Botulinum toxin type A in post-stroke lower limb spasticity: a multicenter, double-blind, placebo-controlled trial

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.

Botulinum toxin type A combined with neurodynamic mobilization for lower limb spasticity: a case report

“…29,30 Ryuji Kaji et al 8 found that BoNT-A significantly reduced spasticity in the lower limb muscles in a study in which 120 patients with lower limb spasticity were randomized to a single treatment with 300 U BoNT-A or placebo. The application of Dysport (BoNT-A) in 74 patients reduced the degree of hip adductor spasticity associated with multiple sclerosis.…”

“…31 Botulinum toxin type A alone was shown to be effective for reducing spasticity in several double-blind, placebocontrolled, randomized controlled trials. [8][9][10][11][12] Botulinum toxin type A was shown to be an effective treatment of painful localized contractures in RHT, even without central nervous system lesions. 32 Therefore, BoNT-A may be a useful option for painful localized contractures that do not respond to standard treatment.…”

“…[5][6][7] Botulinum toxin type A derived from C botulinum, when injected into a spastic muscle, inhibits acetylcholine release, causing blockade of the neuromuscular patches without affecting the antagonist muscles. 8 Preliminary reports have suggested a role for botulinum toxin in the treatment of spasticity because it can reduce the degree of spasticity in both the upper and lower limbs. 4 Botulinum toxin type A has already been shown to be effective in reducing poststroke upper limb spasticity in some double-blind, placebocontrolled, randomized, controlled trials.…”

“…4 Botulinum toxin type A has already been shown to be effective in reducing poststroke upper limb spasticity in some double-blind, placebocontrolled, randomized, controlled trials. [8][9][10][11][12] Moreover, BoNT-A has been used in conjunction with physiotherapeutics to improve function and decrease pain 13,14 and spasticity. 6,15,16 Neurodynamic mobilization (NM) is a form of manual therapy that directs force to neural structures through positioning and movement of multiple joints.…”

Botulinum toxin type A combined with cervical spine manual therapy for masseteric hypertrophy in a patient with Alzheimer-type dementia: a case report

“…6 Botulinum toxin type A is derived from Clostridium botulinum; and when injected into a spastic muscle, it inhibits acetylcholine release, causing a blockade of the neuromuscular patches without affecting the antagonist muscles. 7 Botulinum toxin type A has been used in the past with mild improvements in conjunction with physiotherapeutic approaches. 8,9 However, to our knowledge, publication of this combination with manual therapy has not been reported.…”