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Record W4415001715 · doi:10.1007/s00415-025-13422-4

Clinical characteristics, cerebellar MR spectroscopy and response to 3,4-diaminopyridine in spinocerebellar ataxia 27B: the Sheffield Ataxia Centre experience

2025· article· en· W4415001715 on OpenAlexaff
Ikechukwu Chukwuocha, David Pellerin, Priya Shanmugarajah, Theocharis Tsironis, Emma Foster, Nigel Hoggard, Nick Beauchamp, Lauren Turton, Alisdair McNeill, Bernard Brais, Marios Hadjivassiliou

Bibliographic record

VenueJournal of Neurology · 2025
Typearticle
Languageen
FieldNeuroscience
TopicGenetic Neurodegenerative Diseases
Canadian institutionsMcGill UniversityMontreal Neurological Institute and Hospital
FundersNational Institute for Health and Care Research
KeywordsSpinocerebellar ataxiaNeurologyNeuroradiologyNeuroimagingAtaxiaIn vivo magnetic resonance spectroscopyCentral nervous system disease

Abstract

fetched live from OpenAlex

BACKGROUND: The clinical and genetic heterogeneity of hereditary ataxias presents a significant diagnostic challenge, particularly in sporadic adult-onset cases. Spinocerebellar ataxia type 27B (SCA27B) is caused by an intronic GAA·TTC repeat expansion in the fibroblast growth factor 14 (FGF14) gene and is inherited in an autosomal dominant manner, although with reduced penetrance. This novel ataxia is emerging as a frequent yet underdiagnosed cause of late-onset often sporadic cerebellar ataxia. METHOD: In this study, we describe our experience in clinical presentation, neuroimaging characteristics (including MR spectroscopy of the cerebellum), tremor analysis, and therapeutic response to 3,4-diaminopyridine in a cohort of 50 patients with SCA27B. RESULTS: The mean age at onset was 61.8 years. Episodic symptoms were reported in 28% of cases, while downbeat nystagmus and oscillopsia were observed in 50% and 28% individuals, respectively. Tremor was also present in 22% of patients. Tremor analysis demonstrated bilateral, intermediate-frequency (~ 6 Hz) tremor with both action and resting components, occasionally involving, apart from arms, the lower limbs and head. MRI findings revealed involvement of the superior cerebellar peduncle, and MR spectroscopy of the cerebellum (MRS) demonstrated a progressive decline in NAA/Cr area ratios in the cerebellar hemisphere over time. Notably, treatment with 3,4-diaminopyridine was associated with subjective symptom improvement in most patients and objective stabilization and/or improvement on MRS. CONCLUSION: Our findings expand the clinical, neuroimaging and tremor phenotype of SCA27B and support the use of 3,4-diaminopyridine as a potentially effective therapy.

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)0.001
metaresearch head score (Gemma)0.007
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Bench or experimental · Consensus signal: none
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.433
Threshold uncertainty score0.788

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0010.007
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0010.000
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0010.000
Research integrity0.0000.001
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 head0.025
GPT teacher head0.327
Teacher spread0.302 · 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 designBench or experimental
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

Citations4
Published2025
Admission routes1
Has abstractyes

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