Table 1.
List of patients participating in the study.
Table 2.
Demographic, clinical and radiologic features of hyperCKemia and symptomatic Pompe patients.
Fig 1.
Distribution of muscle weakness in the cohort of AOPD participating in the study.
The heatmap showed the MRC value for all muscles studied. Hip extension and flexion and trunk extension and flexion were the most weak impaired movements of the patients. In contrast, we did not observe distal weakness involving the lower or the upper limbs.
Table 3.
Correlation between MRC Score, Myometry Score, demographic data and muscle function tests.
Fig 2.
Representation of score of muscle infiltration observed in T1 imaging in each muscle of every patient by heatmaps.
(A) Heatmap including muscles of the head, upper limbs and trunk. (B) Heatmap including muscles of the pelvis and lower limbs. In each heatmap, patients (rows) are ordered according to hierarchical clustering with increasing grading in infiltration severity from the top to the bottom. Muscles (columns) are ordered according to dendrogram (upper part of the figures). The score of a muscle in a patient is indicated by the colour of the square in the interaction between the patient and that muscle. The darker the square, the more intense the fatty infiltration of that muscle is.
Fig 3.
T1w Muscle MRI of patients with Pompe disease.
We observed mild fatty infiltration in muscles of hyperCKemia patients: Tongue (Tin A), paraspinal muscles (Ps in B), lateral abdominal muscles (Ab in B) and rectus abdominis (RA in C) and in adductor major muscles (AM in D). The fatty infiltration in symptomatic patients was more evident (E-L). The muscles more commonly involved were tongue (T in E), subscapularis (Sc in F), latissimus dorsi (LD in G), the abdominal (Ab in H) and paraspinal muscles (Ps in H), the Gluteus minor (GMn in I), medius (GMe in J) and maximus (GMa in J), the muscles of the pelvic floor such as the Externus Obturator (Obt. Ext. in K), the posterior muscles of the thighs (Post in L), and the vasti muscles including vastus intermedius (VI in M) and vastus lateralis (VL in M). We observed involvement of rectus femoris and gracillis in advanced patients (RF and Gra in N). Muscles of the lower legs were commonly spared (O).
Fig 4.
Analysis of fatty infiltration in muscle MRIs.
(A) We observed significant differences in the percentage of fatty infiltration quantified using 3-point Dixon technique in most of the muscles between symptomatic (red bars) and hyperckemia patients (green bars). We compared both groups using the Student T test (single asterisk for differences with p<0.05 and double asterisk for differences with p<0.01). (B) Fat-fraction maps of the right thigh in a hyperckemia and a symptomatic AOPD patient. We show the quantification of the fatty involvement of posterior muscles of the thighs using the mean Mercuri Score and the mean 3 point Dixon score (Semitendinosus, Semimembranosus, Biceps Long Head and Biceps Short Head). Pompe 14 patients (hyperckemia patient) had higher strength in knee flexion measured with the myometer than patient 1 (symptomatic patient). We observed predominant fatty infiltration in the posterior muscles of the thighs producing decreased strength in the knee flexion test. (C) There was a strong correlation between knee flexion strength and the degree of muscle fatty infiltration calculated both using 3-point Dixon (left) and the Mercuri scale (right). Green dots showed values of hyperckemia patients, while red ones represent values of symptomatic patients. (D) We found a strong correlation between 3 point Dixon analysis and Mercuri score. We have represented the correlation between the quantification of fat infiltration using the mean Mercuri score and the mean 3-point Dixon score of the posterior thigh muscles (Semitendinosus, Semimembranosus, Biceps Long Head and Biceps Short Head). RF: rectus femoris; VL: vastus laterallis; VM: vastus medialis; VI: vastus intermedius; AM: adductor major; AL: adductor longus; BSH: biceps short head; BLH: biceps long head; ST: semitendinosus; SM: semimembranosus; SA: sartorius; GR: gracillis; MU: multifidus; LO: longissimus; IL: iliocostalis; QU: quadratus femoris; PS: psoas; ABD: lateral abdominal muscles; RA: rectus abdominis.
Fig 5.
Correlation between Muscle MRI and Functional scales.
Patient 30 is a 43 years old man with mild infiltration of pelvic and lower limbs muscles with minor functional impairment. Patient 22 is a 40 years old lady with moderate involvement of trunk, pelvic and thighs muscles. She was able to perform most of her daily live activities with no major problems but her clinical examination showed moderate weakness of pelvic muscles. Patient 2 is a 48 years old lady with a severe involvement of muscle producing severe weakness and notably impairing her daily live activities.
Table 4.
Comparison among MRI score and 3-point Dixon correlations with demographic data and muscle function tests.
Table 5.
Comparison between presymptomatic patients with hyperckemia depending on the results of the MRI.