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Toxins
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The Botulinum Toxin and Spasticity: Exploring New Horizons
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The Botulinum Toxin and Spasticity: Exploring New Horizons

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

Deadline for manuscript submissions: 30 April 2025 | Viewed by 17253

Special Issue Editors

Prof. Dr. Andrea Santamato

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Guest Editor
Physical Medicine and Rehabilitation, Spasticity and Movement Disorder Unit, Policlinico Riuniti, University of Foggia, Viale Pinto 1, 71122 Foggia, Italy
Interests: spasticity; botulinum neurotoxin; neurological rehabilitation; robotics for neurological rehabilitation
Special Issues, Collections and Topics in MDPI journals
Dr. Franco Molteni

E-Mail Website
Guest Editor
Physical Medicine and Rehabilitation Section, Villa Beretta Rehabilitation Center, Via N. Sauro 17, 23845 Costa Masnaga, Italy
Interests: pharmacological treatments for spasticity and movement disorders; robotic technologies for neuroplasticity and recovery; brain and spinal cord injuries

Special Issue Information

Dear Colleagues,

It is with great enthusiasm that we, Prof. Andrea Santamato and Dr. Franco Molteni, invite you to contribute to a pivotal Special Issue of the Toxins journal, entitled "The Botulinum Toxin and Spasticity: Exploring New Horizons". Our shared expertise and commitment to the study and treatment of spasticity have motivated us to bring together this comprehensive collection of studies.

In the dynamic field of neurorehabilitation, the application of the botulinum toxin has emerged as a transformative approach to managing spasticity. This Special Issue is dedicated to unraveling the intricate mechanisms and expanding the clinical applications of the botulinum toxin, thereby improving therapeutic outcomes for patients.

We welcome submissions that delve into the latest research, innovative treatments, and comprehensive reviews on this topic. Areas of particular interest include but are not limited to:

  • Tailoring the botulinum toxin for spasticity due to conditions such as stroke, cerebral palsy, multiple sclerosis, and spinal cord injuries.
  • Highlighting advancements in neurophysiological studies and other tools for improving treatments and understanding patient outcomes.
  • Integrating the botulinum toxin with neurostimulation, physical modalities, robotic strategies and other advanced technologies for a multimodal and holistic patient care approach.
  • Discussing innovative approaches, existing challenges, and future directions in the therapeutic application of the botulinum toxin.
  • Investigating the role of artificial intelligence and machine learning in optimizing the clinical management of spasticity, including diagnostic tools, treatment planning, and outcome prediction.
  • Focusing on the long-term effects and quality of life for patients undergoing botulinum toxin therapy.

Our ambition with this Special Issue is to create a platform that not only consolidates our current knowledge, but also ignites innovative discussions and collaborations in the field of spasticity treatment.

We eagerly anticipate your submissions of original research papers and comprehensive reviews. Your expertise will significantly contribute to advancing our collective understanding of the botulinum toxin in the nuanced management of spasticity and its applications.

Warm regards,

Prof. Dr. Andrea Santamato
Dr. Franco Molteni
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a double-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Toxins is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • botulinum toxin
  • spasticity treatment
  • neurorehabilitation

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Further information on MDPI's Special Issue policies can be found here.

Published Papers (7 papers)

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Research

Jump to: Review, Other

10 pages, 265 KiB  
Article
Do Diagnostic Nerve Blocks Affect the Starting Dose of Botulinum Neurotoxin Type A for Spasticity? A Case-Control Study
by Mirko Filippetti, Stefano Tamburin, Rita Di Censo, Roberto Aldegheri, Elisa Mantovani, Stefania Spina, Marco Battaglia, Alessio Baricich, Andrea Santamato, Nicola Smania and Alessandro Picelli
Toxins 2024, 16(9), 388; https://doi.org/10.3390/toxins16090388 - 6 Sep 2024
Cited by 2 | Viewed by 1820
Abstract
One of the aims of diagnostic nerve blocks is to identify the overactive muscles that lead to a specific spasticity pattern. However, to date, there is no evidence on how nerve blocks may affect botulinum neurotoxin-A (BoNT-A) dose in patients with spasticity. This [...] Read more.
One of the aims of diagnostic nerve blocks is to identify the overactive muscles that lead to a specific spasticity pattern. However, to date, there is no evidence on how nerve blocks may affect botulinum neurotoxin-A (BoNT-A) dose in patients with spasticity. This case-control study aims to assess the role of diagnostic nerve block in defining BoNT-A starting dose at first treatment. Patients with upper and lower limb spasticity treated for the first time with BoNT-A were retrospectively divided into two groups: Group 1 (n = 43) was evaluated with clinical assessment and diagnostic nerve block; Group 2 (n = 56) underwent clinical assessment only. Group 1 was injected with higher BoNT-A doses in some muscles (i.e., flexor digitorum profundus, soleus), and received a higher BoNT-A cumulative dose with a larger number of injected muscles for some spasticity patterns (i.e., “clenched fist”, “flexed fingers”, “adducted thigh”). Diagnostic nerve block may help the clinician to optimize and personalize the BoNT-A dose since the first BoNT-A treatment. Full article
(This article belongs to the Special Issue The Botulinum Toxin and Spasticity: Exploring New Horizons)
24 pages, 4644 KiB  
Article
Feasibility of Adjunct Therapy with a Robotic Hand Orthosis after Botulinum Toxin Injections in Persons with Spasticity: A Pilot Study
by Raffaele Ranzani, Margherita Razzoli, Pierre Sanson, Jaeyong Song, Salvatore Galati, Carlo Ferrarese, Olivier Lambercy, Alain Kaelin-Lang and Roger Gassert
Toxins 2024, 16(8), 346; https://doi.org/10.3390/toxins16080346 - 8 Aug 2024
Viewed by 1677
Abstract
Upper-limb spasticity, frequent after central nervous system lesions, is typically treated with botulinum neurotoxin type A (BoNT-A) injections to reduce muscle tone and increase range of motion. However, performing adjunct physical therapy post-BoNT-A can be challenging due to residual weakness or spasticity. This [...] Read more.
Upper-limb spasticity, frequent after central nervous system lesions, is typically treated with botulinum neurotoxin type A (BoNT-A) injections to reduce muscle tone and increase range of motion. However, performing adjunct physical therapy post-BoNT-A can be challenging due to residual weakness or spasticity. This study evaluates the feasibility of hand therapy using a robotic hand orthosis (RELab tenoexo) with a mobile phone application as an adjunct to BoNT-A injections. Five chronic spastic patients participated in a two-session pilot study. Functional (Box and Block Test (BBT), Action Research Arm Test (ARAT)), and muscle tone (Modified Ashworth Scale (MAS)) assessments were conducted to assess functional abilities and impairment, along with usability evaluations. In the first session, subjects received BoNT-A injections, and then they performed a simulated unsupervised therapy session with the RELab tenoexo in a second session a month later. Results showed that BoNT-A reduced muscle tone (from 12.2 to 7.4 MAS points). The addition of RELab tenoexo therapy was safe, led to functional improvements in four subjects (two-cube increase in BBT as well as 2.8 points in grasp and 1.3 points in grip on ARAT). Usability results indicate that, with minor improvements, adjunct RELab tenoexo therapy could enhance therapy doses and, potentially, long-term outcomes. Full article
(This article belongs to the Special Issue The Botulinum Toxin and Spasticity: Exploring New Horizons)
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15 pages, 1607 KiB  
Article
Botulinum Toxin Type A (BoNT-A) Use for Post-Stroke Spasticity: A Multicenter Study Using Natural Language Processing and Machine Learning
by María Jesús Antón, Montserrat Molina, José Gabriel Pérez, Santiago Pina, Noemí Tapiador, Beatriz De La Calle, Mónica Martínez, Paula Ortega, María Belén Ruspaggiari, Consuelo Tudela, Marta Conejo, Pedro Leno, Marta López, Carmen Marhuenda, Carlos Arias-Cabrales, Pascal Maisonobe, Alberto Herrera and Ernesto Candau
Toxins 2024, 16(8), 340; https://doi.org/10.3390/toxins16080340 - 2 Aug 2024
Cited by 1 | Viewed by 1821
Abstract
We conducted a multicenter and retrospective study to describe the use of botulinum toxin type A (BoNT-A) to treat post-stroke spasticity (PSS). Data were extracted from free-text in electronic health records (EHRs) in five Spanish hospitals. We included adults diagnosed with PSS between [...] Read more.
We conducted a multicenter and retrospective study to describe the use of botulinum toxin type A (BoNT-A) to treat post-stroke spasticity (PSS). Data were extracted from free-text in electronic health records (EHRs) in five Spanish hospitals. We included adults diagnosed with PSS between January 2015 and December 2019, stratified into BoNT-A-treated and untreated groups. We used EHRead® technology, which incorporates natural language processing and machine learning, as well as SNOMED CT terminology. We analyzed demographic data, stroke characteristics, BoNT-A use patterns, and other treatments. We reviewed the EHRs of 1,233,929 patients and identified 2190 people with PSS with a median age of 69 years; in total, 52.1% were men, 70.7% had cardiovascular risk factors, and 63.2% had suffered an ischemic stroke. Among the PSS patients, 25.5% received BoNT-A at least once. The median time from stroke to spasticity onset was 205 days, and the time from stroke to the first BoNT-A injection was 364 days. The primary goal of BoNT-A treatment was pain control. Among the study cohort, rehabilitation was the most common non-pharmacological treatment (95.5%). Only 3.3% had recorded monitoring scales. In conclusion, a quarter of patients with PSS received BoNT-A mainly for pain relief, typically one year after the stroke. Early treatment, disease monitoring, and better data documentation in EHRs are crucial to improve PSS patients’ care. Full article
(This article belongs to the Special Issue The Botulinum Toxin and Spasticity: Exploring New Horizons)
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12 pages, 6015 KiB  
Article
Ultrasound-Guided Botulinum Neurotoxin Injection for Alleviating Cricopharyngeus Muscle Spasticity: A Cadaveric Feasibility Study with Nerve Ending Analysis
by Ji-Hyun Lee, Hyung-Jin Lee and Bo Hae Kim
Toxins 2024, 16(7), 317; https://doi.org/10.3390/toxins16070317 - 12 Jul 2024
Viewed by 1468
Abstract
Botulinum neurotoxin (BNT) injection into the cricopharyngeus muscle (CPM) under ultrasound (US) guidance is a minimally invasive technique performed to relieve cricopharyngeal dysphagia by reducing CPM spasticity. This technique is basically accessible only to both lateral sides of the CPM. This cadaveric study [...] Read more.
Botulinum neurotoxin (BNT) injection into the cricopharyngeus muscle (CPM) under ultrasound (US) guidance is a minimally invasive technique performed to relieve cricopharyngeal dysphagia by reducing CPM spasticity. This technique is basically accessible only to both lateral sides of the CPM. This cadaveric study aimed to evaluate whether US-guided injection could effectively deliver BNT to abundant areas of gross nerve endings within the CPM. We utilized a newly modified Sihler’s staining method to identify regions with abundant neural endings within the CPM while preserving the three-dimensional morphology of the muscle in 10 sides of 5 fresh cadavers. A mixture of 0.2 mL dye was injected into the 16 sides of CPM under US guidance in 8 cadavers. Nerve endings were abundant in posterolateral areas of the CPM; the injected dye was identified at the posterolateral area on 12 sides (12/16 side, 75%) without diffusion into the posterior cricoarytenoid muscle. The injection failed on four sides (two sides of the prevertebral fascia and two sides of the esophagus below the CPM). These results suggest that US-guided injection could be a feasible technique as it can deliver BNT to the most abundant nerve distribution areas within the CPM in most cases. Full article
(This article belongs to the Special Issue The Botulinum Toxin and Spasticity: Exploring New Horizons)
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15 pages, 1992 KiB  
Article
Long-Term Enhancement of Botulinum Toxin Injections for Post-Stroke Spasticity by Use of Stretching Exercises—A Randomized Controlled Trial
by In-Su Hwang, Jin-Whan Ryu, Sol Jin, Soo-A Kim and Min-Su Kim
Toxins 2024, 16(6), 267; https://doi.org/10.3390/toxins16060267 - 11 Jun 2024
Cited by 1 | Viewed by 2757
Abstract
Botulinum toxin A (BONT/A) injections play a central role in the treatment of upper limb spasticity in stroke patients. We proposed structured stretching exercises to enhance the effect of post-stroke spasticity relief of the upper limbs following BONT/A injections. A total of 43 [...] Read more.
Botulinum toxin A (BONT/A) injections play a central role in the treatment of upper limb spasticity in stroke patients. We proposed structured stretching exercises to enhance the effect of post-stroke spasticity relief of the upper limbs following BONT/A injections. A total of 43 patients who had a stroke with grade 2 spasticity or higher on the Modified Ashworth Scale (MAS) in their upper-limb muscles were randomly assigned to the intervention (n = 21) or control group (n = 22). The former received structured stretching exercises after their BONT/A injections for 20 min, 5 days per week, for 6 months at a hospital, while the others conducted self-stretching exercises at home. The outcome measures were assessed before the intervention (T0) and after three (T1) and six months (T2). Significantly greater improvements in the MAS scores of the elbows, wrists, and fingers were found in the intervention group’s patients at T1 and T2. The behavioral outcome measures, including shoulder pain, activities of daily living, and quality of life, and our electrophysiological studies also showed a significantly higher enhancement in this patient group. In conclusion, the structured stretching exercises plus BONT/A injections for six months showed a superior effect in relieving post-stroke upper-limb spasticity compared to self-stretching exercises. Full article
(This article belongs to the Special Issue The Botulinum Toxin and Spasticity: Exploring New Horizons)
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Review

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42 pages, 34187 KiB  
Review
The Role of Botulinum Toxin Type-A in Spasticity: Research Trends from a Bibliometric Analysis
by Salvatore Facciorusso, Stefania Spina, Alessandro Picelli, Alessio Baricich, Gerard E. Francisco, Franco Molteni, Jörg Wissel and Andrea Santamato
Toxins 2024, 16(4), 184; https://doi.org/10.3390/toxins16040184 - 9 Apr 2024
Cited by 9 | Viewed by 5219
Abstract
Botulinum toxin type-A (BoNT-A) has emerged as a key therapeutic agent for the management of spasticity. This paper presents a comprehensive bibliometric and visual analysis of research concerning BoNT-A treatment of spasticity to elucidate current trends and future directions in this research area. [...] Read more.
Botulinum toxin type-A (BoNT-A) has emerged as a key therapeutic agent for the management of spasticity. This paper presents a comprehensive bibliometric and visual analysis of research concerning BoNT-A treatment of spasticity to elucidate current trends and future directions in this research area. A search was conducted in the Web of Science database for articles focused on the use of BoNT-A in spasticity published between 2000 and 2022. We extracted various metrics, including counts of publications and contributions from different countries, institutions, authors, and journals. Analytical methods in CiteSpace were employed for the examination of co-citations, collaborations, and the co-occurrence of keywords. Our search yielded 1489 publications. Analysis revealed a consistent annual increase in research output. The United States, United Kingdom, and Italy were the leading contributors. The top institution in this research was Assistance Publique Hopitaux, Paris. The journal containing the highest number of relevant publications was Toxins. Key frequently occurring keywords were ‘stroke’, ‘cerebral palsy’, ‘adult spasticity’, and ‘upper extremity’. This study identified 12 clusters of keywords and 15 clusters of co-cited references, indicating the main focus areas and emerging themes in this field. This study comprehensively analyzed and summarized trends in BoNT-A research in the field of spasticity over the past 22 years. Full article
(This article belongs to the Special Issue The Botulinum Toxin and Spasticity: Exploring New Horizons)
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Graphical abstract

Other

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23 pages, 928 KiB  
Systematic Review
The Effect of Botulinum Neurotoxin-A (BoNT-A) on Muscle Strength in Adult-Onset Neurological Conditions with Focal Muscle Spasticity: A Systematic Review
by Renée Gill, Megan Banky, Zonghan Yang, Pablo Medina Mena, Chi Ching Angie Woo, Adam Bryant, John Olver, Elizabeth Moore and Gavin Williams
Toxins 2024, 16(8), 347; https://doi.org/10.3390/toxins16080347 - 8 Aug 2024
Cited by 2 | Viewed by 1942
Abstract
Botulinum neurotoxin-A (BoNT-A) injections are effective for focal spasticity. However, the impact on muscle strength is not established. This study aimed to investigate the effect of BoNT-A injections on muscle strength in adult neurological conditions. Studies were included if they were Randomised Controlled [...] Read more.
Botulinum neurotoxin-A (BoNT-A) injections are effective for focal spasticity. However, the impact on muscle strength is not established. This study aimed to investigate the effect of BoNT-A injections on muscle strength in adult neurological conditions. Studies were included if they were Randomised Controlled Trials (RCTs), non-RCTs, or cohort studies (n ≥ 10) involving participants ≥18 years old receiving BoNT-A injection for spasticity in their upper and/or lower limbs. Eight databases (CINAHL, Cochrane, EMBASE, Google Scholar, Medline, PEDro, Pubmed, Web of Science) were searched in March 2024. The methodology followed Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and was registered in the Prospective Register of Systematic Reviews (PROSPERO: CRD42022315241). Quality was assessed using the modified Downs and Black checklist and the PEDro scale. Pre-/post-injection agonist, antagonist, and global strength outcomes at short-, medium-, and long-term time points were extracted for analysis. Following duplicate removal, 8536 studies were identified; 54 met the inclusion criteria (3176 participants) and were rated as fair-quality. Twenty studies were analysed as they reported muscle strength specific to the muscle injected. No change in agonist strength after BoNT-A injection was reported in 74% of the results. Most studies’ outcomes were within six weeks post-injection, with few long-term results (i.e., >three months). Overall, the impact of BoNT-A on muscle strength remains inconclusive. Full article
(This article belongs to the Special Issue The Botulinum Toxin and Spasticity: Exploring New Horizons)
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