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.

Structural brain correlates of cognitive and behavioral impairment in MND

“…In addition to the cortical thinning of the precentral gyrus, cortical thickness measurements were found to be altered in multiple brain areas encompassing (predominantly right-sided) frontal, insular, temporal, parietal, and occipital regions in both MND-motor and MND-plus patients. The evidence of a distributed involvement of extra-motor areas in MND confirms recent pathological data [Brettschneider et al, 2013] and previous neuroimaging studies [Agosta et al, 2012;d'Ambrosio et al, 2014;Mezzapesa et al, 2013;Schuster et al, 2014b;Thorns et al, 2013;Verstraete et al, 2011]. In all cortical regions, we found a trend toward a more severe thinning in MNDplus relative to MND-motor patients underscoring the morphological continuum within the MND spectrum.…”

Neuroimaging Endpoints in Amyotrophic Lateral Sclerosis

“…A surface-based cortical thickness study in 20 patients with ALS did not find any significant changes over 3 to 10 months [68]. This negative result was corroborated by a similar study in a larger cohort of 51 patients with classic ALS, also showing no significant progression of cortical thinning over an average interval of 8 months [114]. Data for both studies were acquired at 3 T.…”

Cortical thickness estimation in individuals with cerebral small vessel disease, focal atrophy, and chronic stroke lesions

“…Cortical thickness quantification obtained from magnetic resonance imaging (MRI) can been used to examine regional variations of the cerebral cortex that have been associated with normal ageing and dementia due to neurodegeneration (1)(2)(3)(4). Cortical thinning in specific topographical regions of the brain has been used to accurately determine patterns of neurodegeneration in mild cognitive impairment (MCI) (5), Alzheimer's disease (AD), frontotemporal dementia (FTD) (6)(7)(8)(9)(10)(11)(12)(13), Parkinson's disease (PD) (14)(15)(16)(17), amyotrophic lateral sclerosis (ALS) (18)(19)(20)(21), and vascular cognitive impairment (22)(23)(24).…”