Applying the D50 disease progression model to gray and white matter pathology in amyotrophic lateral sclerosis

Abstract

HighlightsThe D50 disease progression model well characterized a cross-sectional ALS cohort.VBM reveled ALS-related widespread gray and white matter density decreases.A spread of structural alterations occurs along with D50 model derived disease phases.White-matter alterations were associated with higher disease aggressiveness.

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

“…The D50 model provides parameters of overall disease aggressiveness, local disease activity, and individual disease covered (Poesen et al, 2017;Prell et al, 2020; Steinbach et al, 2020). Figure 1 provides a pictorial overview of how the model estimation was performed based on all the regularly collected ALSFRS‐R scores that were available per patient (Figure 1a).…”

“…This allowed us to classify patients as having either low (D50 ≥ 30 months) or high (D50 < 30 months) disease aggressiveness. The cutoff value of 30 months corresponds to the median of D50 values (here: 28.8 months), that is typically observed in comparable cohorts of patients with ALS treated at our center (Prell et al, 2020;Steinbach et al, 2020). We excluded patients with a D50 value above 100 months and only one ALSFRS-R score, to ensure a high level of reliability for the calculation of the D50 model.…”

“…Briefly, the model incorporates a sigmoidal decline of the ALS Functional Rating Scale (ALSFRS‐R) throughout the disease course because a curvilinear progression was suggested before (Franchignoni, Mora, Giordano, Volanti, & Chio, 2013; Gordon et al, 2010; Senda et al, 2017). The D50 model addresses the difficulty in characterizing functional loss at the individual and population level using traditional clinical indices like the progression rate (PR) (Poesen et al, 2017; Prell, Gaur, Steinbach, Witte, & Grosskreutz, 2020; Steinbach et al, 2020). As such, the model quantitatively (a) captures phenotypic complexity, (b) reduces noise associated with traditional disease progression parameters, and (c) provides distinct descriptors of patients' aggressivity and individual disease covered.…”

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

“…The D50 model provides unified parameters of patients’ individual disease course, e.g., of overall disease aggressiveness (D50) or individual disease covered (rD50) [ 11 , 12 , 13 ]. Calculation of the model is based on the revised ALS functional rating scale (ALSFRS-R), the internationally used scale to quantify the remaining muscle functions of patients affecting their daily life [ 20 ].…”

“…To provide a risk-adapted triage for the highly heterogenous cohort of our ALS patients, we used the recently developed D50 disease progression model [ 11 , 12 , 13 ]. Doing so enabled us to identify patients with higher disease aggressiveness who required special attention and more frequent follow-ups at the peak of the COVID-19 outbreak in Germany and the ensuing period of severe restrictions of public life and elective health care provisions.…”