The evolution of cortical integrity in motor neuron diseases: longitudinal cortical thickness profiles in ALS, PLS and poliomyelitis

Corresponding author: Peter Bede, Computational Neuroimaging Group, Trinity Biomedical Sciences Institute, Trinity College Dublin; email: bedep@tcd.ie Abstract One of the central aspects of clinical heterogeneity in motor neuron diseases is the respective involvement of upper (UMN) and lower motor neurons (LMN). Pure UMN and LMN phenotypes are associated with longer survival than mixed UMN-LMN conditions. The majority of longitudinal imaging studies in MND focus on a specific condition and describe progressive changes in contrast to healthy populations. The juxtaposition of cortical trajectories in several MNDs allows the characterisation of differences in rate of progression, and highlights anatomical patterns of disease burden unique to each condition. In this paper [1] we present longitudinal data from three conditions; (1) a UMN syndrome, primary lateral sclerosis (PLS), (2) a mixed UMN-LMN condition, amyotrophic lateral sclerosis (ALS) and (3) a LMN condition, poliomyelitis. We have acquired longitudinal magnetic resonance data with a uniform follow-up interval of 4 months. T1-weighted MRI data were acquired on a 3 Tesla Philips Achieva scanner with an 8-channel receiver head coil, using a 3D Inversion Recovery Prepared Spoiled Gradient Recalled Echo (IR-SPGR) pulse sequence with following imaging parameters; repetition time (TR) / echo time (TE) = 8.5/3.9 ms, inversion time (TI) = 1060 ms, field-of-view (FOV): 256 x 256 x 160 mm, spatial resolution: 1 mm3. In addition to standard cortical thickness analyses, individual cortical thickness patters were also appraised in each patient using a z-score-based approach. The methodological details regarding pre-processing, atlas-based segmentation, quality control and the statistical framework is described in detail in the companion article. We have identified rapidly progressive cortical thinning in the motor cortex of patients with PLS; expanding motor and extra-motor involvement in patients with ALS, and regions of increased cortical thickness in poliomyelitis survivors. Reference 1. TAHEDL, M., LI HI SHING, S., FINEGAN, E., CHIPIKA, R. H., LOPE, J., HARDIMAN, O. & BEDE, P. Propagation patterns in motor neuron diseases: individual and phenotype-associated disease-burden trajectories across the UMN-LMN spectrum of MNDs. Neurobiology of Aging, 2021 In Press