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Toxins Oct 2022Two decades after reports of the anti-pruritic effects of botulinum neurotoxins (BoNTs), there is still no approved product for the anti-itch indication of BoNTs, and... (Review)
Review
Two decades after reports of the anti-pruritic effects of botulinum neurotoxins (BoNTs), there is still no approved product for the anti-itch indication of BoNTs, and most clinical case reports still focus on the off-label use of BoNTs for various itchy conditions. Few randomized clinical trials have been conducted with controversial results, and the beneficial effects of BoNTs against itch are mainly based on case studies and case series. These studies are valuable in presenting the potential application of BoNTs in chronic pruritic conditions, but due to the nature of these studies, they are categorized as providing lower levels of evidence or lower grades of recommendation. To obtain approval for the anti-pruritic indication of BoNTs, higher levels of evidence are required, which can be achieved through conducting large-scale and well-designed studies with proper control groups and established careful and reliable primary and secondary outcomes. In addition to clinical evidence, presenting the mechanism-based antipruritic action of BoNTs can potentially strengthen, accelerate, and facilitate the current efforts towards further investments in accelerating the field towards the potential approval of BoNTs for itchy conditions. This review, therefore, aimed to provide the state-of-the-art mechanisms underlying the anti-itch effect of BoNTs from basic studies that resemble various clinical conditions with itch as a hallmark. Evidence of the neuronal, glial, and immune modulatory actions of BoNTs in reducing the transmission of itch are presented, and future potential directions are outlined.
Topics: Humans; Botulinum Toxins; Antipruritics; Pruritus; Neurons; Neurotoxins
PubMed: 36287970
DOI: 10.3390/toxins14100701 -
The Cochrane Database of Systematic... Jan 2023Infantile esotropia (IE) is the inward deviation of the eye. Various aspects of the clinical management of IE are unclear; mainly, the most effective type of... (Review)
Review
BACKGROUND
Infantile esotropia (IE) is the inward deviation of the eye. Various aspects of the clinical management of IE are unclear; mainly, the most effective type of intervention and the age at intervention.
OBJECTIVES
To examine the effectiveness and optimal timing of surgical and non-surgical treatment options for IE to improve ocular alignment and achieve or allow the development of binocular single vision.
SEARCH METHODS
We searched CENTRAL, MEDLINE, Embase, one other database, and three trials registers (November 2021). We did not use any date or language restrictions in the electronic searches for trials. SELECTION CRITERIA: We included randomized trials and quasi-randomized trials comparing any surgical or non-surgical intervention for IE.
DATA COLLECTION AND ANALYSIS
We used standard Cochrane methodology and graded the certainty of the body of evidence for six outcomes using the GRADE classification.
MAIN RESULTS
We included two studies with 234 children with IE. The first study enrolled 110 children (mean age 26.9 ± 14.5 months) with an onset of esotropia before six months of age, and large-angle IE defined as esotropia of ≥ 40 prism diopters. It was conducted between 2015 and 2018 in a tertiary care hospital in South Africa. It compared a maximum of three botulinum toxin injections with surgical intervention of bimedial rectus muscle recession, and children were followed for six months. There were limitations in study design and implementation; the risk of bias was high, or we had some concerns for most domains. Surgery may increase the incidence of treatment success, defined as orthophoria or residual esotropia of ≤ 10 prism diopters, compared with botulinum toxin injections, but the evidence was very uncertain (risk ratio (RR) of treatment success 1.88, 95% confidence interval (CI) 1.27 to 2.77; 1 study, 101 participants; very low-certainty evidence). The results should be read with caution because 23 children with > 60 prism diopters at baseline in the surgery arm also received botulinum toxin at the time of surgery to augment the recessions. There was no evidence of an important difference between surgery and botulinum toxin injections for over-correction (> 10 prism diopters) of deviation (RR 0.29, 95% CI 0.06 to 1.37; 1 study, 101 participants; very low-certainty evidence), or additional interventions required (RR 0.66, 95% CI 0.36 to 1.19; 1 study, 101 participants; very low-certainty evidence). No major complications of surgery were observed in the surgery arm, while children experienced various complications in the botulinum toxin arm, including partial transient ptosis in 9 (16.7%) children, transient vertical deviation in 3 (5.6%) children, and consecutive exotropia in 13 (24.1%) children. No other outcome data for our prespecified outcomes were reported. The second study enrolled 124 children with onset of esotropia before one year of age in 12 university hospitals in Germany and the Netherlands. It compared bilateral recession with unilateral recession surgeries, and followed children for three months postoperatively. Very low-certainty evidence suggested that there was no evidence of an important difference between bilateral and unilateral surgeries in the presence of binocular vision (numbers with event unclear, P = 0.35), and over-correction (RR of having exotropia 1.09, 95% CI 0.45 to 2.63; 1 study, 118 participants). Dissociated vertical deviation, latent nystagmus, or both were observed in 8% to 21% of participants.
AUTHORS' CONCLUSIONS
Medial rectus recessions may increase the incidence of treatment success compared with botulinum toxin injections alone, but the evidence was very uncertain. No evidence of important difference was found between bilateral surgery and unilateral surgery. Due to insufficient evidence, it was not possible to resolve the controversies regarding type of surgery, non-surgical intervention, or age of intervention in this review. There is clearly a need to conduct good quality trials in these areas to improve the evidence base for the management of IE.
Topics: Child, Preschool; Humans; Infant; Botulinum Toxins; Esotropia; Exotropia; Strabismus; Treatment Outcome; Ophthalmologic Surgical Procedures
PubMed: 36645238
DOI: 10.1002/14651858.CD004917.pub4 -
European Neurology 2021Botulinum toxin is nowadays approved as an effective medication for various neurological disorders. The extreme toxicity of this toxin-inducing botulism, a severe lethal...
Botulinum toxin is nowadays approved as an effective medication for various neurological disorders. The extreme toxicity of this toxin-inducing botulism, a severe lethal muscle-paralyzing illness, has been well known since the seminal works of the end of the 19th century. Because of this toxicity, botulinum toxin was one of the first agents to be considered for use as a biological weapon. The Second World War was a crucial period for the first attempts to weaponize this toxin even if many unknown factors about botulinum toxin still existed at the outbreak of the war. Using documents from the British National Archives and other published sources, we discuss the main points of the attempts to weaponize this toxin in German and Allied armies. During WW2, Allied intelligence services regularly reported a major German threat related to the potential use of botulinum toxin as a biological weapon, especially during the preparation of Operation Overlord, the Allied invasion to liberate Europe. All these reports would ultimately prove to be inaccurate: botulinum toxin was not part of the German military arsenal even if some German scientists tried to use the results of the French pre-war military research. Misinformation spread by intelligence services stimulated military research at Porton Down facilities in England and at Camp Detrick in the USA. These studies led to a succession of failures and myths about the weaponization of botulinum toxin. Nevertheless, major progress (purification, toxoid) arose from the military research, providing useful data for the first steps of the therapeutic use of botulinum toxin in the post-war years.
Topics: Biological Warfare Agents; Botulinum Toxins; Botulism; Humans; Military Personnel; World War II
PubMed: 33472198
DOI: 10.1159/000512812 -
Clinical and Vaccine Immunology : CVI Dec 2017Select agents (SA) pose unique challenges for licensing vaccines and therapies. In the case of toxin-mediated diseases, HHS assigns guidelines for SA use, oversees... (Review)
Review
Select agents (SA) pose unique challenges for licensing vaccines and therapies. In the case of toxin-mediated diseases, HHS assigns guidelines for SA use, oversees vaccine and therapy development, and approves animal models and approaches to identify mechanisms for toxin neutralization. In this commentary, we discuss next-generation vaccines and therapies against ricin toxin and botulinum toxin, which are regulated SA toxins that utilize structure-based approaches for countermeasures to guide rapid response to future biothreats.
Topics: Animals; Botulinum Toxins; Botulism; Crystallography, X-Ray; Humans; Models, Molecular; Poisoning; Protein Conformation; Ricin; Vaccines
PubMed: 29046310
DOI: 10.1128/CVI.00275-17 -
The Journal of Headache and Pain Sep 2005The authors discuss clinical and international experience about botulinum toxins (BTX types A and B) in headache treatment. Data from literature suggest good results for... (Review)
Review
The authors discuss clinical and international experience about botulinum toxins (BTX types A and B) in headache treatment. Data from literature suggest good results for the treatment of tension-type headache, migraine and chronic tension-type headache. In the present paper mechanisms of action and injection sites will also be discussed.
Topics: Anti-Dyskinesia Agents; Botulinum Toxins; Humans; Migraine Disorders; Tension-Type Headache
PubMed: 16362701
DOI: 10.1007/s10194-005-0222-x -
Drug Design, Development and Therapy 2016Poststroke spasticity affects up to one-half of stroke patients and has debilitating effects, contributing to diminished activities of daily living, quality of life,... (Review)
Review
Poststroke spasticity affects up to one-half of stroke patients and has debilitating effects, contributing to diminished activities of daily living, quality of life, pain, and functional impairments. Botulinum toxin (BoNT) is proven to be safe and effective in the treatment of focal poststroke spasticity. The aim of this review is to highlight BoNT and its potential in the treatment of upper and lower limb poststroke spasticity. We review evidence for the efficacy of BoNT type A and B formulations and address considerations of optimal injection technique, patient and caregiver satisfaction, and potential adverse effects of BoNT.
Topics: Animals; Botulinum Toxins; Humans; Muscle Spasticity; Stroke
PubMed: 27022247
DOI: 10.2147/DDDT.S80804 -
Toxins Jul 2022Spasmodic dysphonia (SD) is a rare neurological disorder that impairs phonatory function by triggering involuntary and intermittent contractions of the intrinsic... (Review)
Review
Spasmodic dysphonia (SD) is a rare neurological disorder that impairs phonatory function by triggering involuntary and intermittent contractions of the intrinsic laryngeal muscles. SD is classified into three types: adductor SD (AdSD), abductor SD (AbSD), and mixed SD. Of these, AdSD accounts for 90-95% of disease; younger females are predominantly affected. Botulinum toxin injection into the laryngeal muscles is safe, minimally invasive, and very effective. Here, we review the history of clinical research for SD conducted in Japan. The first use of botulinum toxin injection therapy to treat SD in Japan was by Kobayashi et al. in 1989. The group developed an objective mora (syllable) method to evaluate SD severity. Recently, we conducted a placebo-controlled, randomized, double-blinded clinical trial of botulinum toxin therapy for AdSD and an open-label trial for AbSD to obtain the approval of such therapy by the Japanese medical insurance system. The mora method revealed significant voice improvement and the evidence was of high quality. Additionally, a clinical trial of type 2 thyroplasty using titanium bridges confirmed the efficacy and safety of such therapy. These studies broadened the SD treatment options and have significantly benefited patients.
Topics: Botulinum Toxins; Botulinum Toxins, Type A; Dysphonia; Female; Humans; Injections; Japan; Laryngeal Muscles; Randomized Controlled Trials as Topic; Treatment Outcome
PubMed: 35878189
DOI: 10.3390/toxins14070451 -
Cleveland Clinic Journal of Medicine Jul 2015The neuromuscular blocker botulinum toxin has a wide variety of medical applications, including overactive bladder and neurogenic detrusor overactivity in patients in... (Review)
Review
The neuromuscular blocker botulinum toxin has a wide variety of medical applications, including overactive bladder and neurogenic detrusor overactivity in patients in whom drug therapy fails or is not well tolerated. Botulinum toxin therapy for these conditions has been shown to be safe and effective in several large multicenter randomized controlled trials. Off-label uses in urology include detrusor external sphincter dyssynergia and pelvic pain syndromes.
Topics: Botulinum Toxins; Female; Humans; Urinary Bladder, Overactive
PubMed: 26185945
DOI: 10.3949/ccjm.82a.13166 -
Toxins Dec 2017Selection of muscles for botulinum toxin injection for limb dystonia is particularly challenging. Limb dystonias vary more widely in the pattern of dystonic movement and... (Review)
Review
Selection of muscles for botulinum toxin injection for limb dystonia is particularly challenging. Limb dystonias vary more widely in the pattern of dystonic movement and involved muscles than cervical dystonia or blepharospasm. The large variation in how healthy individuals perform skilled hand movements, the large number of muscles in the hand and forearm, and the presence of compensatory actions in patients with dystonia add to the complexity of choosing muscles for injection. In this article, we discuss approaches to selecting upper and lower extremity muscles for chemodenervation treatment of limb dystonia.
Topics: Botulinum Toxins; Dystonia; Dystonic Disorders; Humans; Muscles
PubMed: 29286305
DOI: 10.3390/toxins10010020 -
Toxins Jan 2023This review provides an up-to-date literature account on the efficacy of Botulinum toxin treatment for common motor disorders of Parkinson Disease. The reviewed... (Review)
Review
This review provides an up-to-date literature account on the efficacy of Botulinum toxin treatment for common motor disorders of Parkinson Disease. The reviewed disorders include the common motor disorders in PD such as tremor, focal foot dystonia, rigidity and freezing of gait (FOG). In the area of Parkinson tremor, two newly described evaluation/injection techniques (Yale method in USA and Western University method in Canada) offer efficacy with low incidence of hand and finger weakness as side effects. Blinded studies conducted on foot dystonia of PD indicate that botulinum toxin injections into toe flexors are efficacious in alleviating this form of dystonia. Small, blinded studies suggest improvement of Parkinson rigidity after botulinum toxin injection; proof of this claim, however, requires information from larger, blinded clinical trials. In FOG, the improvement reported in open label studies could not be substantiated in blinded investigations. However, there is room for further controlled studies that include the proximal lower limb muscles in the injection plan and/or use higher doses of the injected toxin for this indication.
Topics: Humans; Botulinum Toxins; Parkinson Disease; Dystonia; Tremor; Motor Disorders; Gait Disorders, Neurologic; Dystonic Disorders; Botulinum Toxins, Type A; Treatment Outcome
PubMed: 36828396
DOI: 10.3390/toxins15020081