ArticleJournal of neurology2026
Phrenic nerve amplitude as an effort-independent prognostic biomarker of respiratory failure in amyotrophic lateral sclerosis.
Article in Journal of neurology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
objectiveIn amyotrophic lateral sclerosis (ALS), the effort-dependent respiratory metrics used to determine the timing of non-invasive ventilation (NIV) lose reliability as bulbar and/or cognitive impairment progresses. We tested whether the effort-independent phrenic nerve compound muscle action potential (CMAP) amplitude predicts the timing of NIV independently of forced vital capacity (FVC) and the revised ALS Functional Rating Scale (ALSFRS-R).
methodsPre-registered analysis of a single-centre ALS cohort (n = 1,486) contributing 2968 serial phrenic nerve conduction studies. Amplitude was expressed as percentage of an age- and sex-predicted value (per 10% decrease), and time to NIV initiation was the primary outcome (death competing). We used cause-specific Cox models, time-dependent and bootstrap-validated discrimination, and a Bayesian joint longitudinal-survival model.
resultsLower amplitude predicted earlier NIV (adjusted hazard ratio [HR] 1.22 per 10% decrease, 95% CI 1.16-1.27; likelihood-ratio χ
conclusionsPhrenic nerve conduction studies, an effort-independent neurophysiological marker carried robust, near-term, incremental prognostic information for NIV beyond FVC and ALSFRS-R, establishing diaphragmatic motor amplitude as a candidate biomarker for objective respiratory prognostication in ALS. External validation and recalibration are required before clinical use.
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