors that are sensitive to vestibular dysfunction. These effects were not seen in young (7-week-old) mice. Thus, disrupting the activity of UBCs impairs mice with age-related balance issues and suggest that UBCs are essential for balance and vestibular function in aged mice.</p>","PeriodicalId":50706,"journal":{"name":"Cerebellum","volume":"24 1","pages":"16"},"PeriodicalIF":2.7,"publicationDate":"2024-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142856574","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}