Sensorimotor modulation by botulinum toxin A in post-stroke arm spasticity: Passive hand movement
Introduction
Post-stroke spasticity (PSS) is one of the major sequelae following ischemic stroke [62]. Ischemic lesions of descending tracts result in upper motor neuron syndrome (UMNS) comprising both negative signs (weakness and loss of dexterity) and positive signs (especially spasticity) [39]. Spasticity, defined by Lance as “a motor disorder characterized by a velocity-dependent increase in tonic stretch reflex (muscle tone) with exaggerated tendon jerks, resulting from hyperexcitability of the stretch reflex,” is a component of UMNS [27]. It is generally recognized that post-stroke spasticity (PSS) may interfere with voluntary movement [31]. Disabling PSS affects patient quality of life; significant reductions in manual dexterity, mobility, walking/falling, and performance of activities of daily living (ADL) have been reported among patients with PSS [44]. The disabilities associated with PSS place a significant burden on stroke survivors and subsequently on caregivers [62]. Prevalence data for PSS are limited by a lack of population-based studies; however, current estimates range from 19% to 42.6% [44], [48]. Numerous clinical trials have shown that botulinum toxin type A (BoNT) is a safe and effective therapeutic tool to relieve upper limb PSS and improve function of the affected limb [40], [45], [57]. The current treatment strategy to relieve focal spasticity combines BoNT application and physiotherapy. BoNT blocks acetylcholine release at neuromuscular junctions [15]. In addition to this peripheral site of BoNT-action, there is growing evidence that indirect (remote) effects on the spinal cord and brain may also occur. BoNT-A affects intrafusal fibers as well as extrafusal ones, and thus alters abnormal sensory input to the CNS via Ia afferents [36]. This is probably the mechanism by which BoNT injected in the periphery can induce cortical reorganization [9]. This hypothesis has been supported by studies of focal dystonia [7], [13], [24], [25]. We have consistently studied changes in the sensorimotor cortex elicited by BoNT application in chronic stroke patients with arm spasticity associated with either severe [38], [49], [52] or moderate [47], [49] hand weakness. Effects on task-related cerebral activation have been assessed using functional magnetic resonance imaging (fMRI). In our previous fMRI studies of severely affected patients, kinesthetic imagery of finger movements was used as an experimental task. Motor imagery evokes activation in the cortical areas associated with performed movements [37]; however, such a mental task is difficult to monitor. Unlike motor imagery, passive movement is easy to perform and monitor; on the other hand, it induces sensorimotor cortex activation in another way, with particular emphasis on afferent inputs to the CNS [56]. The aim of the present study was to localize and analyze BoNT-related patterns of cerebral cortex activation during passive flexion-extension movements of the affected hand at the wrist.
Section snippets
Material and methods
Patients were studied using a previously published protocol [47]. The following text summarizes the methodology and highlights the specific differences in the present study.
Clinical
BoNT significantly lowered arm spasticity at W4. The mean MAS change from baseline was 0.93 (p = 0.018, Wilcoxon Signed Ranks Test). The mean MAS score at W11 did not significantly differ from W0 (mean MAS change was 0.25, p = 0.197, Wilcoxon Signed Ranks Test). The mean MAS scores were: 2.18 at W0 (SD 0.43), 1.25 at W4 (SD 0.46), and 1.93 at W11 (SD 0.12). The MAS scores for each subject are listed in Table 1.
Imaging-group average
Across all the sessions, fMRI activation of the ipsilesional sensorimotor cortex (M1, S1,
Discussion
Current research is gradually expanding our knowledge of the central and remote effects of BoNT. The research suggests that successful treatment of focal spasticity modulates cortical and subcortical sensorimotor circuits. In our previous work, we concluded that effective treatment of spasticity led to a reduction of bilateral overactivation in cortical and subcortical areas during actively performed or imagined finger movement [38], [47], [49], [50], [52]. We assumed that the expanded
Conclusion
The present study confirms the feasibility of using passive hand movements to map the cerebral sensorimotor networks in patients with post-stroke arm spasticity and demonstrates that BoNT-induced spasticity relief is associated with changes in task-induced central sensorimotor activation, likely mediated by an altered afferent drive from the spasticity-affected muscles.
Acknowledgments
This study was supported by the grant of the Internal Grant Agency of Ministry of Health of the Czech Republic NT13575, by the grant of the Agency for Healthcare Research of Ministry of Health of the Czech Republic 15-31921 A, and by the Institutional Support RVO FNOL 00098892.
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