Precise quantification of the time course of voluntary activation capacity following Botulinum toxin injections in the biceps brachii muscles of chronic stroke survivors

Abstract

Background: Spasticity is a key motor impairment that affects many hemispheric stroke survivors. Intramuscular botulinum toxin (BT) injections are used widely to clinically manage spasticity-related symptoms in stroke survivors by chemically denervating muscle fibers from their associated motor neurons. In this study, we sought to understand how BT affects muscle activation, motor unit composition and voluntary force generating capacity over a time period of 3 months. Our purpose was to characterize the time course of functional changes in voluntary muscle activity in stroke survivors who are undergoing BT therapy as part of their physician-prescribed clinical plan. Method: Our assessment of the effects of BT was based on the quantification of surface electromyogram (sEMG) recordings in the biceps brachii (BB), an upper arm muscle and of voluntary contraction force. We report here on voluntary force and sEMG responses during isometric elbow contractions across consecutive recording sessions, spread over 12 weeks in three segments, starting with a preliminary session performed just prior to the BT injection. At predetermined time points, we conducted additional clinical assessments and we also recorded from the contralateral limbs of our stroke cohort. Eight subjects were studied for approximately 86 experimental recording sessions on both stroke-affected and contralateral sides. Results: We recorded an initial reduction in force and sEMG in all subjects, followed by a trajectory with a progressive return to baseline over a maximum of 12 weeks, although the minimum sEMG and minimum force were not always recorded at the same time point. Three participants were able to complete only one to two segments. Slope values of the sEMG-force relations were also found to vary across the different time segments. While sEMG-force slopes provide assessments of force generation capacity of the BT injected muscle, amplitude histograms from novel sEMG recordings during the voluntary tasks provide additional insights about differential actions of BT on the overall motor unit (MU) population over time.

Characteristic Variation of Electromechanical Delay After the Botulinum Toxin Injection in Spastic Biceps Brachii Muscles

“…The highest antispastic effect of the BT induces the denervation found within 1 month of the injection affecting the contraction force and the sEMG. This has been reported earlier by several groups including us ( 13 , 43 ).…”

“…Table 2 summarizes the MVC levels for all the subjects across the session. Part of the force values have been restated from our previous work for clarity purposes ( 13 ). In general, the contraction force values across the recording sessions decreased in the sessions just after the BT injection, then gradually increased to sub-baseline levels.…”

“…Botulinum toxin reduces hypertonia and hyperreflexia by means of the chemodenervation at the neuromuscular junction (NMJ) ( 12 ). Generally, the period between successive BT injections chosen by a managing physician is ~10–12 weeks with the survivors of chronic stroke, and the maximum effect is observed within 1 month after the injection ( 13 ). While BT reduces spasticity due to cholinergic blockade of the NMJ, it also alters the neuromuscular control during the contraction ( 14 ) and also affects the passive mechanical properties of the muscle, as well as the MTU ( 15 ).…”

Duration of Treatment Effect Using IncobotulinumtoxinA for Upper-limb Spasticity: A Post-hoc Analysis

“…Although statistically significant, differences between groups were relatively small in the MP of the current study, which may reflect a placebo response consistent with perceived efficacy of the initial treatment. In the authors experience in clinical practice, patients' perceived effects of the first injection are often greater than at subsequent injections where they may return for a repeat injection around 12 weeks post-treatment although the effects have not fully worn off and nascent EMG readings suggest continuing motor unit remodeling (26). In the current study, taking into account only incobotulinumtoxinA treatment intervals, a treatment effect of ≥20 weeks was observed in almost one-quarter of subjects in at least one injection cycle, with most reinjections occurring ≤Week 29, while treatments beyond Week 29 occurred in a few outlier subjects and could be more susceptible to confounding factors.…”

Comprehensive Assessment of the Time Course of Biomechanical, Electrophysiological and Neuro-Motor Effects after Botulinum Toxin Injections in Elbow Flexors of Chronic Stroke Survivors with Spastic Hemiplegia: A Cross Sectional Observation Study

“…There are only few laboratory studies that characterized the time course of different BoNT effects, e.g., on voluntary activation capacity [35], difference in reflex and voluntary responses [32], neural vs. non-neural response [34] and electrophysiological response [33]. As described above, BoNT injections have multiple effects on the spastic muscles, including neural and non-neural components of hypertonia, muscle strength, and motor performance.…”