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.

Triceps Surae Muscle Characteristics in Spastic Hemiparetic Stroke Survivors Treated with Botulinum Toxin Type A: Clinical Implications from Ultrasonographic Evaluation

“…A recent study evaluating the possible degenerative effect of BoNT-A on calf muscles in CP-affected children supports our statement thanks to an MRI examination of MG and SOL that corroborates the hypothesis of a non-significant role of BoNT-A in determining a meaningful fibroadipose infiltration [26].…”

Altered Muscle Contributions are Required to Support the Stance Limb During Voluntary Toe-Walking

“…Specifically, the ankle plantarflexors are shortened during toe-walking and present, therefore, a reduced force-generating capacity ( Herman and Bragin, 1967 ; Hoy et al, 1990 ; Perry et al, 2003 ). Patients with spasticity, prolonged equinus postures, and/or fixed muscular contractures may also present alteration of the underlying muscle morphology and intrinsic mechanical properties ( Tardieu et al, 1982 ; Delp, 2003 ; Weidensteiner et al, 2021 ), even though it was shown that children with diplegic CP were able to generate maximum ankle torques at similar joint angles ( Engsberg et al, 2000 ; Neptune et al, 2007 ). Therefore, restoring a more optimal foot and ankle position, as during heel-to-toe gait, may lead to improvements in muscle functionality and strength.…”

Management of spastic diplegic cerebral palsy and periventricular leukomalacia in a preterm 2-year-old: A case report and review of the literature

“…Although toe walking is frequently observed in children with and without cerebral palsy, the exact underlying mechanism is unknown. It is, however, understood that muscles from CP patients can be spastic and form contractures, which limit the range of motion [32]. This is often seen specifically in the calf muscles, which can lead to toe walking.…”

“…An effective, yet temporary treatment option for toe-walking patients with CP and spastic diplegia is Botulinum toxin A, or Botox injections. Botox can be injected into the bilateral calf muscles to promote functional equinus, control spasticity, and improve gait function [32].…”

“…Oral medications, such as baclofen, are also utilized in treating spasticity and management of general tone [33]. Combining BTX and oral baclofen with custom orthotic devices (i.e., AFO's or casting) and physical/occupational therapy can be effective in helping to loosen muscles, achieve heal-strike, build strength, and promote overall physical healing and wellness over-time, respectively [8,32]. Children with CP are candidates for surgical intervention between the ages of 4 and 10, however there is no general consensus on the exact age [9].…”