Muscle Contractility in Hypokalemic Periodic Paralysis

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

doi:10.1002/mus.28330

Muscle Contractility in Hypokalemic Periodic Paralysis

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

^*Corresponding author for this work

Department of Neurology

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.

Original language	English
Journal	Muscle & Nerve
Volume	71
Issue number	3
Pages (from-to)	360-367
Number of pages	8
ISSN	0148-639X
DOIs	https://doi.org/10.1002/mus.28330
Publication status	Published - Mar 2025

Keywords

Adipose Tissue/physiopathology
Adult
Calcium Channels, L-Type/genetics
Cross-Sectional Studies
Female
Humans
Hypokalemic Periodic Paralysis/physiopathology
Magnetic Resonance Imaging
Male
Middle Aged
Muscle Contraction/physiology
Muscle Strength/physiology
Muscle Weakness/physiopathology
Muscle, Skeletal/physiopathology
Young Adult
hypokalemic periodic paralysis
Dixon MRI
fat replacement
muscle MRI
muscle contractility

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10.1002/mus.28330

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title = "Muscle Contractility in Hypokalemic Periodic Paralysis",

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 = "Adipose Tissue/physiopathology, Adult, Calcium Channels, L-Type/genetics, Cross-Sectional Studies, Female, Humans, Hypokalemic Periodic Paralysis/physiopathology, Magnetic Resonance Imaging, Male, Middle Aged, Muscle Contraction/physiology, Muscle Strength/physiology, Muscle Weakness/physiopathology, Muscle, Skeletal/physiopathology, Young Adult, hypokalemic periodic paralysis, Dixon MRI, fat replacement, muscle MRI, muscle contractility",

author = "Sonja Holm-Yildiz and Thomas Krag and Tina Dysgaard and Pedersen, {Britt St{\ae}vnsbo} and Nanna Witting and Kodal, {Louise Sloth} and Linda Kannuberg and Pedersen, {Jonas Jalili} and Andersen, {Rebecca Kj{\ae}r} and Zhe Lyu and Aagaard, {Morten M{\"u}ller} and Vissing, {Christoffer Rasmus} and Julia Dahlqvist and Nicoline L{\o}kken and Poulsen, {Nanna Scharff} and John Vissing",

note = "{\textcopyright} 2024 Wiley Periodicals LLC.",

year = "2025",

month = mar,

doi = "10.1002/mus.28330",

language = "English",

volume = "71",

pages = "360--367",

journal = "Muscle & Nerve",

issn = "0148-639X",

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T1 - Muscle Contractility in Hypokalemic Periodic Paralysis

AU - Holm-Yildiz, Sonja

AU - Krag, Thomas

AU - Dysgaard, Tina

AU - Pedersen, Britt Stævnsbo

AU - Witting, Nanna

AU - Kodal, Louise Sloth

AU - Kannuberg, Linda

AU - Pedersen, Jonas Jalili

AU - Andersen, Rebecca Kjær

AU - Lyu, Zhe

AU - Aagaard, Morten Müller

AU - Vissing, Christoffer Rasmus

AU - Dahlqvist, Julia

AU - Løkken, Nicoline

AU - Poulsen, Nanna Scharff

AU - Vissing, John

PY - 2025/3

Y1 - 2025/3

N2 - 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.

AB - 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.

KW - Adipose Tissue/physiopathology

KW - Adult

KW - Calcium Channels, L-Type/genetics

KW - Cross-Sectional Studies

KW - Female

KW - Humans

KW - Hypokalemic Periodic Paralysis/physiopathology

KW - Magnetic Resonance Imaging

KW - Male

KW - Middle Aged

KW - Muscle Contraction/physiology

KW - Muscle Strength/physiology

KW - Muscle Weakness/physiopathology

KW - Muscle, Skeletal/physiopathology

KW - Young Adult

KW - hypokalemic periodic paralysis

KW - Dixon MRI

KW - fat replacement

KW - muscle MRI

KW - muscle contractility

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U2 - 10.1002/mus.28330

DO - 10.1002/mus.28330

M3 - Journal article

C2 - 39719667

SN - 0148-639X

VL - 71

SP - 360

EP - 367

JO - Muscle & Nerve

JF - Muscle & Nerve

IS - 3

ER -

Muscle Contractility in Hypokalemic Periodic Paralysis

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Keywords

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