Disability In Amyotrophic Lateral Sclerosis Research Articles

Cognitive, behavioral, and brain functional connectivity correlates of fatigue in amyotrophic lateral sclerosis.

Fatigue is defined as a symptom of exhaustion unexplained by drug effects or psychiatric disorders and comprises two main components (i.e., central or "mental" and peripheral or "physical" components), both influencing global disability in amyotrophic lateral sclerosis (ALS). We aim at investigating the clinical correlations between "physical" and "mental" components of fatigue, measured by the Multidimensional Fatigue Inventory scale, and motor and cognitive/behavioral disability in a large sample of patients with ALS. We also investigated the correlations between these measures of fatigue and resting-state functional connectivity of brain functional magnetic resonance imaging (RS-fMRI) large-scale networks in a subset of patients. One hundred and thirty ALS patients were assessed for motor disability, cognitive and behavioral dysfunctions, fatigue, anxiety, apathy, and daytime sleepiness. Moreover, the collected clinical parameters were correlated with RS-fMRI functional connectivity changes in the large-scale brain networks of 30 ALS patients who underwent MRI. Multivariate correlation analysis revealed that "physical" fatigue was related to anxiety and respiratory dysfunction, while "mental" fatigue was related to memory impairment and apathy. Moreover, the mental fatigue score was directly related to functional connectivity in the right and left insula (within the salience network), and inversely related to functional connectivity in the left middle temporal gyrus (within the default mode network). Although the "physical" component of fatigue may be influenced by the disease itself, in ALS the "mental" component of fatigue correlates with cognitive and behavioral impairment, as well as with alterations of functional connectivity in extra-motor networks.

Measuring disability in amyotrophic lateral sclerosis/motor neuron disease: the WHODAS 2.0-36, WHODAS 2.0-32, and WHODAS 2.0-12

Aim: To investigate whether the World Health Organization Disability Assessment Schedule 2.0 (WHODAS) can provide interval level measurement of disability in Amyotrophic Lateral Sclerosis (ALS), allowing parametric analyses. Methods: Data on the WHODAS 12, 32, and 36-item versions, from 1120 patients studied at one or more time points, were fit to the Rasch model and comparisons made against ALSFRS-R, King’s staging, and mortality. Trajectory modeling was undertaken for a newly diagnosed (≤6 months) cohort of 454 individuals. Results: Total scores for WHODAS 32 and 36-item versions can be converted to interval level measurement suitable for individual clinical use, and the 12-item WHODAS total for group use. The 36-item version is shown to be equivalent to the 32-item version. Expected correlations were seen with King’s staging, ALSFRS-R, and EQ-5D-5L. Trajectory analysis of disability (WHODAS 2.0) showed three clearly demarcated groups with differences in King’s staging, depressive symptomatology and mortality, but not age. Conclusions: The WHODAS 2.0 is a brief patient reported outcome measure which can be used to measure disability in ALS. Provided the patient answers all 36 (32 if not working) items, the conversion table produces an interval level estimate for parametric analyses. The different trajectories demonstrated from diagnosis support the concept of a prodromal period, and suggest the WHODAS 2.0 could be used for surveillance of at risk populations, such as those with genetic predisposition.

The Contribution of Cognitive Impairment to Perceived Motor Disability in Amyotrophic Lateral Sclerosis (P1.1-027)

The Contribution of Cognitive Impairment to Perceived Motor Disability in Amyotrophic Lateral Sclerosis (P1.1-027)

Spinal cord gray matter segmentation using deep dilated convolutions

Gray matter (GM) tissue changes have been associated with a wide range of neurological disorders and were recently found relevant as a biomarker for disability in amyotrophic lateral sclerosis. The ability to automatically segment the GM is, therefore, an important task for modern studies of the spinal cord. In this work, we devise a modern, simple and end-to-end fully-automated human spinal cord gray matter segmentation method using Deep Learning, that works both on in vivo and ex vivo MRI acquisitions. We evaluate our method against six independently developed methods on a GM segmentation challenge. We report state-of-the-art results in 8 out of 10 evaluation metrics as well as major network parameter reduction when compared to the traditional medical imaging architectures such as U-Nets.

Whole-brain magnetic resonance spectroscopic imaging measures are related to disability in ALS.

To demonstrate the sensitivity of a recently developed whole-brain magnetic resonance spectroscopic imaging (MRSI) sequence to cerebral pathology and disability in amyotrophic lateral sclerosis (ALS), and compare with measures derived from diffusion tensor imaging. Whole-brain MRSI and diffusion tensor imaging were undertaken in 13 patients and 14 age-similar healthy controls. Mean N-acetylaspartate (NAA), fractional anisotropy, and mean diffusivity were extracted from the corticospinal tract, compared between groups, and then in relation to disability in the patient group. Significant reductions in NAA were found along the course of the corticospinal tracts on whole-brain MRSI. There were also significant changes in fractional anisotropy (decreased) and mean diffusivity (increased) in the patient group, but only NAA showed a significant relationship with disability (r = 0.65, p = 0.01). Whole-brain MRSI has potential as a quantifiable neuroimaging marker of disability in ALS. It offers renewed hope for a neuroimaging outcome measure with the potential for harmonization across multiple sites in the context of a therapeutic trial.

A randomized, placebo-controlled trial of memantine for functional disability in amyotrophic lateral sclerosis

Our objective is to describe the results of a phase II/III, 12-months, double-blinded, single-centre, randomized, parallel (1:1), clinical trial performed to evaluate the efficacy and safety of memantine in ALS. Patients with probable or definite ALS of less than 36 months disease duration and progression over a one-month lead-in period were randomly assigned to placebo or memantine at 20 mg/day. The primary endpoint was 12-months ALSFRS decline. Forced vital capacity, manual muscle testing, visual analogue scale, quality of life, motor unit number estimation and neurophysiological index were the secondary endpoints. The number of patients included was based on the assumption of a 50% change in the ALSFRS decline. Safety and adverse events were evaluated. Sixty-three patients were included in the trial. Memantine did not show more adverse events or laboratory changes than placebo. Primary and secondary outcomes were not different between groups by intention-to-treat and per-protocol analysis. The most sensitive measurements were neurophysiological, which declined linearly over time. In conclusion, the results of this study show that memantine is well tolerated and safe in ALS patients. We did not observe any evidence of efficacy for memantine but we cannot exclude a positive outcome on survival.

Diffusion anisotropy of the cervical cord is strictly associated with disability in amyotrophic lateral sclerosis

Background: Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease with severe cervical cord damage due to degeneration of the corticospinal tracts and loss of lower motor neurones. Diffusion tensor magnetic...