Diagnostic accuracy and confounders of vagus nerve ultrasound in amyotrophic lateral sclerosis—a single-center case series and pooled individual patient data meta-analysis

Katharina J. Müller, Moritz L. Schmidbauer, Florian Schöberl

Background Several single-center studies proposed utility of vagus nerve (VN) ultrasound for detecting disease severity, autonomic dysfunction, and bulbar phenotype in amyotrophic lateral sclerosis (ALS). However, the resulting body of literature shows opposing results, leaving considerable uncertainty on the clinical benefits of VN ultrasound in ALS.

Methods Relevant studies were identified up to 04/2024 and individual patient data (IPD) obtained from the respective authors were pooled with a so far unpublished cohort (from Munich). An IPD meta-analysis of 109 patients with probable or definite ALS (El Escorial criteria) and available VN cross-sectional area (CSA) was performed, with age, sex, ALS Functional Rating Scale-revised (ALSFRS-R), disease duration, and bulbar phenotype as independent variables.

Results Mean age was 65 years (±12) and 47% of patients (±12) had bulbar ALS. Mean ALSFRS-R was 38 (±7), and mean duration was 18 months (±18). VN atrophy was highly prevalent [left: 67% (±5), mean CSA 1.6mm2 (±0.6); right: 78% (±21), mean CSA 1.8 mm2 (±0.7)]. VN CSA correlated with disease duration (mean slope: left -0.01; right -0.01), but not with ALSFRS-R (mean slope: left 0.004; mean slope: right -0.002). Test accuracy for phenotyping bulbar vs. non-bulbar ALS was poor (summary receiver operating characteristic area under the curve: left 0.496; right 0.572).

Conclusion VN atrophy in ALS is highly prevalent and correlates with disease duration, but not with ALSFRS-R. VN CSA is insufficient to differentiate bulbar from non-bulbar ALS phenotypes. Further studies are warranted to analyze the link between VN atrophy, autonomic impairment, and survival in ALS.

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