A literature review on the efficacy and safety of botulinum toxin: an injection in post-stroke spasticity.

BACKGROUND: A variety of techniques for the management of spasticity have been suggested, including positioning, cryotherapy, splinting and casting, biofeedback, electrical stimulation, and medical management by pharmacological agents, Botulinum toxin A (BTA) is now the pharmacological treatment of choice in focal spasticity. BTA by blocking acetylcholine release at neuromuscular junctions accounts for its therapeutic action to relieve spasticity.
METHODS: A computerized search of Pub Med was carried out to find the latest result about efficacy of BTA in management of post stroke spasticity. RESULT: Among 84 articles were found, frothy of them included in this review and divided to lower and upper extremity.
CONCLUSIONS: BTA is a treatment choice in reducing tone and managing post stroke spasticity .

INTRODUCTION

The high prevalence of stroke is a global problem causing well-known long-term disabilities, one of which is spasticity.[1-3] The incidence of post-stroke spasticity ranges from 17% to 38%, with 4-9% of them suffer from disabling spasticity.[4]

Damage to the pyramidal tract and corticoreticulospinal fibers causes the upper motor neuron syndrome. Spasticity is a common post-stroke feature of the upper motor neuron syndrome.[5] It can have a disabling effect because of pain and reduced mobility of the stroke survivor, which may limit the potential effect of rehabilitation. Quality of life can affected by spasticity and can be highly detrimental to daily functional ability. Spasticity can cause urinary incontinence, limit sexual ability, interfere with walking, sitting, and standing, and could generally reduce one's ability of undertaking activities of daily living. The physical limitations associated with spasticity can raise risk for falls and consequent fractures.[6] A recent study showed that 39% of patients after first stroke are spastic after 12 months.[5]

A variety of techniques for the management of spasticity have been suggested, including positioning, cryotherapy, splinting and casting, biofeedback, electrical stimulation, and medical management by pharmacological agents.[7] Botulinum toxin A (BTA) is now the pharmacological treatment of choice in focal spasticity.[8]

The aim of this review is gathering data about therapeutic usage of BTA in the management of post stroke spasticity in respect of effect in spasticity and motor functions

BOTULINUM TOXIN MECHANISM OF ACTION IN SPASTICITY

Botulinum toxin is a potent neurotoxin which is produced by the bacterium Clostridium botulinum.[9] There are seven Botulinum neurotoxinserotypes (A, B, C1, D, E, F, and G), all of which inhibit acetylcholine release at the neuromuscular junction. BTA and Botulinum toxin E cleave the C terminus of SNAP-25, although BTA has the longest therapeutic effect.[10] There is not any general agreement that the extended action of BTA is due to persistence of catalytic activity or prolonged blocking action by the cleaved SNAP-25. For prolonged periods, cleaved SNAP-25 remains associated with the vesicle-docking protein syntaxin, indicating that it plays a continuous role in blocking vesicle fusion.[11] Nevertheless, this is probably not the only mechanism.[12] The very long duration effect of BTA results in the formation of temporary sprouts which replace for the paralyzed nerve terminal and can cause the wearing-off of clinical effect. A longer period of reinnervation for the parent terminal occurs finally as the sprouts die back.[13]

BTA, by blocking acetylcholine release at neuromuscular junctions, accounts for its therapeutic action to relieve dystonia, spasticity, and related disorders. Also, it has additional therapeutic advantages, not necessarily related to neuromuscular transmission; first, blockade of acetylcholine release at autonomic nerve endings, and second, blockade of transmitter release at peripheral nerve endings which use other mediators.

BTA has effects other than peripheral action, indirect effects may also occur on the spinal cord and brain, which are caused by changes in the normal balance of efferent and afferent signals. Side effects associated with administration of BTA fall into three broad categories: (1) Diffusion of the toxin can lead to unwanted inhibition of transmission at neighboring nerve endings, (2) continued blockade of transmission can cause some effects similar to anatomic denervation, such as muscle atrophy, (3) immunoresistance to BTA is another undesirable side effect[14] [Figure 1].

Figure 1

Mechanism of action of botulinum toxin A

METHODS

A detailed research was conducted in PubMed database during the time period from 1997 to December 2012 and 13,628 articles were identified concerning Botulinum toxin.

RESULTS

Eighty-four studies were identified for inclusion in this review by search for Botulinum toxin, post-stroke spasticity and finally, 40 articles were included in the review, among them eleven are review articles. The individual studies were categorized into the following subsections: Lower extremity, upper extremity, and both upper and lower extremities.

Tables 1–3 provide a brief annotation for each study.

Table 1

Lower extremity

Table 3

Both upper and lower extremity

CONCLUSIONS

As of January 2008, two Botulinum toxin serotypes (A and B) are approved by Food and Drug Administration (FDA) for clinical use in the United States. Botox® is approved for the treatment of strabismus, blepharospasm, cervical dystonia, axillary hyperhidrosis, and glabellar lines; and Myobloc® is approved for cervical dystonia. It is also approved in Europe forfocal adult spasticity.[7]

BTA is a superior treatment for post-stroke spasticity compared to other treatment options like oral therapies, such as diazepam, dantrolene sodium, baclofen, clonidine, gabapentin, and tizanidine; intratechal drug therapies, like intratecha baclofen, morphine sulphate, and fentanyl; focal treatments, such as ethyl alcohol and benzyl alcohol (phenol).[5]

The results of previous studies indicated that BTA is a treatment of choice in reducing tone and managing post stroke spasticity. Nevertheless, its efficacy in improving function remains controversial. Also, compared to other pharmacological treatment options noted above, BTA has higher efficacy and less adverse effects.

Table 2

Upper extremity