Increasing involvement of CAPN1 variants in spastic ataxias and phenotype-genotype correlations

We report the largest published series of 21 novel patients with nine newCAPN1 disease-causing variants and their clinical characteristics from two European university hospitals (Paris and Stockholm). After a formal clinical examination, causative variants were identified by next-generation sequencing and confirmed by Sanger sequencing.CAPN1 variants are a rare cause (~ 1.4%) of young-adult-onset spastic ataxia; however, together with all published cases, they allowed us to better describe the clinical and genetic spectra of this form. Truncating variants are the most frequent, and missense variants lead to earlier age at onset in favor of an additional deleterious effect. Cerebellar ataxia with cerebellar atrophy, dysarthria and lower limb weakness are often associated with spasticity. We also suggest that cognitive impairment and depression should be assessed specifically in the follow-up of SPG76 cases.
Source: Neurogenetics - Category: Genetics & Stem Cells Source Type: research

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AbstractWhile rehabilitation therapies always help patients with ataxia, there are currently no FDA-approved treatments for ataxia. Medications are available to treat symptoms that may complicate an ataxic illness, e.g., tremor, myoclonus, dystonia, and rigidity, which are discussed elsewhere in this volume. Spasticity, pain, fatigue, depression, sleep disturbances, cognitive decline, and bowel and bladder dysfunction, if they occur, all have multiple available drugs and therapies for symptomatic use. There is also an extensive literature on off-label uses of various medications to improve imbalance. The pipeline of emergi...
Source: Neurotherapeutics - Category: Neurology Source Type: research
Publication date: Available online 2 October 2020Source: Biochimica et Biophysica Acta (BBA) - Molecular Basis of DiseaseAuthor(s): Miaozhen Huang, Tom J. de Koning, Marina A.J. Tijssen, Dineke S. Verbeek
Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease - Category: Molecular Biology Source Type: research
Abstract While cerebellar ataxia (CA) is a neurodegenerative disease known for motor impairment, changes in mood have also been reported. A full account of neuropsychiatric symptomology in CA may guide improvements in treatment regimes, measure the presence and severity of sub-clinical neuropsychiatric disturbance symptomology in CA, and compare patient versus informant symptom recognition. Neuropsychiatric phenomena were gathered from CA patients with genetic and unknown etiologies and their informants (e.g., spouse or parent). Information was obtained from in-person interviews and the Center for Epidemiologic St...
Source: Cerebellum - Category: Neuroscience Authors: Tags: Cerebellum Source Type: research
AbstractWhile cerebellar ataxia (CA) is a neurodegenerative disease known for motor impairment, changes in mood have also been reported. A full account of neuropsychiatric symptomology in CA may guide improvements in treatment regimes, measure the presence and severity of sub-clinical neuropsychiatric disturbance symptomology in CA, and compare patient versus informant symptom recognition. Neuropsychiatric phenomena were gathered from CA patients with genetic and unknown etiologies and their informants (e.g., spouse or parent). Information was obtained from in-person interviews and the Center for Epidemiologic Studies Depr...
Source: The Cerebellum - Category: Neurology Source Type: research
We report the case of a 67-year-old male who presented with a six-week history of progressive unsteadiness, cognitive impairment and weight loss, in the context of a recent bereavement. Magnetic resonance imaging (MRI) performed several weeks earlier excluded acute stroke. Examination revealed gross bilateral ataxia, bradyphrenia and physical manifestations of depression. Collateral history suggested rapidly progressing symptoms over three months. Repeat MRI head showed features suggestive of Creutzfeldt-Jakob disease (CJD) including T2 hyperintensities in the basal ganglia. Cerebrospinal ˜fluid (CSF) samples were po...
Source: Journal of the Royal College of Physicians of Edinburgh - Category: General Medicine Tags: J R Coll Physicians Edinb Source Type: research
CONCLUSIONS: Vigabatrin may significantly reduce seizure frequency in people with drug-resistant focal epilepsy. The results largely apply to adults and should not be extrapolated to children under 10 years old. Short-term follow-up of participants showed that some adverse effects were associated with its use. Analysis of longer-term observational studies elsewhere, however, has demonstrated that vigabatrin use can lead to the development of visual field defects. PMID: 32730657 [PubMed - in process]
Source: Cochrane Database of Systematic Reviews - Category: General Medicine Authors: Tags: Cochrane Database Syst Rev Source Type: research
The present outbreak caused by SARS-CoV-2, an influenza virus with neurotropic potential, presents with neurological manifestations in a large proportion of the affected individuals. Disorders of the central and peripheral nervous system are all present, while stroke, ataxia, seizures, and depressed level of consciousness are more common in severely affected patients. People with these severe complications are most likely elderly with medical comorbidities, especially hypertension and other vascular risk factors. However, postinfectious complications are also expected. Neurological disorders as sequelae of influenza viruse...
Source: Neuroepidemiology - Category: Epidemiology Source Type: research
In case you were ever stupid enough to follow Trump’s lead you would have already injected ultraviolets in your eyeballs by now to save you from Covid and maybe bathed in Domestos or sulfuric acid or both! Anyway, his latest bullshine claim is that he’s been taking the antimalarial drug hydroxychloroquine to keep Covid at bay. Well, for starters there is no evidence that this drug acts as a prophylactic against infection with SARS CoV-2 or indeed any pathogen other than the causative agent of otherwise drug-resistant malaria. It’s primary use is in treating lupus. There was some testing done weeks ago to...
Source: David Bradley Sciencebase - Songs, Snaps, Science - Category: Science Authors: Tags: Health and Medicine Source Type: blogs
AbstractSCA36 is an autosomal dominant spinocerebellar ataxia (SCA) affecting many families from Costa da Morte, a northwestern region of Spain. It is caused by an intronic GGCCTG repeat expansion inNOP56. In order to characterize the cognitive and affective manifestations of this cerebellar disease, a group of 30 SCA36 mutation carriers (11 preataxic and 19 ataxic patients) were assessed with a comprehensive battery of standardized tests. Phonological verbal fluency – but not semantic fluency – was already mildly impaired in preataxic subjects. In ataxic patients, both phonological and semantic fluencies were ...
Source: The Cerebellum - Category: Neurology Source Type: research
rnández-Prieto M Abstract SCA36 is an autosomal dominant spinocerebellar ataxia (SCA) affecting many families from Costa da Morte, a northwestern region of Spain. It is caused by an intronic GGCCTG repeat expansion in NOP56. In order to characterize the cognitive and affective manifestations of this cerebellar disease, a group of 30 SCA36 mutation carriers (11 preataxic and 19 ataxic patients) were assessed with a comprehensive battery of standardized tests. Phonological verbal fluency - but not semantic fluency - was already mildly impaired in preataxic subjects. In ataxic patients, both phonological and s...
Source: Cerebellum - Category: Neuroscience Authors: Tags: Cerebellum Source Type: research
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