Cortical Thinning Pattern of Bulbar- and Spinal-onset Amyotrophic Lateral Sclerosis: a Surface-based Morphometry Study.

Objective The precise cortical thinning pattern has not been elucidated for onset subtypes of amyotrophic lateral sclerosis (ALS). The current study aimed to investigate the altered cortical thickness signatures of the bulbar-onset and spinal-onset ALS using surface-based morphometry, and the correlation between the cortical thickness of positive brain regions and clinical variables of the patients.Methods MR structural images were obtained from 65 ALS patients (15 bulbar-onset, 50 spinal-onset) and 65 normal controls (NCs) on a 3.0T MRI system. The structural images were segmented into gray matter and white matter based on DARTEL method and the central cortical surfaces were reconstructed using projection-based thickness method. The surface-based morphometry was performed to identify the alteration of cortical thickness in overall ALS patients, bulbar-onset ALS patients and spinal-onset ALS patients comparing to the NCs. The correlation analysis was applied between the clinical variables and the mean cortical thickness of the abnormal brain regions with age and sex as covariates.Results The cortex thinning of ALS patients was located in the left precentral gyrus, left postcentral gyrus, right gyrus rectus and right medial precentral gyrus. The bulbar-onset ALS (ALS-bulbar) presented motor cortex thinning of left precentral gyrus and right supplementary motor cortex, and the spinal-onset ALS (ALS-spinal) suffered from extra-motor cortex thinning of left posterior insula and right gyrus rectus. In ALS patients, the thickness of right gyrus rectus was negatively correlated to disease duration (r=-0.311, P=0.013), the thickness of right precentral gyrus was positively correlated to the score of ALS functional rating score-revise (ALSFRS-R) (r=0.271, P=0.032). The thickness of motor cortices in ALS-bulbar were not correlated to disease duration and ALSFRS-R score; the thickness of extra-motor cortices in ALS-spinal were negatively correlated to the disease duration (left insula, r=-0.409, P=0.004; right gyrus rectus, r=-0.351, P=0.014).Conclusion The findings suggested that bilateral motor cortex thinning presented in bulbar-onset ALS and extra-motor cortex thinning presented in spinal-onset ALS. The motor cortex thinning may be the intrinsic pathophysiological change that associated to the disease disability, and extra-motor cortex thinning may be secondary pathophysiological change that associated to disease duration.