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Record W3157327845 · doi:10.1002/mds.28610

Regional Brain and Spinal Cord Volume Loss in Spinocerebellar Ataxia Type 3

2021· article· en· W3157327845 on OpenAlexaff
Jennifer Faber, Tamara Schaprian, Koyak Berkan, Kathrin Reetz, Marcondes C. França, Thiago Junqueira Ribeiro de Rezende, Hong Jiang, Weihua Liao, Bart P.C. van de Warrenburg, Judith van Gaalen, Alexandra Dürr, Fanny Mochel, Paola Giunti, Héctor García‐Moreno, Ludger Schoels, Holger Hengel, Matthis Synofzik, Benjamin Bender, Gülin Öz, James M. Joers, J.J. de Vries, Jun‐Suk Kang, Dagmar Timmann‐Braun, Heike Jacobi, Jon Infante, Richard Joules, Sandro Romanzetti, Jörn Diedrichsen, Matthias Schmid, Robin Wolz, Thomas Klockgether

Bibliographic record

VenueMovement Disorders · 2021
Typearticle
Languageen
FieldNeuroscience
TopicGenetic Neurodegenerative Diseases
Canadian institutionsWestern University
FundersIXICOBundesministerium für GesundheitNational Institute of Neurological Disorders and StrokeBundesministerium für Bildung und ForschungRadboud UniversiteitZonMwAgence Nationale de la RechercheNational Institute of Biomedical Imaging and BioengineeringE-RareEU Joint Programme – Neurodegenerative Disease ResearchMedical Research CouncilAveXisBiogenEuropean CommissionPfizerDeutsche ForschungsgemeinschaftRobert Bosch StiftungHersenstichtingEberhard Karls Universität TübingenAlzheimer Forschung InitiativeNational Institutes of HealthNational Ataxia Foundation
KeywordsSpinocerebellar ataxiaPonsSpinal cordAtaxiaCerebellumMedulla oblongataMedicineMachado–Joseph diseasePathologyNeuroscienceAnatomyPsychologyCentral nervous system

Abstract

fetched live from OpenAlex

BACKGROUND: Given that new therapeutic options for spinocerebellar ataxias are on the horizon, there is a need for markers that reflect disease-related alterations, in particular, in the preataxic stage, in which clinical scales are lacking sensitivity. OBJECTIVE: The objective of this study was to quantify regional brain volumes and upper cervical spinal cord areas in spinocerebellar ataxia type 3 in vivo across the entire time course of the disease. METHODS: We applied a brain segmentation approach that included a lobular subsegmentation of the cerebellum to magnetic resonance images of 210 ataxic and 48 preataxic spinocerebellar ataxia type 3 mutation carriers and 63 healthy controls. In addition, cervical cord cross-sectional areas were determined at 2 levels. RESULTS: The metrics of cervical spinal cord segments C3 and C2, medulla oblongata, pons, and pallidum, and the cerebellar anterior lobe were reduced in preataxic mutation carriers compared with controls. Those of cervical spinal cord segments C2 and C3, medulla oblongata, pons, midbrain, cerebellar lobules crus II and X, cerebellar white matter, and pallidum were reduced in ataxic compared with nonataxic carriers. Of all metrics studied, pontine volume showed the steepest decline across the disease course. It covaried with ataxia severity, CAG repeat length, and age. The multivariate model derived from this analysis explained 46.33% of the variance of pontine volume. CONCLUSION: Regional brain and spinal cord tissue loss in spinocerebellar ataxia type 3 starts before ataxia onset. Pontine volume appears to be the most promising imaging biomarker candidate for interventional trials that aim at slowing the progression of spinocerebellar ataxia type 3. © 2021 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

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 distilled prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.000
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Observational · Consensus signal: none
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.304
Threshold uncertainty score0.715

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0000.000

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 head0.029
GPT teacher head0.280
Teacher spread0.251 · 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 teacher head, not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designObservational
Domainnot available
GenreEmpirical

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

Citations59
Published2021
Admission routes1
Has abstractyes

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