Microstructural Brain Alterations in Amyotrophic Lateral Sclerosis Patients

Researchers at the Second University of Naples and the University of Parma in Italy recently characterized the microstructural brain alterations in patients with amyotrophic lateral sclerosis (ALS) during disease progression. The findings were published in the journal PLoS ONE and the study is entitled “Microstructural Changes Across Different Clinical Milestones of Disease in Amyotrophic Lateral Sclerosis.”

ALS is a progressive neurodegenerative disease characterized by the gradual degeneration and atrophy of motor neurons in the brain and spinal cord that are responsible for controlling voluntary muscles such as the ones related to movement, speaking, eating, and even breathing. ALS patients may become totally paralyzed and the majority die due to respiratory failure. There is currently no cure for the disease.

The ALS neurodegenerative process is thought to involve several regions of the brain within and beyond motor areas, although it is not clear how ALS pathology spreads throughout the central nervous system, and what is the extent of the involvement of the brain’s gray and white matter in disease progression.

In this study, 54 ALS patients and 18 healthy controls were assessed for their pattern of diffusion tensor imaging (DTI), a technique to characterize the effects of the disease on microstructures, and brain voxel-based morphometry (VBM), a technique that allows a fully automated whole-brain measurement in terms of regional brain atrophy and cortical thickness. Patients were divided into three groups depending on their ALS clinical stage. The goal was to identify structural patterns that differed between each clinical stage.

Researchers found a sequential spreading of white matter pathology from motor areas to extra-motor areas during ALS progression. On the other hand, gray matter damage was mainly found in both frontal and temporal lobes in less advanced stages of disease; no significant damage was detected in advanced stages. Researchers emphasized that in the earliest clinical stages of the disease, widespread alterations in both white and gray matter were observed that involved several extra-motor frontotemporal regions, results that are in line with the frontotemporal degeneration that has been previously reported in ALS patients.

This study provided for the first time in vivo evidence of a sequential pattern of microstructural damage during ALS progression, from diagnosis to more advanced stages.

The research team concluded that the ALS neurodegenerative process gradually disseminates in a sequential manner along the axonal pathways, developing from motor towards extra-motor areas during disease progression. The biochemical mechanisms underlying the dissemination of the neurodegenerative process are, however, still not clear and require further studies.