Special Issue "Enhancing the Effect of Botulinum Toxin in Neurology, Neurorehabilitation and Pain Medicine"

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

Deadline for manuscript submissions: closed (31 January 2021).

Special Issue Editors

Prof. Giorgio Sandrini
E-Mail Website
Guest Editor
Department of Brain and Behavioral Sciences, University of Pavia, Pavia, Italy
Interests: neurology; neurorehabilitation; headache and pain; extrapyramidal disorders
Prof. Cristina Tassorelli
E-Mail Website
Guest Editor
Department of Brain and Behavioral Sciences, University of Pavia, IRCCS C.Mondino Foundation, Pavia, Italy
Interests: neurology; neurorehabilitation; headache and pain; extrapyramidal disorders
Prof. Dr. Stefano Tamburin
E-Mail Website
Guest Editor
University of Verona, Department of Neurosciences, Biomedicine and Movement Sciences
Interests: neurology; neurorehabilitation; Parkinson’s disease and movement disorders; neuropathic pain; Alzheimer’s disease and dementia

Special Issue Information

Botulinum neurotoxin (BoNT) was introduced in the late 1980s for the treatment of strabismus and some type of focal dystonia, but their indications have been expanded to other types of dystonia, spasticity, hyperhidrosis, chronic migraine, cosmetic use, and overactive bladder. BoNT is used empirically for a variety of neurological, ophthalmological, gastrointestinal, urological, and dermatological conditions. Moreover, a number of pain disorders, including primary headaches and facial pain, as well as neuropathic and nociceptive pain conditions benefit from BoNT injection. Because of this wide number of approved, as well as off-label indications, BoNT plays a key role in the management of neurological conditions, in neurorehabilitation, and is an emerging treatment in the field of pain medicine.

Current strategies to enhance the clinical effect of BoNT include the use of BoNT in combination with rehabilitation procedures and neurostimulation, higher BoNT doses, and stratification of patients according to clinical markers. Future strategies may include modified BoNT injection protocols and instrumental biomarkers.

This Special Issue is devoted to all the above themes, with a particular interest in the fields of neurology, neurorehabilitation, and pain medicine. Randomized controlled trials, original reports, innovative and informative case studies or series, systematic reviews and meta-analyses in human populations, as well as experimental studies in animal models, are all welcome.

Prof. Giorgio Sandrini
Prof. Cristina Tassorelli
Prof. Stefano Tamburin
Guest Editors

Manuscript Submission Information

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Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2400 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 neurotoxin (BoNT)
  • neurology
  • neurorehabilitation
  • rehabilitation
  • Parkinson’s disease
  • dystonia
  • movement disorders
  • pain
  • stroke
  • spasticity

Published Papers (7 papers)

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Research

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Open AccessArticle
The Five-Year Prospective Study of Quality of Life in Hemifacial Spasm Treated with Abo-Botulinum Toxin A
Toxins 2021, 13(3), 215; https://0-doi-org.brum.beds.ac.uk/10.3390/toxins13030215 - 16 Mar 2021
Viewed by 452
Abstract
This study aimed to determine the long-term quality of life (QoL) in hemifacial spasm (HFS) patients after treating with Abo-botulinum toxin A (Abo-BTX). The study assessed the disease-specific QoL (hemifacial spasm questionnaire 30 items; HFS 30), the involuntary movements (abnormal involuntary movement scale; [...] Read more.
This study aimed to determine the long-term quality of life (QoL) in hemifacial spasm (HFS) patients after treating with Abo-botulinum toxin A (Abo-BTX). The study assessed the disease-specific QoL (hemifacial spasm questionnaire 30 items; HFS 30), the involuntary movements (abnormal involuntary movement scale; AIMS), general health QoL (Medical Outcomes 36-Item Short Form Health Survey; SF-36), and Depression (the Center of Epidemiologic Studies-Depression questionnaire; CES-D). A total of 74 HFS patients were enrolled from 2012 to 2017. The disease-specific QoL; involuntary movements; and the general health domain of SF 36 were significantly improved after injections of Abo-BTX A in the first few years (p < 0.04), but significantly decreased at the fifth year of treatment without significant clinical resistance observed (p < 0.001). Only the general health domain of SF 36 showed persistent improvement over five years (p = 0.02). In summary, Abo-BTX A can improved quality of life in the first few years; however only the general health domain of SF-36 showed significant improvement over five years (p = 0.02). No clinical resistance was observed. Full article
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Open AccessArticle
The Effectiveness of Botulinum Toxin Type A (BoNT-A) Treatment in Brazilian Patients with Chronic Post-Stroke Spasticity: Results from the Observational, Multicenter, Prospective BCause Study
Toxins 2020, 12(12), 770; https://0-doi-org.brum.beds.ac.uk/10.3390/toxins12120770 - 04 Dec 2020
Viewed by 646
Abstract
Botulinum toxin type A (BoNT-A) is an effective treatment for post-stroke spasticity; however, some patients cannot access treatment until ≥1 year post-stroke. This Brazilian post-marketing study (NCT02390206) assessed the achievement of person-centered goals in patients with chronic post-stroke spasticity after a BoNT-A injection. [...] Read more.
Botulinum toxin type A (BoNT-A) is an effective treatment for post-stroke spasticity; however, some patients cannot access treatment until ≥1 year post-stroke. This Brazilian post-marketing study (NCT02390206) assessed the achievement of person-centered goals in patients with chronic post-stroke spasticity after a BoNT-A injection. Patients had a last documented stroke ≥1 year before study entry and post-stroke upper limb (UL) spasticity, with or without lower limb (LL) spasticity. Patients received BoNT-A injections at baseline (visit 1) and visit 2 (3–6 months). Primary endpoint was responder rate (achievement of primary goal from Goal Attainment Scaling (GAS)) at visit 2. Overall, 204 patients underwent GAS evaluation at visit 2, mean (SD) age was 56.4 (13.2) years and 90.7% had LL spasticity. Median (range) time between first stroke and onset of spasticity was 3.6 (0−349) months, onset of spasticity and first injection was 22.7 (0−350) months and waiting time for a rehabilitation appointment was 9.0 (1−96) months. At visit 2, 61.3% (95% CI: 54.4, 67.7) of patients were responders, which was similar for UL and LL primary goals (57.8% [95% CI: 49.9, 65.3] vs. 64.1% [95% CI: 48.4, 77.3]). This study provides evidence to support the effectiveness of BoNT-A treatment for chronic post-stroke spasticity. Full article
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Open AccessArticle
Exploring Emotional Distress, Psychological Traits and Attitudes in Patients with Chronic Migraine Undergoing OnabotulinumtoxinA Prophylaxis versus Withdrawal Treatment
Toxins 2020, 12(9), 577; https://0-doi-org.brum.beds.ac.uk/10.3390/toxins12090577 - 08 Sep 2020
Cited by 2 | Viewed by 726
Abstract
This explorative cross-sectional study aims at exploring emotional distress, psychological profiles, and the attitude towards receiving psychological support in eighty-seven patients with chronic migraine (CM) undergoing OnabotulinumtoxinA prophylactic treatment (OBT-A, n = 40) or withdrawal treatment (WT, n = 47). The outcomes were [...] Read more.
This explorative cross-sectional study aims at exploring emotional distress, psychological profiles, and the attitude towards receiving psychological support in eighty-seven patients with chronic migraine (CM) undergoing OnabotulinumtoxinA prophylactic treatment (OBT-A, n = 40) or withdrawal treatment (WT, n = 47). The outcomes were explored through a specific battery of questionnaires. 25% of patients undergoing OBT-A and almost half of the patients undergoing WT reported psychological distress of at least moderate-severe level, respectively. Coping strategies, self-efficacy, and perceived social support were similar in the two groups. Patients undergoing OBT-A presented lower psychological inflexibility than patients undergoing WT. Predictors of higher psychological distress were low perceived social support by friends, low self-efficacy, and higher avoidance strategies. In both groups, most of the patients evaluated receiving psychological support to be useful (79%). The potential beneficial effects of OBT-A on the severity of symptoms and psychological distress might further support its role in the multidisciplinary management of patients with CM. Identifying patients with psychological vulnerabilities who may benefit from psychological support is relevant in patients with CM. Full article

Review

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Open AccessReview
Electrical Stimulation of Injected Muscles to Boost Botulinum Toxin Effect on Spasticity: Rationale, Systematic Review and State of the Art
Toxins 2021, 13(5), 303; https://0-doi-org.brum.beds.ac.uk/10.3390/toxins13050303 - 23 Apr 2021
Viewed by 408
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 [...] Read more.
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. Full article
Open AccessReview
The Central Effects of Botulinum Toxin in Dystonia and Spasticity
Toxins 2021, 13(2), 155; https://0-doi-org.brum.beds.ac.uk/10.3390/toxins13020155 - 17 Feb 2021
Viewed by 512
Abstract
In dystonic and spastic movement disorders, however different in their pathophysiological mechanisms, a similar impairment of sensorimotor control with special emphasis on afferentation is assumed. Peripheral intervention on afferent inputs evokes plastic changes within the central sensorimotor system. Intramuscular application of botulinum toxin [...] Read more.
In dystonic and spastic movement disorders, however different in their pathophysiological mechanisms, a similar impairment of sensorimotor control with special emphasis on afferentation is assumed. Peripheral intervention on afferent inputs evokes plastic changes within the central sensorimotor system. Intramuscular application of botulinum toxin type A (BoNT-A) is a standard evidence-based treatment for both conditions. Apart from its peripheral action on muscle spindles, a growing body of evidence suggests that BoNT-A effects could also be mediated by changes at the central level including cerebral cortex. We review recent studies employing electrophysiology and neuroimaging to investigate how intramuscular application of BoNT-A influences cortical reorganization. Based on such data, BoNT-A becomes gradually accepted as a promising tool to correct the maladaptive plastic changes within the sensorimotor cortex. In summary, electrophysiology and especially neuroimaging studies with BoNT-A further our understanding of pathophysiology underlying dystonic and spastic movement disorders and may consequently help develop novel treatment strategies based on neural plasticity. Full article
Open AccessReview
Botulinum Toxin in Movement Disorders: An Update
Toxins 2021, 13(1), 42; https://0-doi-org.brum.beds.ac.uk/10.3390/toxins13010042 - 08 Jan 2021
Cited by 3 | Viewed by 914
Abstract
Since its initial approval in 1989 by the US Food and Drug Administration for the treatment of blepharospasm and other facial spasms, botulinum toxin (BoNT) has evolved into a therapeutic modality for a variety of neurological and non-neurological disorders. With respect to neurologic [...] Read more.
Since its initial approval in 1989 by the US Food and Drug Administration for the treatment of blepharospasm and other facial spasms, botulinum toxin (BoNT) has evolved into a therapeutic modality for a variety of neurological and non-neurological disorders. With respect to neurologic movement disorders, BoNT has been reported to be effective for the treatment of dystonia, bruxism, tremors, tics, myoclonus, restless legs syndrome, tardive dyskinesia, and a variety of symptoms associated with Parkinson’s disease. More recently, research with BoNT has expanded beyond its use as a powerful muscle relaxant and a peripherally active drug to its potential central nervous system applications in the treatment of neurodegenerative disorders. Although BoNT is the most potent biologic toxin, when it is administered by knowledgeable and experienced clinicians, it is one of the safest therapeutic agents in clinical use. The primary aim of this article is to provide an update on recent advances in BoNT research with a focus on novel applications in the treatment of movement disorders. This comprehensive review of the literature provides a critical review of evidence-based clinical trials and highlights recent innovative pilot studies. Full article
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Open AccessReview
High Dosage of Botulinum Toxin Type A in Adult Subjects with Spasticity Following Acquired Central Nervous System Damage: Where Are We at?
Toxins 2020, 12(5), 315; https://0-doi-org.brum.beds.ac.uk/10.3390/toxins12050315 - 10 May 2020
Viewed by 1147
Abstract
Spasticity is a common disabling disorder in adult subjects suffering from stroke, brain injury, multiple sclerosis (MS) and spinal cord injury (SCI). Spasticity may be a disabling symptom in people during rehabilitation and botulinum toxin type A (BTX-A) has become the first-line therapy [...] Read more.
Spasticity is a common disabling disorder in adult subjects suffering from stroke, brain injury, multiple sclerosis (MS) and spinal cord injury (SCI). Spasticity may be a disabling symptom in people during rehabilitation and botulinum toxin type A (BTX-A) has become the first-line therapy for the local form. High BTX-A doses are often used in clinical practice. Advantages and limitations are debated and the evidence is unclear. Therefore, we analysed the efficacy, safety and evidence for BTX-A high doses. Studies published from January 1989 to February 2020 were retrieved from MEDLINE/PubMed, Embase, Cochrane Central Register. Only obabotulinumtoxinA (obaBTX-A), onabotulinumtoxinA (onaBTX-A), and incobotulinumtoxinA (incoBTX-A) were considered. The term “high dosage” indicated ≥ 600 U. Thirteen studies met the inclusion criteria. Studies had variable method designs, sample sizes and aims, with only two randomised controlled trials. IncoBTX-A and onaBTX-A were injected in three and eight studies, respectively. BTX-A high doses were used predominantly in treating post-stroke spasticity. No studies were retrieved regarding treating spasticity in MS and SCI. Dosage of BTX-A up to 840 U resulted efficacious and safety without no serious adverse events (AEs). Evidence is insufficient to recommend high BTX-A use in clinical practice, but in selected patients, the benefits of high dose BTX-A may be clinically acceptable. Full article
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