Shear wave elastography to assess the effect of botulinum toxin in muscle hypertonia following stroke

Introduction Sonoelastography is a method capable of evaluating the mechanical properties of soft tissues by ultrasound (US). A further development of this technique is shear wave elastography (SWE), which provides a quantitative evaluation of the elastic properties - in terms of tissutal stiffness - by measuring the propagation velocities of the directional shear waves, produced by an ultrasound pulse. Spasticity often appears in stroke patients in the affected limbs. It corresponds to velocity-dependent muscle hypertonia in relation to the hyperexcitability of the stretch reflex. Over time, the paretic muscles develop intrinsic alterations with consequent muscle shortening and increased fibrosis related to reduced use and immobilization. Intramuscular injections of botulinum toxin A (BoNT-A) is an effective treatment which reduces muscle activity by inhibiting the release of acetylcholine at the neuromuscular junction level and is therefore able to reduce neuromediated muscle hypertonicity. The study aims to evaluate the effectiveness of SWE to appreciate changes in stiffness in spastic muscles after treatment with BoNT-A and possibly detect differences between affected muscles and unaffected contralateral ones related to fibrous-fatty remodeling. Materials & Methods 14 adult patients (5F; age: 58,4±14,1 years, m±SD; range:46-78) affected by spasticity were recruited after ischemic or hemorrhagic stroke diagnosed for at least 3 months and with a time interval from the last injection of at least 4 months, if already treated with BoNT-A. They patients underwent a physical examination in which muscle hypertonia was assessed using the modified Ashworth scale (MAS). The assessments were carried out on a sample muscle among the spastic ones favoring the greater volume and better accessibility to the ultrasound probe. SWE was also performed on the homologue non-paretic contralateral muscle. Spasticity was measured as the average electromyographic activity recorded during stretching (reflex by stretching) of the selected muscle at a reproducible speed, according to a previously validated methodology. The SWE evaluation was carried out with US scans across and along the direction of muscular fibers - as assessed by conventional US - covering the entire belly of the selected muscle to obtain a comprehensive estimate of the muscle stiffness both with the maximum shortened and elongated muscle position. Muscle fibrosis was also estimated on conventional B-mode US using the modified Heckmatt scale. All evaluations were performed shortly before botulinum toxin infiltration (T0) and one month later (T1). Clinical, electromyographic and ultrasound evaluation were performed by three different blinded examiners. Depending on data distribution, non-parametric statistical tests for paired data were performed for comparison; Spearman’s r was calculated to assess data correlations. Results A total of 224 SWE values resulted considering both time points. Overall, SWE measurements on paretic muscles assessed with a longitudinal positioning of the probe showed statistically significant reduction at T1 versus T0 both in non stretched conditions (p=0.001) and in stretched conditions (p=0.0029). After BoNT-A injection, a significant reduction in MAS (p=0.009), spastic dystonia (p=0.0043), spasticity (p=0.0019) and longitudinal SWE measurements, both in non stretched conditions (p=0.001) and in stretched conditions (p=0.0029), was observed. No significant changes in SWE parameters were observed on non-paretic versus contralateral muscle . All SWE measurements were higher in the paretic limb than in the contralateral one (p<0.01); higher SWE measurements resulted along the direction of muscular fibers versus across them (p<0.01). Cohen’s d estimate a larger effect on EMG values than longitudinal SWE ones (either in non stretched and in stretched condition), with narrower 95%CI for SWE measurements. No changes resulted by the modified Heckmatt scale US assessments; there was a positive correlation (r: 0.46-0.84) between MHS scores and SWE values. Conclusion This is the first study evaluating the effect of BoNT-A on muscle hypertonia following stroke, assessed by mean of SWE and compared with the stretch reflex. The treatment resulted in a reduction of MAS, stretch reflex and muscular stiffness, in relation to the reduction of the neuro-mediated hypertonia. We have therefore shown that SWE is able to appreciate a reduction in neuro-mediated stiffness. Abolishing the neuro-mediated contribution by keeping the limb in a shortened position and moreover after BoNT-A injection, the SWE values resulted higher in the paretic muscle than in the healthy muscle in the same position. Hence, SWE-driven comparison between the spastic muscle and the contralateral unaffected homologous one is able to disclose the amount of stiffness due only to intrinsic muscular involutive remodeling. Alongside sEMG, SWE could therefore constitute an added-value to clinicians who manage spasticity for the assessment of responses to treatments and monitoring therapeutic interventions.