ETD

• ALS
• ENG
• Intercostal
• Respiratory
• Spirometry
• Ultrasound

Amyotrophic Lateral Sclerosis (ALS) is a progressive neurodegenerative disease characterized by heterogeneous clinical phenotypes and variable prognoses. Respiratory failure is a major cause of morbidity and mortality, with early respiratory involvement representing a crucial determinant of survival. However, its timely detection remains challenging, particularly in patients with bulbar onset or cognitive impairment, which may compromise the reliability of standard spirometry.
M-AERIALS is a monocentric, observational and prospective study conducted at the Neurology Unit of the Azienda Ospedaliero-Universitaria Pisana. It aimed to compare less invasive and effort-independent alternatives, such as phrenic nerve conduction studies (Compound Muscle Action Potential, CMAP) and diaphragm/intercostal ultrasound measurements (Thickening Fraction, TF), to traditional spirometry (using Slow Vital Capacity, SVC ≤ 80%, as a marker of early decline) to evaluate their utility and accuracy.
At baseline, ultrasound-derived parameters demonstrated significant diagnostic accuracy in detecting early respiratory decline. ROC curve analysis in the total cohort yielded an AUC of 0.76 for diaphragmatic TF and 0.78 for intercostal TF. Especially in the spinal-onset subset of patients, intercostal TF has reached an AUC of 0.83. Notably, intercostal TF exhibited 100% sensitivity and a 100% negative predictive value, showing a capacity to rule out a respiratory failure, and indicating a plausible compensatory activation of the parasternal intercostal muscles in response to emerging diaphragmatic weakness. Intercostal TF significantly correlated with baseline SVC (rho=0.741 in the total cohort) further supporting its role as a surrogate respiratory marker.
Longitudinal data trends supported the prognostic role of neuromuscular ultrasound, revealing that a lower baseline intercostal TF significantly correlated with a greater progression of global disability over the clinical follow-up (Δ ALSFRS-R; rho=0.602 in the total cohort, rho=0.857 in the spinal-onset subset). The study also assessed whether clinical features and damage compartmentalization were associated with earlier decline. Additionally, a cross-sectional dissociation between CMAP amplitude and ultrasound parameters confirmed a temporal mismatch between electrical denervation and mechanical execution.
Overall, these findings support the integration of neurophysiological and ultrasound assessments with clinical profiling to more accurately identify ALS patients at risk of respiratory failure, overcoming the limitations of global volumetric parameters and optimizing the timing for non-invasive ventilation initiation.