Temporal and spatial progression of microstructural cerebral degeneration in ALS: A multicentre longitudinal...

Area of Science:

• Neuroimaging
• Neurology
• Biomarker Discovery

Background:

• Amyotrophic lateral sclerosis (ALS) is characterized by progressive neurodegeneration.
• The corticospinal tract (CST) is significantly affected in ALS.
• Diffusion tensor imaging (DTI) can detect microstructural alterations in white matter.

Purpose of the Study:

• To evaluate fractional anisotropy (FA) along the CST as a longitudinal marker of disease progression in ALS.
• To assess microstructural changes in the CST using DTI in ALS patients.
• To establish DTI as a biomarker for cerebral degeneration in ALS.

Main Methods:

• A longitudinal, multicentre study (CALSNIC-2) involving 114 ALS patients and 110 healthy controls.
• Collection of DTI and clinical data using a harmonized protocol across 7 centers.
• Analysis using whole brain-based spatial statistics and tract-of-interest approaches for cross-sectional and longitudinal assessments.

Main Results:

• Reduced FA was observed longitudinally in the CST and mid-corpus callosum (CC) in ALS patients.
• CST and pontine FA correlated with functional impairment (ALSFRS-R) and disease progression rate.
• Longitudinal decline in FA was most pronounced in the lower CST, while cross-sectional changes were maximal in the upper CST.

Conclusions:

• Progressive microstructural alterations in ALS are most prominent in the CST and CC.
• DTI provides a feasible biomarker for cerebral degeneration in ALS.
• Longitudinal white matter changes in ALS are demonstrable within a practical observation period and participant number.