ALS Decline Trajectory Shape Identifies Subgroups Beyond Progression Rate

A registry-based study of 1,686 people with amyotrophic lateral sclerosis (ALS) compared models based on functional decline rate and trajectory shape. The models identified partly distinct phenotypes, including a late-decline group with reduced respiratory reserve; findings were replicated in a second regional registry.

Rate and shape models identified partly distinct ALS phenotypes.
Agreement between classification models was modest (κ=0.273).
Trajectory shape separated survival subgroups within rate classes.
Sparse assessment excluded many patients, including ultrarapid progressors.

Researchers analyzed records from the Piemonte and Valle d’Aosta ALS register from 2000 to 2022, applying a Gaussian mixture model to classify decline rate and a latent-class mixed model with cubic splines to classify trajectory shape. The analysis included 1,686 patients; an external validation used the Emilia-Romagna register. Outcomes included 24-month prognostic performance, calibration, and clinical utility.

Each model identified four groups, but agreement was modest (κ=0.273). Adding trajectory shape to rate changed discrimination little (C-index 0.761 vs 0.755), while distinguishing subgroups within rate classes. In the rate-defined catastrophic group, median survival differed between shape-defined subgroups (30.1 vs 12.0 months). The shape-defined late-decline group had a median forced vital capacity of 83.5% and median survival of 22.7 months. Among 945 patients excluded for sparse assessments, 367 were classified post hoc as ultrarapid progressors, with shorter survival than the rapid-early group.

The findings suggest that decline rate and trajectory shape capture different aspects of ALS progression, and that sparse assessment may miss very rapid progression. The supplied abstract does not provide full methods or detailed external-validation results; these registry findings do not establish a change in clinical practice.

In practice

In ALS, functional decline rate alone may not capture the timing or shape of deterioration. This registry analysis found that trajectory-shape classes distinguished subgroups within rate-defined classes, including a late-decline group with median forced vital capacity of 83.5% and median survival of 22.7 months. The findings may support attention to respiratory reserve and trajectory patterns when interpreting progression, but they do not establish a monitoring strategy or justify changing practice. The abstract provides limited detail on methods and external validation.

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Source

Annals of Neurology: Rate and Shape of Functional Decline in Amyotrophic Lateral Sclerosis Identify Clinically Distinct Amyotrophic Lateral Sclerosis Phenotypes ↗

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