Combining structural brain imaging with molecular and clinical biomarkers allows for a detailed assessment of a patient’s clinical state, regardless of age and amyotrophic lateral sclerosis progression, a new study suggests.
The study, “Combinatory Biomarker Use of Cortical Thickness, MUNIX, and ALSFRS-R at Baseline and in Longitudinal Courses of Individual Patients With Amyotrophic Lateral Sclerosis,” was published in Frontiers in Neurology.
Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease that affects the functionality of upper and lower motor neurons — nerve cells responsible for voluntary muscle control.
ALS varies widely among patients, especially the severity of symptoms in the upper and lower motor neurons, the site of disease onset, progression rate and presence of cognitive and behavioral deficits.
Previous studies focused on developing and characterizing clinical and biological biomarkers that show the multifaceted nature of ALS, especially disease severity and progression.
Structural magnetic resonance imaging (MRI) measures cortical thickness and volume, which can be considered potential biomarkers to evaluate the structure and functionality of brain regions as the disease progresses.
Besides structural MRI, tools such as the ALS-specific functional rating scale revised (ALSFRS-R), which can correlate with patient survival, and the motor unit number index (MUNIX) that estimates the number of functional lower motor neurons, are commonly used to assess ALS progression and severity.
Although MUNIX scores are correlated with ALSFRS-R scores, no study thus far had addressed the relationship between cortical thickness and MUNIX as a biomarker that could be affected by both lower and upper motor neuron dysfunction.
In this study, researchers analyzed thinning of the cortex with structural MRI, along with clinical ALSFRS-R and neurophysiological MUNIX biomarkers on a group of ALS patients.
The study included 20 limb-onset classical ALS patients and 30 age-matched healthy control subjects. ALS patients were treated with Rilutek (riluzole) and additional G-CSF (the granulocyte-colony stimulating factor Filgrastim).
Biomarker correlation analysis was done by comparing the ALS patients to the control subjects. Cortical thinning was extremely varied, and was mainly observed in the ventral section of the precentral cortex. Investigators also found that cortical thickness correlated with ALSFRS-R and MUNIX.
“Cortical thinning was primarily observed in ALS patients with faster progression or advanced-stage disease. Future studies may investigate if enhanced levels of cortical thickness may be associated with processes of neuroplasticity or treatment effects. Finally, heterogeneous alterations in cortical thickness (including increases and decreases) argue for the need of individual perspective on ALS patients beyond group averages,” the authors wrote.
Researchers also monitored a subset of four ALS patients with slow disease progression over a minimum of 18 months. Here, individual biomarker analysis showed significant differences in disease progression and biomarkers’ temporal dynamics.
The findings indicate that MRI is a solid biomarker to assess cortical thinning, and in combination with other clinical and neurophysiological biomarkers provides a strong basis to evaluate the severity and progression of ALS.
“Combinatory biomarker use contributes a substantial gain of information about individual state of disease beyond group averages. Future studies may expand the idea of combining neuroimaging techniques with other clinical or molecular biomarkers to deepen our understanding of multisystem/multifactorial ALS disease progression,” the authors wrote.