AFG3L2 Biallelic Mutation: Clinical Heterogeneity in Two Italian Patients
AbstractAFG3-like matrix AAA peptidase subunit 2 gene (AFG3L2, OMIM * 604,581) biallelic mutations lead to autosomal recessive spastic ataxia-5 SPAX5, OMIM # 614,487), a rare hereditary form of ataxia. The clinical spectrum includes early-onset cerebellar ataxia, spasticity, and progressive myoclonic epilepsy (PME). In Italy, the epidemiology of the disease is probably underestimated. The advent of next generation sequencing (NGS) technologies has speeded up the diagnosis of hereditary diseases and increased the percentage of diagnosis of rare disorders, such as the rare hereditary ataxia groups. Here, we describe two pati...
Source: The Cerebellum - November 18, 2023 Category: Neurology Source Type: research
A Systematic Review on Anti-Yo/PCA-1 Antibody: Beyond Cerebellar Ataxia in Middle-Aged Women with Gynecologic Cancer
AbstractCurrent understanding of anti-Yo/PCA1 antibody-associated cerebellar ataxia is based on case reports and small case series. Our goal was to summarize clinical features, highlighting atypical presentations and gaps of knowledge. Following the PRISMA guidelines, we systematically screened Pubmed/MEDLINE, Embase, Scopus, and Web of Science from inception to April 2022 for all case reports and series concerning anti-Yo antibody-associated cerebellar ataxia. We collected data on clinical presentation, investigation findings, and treatment outcomes. Of 379 included patients, 96% were female with gynecologic cancer (82%)....
Source: The Cerebellum - November 18, 2023 Category: Neurology Source Type: research
Immunotherapies for the Effective Treatment of Primary Autoimmune Cerebellar Ataxia: a Case Series
AbstractPrimary autoimmune cerebellar ataxia (PACA) is an idiopathic sporadic cerebellar ataxia that is thought to be immune-mediated but lacks biomarkers or a known cause. Here, we report two cases of immune-mediated cerebellar ataxia that responded favorably to immunotherapy, in which tissue-based indirect immunofluorescence test for serum or cerebrospinal fluid (CSF) samples yielded positive results. Case 1 was a 78-year-old man who presented with subacute progressive gait ataxia with truncal instability and dysarthria in response to steroids. Case 2 was a 62-year-old man who presented with relapses and remissions of ac...
Source: The Cerebellum - November 18, 2023 Category: Neurology Source Type: research
Machado Joseph-Disease Is Rare in the Peruvian Population
In conclusion,ATXN3 allelic distribution in non-MJD/SCA3 patients with ataxia is similar to the distribution in normal individuals around the world, whereas LN allele frequency reinforces no correlation with the frequency of MJD/SCA3. Evidence of any atypical MJD/SCA3 phenotype was not found. Furthermore, haplotypes are required to confirm the foreign origin of MJD/SCA3 in the Peruvian population. (Source: The Cerebellum)
Source: The Cerebellum - November 18, 2023 Category: Neurology Source Type: research
Correction: A Novel de novo KIF1A Mutation in a Patient with Ataxia, Intellectual Disability and Mild Foot Deformity
(Source: The Cerebellum)
Source: The Cerebellum - November 18, 2023 Category: Neurology Source Type: research
Efficacy and Safety of Repetitive Transcranial Magnetic Stimulation in Spinocerebellar Ataxia Type 3: a Systematic Review and Meta ‑analysis of Randomized Controlled Trials
AbstractTherapeutic alternatives for spinocerebellar ataxia type 3 (SCA3) are limited. Repetitive transcranial magnetic stimulation (rTMS) as a potential intervention has drawn heightened interest because of its ease of implementation, cost-effectiveness, and safety profile. We conducted a systematic review and meta-analysis to evaluate the efficacy of rTMS in the treatment of SCA3. We systematically searched databases —PubMed, Embase, the Cochrane Library, and Springer—for randomized controlled trials (RCTs) investigating the use of rTMS in the treatment of SCA3. Major efficacy outcomes were assessed, including Intern...
Source: The Cerebellum - November 17, 2023 Category: Neurology Source Type: research
Exploring the Therapeutic Effects and Mechanisms of Transcranial Alternating Current Stimulation on Improving Walking Ability in Stroke Patients via Modulating Cerebellar Gamma Frequency Band —a Narrative Review
AbstractThe cerebellum plays an important role in maintaining balance, posture control, muscle tone, and lower limb coordination in healthy individuals and stroke patients. At the same time, the relationship between cerebellum and motor learning has been widely concerned in recent years. Due to the relatively intact structure preservation and high plasticity after supratentorial stroke, non-invasive neuromodulation targeting the cerebellum is increasingly used to treat abnormal gait in stroke patients. The gamma frequency of transcranial alternating current stimulation (tACS) is commonly used to improve motor learning. It ...
Source: The Cerebellum - November 14, 2023 Category: Neurology Source Type: research
Quantitative Gait and Balance Outcomes for Ataxia Trials: Consensus Recommendations by the Ataxia Global Initiative Working Group on Digital-Motor Biomarkers
AbstractWith disease-modifying drugs on the horizon for degenerative ataxias, ecologically valid, finely granulated, digital health measures are highly warranted to augment clinical and patient-reported outcome measures. Gait and balance disturbances most often present as the first signs of degenerative cerebellar ataxia and are the most reported disabling features in disease progression. Thus, digital gait and balance measures constitute promising and relevant performance outcomes for clinical trials.This narrative review with embedded consensus will describe evidence for the sensitivity of digital gait and balance measur...
Source: The Cerebellum - November 13, 2023 Category: Neurology Source Type: research
Diagnostic Yield of NGS Tests for Hereditary Ataxia: a Systematic Review
AbstractNext-generation sequencing (NGS), comprising targeted panels (TP), exome sequencing (ES), and genome sequencing (GS) became robust clinical tools for diagnosing hereditary ataxia (HA). Determining their diagnostic yield (DY) is crucial for optimal clinical decision-making. We conducted a comprehensive systematic literature review on the DY of NGS tests for HA. We searched PubMed and Embase databases for relevant studies between 2016 and 2022 and manually examined reference lists of relevant reviews. Eligible studies described the DY of NGS tests in patients with ataxia as a significant feature. Data from 33 eligibl...
Source: The Cerebellum - November 11, 2023 Category: Neurology Source Type: research
“Hot Cross Bun” Sign in a Patient with Glutamic Acid Decarboxylase 65-KDa Isoform Associated Cerebellar Ataxia: Case Report and Review of the Literature
AbstractThe “hot cross bun” sign (HCBs) is a cruciform hyperintensity on T2-weighted imaging within the pons initially found in patients diagnosed as multiple system atrophy. However, recent findings have broadened the disease spectrum presented with HCBs. Here is a case report at an academic medical center . Cerebral magnetic resonance imaging (MRI), electroneuromyography, serum, and CSF analysis were performed. Literature is comprehensively reviewed. We investigated a woman presented with blurred speech and cerebellar ataxia. Her MRI showed the vertical line of HCBs 2 weeks after disease onset and gr adually enhanced...
Source: The Cerebellum - November 10, 2023 Category: Neurology Source Type: research
The Neuroimmune System and the Cerebellum
This article is meant to provide a brief introduction to the cellular and molecular components of the brain immune system, its functions, and what is known about its role in the cerebellum. The majority of this information comes from studies of animal models and pathological conditions, where upregulation of the system facilitates investigation of its actions. (Source: The Cerebellum)
Source: The Cerebellum - November 10, 2023 Category: Neurology Source Type: research
Patient-Reported Outcome Measure of Ataxia Correlates with Canonical Clinical Assessments in Chinese Spinocerebellar Ataxias
AbstractSpinocerebellar ataxia (SCA) patients ’ reports of their own experiences are essential to the outcome evaluation in clinical trials. To better understand the health condition and well-being of ataxia population, Patient-Reported Outcome Measure of Ataxia (PROM-Ataxia) was developed. The aim of our study was to culturally adapt the PRO M-Ataxia into Chinese version and assess its correlation with canonical clinical assessments. We translated the PROM-Ataxia into Chinese following the ISPOR TCA Task Force guidelines and evaluated its correlation with measures of motor ataxia, non-ataxia signs, quality of life, and ...
Source: The Cerebellum - November 9, 2023 Category: Neurology Source Type: research
Relationship of Morphometrics and Symptom Severity in Female Type I Chiari Malformation Patients with Biological Resilience
AbstractIn the present study we report the relationship among MRI-based skull and cervical spine morphometric measures as well as symptom severity (disability —as measured by Oswestry Head and Neck Pain Scale and social isolation—as measured by the UCLA Loneliness scale) on biomarkers of allostatic load using estrogen, interleukin-6, C-reactive protein, and cortisol in a sample of 46 CMI patients. Correlational analyses showed that McRae line length w as negatively associated with interleukin-6 and C-reactive protein levels, and Analysis of Variance (ANOVA) showed joint effects of morphometric measures (McRae line leng...
Source: The Cerebellum - November 7, 2023 Category: Neurology Source Type: research
The Frequency of Intermediate Alleles in Patients with Cerebellar Phenotypes
Abstract Cerebellar syndromes are clinically and etiologically heterogeneous and can be classified as hereditary, neurodegenerative non-hereditary, or acquired. Few data are available on the frequency of each form in the clinical setting. Growing interest is emerging regarding the genetic forms caused by triplet repeat expansions. Alleles with repeat expansion lower than the pathological threshold, termed intermediate alleles (IAs), have been found to be associated with disease manifestation. In order to assess the relevance of IAs as a cause of cerebellar syndromes, we enrolled 66 unrelated Italian ataxic patients and...
Source: The Cerebellum - October 31, 2023 Category: Neurology Source Type: research
Quantitative Speech Assessment in Ataxia —Consensus Recommendations by the Ataxia Global Initiative Working Group on Digital-Motor Markers
AbstractDysarthria is a common and debilitating symptom of many neurodegenerative diseases, including those resulting in ataxia. Changes to speech lead to significant reductions in quality of life, impacting the speaker in most daily activities. Recognition of its importance as an objective outcome measure in clinical trials for ataxia is growing. Its viability as an endpoint across the disease spectrum (i.e. pre-symptomatic onwards) means that trials can recruit ambulant individuals and later-stage individuals who are often excluded because of difficulty completing lower limb tasks. Here we discuss the key considerations ...
Source: The Cerebellum - October 28, 2023 Category: Neurology Source Type: research
