Specific Gray Matter Regions are More Susceptible to ALS Pathology

A new study on amyotrophic lateral sclerosis (ALS) provided evidence that certain areas of gray matter (GM) are disproportionately and asymmetrically vulnerable to the pathology of ALS. The study entitled “Exposing asymmetric gray matter vulnerability in amyotrophic lateral sclerosis” was published on the NeuroImage: Clinical by Dr. Matthew S. Devine from the Department of Neurology at Royal Brisbane and Women’s Hospital, and School of Medicine at The University of Queensland in Australia, along with colleagues.

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative condition affecting upper and lower motor neurons. Understanding the pathophysiology of ALS is difficult due to considerable variability of clinical, phenotype, patient characteristics and disease progression. Despite this variability, limb weakness in amyotrophic lateral sclerosis (ALS) is a common pattern observed across a wide range of ALS individuals and is typically asymmetric. However, the factors determining the side of onset and direction of spread remain unclear.

The research team used voxel-based morphometry (VBM) to explore gray matter (GM) asymmetry in ALS, in the context of limb dominance. Previous studies have shown vulnerability of the dominant upper limb in ALS using history and clinical examination. The voxel-based morphometry is a neuroimaging technique that enables the evaluation  of local differences in brain anatomy. They analyzed 30 ALS patients matched with 17 healthy controls. All the participants were right-handed. Every patient performed a structural MRI sequence, from which 25 GM segmentations were generated.

The study provided neuroimaging evidence to support these previous observations and suggested an important role for central factors in driving this effect. Moreover, there was the confirmation that there is no preferential involvement of either lower limb, which has already been observed clinically. Current data suggests that the increased complexity of left hemispheric motor networks in right-handers may contribute to greater susceptibility to ALS. The cause of neuronal vulnerability in ALS remains unidentified however possible factors include cellular density, excitability, and hormones.

They found that individuals with dominant limb onset of weakness also showed disproportionate atrophy of areas involved in language and communication. However, formal neuropsychological testing was not performed.

The study has some limitations, mainly that the cohort was restricted to right-handers without assessing these features in left-handed or ambidextrous individuals.

Overall, this study provided evidence that specific areas of gray matter are disproportionately and asymmetrically more susceptible to the pathology of ALS and can be identified using a sensitive VBM method. These findings justify future research on the evaluation of white matter asymmetry in ALS.