Strength and muscle structure preserved during long-term therapy in a patient with hypokalemic periodic paralysis (Cav1.1-R1239G)
- 60 Downloads
We report a young wheelchair-dependent patient with an unclear proximal myopathy and a heterozygous, de-novo Cav1.1-R1239G mutation suggesting hypokalemic periodic paralysis (HypoPP). Sonography showed a loss of the pennate pattern indicative of an edema, whereas fatty degeneration was excluded. Within 7 days of therapy with spironolactone, potassium and physical therapy, muscle strength almost completely normalized, a normal pennate pattern appeared and the edema was markedly reduced. She learned to walk without aid and to do sports and has continued to do so for 11 years until now. Over the years, we tested serum potassium values, muscle strength, muscle edema and muscular sodium content by 1.5 T, 3 T and 7 T 1H and 23Na magnetic resonance imaging. No fatty muscle degeneration developed. Muscular edema-like changes only occurred when she was pregnant and was set to reduced therapy. Because of the ability to do sports again, her mobility was further increased. Our observational study on this single patient may suggest that: (1) muscle imaging and molecular genetics are important diagnostic tools, (2) weakness in periodic paralysis may be reversible, and (3) continued adequate therapy may preserve muscle structure and strength on a longterm, whereas weakness due to fatty degeneration could be considered progressive and irreversible. Although HypoPP is a rare disease, it should be included in differential diagnosis not only if there is paroxysmal weakness, but also in cases of myopathy of unknown origin.
KeywordsMyopathy Paralysis Muscle edema Precision medicine Ion channel disorder
We thank the patient for the perfect compliance. K. J. R. and M. A. W. were supported by the Eva Luise Köhler Research Award for Rare Diseases. F. L. H. was endowed Senior Research Professor of the non-profit Hertie-Foundation. K. J. R., H. L. and F. L. H. were supported by research grants from the German Federal Research Ministry (BMBF, IonNeurONet, 01GM1105A), and K. J. R., M. A. W. and F. L. H. by the German Society for Patients with Muscle Disorders (DGM).
Compliance with ethical standards
Conflicts of interest
The authors report no conflicts of interest.
All human studies have been approved by the appropriate local ethics committee and have been performed in accordance with the ethical standards laid down in the Declaration of Helsinki. Informed consent was obtained prior to inclusion in the study.
- 4.Jurkat-Rott K, Weber MA, Fauler M, Guo XH, Holzherr BD, Paczulla A, Nordsborg N, Joechle W, Lehmann-Horn F (2009) K+-dependent paradoxical membrane depolarization and Na+ overload, major and reversible contributors to weakness by ion channel leaks. Proc Natl Acad Sci USA 106:4036–4041CrossRefGoogle Scholar
- 6.Jurkat-Rott K, Mitrovic N, Hang C, Kouzmekine A, Iaizzo P, Herzog J, Lerche H, Nicole S, Vale-Santos J, Chauveau D, Fontaine B, Lehmann-Horn F (2000) Voltage-sensor sodium channel mutations cause hypokalemic periodic paralysis type 2 by enhanced inactivation and reduced current. Proc Natl Acad Sci USA 97:9549–9554CrossRefGoogle Scholar
- 16.Dias da Silva MR, Cerutti JM, Tengan CH, Furuzawa GK, Vieira TC, Gabbai AA, Maciel RM (2002) Mutations linked to familial hypokalaemic periodic paralysis in the calcium channel alpha1 subunit gene (Cav1.1) are not associated with thyrotoxic hypokalaemic periodic paralysis. Clin Endocrinol (Oxf) 56:367–375CrossRefGoogle Scholar
- 18.Winczewska-Wiktor A, Steinborn B, Lehman-Horn F, Biczysko W, Wiktor M, Gurda B, Jurkat-Rott K (2007) Myopathy as the first symptom of hypokalemic periodic paralysis—case report of a girl from a Polish family with CACNA1S (R1239G) mutation. Adv Med Sci 52(Suppl 1):155–157Google Scholar
- 19.Sansone VA, Burge J, McDermott MP, Smith PC, Herr B, Tawil R, Pandya S, Kissel J, Ciafaloni E, Shieh P, Ralph JW, Amato A, Cannon SC, Trivedi J, Barohn R, Crum B, Mitsumoto H, Pestronk A, Meola G, Conwit R, Hanna MG, Griggs RC (2016) Muscle Study Group. Randomized, placebo-controlled trials of dichlorphenamide in periodic paralysis. Neurology 86:1408–1416CrossRefGoogle Scholar
- 20.Glemser PA, Jaeger H, Nagel AM, Ziegler AE, Simons D, Schlemmer HP, Lehmann-Horn F, Jurkat-Rott K, Weber MA (2017) (23)Na MRI and myometry to compare eplerenone vs. glucocorticoid treatment in Duchenne dystrophy. Acta Myol 36:2–13Google Scholar
- 22.Nagel AM, Amarteifio E, Lehmann-Horn F, Jurkat-Rott K, Semmler W, Schad LR, Weber MA (2011) 3 Tesla sodium inversion recovery magnetic resonance imaging allows for improved visualization of intracellular sodium content changes in muscular channelopathies. Investig Radiol 46:759–766CrossRefGoogle Scholar
- 24.Weber MA, Nagel AM, Marschar AM, Glemser P, Jurkat-Rott K, Wolf MB, Ladd ME, Schlemmer HP, Kauczor HU, Lehmann-Horn F (2016) 7-T (35)Cl and (23)Na MR imaging for detection of mutation-dependent alterations in muscular edema and fat fraction with sodium and chloride concentrations in muscular periodic paralyses. Radiology 280:848–859CrossRefGoogle Scholar