Muscle fat replacement and contractility in patients with skeletal muscle sodium channel disorders

Figures

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  Figure 1. Overview of MRI. (A) Localizer shows the 6 different levels of segmentation on the leg. (B) Example of muscle mapping of the thigh (50%) and calf (33%). (C) T1-w MRI of a 59-year-old patient heterozygous for p.T1313M at 50% length of the thigh. (D–F) Series of T1-w MRI from the same patient at 23, 33 and 43% of the calf, demonstrating significant proximal–distal difference of involvement. In the more distal part of the muscle (at 33% length of the tibia), the gastrocnemius medialis is almost completely replaced by fat.

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  Figure 2. Fat fraction (FF) and contractile cross-sectional area (CCSA) on the different segments. (A,B) Average fat fraction of calf and thigh. Y-axis is fat fraction in percentage. The difference in FF between the proximal segments and distal segments is significant (p < 0.05). (C,D) Average CCSA on cross sections. Y-axis CCSA in mm2. CCSA was significantly higher for patients in the calf, but only nominally so in the thigh, indicating hypertrophy of lower leg muscles.

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  Figure 3. Fat fraction of single muscles. Fat fraction of individual muscles in patients with SCN4A mutations and healthy controls. Error bars represent standard deviation. Muscles with significant difference between patients and controls are marked with an asterisk (p < 0.05).

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  Figure 4. Contractility of the four studied muscle groups. Peak torque (Newton-meter)) divided by contractile cross-sectional area (mm2) reflects contractility. The patients have significantly less contractility in all four studied muscle groups (p < 0.005).

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  Figure 5. Bar plots of contractility and absolute strength between patients and controls. There was a significant difference in contractility for all muscle groups, while absolute strength was only nominally less. Our hypothesis is that increased contractile cross-sectional area compensate for reduced contractility, thus resulting in normalized absolute strength.

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  Figure 6. Bar plots of contractility in subgroups consisting of p.T1313M variants and non-T1313M variant group controls. Error bars are standard deviation. Both p.T1313M and the non-T1313M variants had significantly less contractility in all studied muscle groups (asterisk; p < 0.05).