Cortical thickness in ALS: towards a marker for upper motor neuron involvement

Area of Science:

• Neuroscience
• Neurology
• Medical Imaging

Background:

• Motor neuron diseases (MNDs) encompass a spectrum of conditions affecting motor neurons.
• Upper motor neuron (UMN) and lower motor neuron (LMN) involvement define distinct clinical phenotypes.
• Cortical changes, particularly thinning, are increasingly recognized in neurodegenerative disorders.

Purpose of the Study:

• To determine if cortical thinning is a disease-specific marker in motor neuron diseases.
• To investigate the relationship between cortical thickness and the degree of UMN involvement.
• To explore longitudinal changes in cortical thickness and potential involvement of non-motor regions.

Main Methods:

• Cross-sectional analysis of cortical thickness using 3T MRI in 153 patients with MNDs (ALS, UMN, LMN phenotypes), 60 controls, and 43 mimic disorder patients.
• Follow-up scans for 39 ALS patients to assess longitudinal changes.
• Correlation analysis between cortical thickness and clinical measures (bulbar and arm scores).

Main Results:

• Significant precentral gyrus (PCG) cortical thinning observed in amyotrophic lateral sclerosis (ALS) and UMN phenotype patients, but not in LMN phenotype or mimic disorders.
• PCG cortical thickness was even lower in UMN phenotype patients compared to ALS patients.
• Cortical thinning in specific motor homunculus regions correlated with bulbar and arm functional scores.
• Longitudinal analysis revealed progressive cortical thinning in the left temporal lobe (parahippocampal and fusiform regions) in ALS patients.

Conclusions:

• Cortical thinning of the PCG is a specific indicator of motor neuron disease with UMN involvement.
• Normal cortical thickness in mimic disorders and LMN phenotypes supports UMN pathology as the driver of thinning.
• Progressive temporal lobe thinning in ALS suggests the involvement of non-motor areas over time, indicating disease progression.