Physical and Pharmacological Combination Therapy Incorporating Botulinum Toxins

A special issue of Toxins (ISSN 2072-6651). This special issue belongs to the section "Bacterial Toxins".

Deadline for manuscript submissions: 30 November 2026 | Viewed by 1032

Special Issue Editor


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Guest Editor
1. Department of Palliative Care, Policy and Rehabilitation, Cicely Saunders Institute, Florence Nightingale Faculty of Nursing, Midwifery and Palliative Care, King’s College London, London SE5 9PJ, UK
2. Regional Hyper-Acute Rehabilitation Unit, Northwick Park Hospital, London North West University Healthcare NHS Trust, London HA1 3UJ, UK
Interests: focal spasticity management; rehabilitation in complex disability; goal setting; attainment and outcome evaluation; treatment planning for spasticity management and outcome evaluation using psychometrically robust measurement tools

Special Issue Information

Dear Colleagues,

Botulinum toxin (BoNT) injection is widely used for the treatment of focal spasticity [1] to support physical rehabilitation or management interventions, which spasticity will often inhibit or prevent. BoNT is injected into the specific muscles where spasticity is identified [2]. However, the partial or complete delivery into muscles that are not the therapeutic target can result in the partial or complete absence of the intended therapeutic effect, and may lead to impaired activity in muscles that may be relied upon for function [1,3,4]. The method of localisation for injection is therefore one important element the outcome depends on.

In rehabilitation practice, we spend a significant amount of time and effort on planning interventions and treatment. The focus in spasticity management is the same as in any other area of rehabilitation, with a need to coordinate the physical and pharmacological aspects of management. Botulinum neurotoxins provide an opportunity to manage significant aspects of spasticity and facilitate further rehabilitation treatment or ongoing management. The use of botulinum toxin therefore often requires a combined treatment approach with physical rehabilitation programs forming a mainstay. In this Special Issue, we invite papers which showcase this interplay of the different aspects of treatment, which include treatment planning and coordination, treatment timing, outcome evaluation, and the specific targeting of muscle injection. The Special Issue will consider both patient-level reported outcomes and methods as well as clinical evaluation approaches. We welcome original research articles and reviews that contribute to advancing knowledge in this field.

Reference:

  1. Royal College of Physicians; British Society of Rehabilitation Medicine; The Chartered Society of Physiotherapy; Association of Chartered Physiotherapists Interested in Neurology and the Royal College of Occupational Therapists. Spasticity in adults: management using botulinum toxin. National guidelines. Guideline Development Group: S Ashford (editor); L Turner-Stokes; R Allison, L Duke; P Moore; G Bavikatte; S Kirker, A Ward, D Bilton. London: Royal College of Physicians; 2018.
  2. Zeuner KE, Knutzen A, Kühl C, Moller B, Hellriegel H, Margraf HG. Functional impact of different muscle localization techniques for Botulinum neurotoxin A injections in clinical routine management of post-stroke spasticity. Brain Injury. 2017;31(1):75-82.
  3. Ashford S, Singer B, Rose H, Turner-Stokes L. The impact of spasticity and contractures on dependency and outcomes from rehabilitation. The Journal of the International Society of Physical and Rehabilitation Medicine. 2022;5(3):95-104.
  4. Winston P, Branco Mills P, Reebye R, Vincent D. Cryoneurotomy as a Percutaneous Mini-invasive Therapy for the Treatment of the Spastic Limb: Case Presentation, Review of the Literature, and Proposed Approach for Use. . Archives of Rehabilitation Research and Clinical Translation. 2019;1:3-4.

Dr. Stephen Ashford
Guest Editor

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Keywords

  • botulinum neurotoxins
  • physical therapies
  • goal setting
  • treatment planning
  • outcome measurement

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Published Papers (2 papers)

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Research

10 pages, 251 KB  
Article
Early Use of Botulinum Toxin in Post-Stroke Spasticity Has the Potential to Prevent Post-Stroke Upper Limb Pain—A Secondary Analysis of the EUBoSS Randomised Controlled Trial
by Cameron Lindsay, Fraser Philp and Anand D. Pandyan
Toxins 2026, 18(3), 147; https://doi.org/10.3390/toxins18030147 - 18 Mar 2026
Viewed by 282
Abstract
Post-stroke upper limb pain is prevalent and challenging to manage once established. Early use of botulinum toxin can reduce spasticity and contracture development and has potential to prevent or reduce pain. A secondary analysis of the EUBoSS study was undertaken to report pain [...] Read more.
Post-stroke upper limb pain is prevalent and challenging to manage once established. Early use of botulinum toxin can reduce spasticity and contracture development and has potential to prevent or reduce pain. A secondary analysis of the EUBoSS study was undertaken to report pain prevalence in people post-stroke with severe upper limb impairment and spasticity in a hyper/acute setting, identify if botulinum toxin Type-A (BoNTA) could prevent pain developing and reduce pain if already present and evaluate differences in analgesic use between BoNTA and placebo groups. Odds ratios (OR) with 95% confidence intervals (CI) were calculated. Ninety-three participants (48F:45M) were randomised at a median of 11 days post-stroke (IQR 8–19) and included in the intention-to-treat analysis. Pain prevalence increased from 29.0% (95% CI [20.1–37.9%]) to 63.4% (95% CI [54.0–72.9%]) at six months. BoNTA treatment may prevent the development of pain at six months (OR = 0.42, 95% CI [0.18 to 1.01]) but not at three months (OR = 0.57, 95% CI [0.25 to 1.32]). The odds ratio for being on at least one analgesic at six months in the BoNTA group was 0.35 ([95% 0.14 to 0.87]). This secondary analysis suggests that early treatment of spasticity with BoNTA may potentially help prevent post-stroke upper limb pain and reduce analgesic use but appears less effective once pain is established. Further prospective studies are required to verify the hypotheses generated from this secondary analysis. Full article
12 pages, 259 KB  
Article
Innovative Management of Spastic Shoulder Contractures: A Retrospective Cohort Analysis of Combined Percutaneous Cryoneurolysis and Tenotomy
by Paul Winston, Mahdis Hashemi, Fraser MacRae, Samuel Herzog, Maxime Billot and Romain David
Toxins 2026, 18(3), 137; https://doi.org/10.3390/toxins18030137 - 11 Mar 2026
Viewed by 359
Abstract
Shoulder spasticity is a common consequence of upper motor neuron lesions and may be associated with soft tissue contractures, limiting functional recovery. While both cryoneurolysis and tendon lengthening procedures are used individually in refractory cases, their combined effect has not been clearly established. [...] Read more.
Shoulder spasticity is a common consequence of upper motor neuron lesions and may be associated with soft tissue contractures, limiting functional recovery. While both cryoneurolysis and tendon lengthening procedures are used individually in refractory cases, their combined effect has not been clearly established. It is consequently necessary to assess the efficacy of combining cryoneurolysis and percutaneous pectoral tenotomy in reducing shoulder spasticity and improving passive range of motion in patients with refractory shoulder spasticity and contracture. This retrospective, single-centre cohort study included 15 adults (≥19 years) with chronic shoulder spasticity and clinically confirmed musculotendinous contracture, previously treated with botulinum toxin injections without sufficient functional response, and free of pharmacological effects (last injection >4 months prior). All patients underwent cryoneurolysis targeting motor branches to the pectoral muscles. Outcomes included Modified Ashworth Scale (MAS) and shoulder Passive Range Of Motion (PROM). The combined approach provided significant improvements in spasticity severity for shoulder flexion (p < 0.01) and abduction (p < 0.01), and significant improvements in maximum PROM for shoulder flexion (p < 0.0001) and abduction (p < 0.0001). Combining cryoneurolysis and pectoral tenotomy appears feasible, safe, and clinically beneficial in selected patients with both spasticity and tendon contracture. Cryoneurolysis addresses the neural component, while tenotomy may restore mechanical excursion. This sequential diagnostic and therapeutic approach may enhance personalized management of mixed spastic–contracture shoulder limitations and could be applicable to other joints. Full article
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