Muscle MRI Findings in Childhood/Adult Onset Pompe Disease Correlate with Muscle Function

Abstract

Objectives: Enzyme replacement therapy has shown to be effective for childhood/adult onset Pompe disease (AOPD). The discovery of biomarkers useful for monitoring disease progression is one of the priority research topics in Pompe disease. Muscle MRI could be one possible test but the correlation between muscle MRI and muscle strength and function has been only partially addressed so far.

Methods: We studied 34 AOPD patients using functional scales (Manual Research Council scale, hand held myometry, 6 minutes walking test, timed to up and go test, time to climb up and down 4 steps, time to walk 10 meters and Motor Function Measure 20 Scale), respiratory tests (Forced Vital Capacity seated and lying, Maximun Inspiratory Pressure and Maximum Expiratory Pressure), daily live activities scales (Activlim) and quality of life scales (Short Form-36 and Individualized Neuromuscular Quality of Life questionnaire). We performed a whole body muscle MRI using T1w and 3-point Dixon imaging centered on thighs and lower trunk region.

Results: T1w whole body muscle MRI showed a homogeneous pattern of muscle involvement that could also be found in pre-symptomatic individuals. We found a strong correlation between muscle strength, muscle functional scales and the degree of muscle fatty replacement in muscle MRI analyzed using T1w and 3-point Dixon imaging studies. Moreover, muscle MRI detected mild degree of fatty replacement in paraspinal muscles in pre-symptomatic patients.

Conclusion: Based on our findings, we consider that muscle MRI correlates with muscle function in patients with AOPD and could be useful for diagnosis and follow-up in pre-symptomatic and symptomatic patients under treatment.

Take home message: Muscle MRI correlates with muscle function in patients with AOPD and could be useful to follow-up patients in daily clinic.

Conflict of interest statement

The authors have declared that no competing interests exist.

Figures

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.

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 pSemitendinosus, 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.