Analysis of brain and spinal MRI measures in a common domain to investigate directional neurodegeneration in motor neuron disease

• Published in: Journal of neurology 2023-03, Vol.270 (3), p.1682-1690
• Main Authors: Toh, C., Keslake, A., Payne, T., Onwuegbuzie, A., Harding, J., Baster, K., Hoggard, N., Shaw, P. J., Wilkinson, I. D., Jenkins, T. M.
• Format: Article
• Language: English
• Subjects: Amyotrophic lateral sclerosis; Amyotrophic Lateral Sclerosis - diagnosis; Anisotropy; Brain - diagnostic imaging; Brain - pathology; Cross-Sectional Studies; Diffusion Tensor Imaging - methods; Humans; Hypotheses; Magnetic resonance imaging; Magnetic Resonance Imaging - methods; Medicine; Medicine & Public Health; Motor Neuron Disease - diagnostic imaging; Motor Neuron Disease - pathology; Motor neuron diseases; Motor neurone disease; Neurodegeneration; Neuroimaging; Neurology; Neuroradiology; Neurosciences; Original Communication; Precentral gyrus; Pyramidal tracts; Pyramidal Tracts - diagnostic imaging; Regression analysis; Spinal cord
• ISSN: 0340-5354; 1432-1459
• DOI: 10.1007/s00415-022-11520-1

Background Magnetic resonance imaging (MRI) of the brain and cervical spinal cord is often performed in diagnostic evaluation of suspected motor neuron disease/amyotrophic lateral sclerosis (MND/ALS). Analysis of MRI-derived tissue damage metrics in a common domain facilitates group-level inferences on pathophysiology. This approach was applied to address competing hypotheses of directionality of neurodegeneration, whether anterograde, cranio-caudal dying-forward from precentral gyrus or retrograde, dying-back. Methods In this cross-sectional study, MRI was performed on 75 MND patients and 13 healthy controls. Precentral gyral thickness was estimated from volumetric T1-weighted images using FreeSurfer, corticospinal tract fractional anisotropy (FA) from diffusion tensor imaging using FSL, and cross-sectional cervical cord area between C1-C8 levels using Spinal Cord Toolbox. To analyse these multimodal data within a common domain, individual parameter estimates representing tissue damage at each corticospinal tract level were first converted to z -scores, referenced to healthy control norms. Mixed-effects linear regression models were then fitted to these z -scores, with gradients hypothesised to represent directionality of neurodegeneration. Results At group-level, z -scores did not differ significantly between precentral gyral and intracranial corticospinal tract tissue damage estimates (regression coefficient − 0.24, [95% CI − 0.62, 0.14], p  = 0.222), but step-changes were evident between intracranial corticospinal tract and C1 (1.14, [95% CI 0.74, 1.53], p