[ARTICLE] Botulinum toxin type A in post-stroke lower limb spasticity: a multicenter, double-blind, placebo-controlled trial – Full Text

Abstract

Lower limb spasticity in post-stroke patients can impair ambulation and reduces activities of daily living (ADL) performance of patients. Botulinum toxin type A (BoNTA) has been shown effective for upper limb spasticity. This study assesses the treatment of lower limb spasticity in a large placebo-controlled clinical trial. In this multicenter, randomized, double-blind, parallel-group, placebo-controlled study, we evaluate the efficacy and safety of one-time injections of botulinum toxin type A (BoNTA) in Japanese patients with post-stroke lower limb spasticity. One hundred twenty patients with lower limb spasticity were randomized to a single treatment with BoNTA 300 U or placebo. The tone of the ankle flexor was assessed at baseline and through 12 weeks using the Modified Ashworth Scale (MAS). Gait pattern and speed of gait were also assessed. The primary endpoint was area under the curve (AUC) of the change from baseline in the MAS ankle score. Significant improvement in spasticity with BoNTA 300 U was demonstrated by a mean difference in the AUC of the change from baseline in the MAS ankle score between the BoNTA and placebo groups (−3.428; 95% CIs, −5.841 to −1.016; p = 0.006; t test). A significantly greater decrease from baseline in the MAS ankle score was noted at weeks 4, 6 and 8 in the BoNTA group compared to the placebo group (p < 0.001). Significant improvement in the Clinicians Global Impression was noted by the investigator at weeks 4, 6 and 8 (p = 0.016–0.048, Wilcoxon test), but not by the patient or physical/occupational therapist. Assessments of gait pattern using the Physician’s Rating Scale and speed of gait revealed no significant treatment differences but showed a tendency towards improvement with BoNTA. No marked difference was noted in the frequency of treatment-related adverse events between BoNTA and placebo groups. This was the first large-scale trial to indicate that BoNTA significantly reduced spasticity in lower limb muscles.

Introduction

Spasticity is defined by Lance as a motor disorder characterized by a velocity-dependent increase in tonic stretch reflexes (muscle tone) with exaggerated tendon jerks, resulting from hyperexcitability of the stretch reflex, as one of the components of upper motor neuron syndrome [1].

BoNTA (botulinum toxin type A, onabotulinumtoxinA¹) is a specific formulation of a locally injected muscle relaxant whose active ingredient is botulinum toxin type A produced by Clostridium botulinum. Botulinum toxin type A binds to the receptors in the presynaptic, cholinergic motor nerve terminal and is taken up by the nerve cells where the light chain of toxin cleaves a synaptosome-associated protein (SNAP-25) to inhibit acetylcholine release from the nerve terminal. As its muscle relaxant effect is exerted in the hypertonic muscle, BoNTA offers an alternative treatment for spastic patients who have difficulty with oral muscle relaxants that can produce generalized weakness and drowsiness, cognitive impairment, and/or a reduced level of arousal. Locally injected BoNTA is expected to improve limb position and functional ability, and reduce pain in patients with spasticity. Moreover, BoNTA has no sedative action, unlike existing oral antispastic treatments, and therefore can be used in patients with cognitive impairment or a reduced level of arousal. Based on these considerations, BoNTA is a first-line treatment choice if the upper and lower limb spasticity is focal and reversible without contracture [2].

The efficacy and safety of BoNTA in patients with post-stroke lower limb spasticity have been suggested by randomized-controlled trials of limited scale [3, 4, 5, 6, 7, 8] and meta-analysis [9]. The efficacy of BoNTA in patients with severe brain injury has also been demonstrated in a randomized-control trial [10]. Approved treatments of spasticity in Japan include peripheral and central muscle relaxants, alcohol, phenol block, and intrathecal baclofen (only in cases of severe spastic paralysis). We conducted a clinical study to evaluate the efficacy and safety of BoNTA in Japanese patients with post-stroke lower limb spasticity who received a single placebo-controlled injection of BoNTA followed by open-label repeated treatment of up to three sessions. This article reports the efficacy and safety results of the double-blind phase. […]

 

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[ARTICLE] Physical therapy for a chronic stroke individual following botulinum toxin injection for spasticity: a case report – Full Text PDF

Purpose: In this case report we describe the type and duration of a physical therapy and BoNTA intervention directed at lower limb spasticity and the gait and balance improvement in a patient post-stroke. Treatment of focal spasticity with botulinum toxin type-A (BoNTA) intramuscular injections combined with physical therapy is recommended by rehabilitations experts. However, the optimal type and duration of physical therapy intervention to optimize any functional gains that follow chemodenervation induced by BoNTA has not been established.

Method: One individual with chronic stroke who received BoNTA injections for upper and lower extremity spasticity was included. Physical therapy intervention consisted of 45-60 minute sessions twice weekly for 12 weeks and was based on the Bobath-NDT approach and an activity- based home program.

Results: Following BoNTA injections and physical therapy, the patient made clinically significant improvements in balance and gait speed and became more independent with his ambulation.

Conclusions: This case report demonstrates that physical therapy following BoNTA injections can result in significant functional improvements for individuals with spasticity post-chronic stroke that may not be possible with BoNTA injections alone.

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[POSTER] The Impact of Botulinum Toxin and Upper Limb Rehabilitation on Spasticity, Function and Pain: A Systematic Review

…The combination of BoNTA with UL rehabilitation decreased spasticity to a greater extent than UL rehabilitation plus placebo or UL rehabilitation alone at the 4 week time point only. BoNTA administration did not impact UL function or pain at either the 4 or 12 week post-intervention time point…

via The Impact of Botulinum Toxin and Upper Limb Rehabilitation on Spasticity, Function and Pain: A Systematic Review – Archives of Physical Medicine and Rehabilitation.