Research

11 pages, 1291 KiB

Open AccessArticle

Single OnabotulinumtoxinA Session Add-On to Carbamazepine or Oxcarbazepine in Treatment-Refractory Trigeminal Neuralgia: A Case Series with 24-Week Follow Up

by Georgia Xiromerisiou, Ioannis C. Lampropoulos, Emmanouil V. Dermitzakis, Michail Vikelis, Chrysoula Marogianni, Dimitrios Mysiris and Andreas A. Argyriou

Toxins 2023, 15(9), 539; https://doi.org/10.3390/toxins15090539 - 31 Aug 2023

Viewed by 816

Abstract

We sought to assess the efficacy of combining onabotulinumtoxinA (BoNTA) as add-on therapy to carbamazepine or oxcarbazepine in treatment-refractory patients with trigeminal neuralgia (TGN) who failed to respond (less than 30% response rate) to adequate monotherapy. We conducted a retrospective study on 15 [...] Read more.

We sought to assess the efficacy of combining onabotulinumtoxinA (BoNTA) as add-on therapy to carbamazepine or oxcarbazepine in treatment-refractory patients with trigeminal neuralgia (TGN) who failed to respond (less than 30% response rate) to adequate monotherapy. We conducted a retrospective study on 15 patients with a definite diagnosis of TGN, according to the established criteria, and underwent BoNTA as part of their treatment plan. A single BoNTA session was administered subcutaneously, according to patients’ perceived zone of pain, at different dosages ranging from 30 to 200 units (mean ± standard deviation: 87.3 ± 39.2). All patients (15/15; 100%) reported large reductions in the severity of their TGN-related neuropathic pain. The mean pain score on the VAS scale significantly decreased from 9.3 ± 1.1 to 3.7 ± 1.2 at 2 weeks after injecting BoNTA (p < 0.001) and remained stable at 4 and 24 weeks post-injection. Regarding the impact of BoNTA on patients’ health-related quality of life, there were significant improvements in both the physical and mental health domains (p < 0.05) of SF-36 tool. BoNTA may be a safe and effective treatment option for patients with refractory TGN when added on to carbamazepine or oxcarbazepine. The use of a single BoNTA session for TGN treatment may be an alternative to surgical interventions and as add-on treatment to oral medications, providing patients with a minimally invasive, effective, safe and well-tolerated option. Full article

(This article belongs to the Special Issue Botulinum Neurotoxin: Shared/Common Mechanisms in the Treatment of Pain, Spasticity and Movement Disorders)

► Show Figures

Figure 1

10 pages, 599 KiB

Open AccessArticle

Outcomes of IncobotulinumtoxinA Injection on Myalgia and Arthralgia in Patients Undergoing Temporomandibular Joint Arthroscopy: A Randomized Controlled Trial

by David Faustino Ângelo, David Sanz, Francesco Maffia and Henrique José Cardoso

Toxins 2023, 15(6), 376; https://doi.org/10.3390/toxins15060376 - 03 Jun 2023

Cited by 4 | Viewed by 1413

Abstract

Background: Several studies have considered Botulinum Neurotoxin Type A injections effective in treating temporomandibular joint disorder (TMD) symptoms. A double-blind, randomized, controlled clinical trial investigated the benefit of complementary incobotulinumtoxinA (inco-BoNT/A) injections in the masticatory muscles of patients submitted to bilateral temporomandibular joint [...] Read more.

Background: Several studies have considered Botulinum Neurotoxin Type A injections effective in treating temporomandibular joint disorder (TMD) symptoms. A double-blind, randomized, controlled clinical trial investigated the benefit of complementary incobotulinumtoxinA (inco-BoNT/A) injections in the masticatory muscles of patients submitted to bilateral temporomandibular joint (TMJ) arthroscopy. Methods: Fifteen patients with TMD and an indication for bilateral TMJ arthroscopy were randomized into inco-BoNT/A (Xeomin, 100 U) or placebo groups (saline solution). Injections were carried out five days before TMJ arthroscopy. The primary outcome variable was a Visual Analogue Scale for TMJ arthralgia, and secondary outcomes were the myalgia degree, maximum mouth opening, and joint clicks. All outcome variables were assessed preoperatively (T0) and postoperatively (T1—week 5; T2—6-month follow-up). Results: At T1, the outcomes in the inco-BoNT/A group were improved, but not significantly more than in the placebo group. At T2, significant improvements in the TMJ arthralgia and myalgia scores were observed in the inco-BoNT/A group compared to the placebo. A higher number of postoperative reinterventions with further TMJ treatments were observed in the placebo group compared to inco-BoNT/A (63% vs. 14%). Conclusions: In patients submitted to TMJ arthroscopy, statistically significant long-term differences were observed between the placebo and inco-BoNT/A groups. Full article

(This article belongs to the Special Issue Botulinum Neurotoxin: Shared/Common Mechanisms in the Treatment of Pain, Spasticity and Movement Disorders)

► Show Figures

Figure 1

16 pages, 1158 KiB

Open AccessArticle

The Relationship between Pain and Spasticity and Tell-Tale Signs of Pain in Children with Cerebral Palsy

by Christian Wong

Toxins 2023, 15(2), 152; https://doi.org/10.3390/toxins15020152 - 13 Feb 2023

Cited by 2 | Viewed by 1849

Abstract

Pain and quality of life are closely interrelated in children with cerebral palsy (CCP). Even though 67% of CCP experience pain, it is overlooked and untreated. In this study, our purpose was two-fold: first, to examine the relationship between pain and spasticity by [...] Read more.

Pain and quality of life are closely interrelated in children with cerebral palsy (CCP). Even though 67% of CCP experience pain, it is overlooked and untreated. In this study, our purpose was two-fold: first, to examine the relationship between pain and spasticity by evaluating the effects of AbobotulinumtoxinA/Dysport (BoNT), and second, to describe the symptoms and location of pain in CCP. The subjects were 22 CCP in at least moderate pain. They were evaluated for spasticity by the modified Ashworth and Tardieu scale and for pain by the r-FLACC and the pediatric pain profile. After one injection of BoNT, the subjects were re-evaluated. We found a significant reduction in pain, but no significant relationship between the reduction of pain and spasticity. We found no association between the dose of BoNT and pain or spasticity. Pain in the lower extremity was located primarily in the hip region. The effect of ultrasound-guided intermuscular injections of BoNT suggests that pain in CCP has an extra-articular component. We found that pain in CCP manifests as specific tell-tale signs and problems in daily living. In conclusion, we found no relationship between pain and spasticity. Signs and manifestations of pain are described in detail. Lower extremity (hip) pain seems to have a soft tissue/extra-articular component. Full article

(This article belongs to the Special Issue Botulinum Neurotoxin: Shared/Common Mechanisms in the Treatment of Pain, Spasticity and Movement Disorders)

► Show Figures

Figure 1

7 pages, 278 KiB

Open AccessCommunication

IncobotulinumtoxinA Injection for Treating Children with Idiopathic Toe Walking: A Retrospective Efficacy and Safety Study

by Mirko Filippetti, Alessandro Picelli, Rita Di Censo, Sabrina Vantin, Pietro Nicola Randazzo, Giorgio Sandrini, Cristina Tassorelli, Roberto De Icco, Nicola Smania and Stefano Tamburin

Toxins 2022, 14(11), 792; https://doi.org/10.3390/toxins14110792 - 13 Nov 2022

Viewed by 1860

Abstract

There is no gold-standard treatment for idiopathic toe walking (ITW). Some previous evidence suggested that botulinum neurotoxin-A injection might improve ITW. This is a single-center retrospective study on children with ITW treated with incobotulinumtoxinA injection in the gastrocnemius medialis/lateralis muscles. We screened the [...] Read more.

There is no gold-standard treatment for idiopathic toe walking (ITW). Some previous evidence suggested that botulinum neurotoxin-A injection might improve ITW. This is a single-center retrospective study on children with ITW treated with incobotulinumtoxinA injection in the gastrocnemius medialis/lateralis muscles. We screened the charts of 97 ITW children treated with incobotulinumtoxinA (January 2019–December 2021), and the data of 28 of them, who satisfied the inclusion/exclusion criteria, were analyzed. The maximal passive ankle dorsiflexion (knee extended) was assessed at three time points, i.e., immediately before incobotulinumtoxinA injection (T0), after incobotulinumtoxinA injection during the timeframe of its effect (T1), and at follow-up, when the effect was expected to disappear (T2). The maximal passive ankle dorsiflexion was improved by incobotulinumtoxinA injection, and the effect lasted up to 6 months in some children. No adverse effects were reported to incobotulinumtoxinA injections. The treatment with incobotulinumtoxinA might improve the maximal passive ankle dorsiflexion and is safe and well-tolerated in ITW with a longer-than-expected effect in comparison to cerebral palsy. These results may offer ground to future randomized controlled trials and studies assessing the effect of BoNT-A in combination with other non-invasive approaches and exercise programs in children with ITW. Full article

(This article belongs to the Special Issue Botulinum Neurotoxin: Shared/Common Mechanisms in the Treatment of Pain, Spasticity and Movement Disorders)

13 pages, 442 KiB

Open AccessArticle

Goal-Setting in Multiple Sclerosis-Related Spasticity Treated with Botulinum Toxin: The GASEPTOX Study

by Ines Baccouche, Djamel Bensmail, Emilie Leblong, Bastien Fraudet, Claire Aymard, Victorine Quintaine, Sandra Pottier, Thibaud Lansaman, Claire Malot, Philippe Gallien and Jonathan Levy

Toxins 2022, 14(9), 582; https://doi.org/10.3390/toxins14090582 - 24 Aug 2022

Cited by 4 | Viewed by 1703

Abstract

Spasticity is one of the most disabling symptoms in multiple sclerosis (MS). Botulinum toxin injection (BTI) is a first-line treatment for focal spasticity. There is a lack of evidence of a functional improvement following BTI in MS-related spasticity. To describe goal-setting for BTI [...] Read more.

Spasticity is one of the most disabling symptoms in multiple sclerosis (MS). Botulinum toxin injection (BTI) is a first-line treatment for focal spasticity. There is a lack of evidence of a functional improvement following BTI in MS-related spasticity. To describe goal-setting for BTI in MS, and evaluate the degree of attainment, using goal attainment scaling (GAS) 4-to-6 weeks after injection session, a one-year multi-center retrospective observational study assessing goal-setting and achievement during BTI session in spastic patients with MS was set up. Following the GAS method, patients and their physicians set up to three goals and scored their achievement 4 to 6 weeks thereafter. Commonly used goals from three centers were combined into a standardized list and 125 single BTI sessions were analyzed. The most frequent goals regarded lower limb (LL) impairments (equinovarus foot, toe claw) or locomotion (stability, walking distance, clinging) and accounted for 89.1%, versus 10.9% for upper limb (UL), mostly for mild-to-moderate MS. Overall, goals were frequently achieved (85.77%) mainly when related to gait and mobility rather than hygiene and ease of care. This study gives an overview on the most frequent, relevant, and achievable goals to be set in real-life practice of BTI for spasticity management in MS. Full article

(This article belongs to the Special Issue Botulinum Neurotoxin: Shared/Common Mechanisms in the Treatment of Pain, Spasticity and Movement Disorders)

► Show Figures

Figure 1

26 pages, 2326 KiB

Open AccessEditor’s ChoiceArticle

Pooled Analysis of Real-World Evidence Supports Anti-CGRP mAbs and OnabotulinumtoxinA Combined Trial in Chronic Migraine

by Damiana Scuteri, Paolo Tonin, Pierluigi Nicotera, Marilù Vulnera, Giuseppina Cristina Altieri, Assunta Tarsitano, Giacinto Bagetta and Maria Tiziana Corasaniti

Toxins 2022, 14(8), 529; https://doi.org/10.3390/toxins14080529 - 01 Aug 2022

Cited by 16 | Viewed by 3133

Abstract

OnabotulinumtoxinA, targeting the CGRP machinery, has been approved for the last two decades for chronic migraine prevention. The recently approved monoclonal antibodies (mAbs) directed towards the calcitonin gene-related peptide (CGRP) pathway open a new age for chronic migraine control. However, some 40% patients [...] Read more.

OnabotulinumtoxinA, targeting the CGRP machinery, has been approved for the last two decades for chronic migraine prevention. The recently approved monoclonal antibodies (mAbs) directed towards the calcitonin gene-related peptide (CGRP) pathway open a new age for chronic migraine control. However, some 40% patients suffering from chronic migraine is still resistant to treatment. The aim of this work is to answer the following PICOS (participants intervention comparator outcome study design) question: Is there evidence of efficacy and safety of the combined administration of anti-CGRP mAbs and onabotulinumtoxinA in chronic migraine? A systematic review and meta-analysis [Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 recommendations] was made up to 19 April 2022. The results are encouraging: the combined treatment proved to afford ≥50% monthly headache days (MHDs)/frequency reduction respect to baseline in up to 58.8% of patients; in comparison, anti-CGRP mAbs reduce MHDs of 1.94 days from baseline and botulinum toxin of 1.86 days. Our study demonstrates for the first time that the combination therapy of onabotulinumtoxinA with anti-CGRP mAbs affords a reduction of 2.67 MHDs with respect to onabotulinumtoxinA alone, with moderate certainty of evidence. Adequately powered, good-quality studies are needed to confirm the response to combination therapy in terms of efficacy and safety. PROSPERO registration: CRD42022313640. Full article

(This article belongs to the Special Issue Botulinum Neurotoxin: Shared/Common Mechanisms in the Treatment of Pain, Spasticity and Movement Disorders)

► Show Figures

Figure 1

10 pages, 965 KiB

Open AccessArticle

Prospective Comparison of Longer Needle Lengths to Assess the Risk of OnabotulinumtoxinA-Associated Neck Pain in Patients with Chronic Migraine

by Emmanouil V. Dermitzakis, Michail Vikelis, George S. Vlachos and Andreas A. Argyriou

Toxins 2022, 14(7), 434; https://doi.org/10.3390/toxins14070434 - 24 Jun 2022

Cited by 3 | Viewed by 1309

Abstract

Background: We aimed to prospectively assess the role of needle length in improving the tolerability/safety profile of OnabotulinumtoxinA (BoNTA) for chronic migraine (CM) prophylaxis, with a specific focus on neck pain, based on patients’ body habitus and other variables. Methods: BoNTA was administered [...] Read more.

Background: We aimed to prospectively assess the role of needle length in improving the tolerability/safety profile of OnabotulinumtoxinA (BoNTA) for chronic migraine (CM) prophylaxis, with a specific focus on neck pain, based on patients’ body habitus and other variables. Methods: BoNTA was administered quarterly for two consecutive cycles, using the standard 0.5-inch 27 G needle at all pre-defined PREEMPT injection sites, except the left-hand side trapezius and paraspinal muscles, which were injected using longer needles of 1-inch 23 G at first and 1-inch 27 G at second infusion. Participants were interviewed at day 14 following each session for evidence of neck pain. The predictive significance of Body Mass Index (BMI) and other variables with neck pain was also examined. Results: A total of 100 consecutive CM patients were evaluated, and each patient served as her/his self-control. The incidence, duration and intensity of neck pain did not significantly differ using either 1-inch needle compared with standard 0.5-inch 27 G needle, although the incidence and characteristics of neck pain with the use of longer needles appeared slightly higher and more intense. The BMI index and other tested variables remained unrelated to neck pain. Conclusions: We were not able to identify significant differences or correlations in the incidence, characteristics and location of neck pain with the use of different needle length to inject BoNTA, although the use of the longer 1-inch needles likely increased the risk of this adverse event. Full article

(This article belongs to the Special Issue Botulinum Neurotoxin: Shared/Common Mechanisms in the Treatment of Pain, Spasticity and Movement Disorders)

► Show Figures

Figure 1

9 pages, 1478 KiB

Open AccessArticle

Assessing the Significance of the Circadian Time of Administration on the Effectiveness and Tolerability of OnabotulinumtoxinA for Chronic Migraine Prophylaxis

by Emmanouil V. Dermitzakis, Michail Vikelis, George S. Vlachos and Andreas A. Argyriou

Toxins 2022, 14(5), 296; https://doi.org/10.3390/toxins14050296 - 21 Apr 2022

Cited by 3 | Viewed by 1705

Abstract

We aimed to provide insights on the role of the circadian time of administration in influencing the efficacy and tolerability/safety profile of OnabotulinumtoxinA (BoNTA) for chronic migraine (CM) prophylaxis. Methods: We retrospectively reviewed the medical files of BoNTA-naïve patients with CM who completed [...] Read more.

We aimed to provide insights on the role of the circadian time of administration in influencing the efficacy and tolerability/safety profile of OnabotulinumtoxinA (BoNTA) for chronic migraine (CM) prophylaxis. Methods: We retrospectively reviewed the medical files of BoNTA-naïve patients with CM who completed three consecutive cycles of treatment, according to the standard PREEMPT paradigm. Participants were classified to those scheduled to be treated in the morning hours from 8:00 to 12:00 (AM) or afternoon hours from 13:00 to 18:00 (PM). We then assessed and compared between groups the changes from baseline (T0—trimester before BoNTA’s first administration) to the period after its third administration (T3) in the following efficacy outcomes: (i) mean number of headache days/month, (ii) mean number of days/month with peak headache intensity of >4/10, (iii) mean number of days/month with consumption of any abortive treatment. Safety–tolerability was also compared between groups. Results: A total of 50 AM and 50 PM-treated patients were evaluated. The within-group analysis in both groups showed a significant decrease in all efficacy variables between T0 and T3. However, the between-group comparisons of all BoNTA-related efficacy outcomes at T3 vs. T0 documented comparable improvements between AM vs. PM-treated patients. Safety/tolerability was also similar between groups. Conclusions: We were not able to identify significant differences between patients treated in the AM vs. PM, so as to demonstrate that the circadian time of administration should be considered before initiating BoNTA in CM patients. Full article

(This article belongs to the Special Issue Botulinum Neurotoxin: Shared/Common Mechanisms in the Treatment of Pain, Spasticity and Movement Disorders)

► Show Figures

Figure 1

Review

Jump to: Research, Other

12 pages, 593 KiB

Open AccessReview

Botulinum Toxin—A High-Dosage Effect on Functional Outcome and Spasticity-Related Pain in Subjects with Stroke

by Domenico Intiso, Antonello Marco Centra, Michele Gravina, Angelo Chiaramonte, Michelangelo Bartolo and Filomena Di Rienzo

Toxins 2023, 15(8), 509; https://doi.org/10.3390/toxins15080509 - 18 Aug 2023

Cited by 1 | Viewed by 1150

Abstract

Stroke patients can develop spasticity and spasticity-related pain (SRP). These disorders are frequent and can contribute to functional limitations and disabling conditions. Many reports have suggested that higher doses than initially recommended of BTX-A can be used effectively and safely, especially in the [...] Read more.

Stroke patients can develop spasticity and spasticity-related pain (SRP). These disorders are frequent and can contribute to functional limitations and disabling conditions. Many reports have suggested that higher doses than initially recommended of BTX-A can be used effectively and safely, especially in the case of severe spasticity; however, whether the treatment produces any benefit on the functional outcome and SRP is unclear. Studies published between January 1989 and December 2022 were retrieved from MEDLINE/PubMed, Embase, and Cochrane Central Register. Only obabotulinumtoxinA (obaBTX-A), onabotulinumtoxinA, (onaBTX-A), and incobotulinumtoxinA (incoBTX-A) were considered. The term “high dosage” indicates ≥600 U. Nine studies met the inclusion criteria. Globally, 460 subjects were treated with BTX-A high dose, and 301 suffered from stroke. Studies had variable method designs, sample sizes, and aims. Only five (55.5%) reported data about the functional outcome after BTX-A injection. Functional measures were also variable, and the improvement was observed predominantly in the disability assessment scale (DAS). SRP pain was quantified by visual analog scale (VAS) and only three studies reported the BTX-A effect. There is no scientific evidence that this therapeutic strategy unequivocally improves the functionality of the limbs. Although no clear-cut evidence emerges, certain patients with spasticity might obtain goal-oriented improvement from high-dose BTX-A. Likewise, data are insufficient to recommend high BTX dosage in SRP. Full article

(This article belongs to the Special Issue Botulinum Neurotoxin: Shared/Common Mechanisms in the Treatment of Pain, Spasticity and Movement Disorders)

► Show Figures

Figure 1

15 pages, 1430 KiB

Open AccessReview

Botulinum Toxin Injection for the Treatment of Upper Esophageal Sphincter Dysfunction

by Pengxu Wei

Toxins 2022, 14(5), 321; https://doi.org/10.3390/toxins14050321 - 30 Apr 2022

Cited by 7 | Viewed by 6330

Abstract

Dysphagia associated with upper esophageal sphincter (UES) dysfunction remarkably affects the quality of life of patients. UES injection of botulinum toxin is an effective treatment for dysphagia. In comparison with skeletal muscles of the limb and trunk, the UES is a special therapeutic [...] Read more.

Dysphagia associated with upper esophageal sphincter (UES) dysfunction remarkably affects the quality of life of patients. UES injection of botulinum toxin is an effective treatment for dysphagia. In comparison with skeletal muscles of the limb and trunk, the UES is a special therapeutic target of botulinum toxin injection, owing to its several anatomical, physiological, and pathophysiological features. This review focuses on (1) the anatomy and function of the UES and the pathophysiology of UES dysfunction in dysphagia and why the entire UES rather than the cricopharyngeal muscle before/during botulinum toxin injection should be examined and targeted; (2) the therapeutic mechanisms of botulinum toxin for UES dysfunction, including the choice of injection sites, dose, and volume; (3) the strengths and weaknesses of guiding techniques, including electromyography, ultrasound, computed tomography, and balloon catheter dilation for botulinum toxin injection of the UES. Full article

(This article belongs to the Special Issue Botulinum Neurotoxin: Shared/Common Mechanisms in the Treatment of Pain, Spasticity and Movement Disorders)

► Show Figures

Figure 1

Other

Jump to: Research, Review

20 pages, 1502 KiB

Open AccessEditor’s ChoiceSystematic Review

Safety of Onabotulinumtoxin A in Chronic Migraine: A Systematic Review and Meta-Analysis of Randomized Clinical Trials

by Maria Tiziana Corasaniti, Giacinto Bagetta, Pierluigi Nicotera, Assunta Tarsitano, Paolo Tonin, Giorgio Sandrini, Gary W. Lawrence and Damiana Scuteri

Toxins 2023, 15(5), 332; https://doi.org/10.3390/toxins15050332 - 12 May 2023

Cited by 3 | Viewed by 2090

Abstract

Some 14% of global prevalence, based on high-income country populations, suffers from migraine. Chronic migraine is very disabling, being characterized by at least 15 headache days per month of which at least 8 days present the features of migraine. Onabotulinumtoxin A, targeting the [...] Read more.

Some 14% of global prevalence, based on high-income country populations, suffers from migraine. Chronic migraine is very disabling, being characterized by at least 15 headache days per month of which at least 8 days present the features of migraine. Onabotulinumtoxin A, targeting the machinery for exocytosis of neurotransmitters and neuropeptides, has been approved for use in chronic migraine since 2010. This systematic review and meta-analysis appraises the safety of onabotulinumtoxin A treatment for chronic migraine and the occurrence of treatment-related adverse events (TRAEs) in randomized, clinical studies in comparison with placebo or other comparators and preventative treatments according to the most updated Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) 2020 recommendations. The search retrieved 888 total records. Nine studies are included and seven were eligible for meta-analysis. The present study demonstrates that toxin produces more TRAEs than placebo, but less than oral topiramate, supporting the safety of onabotulinumtoxin A, and highlights the heterogeneity of the studies present in the literature (I² = 96%; p < 0.00001). This points to the need for further, adequately powered, randomized clinical trials assessing the safety of onabotulinumtoxin A in combination with the newest treatment options. Full article

(This article belongs to the Special Issue Botulinum Neurotoxin: Shared/Common Mechanisms in the Treatment of Pain, Spasticity and Movement Disorders)

► Show Figures

Figure 1

Journal Menu

Journal Browser

Botulinum Neurotoxin: Shared/Common Mechanisms in the Treatment of Pain, Spasticity and Movement Disorders

Share This Special Issue

Special Issue Editors

Special Issue Information

Keywords

Published Papers (11 papers)

Research

Review

Other

Further Information

Guidelines

MDPI Initiatives

Follow MDPI