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Treatment and Management of Autosomal Recessive Cerebellar Ataxias: Current Advances and Future Perspectives

2022· review· en· W4224250926 on OpenAlexaff
Nicolas Dupré, Ikhlass Haj Salem, Marie Beaudin, Christopher J. Klein

Bibliographic record

VenueCNS & Neurological Disorders - Drug Targets · 2022
Typereview
Languageen
FieldNeuroscience
TopicGenetic Neurodegenerative Diseases
Canadian institutionsUniversité LavalCentre hospitalier universitaire de Québec
Fundersnot available
KeywordsMedicineDysmetriaDiseaseDysarthriaQuality of life (healthcare)Cerebellar ataxiaNeuroscienceAtaxiaBioinformaticsPathologyPsychologyBiologyAudiologyPsychiatry

Abstract

fetched live from OpenAlex

The autosomal recessive cerebellar ataxias (ARCAs) compose a clinically and genetically heterogeneous group of neurodegenerative diseases characterized by prominent cerebellar ataxia, dysmetria, dysarthria, and nystagmus that are inherited in an autosomal recessive fashion. The diagnosis of ARCAs is challenging because of their low prevalence, poor medical recognition, and heterogeneous clinical presentation with many overlapping features between entities. There currently exist no disease-modifying therapies for most ARCAs, and treatment is mainly symptomatic, aimed at prolonging independence and maintaining the quality of life. As knowledge of the common pathogenic pathways underlying several ARCAs grows, so do these pathways to target with new drugs. Chelation or enzyme replacement therapies are available for some specific ataxias caused by amenable metabolic alterations. A large number of drug trials are ongoing and aim to identify new therapeutic approaches to expand the options in our repertoire. Improved protocols of motor rehabilitation and noninvasive cerebellar stimulation have been shown to delay disease progression and maintain quality of life. Furthermore, recent progress in gene and molecular targeting therapies is rapidly expanding and holds promise for repairing defective genes. Neurotransplantation of grafted stem cells, which is still at the experimental preclinical stage, has opened new therapeutic strategies aimed at delaying cell degeneration and facilitating compensatory functions. This article is an overview of the current management and treatment strategies with an emphasis on promising perspectives for patients with ARCAs.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame machine prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.

metaresearch head score (Codex)0.001
metaresearch head score (Gemma)0.001
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Not applicable · Consensus signal: none
GenreCandidate signal: Review · Consensus signal: Review
Teacher disagreement score0.003
Threshold uncertainty score0.009

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0010.001
Meta-epidemiology (narrow)0.0010.000
Meta-epidemiology (broad)0.0010.001
Bibliometrics0.0020.001
Science and technology studies0.0000.000
Scholarly communication0.0010.001
Open science0.0010.001
Research integrity0.0010.002
Insufficient payload (model declined to judge)0.0030.001

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.033
GPT teacher head0.313
Teacher spread0.280 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designNot applicable
Domainnot available
GenreReview

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

Quick stats

Citations2
Published2022
Admission routes1
Has abstractyes

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Same venueCNS & Neurological Disorders - Drug TargetsSame topicGenetic Neurodegenerative DiseasesFrench-language works237,207