Can the early use of botulinum toxin in post stroke spasticity reduce contracture development? A randomised controlled trial

Cameron Lindsay, Sissi Ispoglou, Brinton Helliwell, Dawn Hicklin, Steve Sturman, Anand Pandyan, Cameron Lindsay, Sissi Ispoglou, Brinton Helliwell, Dawn Hicklin, Steve Sturman, Anand Pandyan

Abstract

Objective: Does early treatment of spasticity with botulinum-toxin (BoNTA), in (hyper)acute stroke patients without arm-function, reduce contractures and improve function.

Design: Randomised placebo-controlled-trial.

Setting: Specialised stroke-unit.

Participants & intervention: Patients with an Action Research Arm Test (ARAT) grasp-score⩽2 who developed spasticity within six-weeks of a first stroke were randomised to receive injections of: 0.9%sodium-chloride solution (placebo) or onabotulinumtoxin-A (treatment).

Outcome-measures: Spasticity, contractures, splint use and arm function (ARAT) were taken at baseline, 12-weeks post-injection and six-months after stroke. Additionally, spasticity and contractures were measured at weeks-two, four and six post-injection.

Results: Ninety three patients were randomised. Mean time to intervention was 18-days (standard deviation = 9.3). Spasticity was lower in the treatment group with difference being significant between week-2 to 12 (elbow) and week-2 to 6 (wrist). Mean-difference (MD) varied between -8.5(95% CI -17 to 0) to -9.4(95% CI -14 to -5) µV.Contracture formation was slower in the treatment group. Passive range of motion was higher in the treatment group and was significant at week-12 (elbow MD6.6 (95% CI -0.7 to -12.6)) and week-6 (wrist MD11.8 (95% CI 3.8 to 19.8)). The use of splints was lower in the treatment group odds ratio was 7.2 (95% CI 1.5 to 34.1) and 4.2 (95% CI 1.3 to 14.0) at week-12 and month-6 respectively.Arm-function was not significantly different between the groups MD2.4 (95% CI -5.3 to 10.1) and 2.9 (95% CI -5.8 to 11.6) at week-12 and month-6 respectively.

Conclusion: BoNTA reduced spasticity and contractures after stroke and effects lasted for approximately 12-weeks. BoNTA reduced the need for concomitant contracture treatment and did not interfere with recovery of arm function.

Trial registration: EudraCT (2010-021257-39) and ClinicalTrials.gov-Identifier: NCT01882556.

Keywords: Stroke; arm; botulinum toxin; spasticity; upper limb.

Conflict of interest statement

Declaration of conflicting interests: The author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: CL, ADP, SS and DH have all received honorarium and funding to attend courses from Allergan, Ipsen and Merz. SI and BH have no competing interests.

Figures

Figure 1.
Figure 1.
Consort flow chart summarising the flow of participants through the study. The last value was carried forward in case of missing values. SAH: subarachnoid heamorahhage; SOL: space occupying lesion.

References

    1. Winters C, van Wegen EE, Daffertshofer A, et al.. Generalizability of the proportional recovery model for the upper extremity after an ischemic stroke. Neurorehabil Neural Repair 2015; 29(7): 614–622.
    1. Ada L, O’Dwyer N, Ada L, et al.. Relation between spasticity, weakness and contracture of the elbow flexors and upper limb activity after stroke: An observational study. Disabil Rehabil 2006; 28(13–14): 891–897.
    1. Pandyan AD, Cameron M, Powell J, et al.. Contractures in the post-stroke wrist: a pilot study of its time course of development and its association with upper limb recovery. Clin Rehabil 2003; 17(1): 88–95.
    1. Malhotra S, Pandyan AD, Rosewilliam S, et al.. Spasticity and contractures at the wrist after stroke: time course of development and their association with functional recovery of the upper limb. Clin Rehabil 2011; 25(2): 184–191.
    1. Pandyan AD, Gregoric M, Barnes MP, et al.. Spasticity: clinical perceptions, neurological realities and meaningful measurement. Disabil Rehabil 2005; 27(1–2): 2–6.
    1. Malhotra S, Cousins E, Ward A, et al.. An investigation into the agreement between clinical, biomechanical and neurophysiological measures of spasticity. Clin Rehabil 2008; 22(12): 1105–1115.
    1. Lannin NA, Cusick A, McCluskey A, et al.. Effects of splinting on wrist contracture after stroke a randomized controlled trial. Stroke 2007; 38(1): 111–116.
    1. Kwah LK, Harvey LA, Diong JH, et al.. Half of the adults who present to hospital with stroke develop at least one contracture within six months: an observational study. J Physiother 2012; 58(1): 41–47.
    1. Malhotra S, Rosewilliam S, Hermens H, et al.. A randomized controlled trial of surface neuromuscular electrical stimulation applied early after acute stroke: effects on wrist, spasticity and contractures. Clin Rehabil 2013; 27(7): 579–590.
    1. Lindsay C, Simpson J, Ispoglou S, et al.. The early use of botulinum toxin in post-stroke spasticity: study protocol for a randomised controlled trial. Trials 2014; 15: 12.
    1. Lyle RC. A performance test for assessment of upper limb function in physical rehabilitation treatment and research. Int J Rehabil Res 1981; 4(4): 483–492.
    1. Pandyan AD, Price CIM, Rodgers H, et al.. Biomechanical examination of a commonly used measure of spasticity. Clin Biomech 2001; 16(10): 859–865.
    1. Cousins E, Ward A, Roffe C, et al.. Does low-dose botulinum toxin help the recovery of arm function when given early after stroke? A phase II randomized controlled pilot study to estimate effect size. Clin Rehabil 2010; 24(6): 501–513.
    1. Matthews PB. Evidence from the use of vibration that the human long-latency stretch reflex depends upon spindle secondary afferents. J Physiol 1984; 348: 383–415.
    1. de Paiva A, Meunier FA, Molgo J, et al.. Functional repair of motor endplates after botulinum neurotoxin type A poisoning: biphasic switch of synaptic activity between nerve sprouts and their parent terminals. Proc Natl Acad Sci U S A 1999; 96(6): 3200–3205.
    1. Simpson DM, Gracies JM, Yablon SA, et al.. Botulinum neurotoxin versus tizanidine in upper limb spasticity: a placebo-controlled study. J Neurol Neurosurg Psychiatry 2009; 80(4): 380–385.
    1. Willerslev-Olsen M, Lundbye-Jensen J, Petersen TH, et al.. The effect of baclofen and diazepam on motor skill acquisition in healthy subjects. Exp Brain Res 2011; 213(4): 465–474.
    1. Lindsay C, Kouzouna A, Simcox C, et al.. Pharmacological interventions other than botulinum toxin for spasticity after stroke. Cochrane Database of Syst Rev 2016; 10(10): CD010362.
    1. Rosales RL, Kong KH, Goh KJ, et al.. Botulinum toxin injection for hypertonicity of the upper extremity within 12 weeks after stroke a randomized controlled trial. Neurorehabil Neural Repair 2012; 26(7): 812–821.
    1. Hesse S, Mach H, Fröhlich S, et al.. An early botulinum toxin A treatment in subacute stroke patients may prevent a disabling finger flexor stiffness six months later: a randomized controlled trial. Clin Rehabil 2012; 26(3): 237–245.
    1. Fleuren JF, Voerman GE, Erren-Wolters CV, et al.. Stop using the Ashworth Scale for the assessment of spasticity. J Neurol Neurosurg Psychiatry 2010; 81(1): 46–52.
    1. Williams PE, Goldspink G. Connective tissue changes in immobilised muscle. J Anat 1984; 138(Pt 2): 343–350.
    1. Dimitrijevic MM, Stokie DS, Wawro AW, et al.. Modification of motor control of wrist extension by mesh-glove electrical afferent stimulation in stroke patients. Arch Phys Med Rehabil 1996; 77(3): 252–258.
    1. Stinear CM, Barber PA, Petoe M, et al.. The PREP algorithm predicts potential for upper limb recovery after stroke. Brain 2012; 135(Pt 8): 2527–2535.
    1. Stockley R, Peel R, Jarvis K, et al.. Current therapy for the upper limb after stroke: a cross-sectional survey of UK therapists. BMJ Open 2019; 9(9): e030262.

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