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The difference in the diaphragmatic physiological measures between inspiratory and expiratory phases in ALS

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Abstract

Introduction

We aimed to clarify the differences in static and dynamic diaphragm parameters between the expiratory and inspiratory phases in amyotrophic lateral sclerosis (ALS).

Methods

Twenty patients with early-stage ALS and 16 healthy controls were enrolled in the study. We measured the amplitudes of compound muscle action potential (phCMAP) by electrical stimulation of the phrenic nerve and the zone of apposition wall thickness of the diaphragm (DT) using ultrasonography. We analyzed the differences in phCMAP (∆phCMAP) and DT (∆DT) between the end-inspiratory and end-expiratory phases and their correlation with forced vital capacity (FVC).

Results

The ΔphCMAP (mean 129.7 ± SD 204.7 µV) and ∆DT (0.80 ± 0.88 cm) in patients were significantly smaller than those in controls (348.6 ± 247.7 µV, p = 0.0003 and 1.89 ± 1.10 cm, p = 0.0002, respectively). Although ∆DT was significantly correlated with FVC, we found no correlation between ∆phCMAP and FVC. The phCMAP was paradoxically smaller during inspiration than during expiration in 35% of patients but in none of the controls.

Conclusion

Dynamic parameters of the diaphragm were abnormal in early-stage ALS. The paradoxical reduction in phCMAP during inspiration may reflect early respiratory dysfunction. Assessment of dynamic abnormalities of the diaphragm may provide helpful information for respiratory management in patients with ALS.

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Acknowledgements

The authors thank Kiyomi Koike, Kohko Yoshimoto, Noriko Murayama, Kazuma Shinozuka, and Sachiko Kaneko from the Division of Neurophysiology, Tokyo Metropolitan Neurological Hospital for providing technical support.

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Authors and Affiliations

  1. Department of Neurology, Tokyo Metropolitan Neurological Hospital, 2-6-1, Musashidai, Fuchu, Tokyo, 183-0042, Japan

    Ryo Morishima, Toshio Shimizu, Hideki Kimura, Kota Bokuda & Kazushi Takahashi

  2. Course of Molecular and Cellular Medicine, Niigata University Graduate School of Medicine, 757, Tori-Ichibancho, Asahimachi, Chuo-ku, Niigata, 951-8510, Japan

    Ryo Morishima & Masanari Itokawa

  3. Department of Clinical Laboratory Medicine, Tokyo Metropolitan Komagome Hospital, 3-18-22, Honkomagome, Bunkyo, Tokyo, 113-8677, Japan

    Yukie Ishizaka

  4. Deputy Director General, Tokyo Metropolitan Institute of Medical Science, 2-1-6, Kamikitazawa, Setagaya, Tokyo, 156-8506, Japan

    Masanari Itokawa

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Contributions

RM and TS designed this study. RM, YI, HK, and KB performed the nerve conduction study and ultrasonography. RM and TS analyzed the data and drafted the manuscript. KT and MI supervised the study and approved the final manuscript for publication. All authors have approved the final article.

Corresponding author

Correspondence to Ryo Morishima.

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The authors declare that they have no known competing financial interests or personal relationships that could have influenced the work reported in this study.

Ethical approval

The study was approved by the Ethics Committee of Tokyo Metropolitan Neurological Hospital (TS-H29-004).

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All participants provided written informed consent for the study.

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Supplementary Information

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10072_2022_6371_MOESM1_ESM.pdf

Supplementary file1 Fig. S1. Heatmap showing p-values between parameters by Pearson's correlation coefficient in patients with ALS. SVC: slow vital capacity, FVC: forced vital capacity, phCMAPe: the amplitudes of phCMAP at end-expiratory phases, phCMAPi: the amplitudes of phCMAP at end-inspiratory phases, ΔphCMAP: difference between phCMAPe and phCMAPi, phCMAP ratio: phCMAPi/phCMAPe, CMAP fraction: 100 x (phCMAPi – phCMAPe)/(phCMAPe), DTe: DT at end-expiratory phases, DTi: DT at end-inspiratory phases, ΔDT: difference between DTe and DTi, DT ratio: DTi/DTe, TFdi: 100 x (phCMAPi-phCMAPe)/(phCMAPe), Vi: the maximum velocity of the diaphragm in M-mode during normal inhalation, Vf: the maximum velocity of the diaphragm in M-mode during forced inhalation, Vs: the maximum velocity of the diaphragm in M-mode during sniffing. Fig. S2: Heatmap showing R-values between parameters by Pearson's correlation coefficient in patients with ALS. SVC: slow vital capacity, FVC: forced vital capacity, phCMAPe: the amplitudes of phCMAP at end-expiratory phases, phCMAPi: the amplitudes of phCMAP at end-inspiratory phases, ΔphCMAP: difference between phCMAPe and phCMAPi, phCMAP ratio: phCMAPi/phCMAPe, CMAP fraction: 100 x (phCMAPi – phCMAPe)/(phCMAPe), DTe: DT at end-expiratory phases, DTi: DT at end-inspiratory phases, ΔDT: difference between DTe and DTi, DT ratio: DTi/DTe, TFdi: 100 x (phCMAPi-phCMAPe)/(phCMAPe), Vi: the maximum velocity of the diaphragm in M-mode during normal inhalation, Vf: the maximum velocity of the diaphragm in M-mode during forced inhalation, Vs: the maximum velocity of the diaphragm in M-mode during sniffing. Fig. S3. Correlations between slow vital capacity (SVC, %) and phrenic nerve compound muscle action potential (phCMAP) in patients with amyotrophic lateral sclerosis using Pearson’s correlation coefficient. (A) phCMAPe: the amplitudes of phCMAP at end-expiratory phases. (B) phCMAPi: the amplitudes of phCMAP at end-inspiratory phases. (C) ΔphCMAP: difference between phCMAPe and phCMAPi. (D) phCMAP ratio: phCMAPi/phCMAPe. (E) CMAP fraction: 100 x (phCMAPi – phCMAPe)/(phCMAPe). Fig. S4. Correlations between slow vital capacity (SVC, %) and diaphragm thickness (DT) parameters in patients with amyotrophic lateral sclerosis using Pearson’s correlation coefficient. (A) DTe: DT at end-expiratory phases. (B) DTi: DT at end-inspiratory phases. (C) ΔDT: difference between DTe and DTi. (D) DT ratio: DTi/DTe. (E) TFdi: 100 x (phCMAPi-phCMAPe)/(phCMAPe). Fig. S5. Correlations between slow vital capacity (FVC, %) and parameters of dome movement velocity using Pearson’s correlation coefficient. (A) Vi: the maximum velocity of the diaphragm in M-mode during normal inhalation, (B) Vf: the maximum velocity of the diaphragm in M-mode during forced inhalation, (C) Vs: the maximum velocity of the diaphragm in M-mode during sniffing (PDF 169 KB)

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Morishima, R., Shimizu, T., Ishizaka, Y. et al. The difference in the diaphragmatic physiological measures between inspiratory and expiratory phases in ALS. Neurol Sci 43, 6821–6830 (2022). https://doi.org/10.1007/s10072-022-06371-7

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