Electrical Stimulation of Injected Muscles to Boost Botulinum Toxin Effect on Spasticity: Rationale, Systematic Review and State of the Art.

Alessandro Picelli,Cristina Tassorelli,Nicola Smania,Stefano Tamburin,Giorgio Sandrini,Mirko Filippetti,Roberto De Icco

doi:10.3390/toxins13050303

Abstract

Botulinum toxin type A (BoNT-A) represents a first-line treatment for spasticity, a common disabling consequence of many neurological diseases. Electrical stimulation of motor nerve endings has been reported to boost the effect of BoNT-A. To date, a wide range of stimulation protocols has been proposed in the literature. We conducted a systematic review of current literature on the protocols of electrical stimulation to boost the effect of BoNT-A injection in patients with spasticity. A systematic search using the MeSH terms “electric stimulation”, “muscle spasticity” and “botulinum toxins” and strings “electric stimulation [mh] OR electrical stimulation AND muscle spasticity [mh] OR spasticity AND botulinum toxins [mh] OR botulinum toxin type A” was conducted on PubMed, Scopus, PEDro and Cochrane library electronic databases. Full-text articles written in English and published from database inception to March 2021 were included. Data on patient characteristics, electrical stimulation protocols and outcome measures were collected. This systematic review provides a complete overview of current literature on the role of electrical stimulation to boost the effect of BoNT-A injection for spasticity, together with a critical discussion on its rationale based on the neurobiology of BoNT-A uptake.

Highlights

Botulinum neurotoxin type A (BoNT-A) is a single-chain polypeptide of about 150,000 Da molecular weight produced by Clostridium botulinum [1]
Based on Botulinum toxin type A (BoNT-A) uptake neurobiology, we suggest a single electrical stimulation session lasting 30–60 min applied on the injected muscles immediately after BoNT-A administration
The output of this systematic analysis of the literature shows that a wide range of electrical stimulation protocols have been proposed to boost the effect of BoNT-A in spasticity [29,30,31,32,33,34,35,36,37,38,39,40,41,42], but only a few were designed considering the timing of toxin uptake

Summary

Introduction

Botulinum neurotoxin type A (BoNT-A) is a single-chain polypeptide of about 150,000 Da molecular weight produced by Clostridium botulinum [1]. BoNT-A is composed of a heavy chain and a light chain linked together by a single disulfide bond, with the C-terminal of the heavy chain mainly responsible for binding; its N-terminal is involved in the membrane translo- 4.0/). BoNT-A binds with high affinity to the presynaptic cell membrane of skeletal cholinergic nerve terminals. This peculiar tropism and catalytic activity, which leads to neuromuscular transmission transient blockade, are the basis of the therapeutic use of BoNT-A in patients with neurological conditions associated with overactive muscle conditions [4]. In addition to BoNT-A, other treatment options for managing spasticity are oral medications, chemodenervation with phenol or alcohol, intrathecal baclofen, rehabilitation procedures, physical modalities, and surgical interventions [9,10]

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Conclusion