Structural disconnection and functional reorganization in Fabry disease: a multimodal MRI study

Area of Science:

• Neuroscience
• Radiology
• Genetics

Background:

• Fabry disease is a rare X-linked lysosomal storage disorder with known central nervous system involvement.
• Previous research identified functional and microstructural brain changes, but macro-scale connectivity alterations remain understudied.

Purpose of the Study:

• To investigate macro-scale structural and functional brain connectivity changes in Fabry disease using connectomic analysis.
• To explore the relationship between these connectivity changes and clinical correlates, including cognitive performance.

Main Methods:

• Retrospective cross-sectional study including 46 Fabry disease patients and 49 healthy controls.
• Diffusion and resting-state functional MRI were used to create quantitative structural and functional connectomes.
• Graph theory measures and network-based statistics were applied to analyze global and subnetwork differences.

Main Results:

• Patients with Fabry disease showed reduced global efficiency and mean strength in structural connectomes.
• Increased modularity was observed in functional networks of Fabry disease patients.
• A subnetwork with decreased structural connectivity, primarily in frontal and deep grey matter areas, was identified in patients.
• Structural and functional disruptions correlated with verbal/working memory and executive functioning deficits, respectively.

Conclusions:

• Fabry disease is associated with widespread structural brain disconnection and functional reorganization.
• These alterations are linked to axonal integrity loss and impact cognitive performance.
• Functional changes may play a compensatory role in mitigating cognitive deficits.