Related Experiment Video
Updated: Jul 30, 2025
Comprehensive Autopsy Program for Individuals with Multiple Sclerosis
Published on: July 19, 2019
The longitudinal progression of MRI changes in pre-ataxic carriers of SCA3/MJD
Camila Maria de Oliveira1,2, Vanessa Bielefeldt Leotti3,4, Sandra Polita5
1Programa de Pós-Graduação em Ciências Médicas, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil.
Background:
The natural history of magnetic resonance imaging (MRI) in pre-ataxic stages of spinocerebellar ataxia type 3/Machado-Joseph disease (SCA3/MJD) is not well known. We report cross-sectional and longitudinal data obtained at this stage.
Methods:
Baseline (follow-up) observations included 32 (17) pre-ataxic carriers (SARA < 3) and 20 (12) related controls. The mutation length was used to estimate the time to onset (TimeTo) of gait ataxia. Clinical scales and MRIs were performed at baseline and after a median (IQR) of 30 (7) months. Cerebellar volumetries (ACAPULCO), deep gray-matter (T1-Multiatlas), cortical thickness (FreeSurfer), cervical spinal cord area (SCT) and white matter (DTI-Multiatlas) were assessed. Baseline differences between groups were described; variables that presented a p < 0.1 after Bonferroni correction were assessed longitudinally, using TimeTo and study time. For TimeTo strategy, corrections for age, sex and intracranial volume were done with Z-score progression. A significance level of 5% was adopted.
Results:
SCT at C1 level distinguished pre-ataxic carriers from controls. DTI measures of the right inferior cerebellar peduncle (ICP), bilateral middle cerebellar peduncles (MCP) and bilateral medial lemniscus (ML), also distinguished pre-ataxic carriers from controls, and progressed over TimeTo, with effect sizes varying from 0.11 to 0.20, larger than those of the clinical scales. No MRI variable showed progression over study time.
Discussion:
DTI parameters of the right ICP, left MCP and right ML were the best biomarkers for the pre-ataxic stage of SCA3/MJD. TimeTo is an interesting timescale, since it captured the longitudinal worsening of these structures.
Insights
Diffusion tensor imaging (DTI) of the brain shows early changes in spinocerebellar ataxia type 3/Machado-Joseph disease (SCA3/MJD). These DTI parameters are better biomarkers than clinical scales for detecting pre-ataxic stages.
Area of Science:
- Neuroimaging
- Neurology
- Genetics
Background:
- The natural history of spinocerebellar ataxia type 3/Machado-Joseph disease (SCA3/MJD) in its pre-ataxic stages is not well understood.
- This study investigates cross-sectional and longitudinal magnetic resonance imaging (MRI) data in pre-ataxic SCA3/MJD carriers.
Purpose of the Study:
- To identify reliable MRI biomarkers for the early detection of SCA3/MJD.
- To understand the progression of neuroimaging markers in relation to the estimated time to ataxia onset.
Main Methods:
- Cross-sectional and longitudinal MRI scans were performed on 32 pre-ataxic SCA3/MJD carriers and 20 controls.
- Cerebellar volumetry, deep gray matter, cortical thickness, cervical spinal cord area (SCT), and white matter integrity (DTI) were assessed.
- Diffusion tensor imaging (DTI) parameters were analyzed in relation to mutation length and estimated time to ataxia onset (TimeTo).
Main Results:
- Cervical spinal cord area (SCT) at C1 level differentiated carriers from controls.
- Diffusion tensor imaging (DTI) measures of the right inferior cerebellar peduncle (ICP), bilateral middle cerebellar peduncles (MCP), and bilateral medial lemniscus (ML) distinguished pre-ataxic carriers from controls.
- These DTI measures showed progression over the estimated time to ataxia onset (TimeTo), with larger effect sizes than clinical scales.
Conclusions:
- Diffusion tensor imaging (DTI) parameters of the right ICP, left MCP, and right ML are sensitive biomarkers for the pre-ataxic stage of SCA3/MJD.
- The estimated time to ataxia onset (TimeTo) is a valuable timescale for capturing longitudinal changes in these neuroimaging structures.
More Related Videos
09:06Whole-brain Segmentation and Change-point Analysis of Anatomical Brain MRI—Application in Premanifest Huntington's Disease
Published on: June 9, 2018
11:50A Standardized Pipeline for Examining Human Cerebellar Grey Matter Morphometry using Structural Magnetic Resonance Imaging
Published on: February 4, 2022