Objective: To determine the pattern of muscle edema occurring in the lower limb muscles of Asian hypokalaemic periodic paralysis (hypoPP) patients using magnetic resonance imaging (MRI). Specifically, the relationship between muscle edema and muscle activity during daily use was examined by comparing the lower limb muscle MRI of healthy subjects following exercise and hypoPP patients. Methods: Twenty Asian patients (mean age: 29.3 +/- 7.53 years) clinically diagnosed with hypoPP were enrolled in the present study. Ten healthy subjects were also enrolled. Direct automated DNA sequencing of the S4 regions of CACNA1S and SCN4A in all hypoPP patients was performed. The upper and lower legs of all hypoPP patients during the time interval between attacks and healthy subjects pre- and post-exercise were examined on a 3 T system with T2-weighted fat saturation sequence. Images were evaluated by means of a region of interest analysis. A scoring from 0 to 3 was used to compare the degree of muscle edema among individual muscles. Results: Three hypoPP patients were identified with mutations in the screened genes: R1239H and R900S of CACNA1S and R672H of SCN4A. The lower leg muscles of both hypoPP patients and healthy subjects after exercise displayed significantly higher MRI signal intensities compared to healthy subjects before exercise (P<0.0001 and P<0.0001, respectively). In contrast, there was no significant change in the upper leg muscle signal intensities of hypoPP patients and healthy subjects following exercise compared to pre-exercise healthy subjects (P = 0.7598 and P = 0.9651, respectively). In the hypoPP patient group, high signal intensity in the upper leg muscles was seen only in the patient with the R1239H mutation. In the lower legs, muscle edema was most frequently seen in the gastrocnemius lateralis, soleus, and gastrocnemius medialis in the hypoPP patient group. Furthermore, the degree of muscle edema was the greatest in these muscles. This similar pattern of muscle edema was also seen in healthy subjects after exercise. Conclusions: In Asian hypoPP patients, muscle edema as well as the underlying abnormal ion distributions across the muscle membrane is present even during the time interval between attacks of muscle weakness. The muscles of the lower leg are more likely to be edematous than muscles of the upper leg since these muscles are more actively used in daily life. Thus, muscles subjected to high activity are more likely to be edematous and sodium-overloaded.