Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2024 Dec 3;10(6):e200211.
doi: 10.1212/NXG.0000000000200211. eCollection 2024 Dec.

Quantitative Muscle MRI to Monitor Disease Progression in Hypokalemic Period 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 , Zhe Lyu  1 , Morten Müller Aagaard  1 , John Vissing  1
Affiliations

Quantitative Muscle MRI to Monitor Disease Progression in Hypokalemic Period Paralysis

Sonja Holm-Yildiz et al. Neurol Genet. .

Erratum in

Abstract

Background and objectives: Primary hypokalemic periodic paralysis (HypoPP) is a muscle channelopathy that can cause periodic paralysis and permanent weakness. Currently, little is known about how progressive this myopathy is. Natural history data for HypoPP can potentially answer the question of progressiveness and form the basis for outcome measures to be used in follow-up and emerging treatment trials. We aimed to describe the natural history of HypoPP and assess whether quantitative fat imaging is a valuable biomarker to monitor disease progression.

Methods: In this prospective follow-up study, we examined disease progression using Dixon MRI to monitor changes in fat replacement of the muscle and stationary dynamometry to monitor changes in muscle strength.

Results: We included 37 persons (mean age 43 years, range 18-79 years) with HypoPP-causing variants in CACNA1S. Three participants were asymptomatic carriers, 22 had periodic paralysis, 3 had permanent weakness, and 9 had periodic paralysis in combination with permanent weakness. The median follow-up time was 20 months (range 12-25). We found that fat fraction increased in 10 of 21 examined muscles. An increase in the composite fat fraction of at least 1 muscle group was found in all symptomatic phenotypes. By contrast, we found no significant change in muscle strength.

Discussion: The results from this follow-up study support the use of quantitative muscle MRI to monitor subclinical disease progression in HypoPP in patients with and without attacks of paralysis.

PubMed Disclaimer

Conflict of interest statement

The authors report no relevant disclosures. Go to Neurology.org/NG for full disclosures.

Figures

Figure 1
Figure 1. Fat Fraction of Individual Muscles of Patients With HypoPP at Baseline
(A) The map is ordered by age at baseline. Every patient represents a row. The color visualizes the severity of fat replacement by fat fraction (%). White bar: muscle excluded because of poor quality of MRI. (B) Relationship between the composite fat fraction (%) of all examined muscles and age at baseline.
Figure 2
Figure 2. Muscle Strength and Fat Replacement of Individual Muscles
Muscle strength (A) and muscle fat fraction (B) at baseline and follow-up. Values are mean ± SD. An asterisk * indicates a significant difference. Boxplots of change in muscle fat fraction (%) in individual muscles during follow-up (C).
Figure 3
Figure 3. Change of Muscle Fat Fraction in Different Phenotypes
The boxplot shows the composite fat fraction of the thighs (A), calves (B), and lumbar level (C) of asymptomatic carriers, participants with periodic paralysis, and participants with permanent weakness with or without period paralysis. An asterisk * indicates a significant difference.
See this image and copyright information in PMC

References

    1. Stunnenberg BC, Raaphorst J, Deenen JCW, et al. . Prevalence and mutation spectrum of skeletal muscle channelopathies in The Netherlands. Neuromuscul Disord. 2018;28(5):402-407. doi:10.1016/j.nmd.2018.03.006 - DOI - PubMed
    1. Horga A, Raja Rayan DL, Matthews E, et al. . Prevalence study of genetically defined skeletal muscle channelopathies in England. Neurology. 2013;80(16):1472-1475. doi:10.1212/WNL.0b013e31828cf8d0 - DOI - PMC - PubMed
    1. Brugnoni R, Canioni E, Filosto M, et al. . Mutations associated with hypokalemic periodic paralysis: from hotspot regions to complete analysis of CACNA1S and SCN4A genes. Neurogenetics. 2022;23(1):19-25. doi:10.1007/s10048-021-00673-2 - DOI - PubMed
    1. Venance SL, Cannon SC, Fialho D, et al. . The primary periodic paralyses: diagnosis, pathogenesis and treatment. Brain. 2006;129(Pt 1):8-17. doi:10.1093/brain/awh639 - DOI - PubMed
    1. Sasaki R, Nakaza M, Furuta M, Fujino H, Kubota T, Takahashi MP. Mutation spectrum and health status in skeletal muscle channelopathies in Japan. Neuromuscul Disord. 2020;30(7):546-553. doi:10.1016/j.nmd.2020.06.001 - DOI - PubMed

LinkOut - more resources