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. 2025 Mar;71(3):360-367.
doi: 10.1002/mus.28330. Epub 2024 Dec 24.

Muscle Contractility in Hypokalemic Periodic Paralysis

Sonja Holm-Yildiz  1 , Thomas Krag  1 , Tina Dysgaard  1 , Britt Stævnsbo Pedersen  1 , Nanna Witting  1 , Louise Sloth Kodal  1 , Linda Kannuberg  1 , Jonas Jalili Pedersen  1 , Rebecca Kjær Andersen  1 , Zhe Lyu  1 , Morten Müller Aagaard  1 , Christoffer Rasmus Vissing  1 , Julia Dahlqvist  1 , Nicoline Løkken  1 , Nanna Scharff Poulsen  1 , John Vissing  1
Affiliations

Muscle Contractility in Hypokalemic Periodic Paralysis

Sonja Holm-Yildiz et al. Muscle Nerve. 2025 Mar.

Abstract

Introduction/aims: Primary hypokalemic periodic paralysis (HypoPP) can present with periodic paralysis and/or permanent muscle weakness. Permanent weakness is accompanied by fat replacement of the muscle. It is unknown whether the permanent muscle weakness is solely due to fat replacement or if other factors affect the ability of the remaining muscle fibers to contract. We aimed to investigate muscle fat replacement and contractility in persons with HypoPP-causing variants in CACNA1S and to compare the results to healthy controls.

Methods: In this cross-sectional study, we used T1-weighted and 2-point Dixon magnetic resonance imaging (MRI) to assess fat replacement of the muscle and stationary dynamometry to assess muscle strength. Contractility was determined by maximal muscle contraction divided by the contractile cross-sectional muscle area.

Results: We included 45 persons with HypoPP-causing variants in CACNA1S and data from 37 healthy controls. We found that fat fraction was increased in ankle dorsiflexors and knee extensors and flexors, and further found that muscle strength was decreased in knee extensors and flexors in persons with HypoPP-causing variants in CACNA1S compared to healthy controls. Additionally, we found decreased contractility of thigh muscles in persons with HypoPP-causing variants in CACNA1S compared to healthy controls.

Discussion: The decreased contractility could relate to skeletal muscle voltage-gated calcium channel dysfunction, subclinical attacks of paralysis, and/or changed muscle architecture, but this needs further investigation.

Keywords: Dixon MRI; fat replacement; hypokalemic periodic paralysis; muscle MRI; muscle contractility.

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References

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