Progressive White Matter Changes in Mitochondrial Disease: A Quantitative MRI Study

Area of Science:

• Neurology
• Neuroimaging
• Mitochondrial Diseases

Background:

• Primary mitochondrial diseases often impact the central nervous system.
• White matter hyperintensities (WMHs) in mitochondrial disorders are not well understood, especially regarding quantitative progression.
• Mitochondrial disorders may cause white matter injury via unique vascular and metabolic pathways, distinct from small-vessel disease.

Purpose of the Study:

• To characterize the extent, distribution, and longitudinal progression of white matter hyperintensities (WMHs) in patients with primary mitochondrial diseases.
• To quantitatively assess WMH volumes and lesion progression using advanced neuroimaging analysis.
• To explore potential differences in WMH burden based on sex, specific mitochondrial DNA variants (m.3243A>G), and clinical history.

Main Methods:

• Retrospective single-centre study of 36 patients with mitochondrial disease, including 15 with longitudinal MRI data.
• Analysis of 3D T1-weighted and FLAIR brain MRI scans (1.5/3T) using the cNeuro tool for automated WMH and lesion volumetrics and Fazekas scoring.
• Intracranial volume normalization was applied to WMH and lesion volumes.

Main Results:

• WMHs were prevalent across all supratentorial regions at baseline in patients with mitochondrial disease.
• Significant increases in WMH volumes were observed over time in periventricular, deep, and juxtacortical areas.
• Patients with the m.3243A>G variant and women showed a greater WMH and lesion burden compared to others.

Conclusions:

• Mitochondrial disease is linked to early and progressive accumulation of white matter hyperintensities.
• The m.3243A>G variant is associated with a more significant WMH burden, suggesting a disease-specific vulnerability.
• Quantitative MRI is essential for monitoring white matter changes and disease progression in mitochondrial disorders.