Motor unit number index (MUNIX) loss of 50% occurs in half the time of 50% functional loss according to the D50 disease progression model of ALS.

Capturing disease progression in amyotrophic lateral sclerosis (ALS) is challenging and refinement of progression markers is urgently needed. This study introduces new motor unit number index (MUNIX), motor unit size index (MUSIX) and compound muscle action potential (CMAP) parameters called M50, MUSIX200 and CMAP50. M50 and CMAP50 indicate the time in months from symptom onset an ALS patient needs to lose 50% of MUNIX or CMAP in relation to the mean values of controls.

Motor unit number index (MUNIX) in the D50 disease progression model reflects disease accumulation independently of disease aggressiveness in ALS.

The neurophysiological technique motor unit number index (MUNIX) is increasingly used in clinical trials to measure loss of motor units. However, the heterogeneous disease course in amyotrophic lateral sclerosis (ALS) obfuscates robust correlations between clinical status and electrophysiological assessments. To address this heterogeneity, MUNIX was applied in the D50 disease progression model by analyzing disease aggressiveness (D50) and accumulation (rD50 phase) in ALS separately.

Cortical and subcortical grey matter atrophy in Amyotrophic Lateral Sclerosis correlates with measures of disease accumulation independent of disease aggressiveness.

There is a growing demand for reliable biomarkers to monitor disease progression in Amyotrophic Lateral Sclerosis (ALS) that also take the heterogeneity of ALS into account. In this study, we explored the association between Magnetic Resonance Imaging (MRI)-derived measures of cortical thickness (CT) and subcortical grey matter (GM) volume with D50 model parameters. T1-weighted MRI images of 72 Healthy Controls (HC) and 100 patients with ALS were analyzed using Surface-based Morphometry for cortical structures and Voxel-based Morphometry for subcortical Region-Of-Interest analyses using the Computational Anatomy Toolbox (CAT12).

Common and rare variant association analyses in amyotrophic lateral sclerosis identify 15 risk loci with distinct genetic architectures and neuron-specific biology.

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease with a lifetime risk of one in 350 people and an unmet need for disease-modifying therapies. We conducted a cross-ancestry genome-wide association study (GWAS) including 29,612 patients with ALS and 122,656 controls, which identified 15 risk loci. When combined with 8,953 individuals with whole-genome sequencing (6,538 patients, 2,415 controls) and a large cortex-derived expression quantitative trait locus (eQTL) dataset (MetaBrain), analyses revealed locus-specific genetic architectures in which we prioritized genes either through rare variants, short tandem repeats or regulatory effects.

Patterns of grey and white matter changes differ between bulbar and limb onset amyotrophic lateral sclerosis.

Amyotrophic Lateral Sclerosis (ALS) is a progressive neurodegenerative disease that is characterized by a high heterogeneity in patients' disease course. Patients with bulbar onset of symptoms (b-ALS) have a poorer prognosis than patients with limb onset (l-ALS). However, neuroimaging correlates of the assumed biological difference between b-ALS and l-ALS may have been obfuscated by patients' diversity in the disease course.

Disease aggressiveness signatures of amyotrophic lateral sclerosis in white matter tracts revealed by the D50 disease progression model.

Numerous neuroimaging studies in amyotrophic lateral sclerosis (ALS) have reported links between structural changes and clinical data; however phenotypic and disease course heterogeneity have occluded robust associations. The present study used the novel D50 model, which distinguishes between disease accumulation and aggressiveness, to probe correlations with measures of diffusion tensor imaging (DTI). DTI scans of 145 ALS patients and 69 controls were analyzed using tract-based-spatial-statistics of fractional anisotropy (FA), mean- (MD), radial (RD), and axial diffusivity (AD) maps.

Triage of Amyotrophic Lateral Sclerosis Patients during the COVID-19 Pandemic: An Application of the D50 Model.

Amyotrophic lateral sclerosis (ALS) is a progressive neuromuscular disease, the management of which requires the continuous provision of multidisciplinary therapies. Owing to the novel coronavirus disease (COVID-19) pandemic, regular contact with ALS patients at our center was severely restricted and patient care was at risk by delay of supportive therapies. We established a triage system based on the D50 disease progression model and were thus able to identify a prospective cohort with high disease aggressiveness (D50 < 30).