Unbiased MRI Analyses Identify Micropathologic Differences Between Upper Motor Neuron-Predominant ALS Phenotypes.

Area of Science:

• Neuroimaging
• Neurology
• Neurodegenerative Diseases

Background:

• Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease with varied clinical presentations.
• Specific MRI findings, like T2/PD-weighted hyperintensity along the corticospinal tract (CST), are observed in some ALS patients with upper motor neuron (UMN) signs.
• These patients often exhibit younger age and accelerated disease progression.

Purpose of the Study:

• To investigate whether ALS patients with CST hyperintensity (ALS-CST+) constitute a distinct clinical subtype.
• To differentiate ALS-CST+ from other ALS subtypes, including UMN-predominant ALS without CST hyperintensity, classic ALS, and ALS with frontotemporal dementia (FTD).

Main Methods:

• Utilizing conventional MRI (cMRI) with T2-, PD-, and FLAIR-weighted sequences for initial identification of CST hyperintensity.
• Employing advanced MR techniques, including diffusion tensor imaging (DTI).
• Applying fractal dimension analysis on cMRI data.

Main Results:

• Neuroimaging analyses, including fractal dimension and DTI, revealed significant differences between the ALS-CST+ group and other ALS subtypes.
• The ALS-CST+ group is distinguishable from other ALS subtypes based on these neuroimaging findings.

Conclusions:

• ALS patients with CST hyperintensity represent a distinct clinical subtype.
• This subtype can be identified using conventional MRI techniques.
• Potential differences in disease pathogenesis may exist within the ALS-CST+ group.