Redefining periodic paralysis with CACNA1S mutation in a Spanish cohort

Area of Science:

• Neurology
• Genetics
• Musculoskeletal Disorders

Background:

• Hypokalemic periodic paralysis (HypoPP) diagnosis often relies on muscle MRI and electrophysiological testing.
• Clinical presentation varies significantly between sexes, but data on asymptomatic individuals are limited.

Purpose of the Study:

• To investigate muscle MRI and electrophysiological exercise test findings in symptomatic and asymptomatic carriers of the p.R528H CACNA1S mutation in HypoPP.
• To assess the utility of these tests as screening tools in a homogeneous cohort.

Main Methods:

• Recruited 11 individuals with HypoPP from 4 families (p.R528H CACNA1S mutation), including 8 symptomatic men and 3 asymptomatic women, plus 9 controls.
• Evaluated muscle MRI and electrophysiological long exercise test results in this cohort.

Main Results:

• Muscle MRI revealed atrophy and fatty infiltration in posterior thigh muscles (adductor magnus, semimembranosus) in all carriers, correlating with age.
• Long exercise test showed delayed compound muscle action potential decrement in all carriers, irrespective of symptoms.
• Test sensitivity reached 100% after 35 minutes of exercise.

Conclusions:

• Muscle MRI and exercise testing findings are consistent between symptomatic and asymptomatic HypoPP carriers with the p.R528H mutation.
• These non-invasive tests are valuable screening tools for identifying affected individuals, including those without clinical symptoms.