Quantification and Monitoring of the Effect of Botulinum Toxin A on Paretic Calf Muscles of Children With Cerebral Palsy With MRI: A Preliminary Study

Abstract

Background: Muscles from patients with cerebral palsy (CP) are often spastic and form contractures that limit the range of motion. Injections of botulinum toxin A (BTX) into the calf muscles are an important treatment for functional equinus; however, improvement in gait function is not always achieved. BTX is also used to test muscle weakening for risk evaluation of muscle lengthening surgery. Our aim was to assess the effect of BTX over time on calf muscle properties in pediatric CP patients with MRI. Material and Methods: Six toe-walking CP patients (mean age 11.6 years) with indication for lengthening surgery were prospectively enrolled and received BTX injections into the gastrocnemius and soleus muscles. MRI scans at 3T of the lower legs and clinical examinations were performed pre-BTX, 6 weeks (6w), and 12 weeks (12w) post-BTX. A fat-suppressed 2D multi-spin-echo sequence was used to acquire T₂ maps and for segmentation. Fat fraction maps were calculated from 3D multi-echo Dixon images. Diffusion tensor imaging (DTI) with a 2D echo-planar imaging (EPI) sequence yielded maps of the mean apparent diffusion coefficient (ADC) and of the fractional anisotropy (FA). Hyperintense regions of interest (ROIs) on the T₂-weighted (T₂w) images at 6w were segmented in treated muscles. Mean values of T₂, fat fraction, ADC, and FA were calculated in hyperintense ROIs and in reference ROIs in non-treated muscles. Results: Hyperintensity on T₂w scans and increased T₂ (group mean ± standard deviation: 35 ± 1 ms pre-BTX, 45 ± 2 ms at 6w, and 44 ± 2 ms at 12w) were observed in all patients at the injection sites. The T₂ increase was spatially limited to parts of the injected muscles. FA increased (0.30 ± 0.03 pre-BTX, 0.34 ± 0.02 at 6w, and 0.36 ± 0.03 at 12w) while ADC did not change in hyperintense ROIs, indicating a BTX-induced increase in extracellular space and a simultaneous decrease of muscle fiber diameter. Fat fraction showed a trend for increase at 12w. Mean values in reference ROIs remained unchanged. Conclusion: MRI showed limited spatial distribution of the BTX-induced effects in pediatric CP patients. It could be a promising non-invasive tool for future studies to test BTX treatment protocols.

Keywords: MRI; T2; botulinum toxin A; calf muscles; cerebral palsy; diffusion; fat fraction; pediatric.

Figure 1

Axial and sagittal T₂-weighted images in the calf of patient 2 (hemiparetic) pre-BTX and 6 weeks (6w) and 12 weeks (12w) post-BTX (top row) showing hyperintensity at the sites of injection in the soleus (S), gastrocnemius medialis, and lateralis (GM, GL). A region of interest (ROI) comprising the hyperintense regions was segmented and is shown as red overlay in the middle row. The increased T₂ post-BTX can be seen in the calculated T₂ maps (bottom row). BTX, botulinum toxin A; y, years; T₂w, T₂-weighted; TE, echo time; sag, sagittal.

Figure 2

Axial and coronal T₂-weighted images in the calves of patient 3 (hemiparetic) and patient 6 (diparetic) 6 weeks post-BTX (top and bottom row) showing hyperintensity at the sites of injection in the soleus (S), gastrocnemius medialis, and lateralis (GM, GL) for patient 3, and the GM and GL for patient 6. The increased T₂ post-BTX can be seen in the calculated T₂ maps (middle row). BTX, botulinum toxin A; y, years; T₂w, T₂-weighted; TE, echo time; cor, coronal.

Figure 3

Time courses of T₂, fat fraction, apparent diffusion coefficient (ADC), and fractional anisotropy (FA) in all six patients at time points pre-BTX, 6 weeks (6w), and 12 weeks (12w) post-BTX. The values are displayed as mean values in the hyperintense ROI (orange) and the reference ROI (blue). The error bars show the standard deviation in the ROIs. ROI, region of interest; BTX, botulinum toxin A.

Figure 4

Overview of all ROI mean values (T₂, fat fraction, ADC, and FA) in the hyperintense (orange) and reference ROIs (blue) for all six patients at time points pre-BTX, 6 weeks (6w), and 12 weeks (12w) post-BTX. ROI, region of interest; BTX, botulinum toxin A; ADC, apparent diffusion coefficient; FA, fractional anisotropy.