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Clinically meaningful MR endpoints sensitive to preataxic SCA1 and SCA3
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4 2023
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Source: Ann Neurol. 93(4):686-701
[PDF-2.60 MB]
Details:
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Alternative Title:Ann Neurol
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Personal Author:
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Description:Objective:
To identify MR metrics that are most sensitive to early changes in the brain in spinocerebellar ataxia type 1 (SCA1) and type 3 (SCA3) using an advanced multi-modal MRI protocol in the multi-site trial setting.
Methods:
SCA1 or SCA3 mutation carriers and controls (n=107) underwent MR scanning in the US-European READISCA study to obtain structural, diffusion MRI and MR spectroscopy data using an advanced protocol at 3T. Morphometric, microstructural, and neurochemical metrics were analyzed blinded to diagnosis and compared between preataxic (n=11 SCA1, 28 SCA3), ataxic (n=14 SCA1, 37 SCA3) SCA and control (n=17) groups using non-parametric testing accounting for multiple comparisons. MR metrics that were most sensitive to preataxic abnormalities were identified using receiver operating characteristic (ROC) analyses.
Results:
Atrophy and microstructural damage in the brainstem and cerebellar peduncles and neurochemical abnormalities in the pons were prominent in both preataxic groups, when patients did not differ from controls clinically. MR metrics were strongly associated with ataxia symptoms, activities of daily living and estimated ataxia duration. A neurochemical measure was the most sensitive metric to preataxic changes in SCA1 (ROC area under the curve (AUC) =0.95) and a microstructural metric was the most sensitive metric to preataxic changes in SCA3 (AUC =0.92).
Interpretation:
Changes in cerebellar afferent and efferent pathways underlie the earliest symptoms of both SCAs. MR metrics collected with a harmonized advanced protocol in the multi-site trial setting allow detecting disease effects in individuals before ataxia onset with potential clinical trial utility for subject stratification.
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Source:
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Pubmed ID:36511514
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Pubmed Central ID:PMC10261544
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Funding:
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Volume:93
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Issue:4
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