Cerebellum最新文献

Clinically-relevant variants in the STUB1 gene have been associated with an autosomal dominant spinocerebellar ataxia 48 (SCA48), a recently described inherited neurodegenerative condition that is characterised by cognitive and psychiatric changes. To describe the clinical phenotype and genetic findings of three new Australian probands with STUB1 to expand the current understanding of the spectrum of clinical presentation and natural history of SCA48. Clinical and genetic review of patients diagnosed with SCA48 ataxia drawn from our centres. The third case was derived from a collaborating centre (Royal Brisbane Hospital). We identified three unrelated SCA48 patients with heterozygous pathogenic STUB1 variants. All presented with slowly progressive cerebellar ataxia with tremor and additional findings of dysarthria, parkinsonism, hypertonia, cognitive and psychiatric symptoms. Age of onset varied from 34 to 65 years of age. Brain MRI showed significant diffuse cerebellar atrophy, affecting the vermis and cerebellar hemispheres. We identified two novel pathogenic variants of STUB1 gene, and one previously reported pathogenic variant. Genetic testing for intermediate expansions of TBP (SCA17) identified TBP repeats within the normal range of 25-40 in all 3 probands. Our case series expands the clinical spectrum of SCA48. We highlight the importance of tremor as part of the clinical phenotype including upper limb rest tremor and Parkinsonian signs. Our cases lacked pathological TBP expansions and provide additional evidence that STUB1 (SCA48) can manifest as a monogenic disease.

Whereas several studies have reported on quantitative oculomotor and vestibular measurements in spinocerebellar ataxia type 6 (SCA6), selecting the most suitable paradigms remains challenging. We aimed to address this knowledge gap through a systematic literature review and providing disease-specific recommendations for a tailored set of eye-movement recordings in SCA6. A literature search (MEDLINE, Embase) was performed focusing on studies reporting on quantitative oculomotor and/or vestibular measurements in SCA6-patients. Oculomotor and vestibular parameters were extracted and correlations with various epidemiologic and clinical parameters were sought. Twenty-two studies were included reporting on 154 patients. Abnormalities observed included reduced pursuit gain (58/69), frequent square-wave jerks (23/40), spontaneous downbeat nystagmus (DBN, 34/55) and triggered nystagmus including positional nystagmus (25/34) and vertical ("perverted") head-shaking nystagmus (21/34), gaze-evoked nystagmus (48/70) and angular vestibulo-ocular reflex (aVOR)-suppression (21/25), and high-frequency aVOR-deficits (26/33). For horizontal visually-guided saccades (VGS), changes in metrics (36/66) were frequently observed, whereas saccade velocity was usually preserved (39/44) and saccade latency within normal limits. Reduced high-frequency aVOR gains, VGS-latency and metrics correlated with disease severity. Longitudinal data indicated deterioration of individual video-head-impulse testing gains over time. A broad range of oculomotor and vestibular domains are affected in SCA6. Impairments in pursuit, saccade metrics, gaze-holding (gaze-evoked nystagmus, DBN) and high-frequency aVOR were most frequently identified and as such, should be prioritized as disease markers. Quantitative oculomotor testing in SCA6 may facilitate an early diagnosis and prove valuable in monitoring disease progression.

Essential tremor (ET) is a prevalent movement disorder that impairs gait function, including gait speed - a critical marker of mobility disability and adverse outcomes. This meta-analysis aimed to quantify differences in gait speed between individuals diagnosed with ET compared to people without a movement disorder diagnosis. Electronic databases were searched for studies comparing gait speed in ET patients and controls. Effect sizes were calculated using standardized mean differences (Hedges' g) and pooled using a random-effects model. Eight studies (390 ET, 227 controls) were included. ET patients exhibited significantly slower gait speeds than controls. The effect size (Hedges' g = -1.06, 95% CI -1.47 to -0.65, p < .001) indicates a large, clinically significant difference. Substantial study heterogeneity was observed (I² = 76.9%). These findings suggest that gait speed deficits are a significant feature of ET, potentially reflecting cerebellar dysfunction. This highlights the need for gait assessment and targeted interventions in ET management to reduce fall risk and improve quality of life. Understanding the moderating factors such as medication type and state, disorder severity, and age could provide significant benefits in the treatment and management of ET.

Glutamic acid decarboxylase 65 (GAD65) antibody-associated epilepsy and diplopia are relatively rare. This article retrospectively analyzed the disease development, diagnosis and treatment process of two cases of GAD65-associated epilepsy with diplopia. Both patients initially exhibited seizures, followed by the onset of diplopia and nystagmus. Due to differences in their diagnostic processes, the two patients showed varying prognoses after treatment. When diplopia and nystagmus are present in patients with epilepsy, these symptoms are often easily attributed to the side effects of antiepileptic medications or not associated with the epilepsy, potentially leading to the oversight of the possibility of GAD65 neurological syndrome. Therefore, clinicians should be aware of the potential association of anti-GAD65 antibodies in epilepsy patients presenting with diplopia, avoidance of missed diagnosis. Furthermore, diplopia and nystagmus may be precursors to ataxia, therefore, when diplopia occurs, proactive treatment should be initiated to prevent disease progression and avoid poor patient outcomes.

Damage to cerebellar peduncles is common in patients with relapsing-remitting multiple sclerosis (RRMS). This can lead to a diverse range of motor and cognitive disabilities. Here, we aimed to evaluate the quantitative alterations of cerebellar peduncles using diffusion tensor imaging (DTI). After a comprehensive search in Web of Science, PubMed, Embase, and Scopus and a rigorous screening, eligible studies underwent data extraction and risk of bias assessment. Standardized Mean Difference (SMD) with a 95% CI was used as effect size. We compared DTI metrics in the cerebellar peduncle regions (SCP, MCP, ICP) between RRMS patients and healthy controls (HC). Sensitivity analysis employed the leave-one-out method. Contour-enhanced funnel plots and Pustejovsky test were used to evaluate the publication bias. Additionally, subgroup analysis was performed using available variables. In eleven included studies encompassing 623 RRMS patients and 416 HC, RRMS patients exhibited significantly decreased fractional anisotropy (FA) values in the SCP (SMD - 0.26) and MCP (SMD - 1.03), increased mean diffusivity (MD) values in the SCP (SMD 1.46), MCP (SMD 0.48) and ICP (SMD 0.70), elevated radial diffusivity (RD) values in the MCP (SMD 0.85) and ICP (SMD 1.20) compared to HC. The subgroup analysis revealed that individuals with elevated EDSS scores exhibited reduced FA and increased MD in the SCP region. No considerable publication bias was detected. No outliers were detected in the sensitivity analysis. DTI proves promising for identifying microstructural abnormalities in cerebellar peduncles of RRMS patients, with decreased FA and increased RD, and MD values observed.

The use of F-wave study may help to gain insight into electrophysiological significance of spinocerebellar Ataxias (SCAs). Particularly, the difference of F-wave features between Chinese SCA1, SCA2 and SCA3 patients were scarcely reported. 20 SCA1, 20 SCA2, 46 SCA3 patients and 30 healthy controls underwent nerve (median, ulnar, tibial) conduction and F-wave studies, and electrophysiology parameters were compared between them. Clinical data including ataxia and non-ataxia features was recorded. The study revealed peripheral neuropathological involvement in 80% of SCA1, 100% of SCA2, and 50% of SCA3 Chinese patients. Most patients of all subtypes presented with sensory neuropathy, and F-wave changes. We observed that SCA1 patients had prolonged F-wave latency as well as increased maximum F-wave amplitude and F/M amplitude ratio compared to controls for the first time. Besides, SCA2 patients had decreased F-wave persistence as well as increased maximum F-wave amplitude, F/M amplitude ratio and frequency of giant F-wave. The maximum amplitude of SCA1 correlated positively with disease severity and disease duration. The value of F/M amplitude ratio of SCA2 correlated positively with disease duration. In all subtypes, F-wave of the tibial nerve was the most sensitive measurement index. This study exhibits F-wave characteristics and inter-group differences of the most common Chinese SCAs. F-wave may be a potential biomarker for evaluating the progression of SCAs.

Neuronal ceroid lipofuscinosis type 10 (NCL10) is a rare progressive neurodegenerative disease associated with homozygous or compound heterozygous mutations in the CTSD gene encoding cathepsin D protein. It is classified as congenital, infantile, or juvenile NCL10 according to the age at onset of symptoms. Six cases of juvenile onset NCL10 (JNCL10) have been reported thus far in the literature. Herein, we report a nine-year-six-month-old girl with speech disorders, cognitive and motor decline, ataxia, and visual impairment. Developmental milestones were reported to be normal up to the age of 7 years. Biochemical and metabolic studies were normal. Electroencephalography showed intermittent generalized high-amplitude delta-wave activity during light sleep. Brain magnetic resonance imaging showed mild cerebellar atrophy. Whole-exome sequencing (WES) revealed a novel homozygous missense variant of c.1097G > A (p. Cys366Tyr) in the CTSD gene. Based on clinical, laboratory, and genetic findings, the patient was diagnosed with JNCL10. To the best of our knowledge, this is a novel variant and the first case reported in Turkey, and it is important in terms of broadening ethnicity and the spectrum of EEG findings.

To evaluate the alterations in brain dynamics in patients suffering from brainstem or cerebellar infarctions and their potential associations with cognitive function. In this study, 37 patients were recruited who had acute cerebellar infarction (CI), 32 patients who had acute brainstem infarction (BsI), and 40 healthy controls (HC). Every participant had their resting-state electroencephalogram (EEG) data captured, and the EEG microstates were analyzed. The cognitive function was measured by the Neuropsychological Cognitive Scale including the Mini-Mental State Examination (MMSE), the Montreal Cognitive Assessment (MoCA), the Boston Naming Test (BNT), the Digit Span Test (Digitspan), and the Symbol Digit Modalities Test (SDMT). Compared with the HC group, the transition probabilities from Microstate A(MsA) and MsD to MsC significantly decreased while the transition probabilities from MsA to MsD and from MsD to MsB significantly increased in the BsI group. By contrast, the CI group showed a significant increase in transition probabilities from MsA and MsD to MsC, whereas the transitions from MsD to MsB significantly decreased. Subgroup analysis within the CI group demonstrated that the CI patients with dizziness showed increased coverage and duration in MsB but decreased MsD occurrence than those of CI patients with vertigo. In addition, the BsI patients with pons infarction performed a decreased transition probability between MsA and MsD than those of BsI patients with medulla oblongata infarctions. Moreover, the changes in Microstate (Ms) were significantly correlated with cognitive scales in patients with CI or BsI. Altered brain dynamics in patients with CI or BsI suggested that disturbances in resting brain networks might play a functional role in the cognitive impairment of the CI or BsI patients. Through the use of microstate analysis, the dizziness or vertigo following CI could be differentiated. These findings may serve as a powerful tool in our future clinical practices.

Genetic alterations in the ERCC4 gene typically cause Xeroderma pigmentosum and other nucleotide excision repair disorders. Neurologic symptoms are present in some of these patients. In rare cases, ERCC4-mutations can manifest with prominent neurologic symptoms. We report a 62-year-old woman who presented with a movement disorder caused by a homozygous pathogenic variant in the ERCC4 gene. She presented with a hyperkinetic movement disorder (chorea) that affected the distal limbs as well as facial muscles and jaw. There was no ataxia. Extensive clinical evaluation revealed predominantly fronto-parietal and cerebellar atrophy on brain MRI with sparing of the basal ganglia and mesial temporal lobe. Iron and sparse Ca²⁺ deposits were found in the basal ganglia. The detailed neuropsychological evaluation revealed deficits indicating subcortical-prefrontal, subcortical-parietal and frontotemporal dysfunction, without significant impairments in activities of daily living. The audiogram revealed mild age-related hearing impairment, electroneurography was unremarkable without signs of polyneuropathy. The dermatologic examination showed no signs of skin cancer. Knowledge about ERCC4-related neurodegeneration is limited and the disease is likely underdiagnosed. Nucleotide Excision Repair Disorder-related neurodegeneration should be considered as a differential diagnosis in patients with adult-onset neurodegenerative disorders, even if dermatologic complications are absent and the family history is negative. The preserved caudate volume in our ERCC4 patient could be a hint towards this rare condition. Treatment is symptomatic. Once the diagnosis is established, patients need to be advised to have regular medical consultations to prevent disease complications such as skin cancer.

Spinocerebellar ataxias (SCAs) types 1, 2, and 3 are the most common subtypes of SCAs. However, the atrophy patterns of these three subtypes still need to be fully clarified. In this study, a total of 130 genetically confirmed SCA patients (SCA1: n = 16; SCA2: n = 13; symptomatic SCA3: n = 76; pre-symptomatic SCA3: n = 25) along with 65 age- and sex-matched healthy controls (HCs) were enrolled. MR volumetric analysis was used to explore the different atrophied patterns in these three SCA subtypes and the associations between significant morphometry alterations and clinical variables were further analyzed. Compared with HCs, the global brain grey matter (GM) of the three SCA subtypes and white matter (WM) volumes of the SCA2 and SCA3 were significantly reduced. SCA2 had significantly more severe GM volume atrophy than symptomatic SCA3. For local GM and WM volumes, all three subtypes of SCA have significant atrophy in infra- and supratentorial areas than HCs. The pre-symptomatic SCA3 patients had already demonstrated substantial WM atrophy. The SCAs subgroup comparisons showed that compared with symptomatic SCA3, SCA1 and SCA2 demonstrated more severe atrophy in regions of the cerebral and cerebellum, but symptomatic SCA3 had significantly atrophied bilateral lenticular nuclei. Besides, no significant difference was found in the local GM or WM volume between SCA1 and SCA2. Furthermore, some affected GM and WM regions, especially the damaged cerebellar peduncles, showed significant correlations with disease duration and severity in SCA1 and symptomatic SCA3. Our research results indicate differences in MRI brain injury patterns among common SCA subtypes, which might shed light on the deeper understanding of the pathophysiological mechanisms of SCAs.