Phrenic nerve conduction studies as a biomarker of respiratory insufficiency in amyotrophic lateral sclerosis

Abstract

Our objective was to examine the value of phrenic nerve conduction studies (PNCS) in quantifying diaphragm dysfunction in ALS, as no ideal test of respiratory insufficiency exists in ALS. We prospectively recorded bilateral PNCS, forced vital capacity (FVC), maximum inspiratory pressure (MIP), sniff nasal inspiratory pressure (SNIP), respiratory rate, ALSFRS-R, and respiratory symptoms in 100 ALS patients attending our clinic over a nine-month period. Survival data were collected for two years. Results showed that PNCS were reproducible and well tolerated. When the Pamp was abnormal (<0.3 mV), the relative risk of a respiratory rate >18 was 7.2 (95% CI 2.2–37.2, p <0.01) compared with a Pamp ≥0.3 mV. Similarly, the relative risk of orthopnea was 3.5 (95% CI 1.6–8.7, p <0.01) and dyspnea 2.4 (95% CI 1.4–4.0, p <0.01). FVC had the strongest correlation with Pamp (R² = 0.48 (p <0.001)). Fourteen of 15 patients with a FVC <50% had a Pamp <0.3 mV. However, eight with a Pamp <0.3 had a FVC >80%. The median survival was 1.07 years when the Pamp was <0.3 mV and >2 years when the Pamp was >0.3 mV (p <0.001). In conclusion, the phrenic Pamp correlated closely with multiple symptoms, signs, and laboratory measures of respiratory insufficiency and may prove to be a useful biomarker of respiratory dysfunction in ALS.

Key words:

• Phrenic
• amyotrophic lateral sclerosis
• neurophysiology
• biomarker
• ventilation

Acknowledgements

We are grateful to our patients for their generous contribution to our research.

J.S. Katz received research support from the Muscular Dystrophy Association, the ALS Association and Synapse Biomedical. L. Guion has received research support from Philips Respironics and the Will Rogers Respiratory Institute of the ALS Association. R.G. Miller is on the scientific advisory board for Cytokinetics and Mitsubishi Tanabe is on the editorial advisory board for Lancet Neurology, and has received research support from the Muscular Dystrophy Association.

Declaration of interest

The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.