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Toxins
Special Issues
Spastic Muscle Features: Evaluation and Implications for Botulinum Toxin Treatment
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Spastic Muscle Features: Evaluation and Implications for Botulinum Toxin Treatment

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

Deadline for manuscript submissions: closed (31 October 2021) | Viewed by 41104

Special Issue Editor

Dr. Alessandro Picelli

E-Mail Website
Guest Editor
Department of Neurosciences, Biomedicine and Movement Sciences, University of Verona, 37100 Verona, Italy
Interests: botulinum toxins; muscle spasticity; movement disorders; rehabilitation; ultrasound
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Botulinum toxin (BoNT) has been proven to be effective and safe for the focal treatment of muscle spasticity. It acts in the cytosol of nerve endings and inhibits the release of acetylcholineat neuromuscular junctions by cleaving the synaptosomal-associated protein of 25 kDa, which is required for vesicle docking and, consequently, neurotransmitter release. The major causes of the loss of BoNT response in patients with focal spasticity are: inaccurate selection and identification of the correct muscle for injection, insufficient drug dosages, an inadequate injection technique, development of changes in the muscle, and formation of neutralizing antibodies. In particular, despite the fact that the features of spastic muscles (e.g., composition, neuromuscular activity, structure, rheological/mechanical properties, and metabolic state) may have some implications for BoNT treatment (e.g., drug response, dose definition, and injection targeting) they are not fully understood and considered in daily clinical practice, representing a sort of “black box” in some cases. The aim of this Special Issue is to present a collection of original research articles, reviews, and short communications on the evaluation of spastic muscle features from a BoNT administration perspective, with the aim of identifying their implications for the focal treatment of muscle spasticity.

Dr. Alessandro Picelli
Guest Editor

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

  • muscle spasticity
  • botulinum toxins
  • diagnostic imaging
  • electromyography
  • ultrasonography
  • nerve blocks
  • diagnostic techniques
  • neurology
  • biomarkers
  • rehabilitation

Published Papers (6 papers)

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Research

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14 pages, 2078 KiB  
Article
Triceps Surae Muscle Characteristics in Spastic Hemiparetic Stroke Survivors Treated with Botulinum Toxin Type A: Clinical Implications from Ultrasonographic Evaluation
by Marco Battaglia, Lucia Cosenza, Lorenza Scotti, Michele Bertoni, Marco Polverelli, Alberto Loro, Andrea Santamato and Alessio Baricich
Toxins 2021, 13(12), 889; https://doi.org/10.3390/toxins13120889 - 12 Dec 2021
Cited by 3 | Viewed by 2970
Abstract
Equinovarus foot is one of the most commonly spasticity related conditions in stroke survivors, leading to an impaired gait and poor functional performances. Notably, spastic muscles undergo a dynamic evolution following typical pathophysiological patterns. Botulinum Neurotoxin Type A (BoNT-A) is the gold standard [...] Read more.
Equinovarus foot is one of the most commonly spasticity related conditions in stroke survivors, leading to an impaired gait and poor functional performances. Notably, spastic muscles undergo a dynamic evolution following typical pathophysiological patterns. Botulinum Neurotoxin Type A (BoNT-A) is the gold standard for focal spasticity treatment, and ultrasound (US) imaging is widely recommended to guide injections and monitor muscle evolution. The role of BoNT-A in influencing muscle fibroadipose degeneration is still unclear. In this study, we analyzed medial gastrocnemius (MG) and soleus (SOL) US characteristics (cross-sectional area, muscle thickness, pennation angle, and mean echo intensity) in 53 patients. MG and SOL alterations, compared to the unaffected side, depend on the spasticity only and not on the BoNT-A treatment. In functionally preserved patients (functional ambulation classification, FAC > 3; modified Ashworth scale, MAS ≤ 2), the ultrasonographic changes of MG compared to ipsilateral SOL observed in the paretic limb alone seems to be due to histological, anatomical, pathophysiological, and biomechanical differences between the two muscles. In subjects with poor walking capability and more severe spasticity, such ipsilateral difference was found in both calves. In conclusion, BoNT-A does not seem to influence muscle degeneration. Similar muscles undergo different evolution depending on the grade of walking deficit and spasticity. Full article
(This article belongs to the Special Issue Spastic Muscle Features: Evaluation and Implications for Botulinum Toxin Treatment)
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13 pages, 1984 KiB  
Article
Ultrasonographic Evaluation of Three Approaches for Botulinum Toxin Injection into Tibialis Posterior Muscle in Chronic Stroke Patients with Equinovarus Foot: An Observational Study
by Stefania Spina, Salvatore Facciorusso, Chiara Botticelli, Domenico Intiso, Maurizio Ranieri, Antonio Colamaria, Pietro Fiore, Chiara Ciritella, François Genêt and Andrea Santamato
Toxins 2021, 13(11), 829; https://doi.org/10.3390/toxins13110829 - 22 Nov 2021
Cited by 3 | Viewed by 4904
Abstract
Spastic equinovarus (SEV) foot deformity is commonly observed in patients with post-stroke spasticity. Tibialis posterior (TP) is a common target for botulinum toxin type-A (BoNT-A) injection, as a first-line treatment in non-fixed SEV deformity. For this deep muscle, ultrasonographic guidance is crucial to [...] Read more.
Spastic equinovarus (SEV) foot deformity is commonly observed in patients with post-stroke spasticity. Tibialis posterior (TP) is a common target for botulinum toxin type-A (BoNT-A) injection, as a first-line treatment in non-fixed SEV deformity. For this deep muscle, ultrasonographic guidance is crucial to achieving maximum accuracy for the BoNT-A injection. In current clinical practice, there are three approaches to target the TP: an anterior, a posteromedial, and a posterior. To date, previous studies have failed to identify the best approach for needle insertion into TP. To explore the ultrasonographic characteristics of these approaches, we investigated affected and unaffected legs of 25 stroke patients with SEV treated with BoNT-A. We evaluated the qualitative (echo intensity) and quantitative (muscle depth, muscle thickness, overlying muscle, subcutaneous tissue, cross-sectional area) ultrasound characteristics of the three approaches for TP injection. In our sample, we observed significant differences among almost all the parameters of the three approaches, except for the safety window. Moreover, our analysis showed significant differences in cross-sectional area between treated and untreated. Advantages and disadvantages of each approach were investigated. Our findings can thus provide a suitable reference for clinical settings, especially for novice operators. Full article
(This article belongs to the Special Issue Spastic Muscle Features: Evaluation and Implications for Botulinum Toxin Treatment)
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16 pages, 1664 KiB  
Article
Efficacy and Optimal Dose of Botulinum Toxin A in Post-Stroke Lower Extremity Spasticity: A Systematic Review and Meta-Analysis
by Thanh-Nhan Doan, Mei-Ying Kuo and Li-Wei Chou
Toxins 2021, 13(6), 428; https://doi.org/10.3390/toxins13060428 - 18 Jun 2021
Cited by 14 | Viewed by 5580
Abstract
Post-stroke spasticity impedes patients’ rehabilitation progress. Contradictory evidence has been reported in using Botulinum Neurotoxin type A (BoNT-A) to manage post-stroke lower extremity spasticity (PLES); furthermore, an optimum dose of BoNT-A for PLES has not yet been established. Therefore, we conducted a systematic [...] Read more.
Post-stroke spasticity impedes patients’ rehabilitation progress. Contradictory evidence has been reported in using Botulinum Neurotoxin type A (BoNT-A) to manage post-stroke lower extremity spasticity (PLES); furthermore, an optimum dose of BoNT-A for PLES has not yet been established. Therefore, we conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) to identify the efficacy and optimal dose of BoNT-A on PLES. "Meta" and "Metafor" packages in R were used to analyze the data. Hedges’ g statistic and random effect model were used to calculate and pool effect sizes. Twelve RCTs met the eligibility criteria. Muscle tone significantly improved in week four, week eight, and maintained to week twelve after BoNT-A injection. Improvements in functional outcomes were found, some inconsistencies among included studies were noticed. Dosage analysis from eight studies using Botox® and three studies using Dysport® indicated that the optimum dose for the commonest pattern of PLES (spastic plantar flexors) is medium-dose (approximately 300U Botox® or 1000 U Dysport®). BoNT-A should be regarded as part of a rehabilitation program for PLES. Furthermore, an optimal rehabilitation program combined with BoNT-A management needs to be established. Further studies should also focus on functional improvement by BoNT-A management in the early stage of stroke. Full article
(This article belongs to the Special Issue Spastic Muscle Features: Evaluation and Implications for Botulinum Toxin Treatment)
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7 pages, 473 KiB  
Communication
Does Botulinum Toxin Treatment Affect the Ultrasonographic Characteristics of Post-Stroke Spastic Equinus? A Retrospective Pilot Study
by Alessandro Picelli, Mirko Filippetti, Camilla Melotti, Flavio Guerrazzi, Angela Modenese and Nicola Smania
Toxins 2020, 12(12), 797; https://doi.org/10.3390/toxins12120797 - 14 Dec 2020
Cited by 5 | Viewed by 2182
Abstract
Equinovarus/equinus foot is a pattern most commonly treated with botulinum toxin type A in patients with post-stroke spasticity involving the lower limbs; the gastrocnemius is the muscle most frequently injected. Spastic equinovarus/equinus can present a mixture of conditions, including spasticity, muscle/tendon shortening, muscle [...] Read more.
Equinovarus/equinus foot is a pattern most commonly treated with botulinum toxin type A in patients with post-stroke spasticity involving the lower limbs; the gastrocnemius is the muscle most frequently injected. Spastic equinovarus/equinus can present a mixture of conditions, including spasticity, muscle/tendon shortening, muscle weakness and imbalance. In this study, we wanted to determine whether botulinum toxin treatment affects the ultrasonographic characteristics of post-stroke spastic equinus. The same dose of AbobotulinumtoxinA was injected into the gastrocnemius medialis and lateralis of 21 chronic stroke patients with spastic equinus. Clinical (Ashworth scale and ankle range of motion) and ultrasound (conventional and sonoelastography) evaluation of the treated leg was carried out before and 4 weeks after injection. No significant effects of botulinum toxin treatment on the ultrasonographic characteristics of spastic equinus were observed. As expected, there were significant improvements in ankle passive dorsiflexion range of motion and calf muscle spasticity at 1 month after treatment. There was a direct association between Achilles tendon elasticity and calf muscle spasticity at baseline evaluation. Larger studies with a long-term timeline of serial evaluations are needed to further investigate the possible effects of botulinum toxin injection on spastic muscle characteristics in patients with post-stroke spasticity. Full article
(This article belongs to the Special Issue Spastic Muscle Features: Evaluation and Implications for Botulinum Toxin Treatment)
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9 pages, 2438 KiB  
Communication
Ankle and Foot Spasticity Patterns in Chronic Stroke Survivors with Abnormal Gait
by Sheng Li
Toxins 2020, 12(10), 646; https://doi.org/10.3390/toxins12100646 - 7 Oct 2020
Cited by 32 | Viewed by 18500
Abstract
Chronic stroke survivors with spastic hemiplegia have various clinical presentations of ankle and foot muscle spasticity patterns. They are mechanical consequences of interactions between spasticity and weakness of surrounding muscles during walking. Four common ankle and foot spasticity patterns are described and discussed [...] Read more.
Chronic stroke survivors with spastic hemiplegia have various clinical presentations of ankle and foot muscle spasticity patterns. They are mechanical consequences of interactions between spasticity and weakness of surrounding muscles during walking. Four common ankle and foot spasticity patterns are described and discussed through sample cases. The patterns discussed are equinus, varus, equinovarus, and striatal toe deformities. Spasticity of the primary muscle(s) for each deformity is identified. However, it is emphasized that clinical presentation depends on the severity of spasticity and weakness of these muscles and their interactions. Careful and thorough clinical assessment of the ankle and foot deformities is needed to determine the primary cause of each deformity. An understanding of common ankle and foot spasticity patterns can help guide clinical assessment and selection of target spastic muscles for botulinum toxin injection or nerve block. Full article
(This article belongs to the Special Issue Spastic Muscle Features: Evaluation and Implications for Botulinum Toxin Treatment)
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17 pages, 3164 KiB  
Opinion
Ergonomic Recommendations in Ultrasound-Guided Botulinum Neurotoxin Chemodenervation for Spasticity: An International Expert Group Opinion
by Philippe Lagnau, Alto Lo, Ryan Sandarage, Katharine Alter, Alessandro Picelli, Jorg Wissel, Monica Verduzco-Gutierrez, Areerat Suputtitada, Michael C. Munin, Stefano Carda, Omar Khan, Serdar Koçer and Rajiv Reebye
Toxins 2021, 13(4), 249; https://doi.org/10.3390/toxins13040249 - 31 Mar 2021
Cited by 9 | Viewed by 5647
Abstract
Ultrasound (US)-guided botulinum neurotoxin (BoNT) injections are becoming a mainstay in the treatment of muscle spasticity in upper motor neuron syndromes. As a result, there has been a commensurate increase in US-guided BoNT injection for spasticity training courses. However, many of these courses [...] Read more.
Ultrasound (US)-guided botulinum neurotoxin (BoNT) injections are becoming a mainstay in the treatment of muscle spasticity in upper motor neuron syndromes. As a result, there has been a commensurate increase in US-guided BoNT injection for spasticity training courses. However, many of these courses do not emphasize the importance of ergonomics. This paper aims to highlight the importance of ultrasound ergonomics and presents ergonomic recommendations to optimize US-guided BoNT injection techniques in spasticity management. Expert consensus opinion of 11 physicians (4 different continents; representing 8 countries, with an average of 12.6 years of practice using US guidance for BoNT chemodenervation (range 3 to 22 years)). A search using PubMed, College of Physicians and Surgeons of British Columbia database, EMbase was conducted and found no publications relating the importance of ergonomics in US-guided chemodenervation. Therefore, recommendations and consensus discussions were generated from the distribution of a 20-question survey to a panel of 11 ultrasound experts. All 11 surveyed physicians considered ergonomics to be important in reducing physician injury. There was complete agreement that physician positioning was important; 91% agreement that patient positioning was important; and 82% that ultrasound machine positioning was important. Factors that did not reach our 80% threshold for consensus were further discussed. Four categories were identified as being important when implementing ultrasound ergonomics for BoNT chemodenervation for spasticity; workstation, physician, patient and visual ergonomics. Optimizing ergonomics is paramount when performing US-guided BoNT chemodenervation for spasticity management. This includes proper preparation of the workspace and allowing for sufficient pre-injection time to optimally position both the patient and the physician. Lack of awareness of ergonomics for US-guided BoNT chemodenervation for spasticity may lead to suboptimal patient outcomes, increase work-related injuries, and patient discomfort. We propose key elements for optimal positioning of physicians and patients, as well as the optimal setup of the workspace and provide clinical pearls in visual identification of spastic muscles for chemodenervation. Full article
(This article belongs to the Special Issue Spastic Muscle Features: Evaluation and Implications for Botulinum Toxin Treatment)
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