White matter alterations differ in primary lateral sclerosis and amyotrophic lateral sclerosis

Area of Science:

• Neuroscience
• Neurology
• Radiology

Background:

• Primary lateral sclerosis (PLS) is a rare motor neuron disorder with progressive corticospinal dysfunction.
• PLS is distinct from amyotrophic lateral sclerosis (ALS) due to the absence of lower motor neuron signs and longer survival.
• The precise relationship and pathological differences between PLS and ALS remain unclear.

Purpose of the Study:

• To investigate in vivo structural differences in white matter tracts between PLS and ALS using diffusion tensor imaging (DTI).
• To compare white matter integrity in the corticospinal tract and corpus callosum between PLS patients, ALS patients, and healthy controls.

Main Methods:

• Diffusion tensor imaging (DTI) and fiber tracking were performed on 19 PLS patients, 18 ALS patients, and 19 age-matched controls.
• Analysis focused on the corticospinal tract and specific regions of the corpus callosum (genu, splenium, motor cortex connections).
• Tract-based spatial statistics (TBSS) were used for voxelwise comparison of white matter diffusion properties across the whole brain.

Main Results:

• Both PLS and ALS groups exhibited reduced fractional anisotropy (FA) and increased mean diffusivity (MD) in corticospinal and callosal motor fibers compared to controls.
• ALS patients showed maximal FA reduction in distal corticospinal tracts, indicative of axonal degeneration.
• PLS patients displayed maximal FA reduction and MD increase in subcortical white matter beneath the motor cortex, suggesting tissue loss.
• Clinical upper motor neuron dysfunction correlated with DTI measures in both patient groups.
• Corpus callosum diffusion changes correlated with corticospinal tract changes in patients, but not controls.

Conclusions:

• DTI reveals distinct white matter degeneration patterns in PLS (subcortical tissue loss) and ALS (distal axonal degeneration).
• Degeneration in these motor neuron disorders affects both corticospinal and callosal motor neurons.
• Findings suggest shared and distinct pathological mechanisms underlying PLS and ALS.