Neuroimaging in amyotrophic lateral sclerosis: insights into structural and functional changes

Area of Science:

• Neuroscience
• Neurology
• Medical Imaging

Background:

• Longstanding views on amyotrophic lateral sclerosis (ALS) pathophysiology are challenged by recent neuroimaging findings.
• Structural and functional neuroimaging demonstrate lesions extend beyond the motor cortex and corticospinal tracts.

Purpose of the Study:

• To review and synthesize neuroimaging findings in ALS pathophysiology.
• To highlight the extended network of brain regions affected in ALS.
• To identify limitations in current neuroimaging studies and propose future directions.

Main Methods:

• Review of structural and functional neuroimaging studies (MRI, PET) over the past two decades.
• Analysis of lesion distribution and involvement of various brain structures.
• Assessment of cellular changes like interneuron loss and gliosis.

Main Results:

• Neuroimaging reveals widespread anatomical and functional lesions in ALS, including the corpus callosum, frontal, sensory, and premotor cortices, thalamus, and midbrain.
• Early and diffuse loss of inhibitory cortical interneurons and gliosis in white-matter tracts are observed.
• ALS endophenotypes show diverse lesion patterns and varying impairments in functional and structural connectivity.

Conclusions:

• Neuroimaging has significantly advanced our understanding of ALS pathophysiology, revealing a more complex and widespread disease process.
• Positron Emission Tomography (PET) may play a role in ALS diagnosis.
• Future research requires large, well-characterized patient cohorts with standardized assessments and international collaboration to overcome current study limitations and elucidate ALS pathogenesis.