Stroke is a leading cause of mortality and morbidity globally. It is the third most common cause of disability globally among people over 65 years of age.1 Post-stroke spasticity is one of the important impairments following stroke along with cognitive and other sensory motor problems. Prevalence post-stroke spasticity ranges from 4% to 42.6%.2
Spasticity is one of the upper motor neuron symptoms experienced by the stroke survivors and defined 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 (muscle tone) as one component of the upper motor neuron syndrome.1
Post-stroke spasticity typically affects one-half of the body, usually the upper and the lower limb, giving rise to spastic hemiparesis. Spasticity can significantly impair functions, such as mobility and activities of daily living of stroke survivors. In the lower limb, post-stroke spasticity manifests as adducted hip, stiff knee and most commonly equinovarus foot.3 Equinovarus deformity in the ankle and foot is caused by spastic or overactive gastrocnemius, soleus and/or tibialis posterior muscles. Other foot muscles, such as flexor hallucis longus and flexor digitorum longus can also be involved causing clawing of toes. The other spastic lower limb muscles, such as the quadriceps, can cause stiff knee gait,4 hamstrings knee flexion and the hip adductors (adductor magnus, brevis and longus) adduction of the hip. Spastic lower limb gives rise to the characteristic hemiplegic or circumducting gait.
Lower limb muscles are important for transferring from bed to chair, standing from a sitting position and maintaining standing balance before taking steps to walk. The deformities caused by the spastic lower limb muscles in isolation or with other impairments can potentially impede all aspects of mobility as outlined. Post-stroke spasticity can also result in spasm, pain and contracture (permanent deformity), further compounding mobility. Inability to move and lack of independence give rise to activity limitation and participation restriction, leading to poor quality of life (QoL). In some cases, spasticity associated with weakness and lack of voluntary control can lead to adverse health outcomes such as falls and fractures.5 The burden of post-stroke spasticity is high on the stroke survivor’s active function, QoL and also on the carer. Besides the human cost, there is a significant economic cost associated with post-stroke spasticity.6
Spasticity is managed by multidisciplinary rehabilitation team and by oral antispasticity medications such as baclofen, dantrolene, diazepam and clonidine and by blocking nerves with phenol or alcohol. The evidence on the efficacy of oral medications is marginal and their use is associated with adverse effects.7 Botulinum toxin type A is an important adjunctive treatment along with stretching, strengthening exercise and bracing intervention for spasticity.
Botulinum toxin (BT) is a neurotoxin and works by blocking the acetylcholine at the neuromuscular junction weakens the muscle. This is a reversible action which lasts for two to four months8, and the injection has to be repeated. There are three varieties of botulinum toxin type A – onabotulinum toxin or Botox (by Allergan), abobotulinum toxin or Dysport (Ipsen) and incobotulinum toxin or Xeomin (Merz), the first two of which are used widely. A number of studies have shown that the botulinum toxin is safe and effective in reducing focal spasticity.8,9 It has been argued that the botulinum toxin should be the first-line treatment for post-stroke spasticity.10
Botulinum toxin is expensive and the licensed indication in many countries is often restricted to the post-stroke upper limb spasticity.11 There is a number of studies demonstrating a reduction of upper limb spasticity measured by the Modified Ashworth Scale and associated disability with botulinum toxin.12 The effectiveness of the toxin in improving function is less certain – more so in the lower limbs.8 Studies have revealed strong evidence that the BT in the lower limb reduces spasticity. There have not been many randomized controlled trials (RCTs) in the lower limb showing improvement in lower limb functioning such as gait (velocity and/or distance) and improving the QoL. This may be the reason the toxin is still not approved by the pharmaceutical benefit scheme for use in the lower limb in many countries including Australia. A systematic review and meta-analysis revealed that use of BT was associated with a small but statistically significant increase in gait velocity.3 Since then, some RCTs have been carried out with BT in lower limb. From a stroke survivor’s perspective, the ability to walk remains one of the most important goals. Botulinum toxin is also useful for passive functions such as hygiene, preventing contracture and lessening the carer’s burden and in combination with physiotherapy is found to reduce the economic cost in patients with post-stroke spasticity.6 There is a recent systematic review and meta-analysis using on the efficacy of botulinum toxin type A for improving activity restriction and QoL of patients using the GRADE approach.13 This systematic review included RCTs comprising a heterogeneous group of patients with spasticity in upper or lower limb from different causes and was not specific to post stroke lower limb spasticity. Currently, no systematic review is available synthesizing evidence from RCTs focusing on the efficacy of botulinum toxin in improving gait and walking distance and QoL among post-stroke patients with lower limb spasticity.
Hence, the present systematic review aims to synthesize and evaluate the current best available evidence, drawn from RCTs, on the effectiveness of botulinum toxin type A therapy on gait velocity, walking distance and QoL, specifically in adult post-stroke patients with lower limb spasticity. The studies to be included in this review will not be restrictive of the injection technique or dosage of botulinum toxin A used to enable a comprehensive assessment of the effectiveness of the treatment. Findings from the present review will serve to inform the usefulness of botulinum toxin type A in improving the functional outcomes of patients with post-stroke lower limb spasticity over the course of rehabilitation.