Abstract
Objective: Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative process affecting upper and lower motor neurons as well as non-motor systems. In this study, precentral and postcentral cortical thinning detected by structural magnetic resonance imaging (MRI) were combined with clinical (ALS-specific functional rating scale revised, ALSFRS-R) and neurophysiological (motor unit number index, MUNIX) biomarkers in both cross-sectional and longitudinal analyses.Methods: The unicenter sample included 20 limb-onset classical ALS patients compared to 30 age-related healthy controls. ALS patients were treated with standard Riluzole and additional long-term G-CSF (Filgrastim) on a named patient basis after written informed consent. Combinatory biomarker use included cortical thickness of atlas-based dorsal and ventral subdivisions of the precentral and postcentral cortex, ALSFRS-R, and MUNIX for the musculus abductor digiti minimi (ADM) bilaterally. Individual cross-sectional analysis investigated individual cortical thinning in ALS patients compared to age-related healthy controls in the context of state of disease at initial MRI scan. Beyond correlation analysis of biomarkers at cross-sectional group level (n = 20), longitudinal monitoring in a subset of slow progressive ALS patients (n = 4) explored within-subject temporal dynamics of repeatedly assessed biomarkers in time courses over at least 18 months.Results: Cross-sectional analysis demonstrated individually variable states of cortical thinning, which was most pronounced in the ventral section of the precentral cortex. Correlations of ALSFRS-R with cortical thickness and MUNIX were detected. Individual longitudinal biomarker monitoring in four slow progressive ALS patients revealed evident differences in individual disease courses and temporal dynamics of the biomarkers.Conclusion: A combinatory use of structural MRI, neurophysiological and clinical biomarkers allows for an appropriate and detailed assessment of clinical state and course of disease of ALS.
Highlights
Amyotrophic lateral sclerosis (ALS) is a rapidly progressive neurodegenerative disorder affecting upper and lower motor neurons as well as non-motor systems [1]
ALSFRS-R sum scores correlated with cortical thickness of the precentral ventral cortex (r = 0.570, p = 0.009) and the postcentral ventral region (r = 0.481, p = 0.032)
motor unit number index (MUNIX) scores for the left (r = 0.767, p < 0.05, corrected) and right (r = 0.791, p < 0.05, corrected) abductor digiti minimi (ADM) correlated with ALSFRS-R sum scores
Summary
Amyotrophic lateral sclerosis (ALS) is a rapidly progressive neurodegenerative disorder affecting upper and lower motor neurons as well as non-motor systems [1]. The great clinical heterogeneity in ALS is reflected by different phenotypes with variability regarding the involvement of upper motor neuron (UMN) and lower motor neuron (LMN) signs, site of onset (bulbar, limb), rate of progression, and involvement of neurobehavioral deficits [2, 4]. Not all published MRI studies detected alterations in the cortical thickness [17] or cortical volume [18, 19] of the precentral cortex of ALS patients. Precentral cortical thinning was reported to be focal, and dependent on the clinical phenotype, rate of progression, and age [8, 11, 13]. Several longitudinal MRI studies revealed no further cortical thinning of the precentral cortex in the course of disease [9, 14,15,16,17]
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