title: Longitudinal course of cortical thickness decline in amyotrophic lateral sclerosis.
abstract: To determine longitudinal rates of cortical atrophy in classical Amyotrophic lateral sclerosis (ALS) and ALS variants. Rates of cortical thinning were determined between 2 scans, 3-15 months apart, in 77 ALS patients: 51 classical, 12 upper motor neuron (UMN), and 14 lower motor neuron (LMN) ALS variants. Cortical thickness at the first assessment was compared with 60 healthy controls matched by age and gender. Atrophy rates were compared between patient sub-groups and correlated with disease duration, progression, and severity. Using a cross-sectional analysis, we found a significant difference in cortical thickness between ALS patients and controls in the motor and extra-motor areas (left medial orbito frontal gyrus, left inferior parietal gyrus, bilateral insular cortex, right fusiform gyrus, bilateral precuneus). Using a longitudinal analysis, we found a significant decline of cortical thickness in frontal, temporal, and parietal regions over the course of the study in ALS patients. Effects were independent of the clinical subtype, with exception of the precentral gyrus (p < 0.001). The LMN ALS variants demonstrated the highest rates of cortical thinning in the precentral gyrus, the UMN-dominant subjects exhibited intermediate rates of atrophy, and the classical ALS patients exhibited no such change. Atrophy of the precentral gyrus in classical ALS indicates a floor effect at the first assessment, resulting in a lack of further atrophy over time. Structural loss of the precentral gyrus appears to be an early sign of classical ALS. Over time, patterns of cortical thinning in extra-motor areas can be identified in ALS, regardless of the phenotype.
authors.affiliation: German Center for Neurodegenerative Diseases (DZNE), Gehlsheimer Str. 20, 18147, Rostock, Germany.
authors.forename: Christina
authors.initials: C
authors.lastname: Schuster
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Kasper
authors.forename: Judith
authors.initials: J
authors.lastname: Machts
authors.forename: Daniel
authors.initials: D
authors.lastname: Bittner
authors.forename: Jörn
authors.initials: J
authors.lastname: Kaufmann
authors.forename: Reiner
authors.initials: R
authors.lastname: Benecke
authors.forename: Stefan
authors.initials: S
authors.lastname: Teipel
authors.forename: Stefan
authors.initials: S
authors.lastname: Vielhaber
authors.forename: Johannes
authors.initials: J
authors.lastname: Prudlo
mesh_terms: D000368:Aged; D000690:Amyotrophic Lateral Sclerosis / Q000145:classification / Q000150:complications* / Q000473:pathology; D001930:Brain Injuries / Q000209:etiology* / Q000473:pathology*; D016022:Case-Control Studies; D002540:Cerebral Cortex / Q000473:pathology*; D003430:Cross-Sectional Studies; D005260:Female; D007839:Functional Laterality; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008137:Longitudinal Studies; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged