Search

Hyperhidrosis is a dermatological condition defined by excessive sweating beyond thermoregulatory needs with significant effects on patients' quality of life. Hyperhidrosis is categorized as primary or secondary: primary hyperhidrosis is mostly focal and idiopathic, whereas secondary hyperhidrosis is commonly generalized and caused by an underlying medical condition or use of medications. Various surgical and nonsurgical therapies exist for primary hyperhidrosis. Although botulinum toxin is one of the deadliest toxins known, when used in small doses, it is one of the most effective therapies for primary hyperhidrosis. Botulinum toxin injections are widely used as a second-line primary hyperhidrosis treatment option once topical treatment strategies have failed. This article provides an overview of the commercially available botulinum toxin formulations and their applications in the treatment of primary hyperhidrosis. [ABSTRACT FROM AUTHOR]

Michelle Kaku, David M Simpson Department of Neurology, Icahn School of Medicine at Mount Sinai, New York, NY, USA Abstract: 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. Keywords: poststroke spasticity, botulinum toxin, onabotulinumtoxinA, incobotulinumtoxinA, rimabotulinumtoxinB

Avram Fraint,1 Padmaja Vittal,2 Cynthia Comella2 1Department of Neurological Sciences, 2Section of Movement Disorders, Rush University Medical Center, Chicago, IL, USA Introduction: Botulinum toxin (BoNT) is the treatment of choice for many neurologic movement disorders, including blepharospasm, hemifacial spasm, and cervical dystonia. There are two serotypes approved for use by the US Food and Drug Administration: three brands of serotype A and one of serotype B. Many attempts have been made at establishing dose conversion ratios between brands and serotypes. This review focuses on the existing data comparing different formulations of the same BoNT serotypes as well as that comparing different serotypes with one another. We focus on existing data regarding switching from one formulation or serotype to another and will also discuss the issue of immunogenicity of BoNT. With this information as a foundation, recommendations on safety of switching agents are addressed. Method: Literature review searching PubMed and Google Scholar using the search terms “switching botox”, “dosing equivalency in botox”, and “comparing botox”. Results/conclusion: Overall, there are many studies that demonstrate the efficacy and safety of each of the brands of BoNTs used in clinical practice. However, determination of dosing equivalencies among these brands and serotypes is complex with inconsistencies among the studies. When switching from one brand to another, the clinician should be aware of these issues, and not make the assumption that such ratios exist. Tailoring the dosage of each brand of BoNT to the clinical situation is the most prudent treatment strategy rather than focusing closely on conversion factors and concerns for immunogenicity. Keywords: botulinum toxin, BoNT, abobotulinumtoxin A, onabotulinumtoxin A, incobotulinumtoxin A, rimabotulinumtoxin B

Patients with cervical dystonia (CD) receive much of their care at university based hospital outpatient clinics. This study aimed to describe the clinical characteristics and treatment experiences of patients who continued care at our university based movement disorders clinic, and to document the reasons for which a subset discontinued care. Seventy patients (77% female) were recruited from all patients at the clinic (n = 323). Most (93%) were treated with botulinum neurotoxin (BoNT) injection, and onabotulinumtoxinA was initially used in 97%. The average dose of onabotulinumtoxinA was 270.4 U (range 50–500) and the median number of injections was 14 (range: 1–39). Twenty one patients later received at least one cycle of rimabotulinumtoxinB (33%); of those, 10 switched back to onabotulinumtoxinA (48%). The initial rimabotulinumtoxinB dose averaged 11,996 units (range: 3000–25,000 over 1–18 injections). Twenty one patients (30%) discontinued care. Reasons cited included suboptimal response to BoNT therapy (62%), excessive cost (24%), excessive travel burden (10%), and side effects of BoNT therapy (10%). Most patients (76%) did not seek further care after leaving the clinic. Patients who terminated care received fewer treatment cycles (5.5 vs. 13.0, p = 0.020). There were no other identifiable differences between groups in gender, age, disease characteristics, toxin dose, or toxin formulation. These results indicate that a significant number of CD patients discontinue care due to addressable barriers to access, including cost and travel burden, and that when leaving specialty care, patients often discontinue treatment altogether. These data highlight the need for new initiatives to reduce out-of-pocket costs, as well as training for community physicians on neurotoxin injection in order to lessen the travel burden patients must accept in order to receive standard-of-care treatments.

Botulinum toxin (BoNT) formulations are being used for a variety of medical applications. The use of BoNT preparations is continuously expanding with new formulations and indications. Of the seven antigenically distinct BoNTs, only two serotypes, type A and type B are commonly available for therapeutic use. The four available BoNT products are not equivalent and the knowledge of their formulations is crucial for product selection, avoidance of medication errors, therapeutic efficacy and safety. Generally, BoNT injection is a safe procedure when administered by an experienced injector. Side effects are always transient, and in the majority of cases they are mild and tolerable. [ABSTRACT FROM AUTHOR]

Objectives To investigate efficacy, saliva flow, and composition in repeated Bo NT-B treatments of drooling. Materials and methods Seventeen neurological patients (median 66 years), referred for treatment of drooling participated in this observational study. Median total doses of 4000 units botulinum toxin type B (Bo NT-B, Neurobloc®) were injected with at least 3 months intervals into parotid and submandibular glands using ultrasound guidance. Measures of drooling and saliva collection for analysis were obtained before treatment, and 6, 12, and eventually 18 weeks after. Results Number of treatment series in each patient was 1-7. Compared to baseline, saliva flow rate and drooling were reduced 30-70% 6 weeks after treatment in the first series, while sodium, chloride, and total protein increased 20-80% (t-tests; P < 0.05). After 12 weeks, drooling was still significantly reduced, saliva flow tended to be, and saliva composition was back to baseline. Frequent side effects were viscous saliva and dry mouth. Due to fading effect in eight patients, individual decisions were taken to change from Bo NT-B to Bo NT-A. Similarly, the outcome was significantly reduced over time in six patients completing five subsequent Bo NT-B treatment series ( ANOVA; P < 0.05). Conclusion In the first series, Bo NT-B treatment resulted in marked reduction of drooling and saliva flow rate with some relapse after 12 weeks. The viscous saliva was ascribed to increased total protein content and compensatory mechanisms related to ß-adrenergic receptor-specific actions. With patients needing long-term treatment, it should be noted that the efficacy of repeated Bo NT-B may fade with time. [ABSTRACT FROM AUTHOR]

Background: Masseter hypertrophy can be ameliorated by botulinum toxin. Objective: To compare the efficacy and safety of RimabotulinumtoxinB (BTX-B) and OnabotulinumtoxinA (BTX-A) in the treatment of masseter hypertrophy. Methods: Sixteen women with bilateral masseter hypertrophy received single injections of BTX-A or BTX-B at a dose ratio of 1:50 or 1:70 in a 24-week double-blind randomized split-face study. Results: Both BTX-A and BTX-B produced significant improvements in masseter hypertrophy. The maximum volume reduction, as determined by computed tomography scanning, at week 12 was comparable between BTX-A and BTX-B at a dose ratio of 1:70 (15.6 and 14.2%, respectively). At week 24, only masseters treated with BTX-A maintained a significant volume reduction. Investigator ratings and patient satisfaction scores paralleled objective computed tomography measurements. Conclusion: Both BTX-A and BTX-B are effective in the treatment of masseter hypertrophy. BTX-B, at a dose ratio of 1:70, has a comparable efficacy but a shorter duration of action than BTX-A. Copyright © 2013 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Abstract: Botulinum neurotoxin (BoNT) can be injected to achieve therapeutic benefit across a large range of clinical conditions. To assess the efficacy and safety of BoNT injections for the treatment of certain movement disorders, including blepharospasm, hemifacial spasm, oromandibular dystonia, cervical dystonia, focal limb dystonias, laryngeal dystonia, tics, and essential tremor, an expert panel reviewed evidence from the published literature. Data sources included English-language studies identified via MEDLINE, EMBASE, CINAHL, Current Contents, and the Cochrane Central Register of Controlled Trials. Evidence tables generated in the 2008 Report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology (AAN) review of the use of BoNT for movement disorders were also reviewed and updated. The panel evaluated evidence at several levels, supporting BoNT as a class, the serotypes BoNT-A and BoNT-B, as well as the four individual commercially available formulations: abobotulinumtoxinA (A/Abo), onabotulinumtoxinA (A/Ona), incobotulinumtoxinA (A/Inco), and rimabotulinumtoxinB (B/Rima). The panel ultimately made recommendations for each therapeutic indication, based upon the strength of clinical evidence and following the AAN classification scale. For the treatment of blepharospasm, the evidence supported a Level A recommendation for BoNT-A, A/Inco, and A/Ona; a Level B recommendation for A/Abo; and a Level U recommendation for B/Rima. For hemifacial spasm, the evidence supported a Level B recommendation for BoNT-A and A/Ona, a Level C recommendation for A/Abo, and a Level U recommendation for A/Inco and B/Rima. For the treatment of oromandibular dystonia, the evidence supported a Level C recommendation for BoNT-A, A/Abo, and A/Ona, and a Level U recommendation for A/Inco and B/Rima. For the treatment of cervical dystonia, the published evidence supported a Level A recommendation for all four BoNT formulations. For limb dystonia, the available evidence supported a Level B recommendation for both A/Abo and A/Ona, but no published studies were identified for A/Inco or B/Rima, resulting in a Level U recommendation for these two formulations. For adductor laryngeal dystonia, evidence supported a Level C recommendation for the use of A/Ona, but a Level U recommendation was warranted for B/Rima, A/Abo, and A/Inco. For the treatment of focal tics, a Level U recommendation was warranted at this time for all four formulations. For the treatment of tremor, the published evidence supported a level B recommendation for A/Ona, but no published studies were identified for A/Abo, A/Inco, or B/Rima, warranting a Level U recommendation for these three formulations. Further research is needed to address evidence gaps and to evaluate BoNT formulations where currently there is insufficient or conflicting clinical data. [Copyright &y& Elsevier]

Abstract: Comparative literature assessing the relative safety and efficacy of different BoNT products is limited. The quantity and quality of data vary by preparation and indication. Clinicians seeking data relevant to the care of patients with specific conditions may find only reports about small numbers of patients with varying symptoms. While a literature search for “botulinum neurotoxins” will yield a large number of publications; only a fraction of these meet criteria for an academic evidence-based review. Patients may have been treated with a different BoNT formulation than that with which the physician is familiar, or there may be little or no clinical data on the use of a specific BoNT product for the proposed intervention. This paper is an introduction to a series of papers (which follow) in which an expert panel reviewed the BoNT clinical trial literature in order to provide evidence-based recommendations regarding the clinical use and efficacy of available BoNT preparations for four major therapeutic areas: movement disorders, spasticity, urology, and secretory disorders. Expert opinion is also included to address practical issues where more evidence and further research is needed. [Copyright &y& Elsevier]

Patients with cervical dystonia (CD) receive much of their care at university based hospital outpatient clinics. This study aimed to describe the clinical characteristics and treatment experiences of patients who continued care at our university based movement disorders clinic, and to document the reasons for which a subset discontinued care. Seventy patients (77% female) were recruited from all patients at the clinic (n = 323). Most (93%) were treated with botulinum neurotoxin (BoNT) injection, and onabotulinumtoxinA was initially used in 97%. The average dose of onabotulinumtoxinA was 270.4 U (range 50-500) and the median number of injections was 14 (range: 1-39). Twenty one patients later received at least one cycle of rimabotulinumtoxinB (33%); of those, 10 switched back to onabotulinumtoxinA (48%). The initial rimabotulinumtoxinB dose averaged 11,996 units (range: 3000-25,000 over 1-18 injections). Twenty one patients (30%) discontinued care. Reasons cited included suboptimal response to BoNT therapy (62%), excessive cost (24%), excessive travel burden (10%), and side effects of BoNT therapy (10%). Most patients (76%) did not seek further care after leaving the clinic. Patients who terminated care received fewer treatment cycles (5.5 vs. 13.0, p = 0.020). There were no other identifiable differences between groups in gender, age, disease characteristics, toxin dose, or toxin formulation. These results indicate that a significant number of CD patients discontinue care due to addressable barriers to access, including cost and travel burden, and that when leaving specialty care, patients often discontinue treatment altogether. These data highlight the need for new initiatives to reduce out-of-pocket costs, as well as training for community physicians on neurotoxin injection in order to lessen the travel burden patients must accept in order to receive standard-of-care treatments. [ABSTRACT FROM AUTHOR]

Botulinum neurotoxin (Bo NT) is an acetylcholine release inhibitor and a neuromuscular-blocking agent used for the treatment of a variety of medical and cosmetic indications. Currently, in the United States, there are four Bo NT formulations licensed for use: abobotulinumtoxinA, incobotulinumtoxinA, onabotulinumtoxinA, and rimabotulinumtoxinB. These revised name designations were established to reinforce the understanding that each Bo NT product has an individual potency and is not interchangeable with any other Bo NT product. The therapeutic use of Bo NTs is expanding and new formulations are on the horizon. This article is a primer that describes distinctions among currently available, licensed Bo NT formulations. Toxin pharmacology, product characteristics, storage, handling, preparation, and dosages will be reviewed. In addition, issues related to dose equivalency ratios, immunogenicity, potency, and toxin spread will be discussed. Therapeutic indications and safety are discussed briefly. Knowledge of the available and licensed Bo NT formulations and the ability to make distinctions in toxin pharmacology, product characteristics, and indications are vital for product selection, preparation, drug information, avoidance of drug errors, quality assurance, and patient safety. [ABSTRACT FROM AUTHOR]

Abstract: Botulinum neurotoxins (BoNTs) inhibit neurotransmitter release by hydrolysing SNARE proteins essential for exocytosis. The synaptic vesicle protein synaptotagmin-II of rat and mouse acts as neuronal high affinity receptor for BoNT/B and BoNT/G. Here, we show that human synaptotagmin-II is not a high affinity receptor for BoNT/B and G due to a phenylalanine to leucine mutation in its luminal domain present only in humans and chimpanzees. It eliminates one of three major interactions between synaptotagmin-II and BoNT/B and hereby explains the disparity in potency of BoNT/B in humans and mice as well as the 40-fold higher dosage of rimabotulinumtoxinB versus onabotulinumtoxinA. Structured summary of protein interactions: rSyt-II binds to BoNT/G by pull down (View Interaction: 1 , 2 ) rSyt-II binds to BoNT/B by pull down (View Interaction: 1 , 2 ) [Copyright &y& Elsevier]

Objectives: Evaluate the safety and efficacy of a sequential dose escalation of rimabotulinumtoxinB (BoNT-B) in cervical dystonia (CD) subjects. Methods: This multicenter, open-label, within-subject, sequential dose-escalation study (BoNT-B dosed at 10,000, 12,500, and 15,000 Units) evaluated subjects over each phase of treatment at preinjection and at periodic intervals postinjection. Adverse events, vital signs, and laboratory results were recorded. Efficacy measures included the Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) and three visual analog scales (VASs). Results: 119 out of 145 CD subjects received all three doses in sequence. Dry mouth and dysphagia were the most common adverse events, and both decreased in frequency by the final injection, despite the increasing doses of the escalation. TWSTRS-Total and subscale scores demonstrated significant improvements following all doses at the week 2, 4, 8, and 12 assessments, with the exception of disability and pain at week 12 with the lowest dose. All VAS scores demonstrated similar improvements following all doses. The mean number of weeks in each phase of the study was 12.1 weeks (10,000 Units), 12.9 weeks (12,500 Units), and 13.9 weeks (15,000 Units). Conclusion: BoNT-B was well tolerated and efficacious at 10,000, 12,500, and 15,000 Units in this within-subject, sequential dose-escalation study in CD subjects. [ABSTRACT FROM AUTHOR]

Initially used to treat strabismus in the 1970s, botulinum toxin now has more than a hundred possible medical applications. Its utility in neurologic conditions has largely involved treating movement disorders (particularly dystonia and conditions with muscle hyperactivity), although practically any hyperkinetic movement disorder may be relieved by botulinum toxin, including hemifacial spasm, tremor, tics, myoclonus, and spasticity. Although initially thought to inhibit acetylcholine release only at the neuromuscular junction, botulinum toxins are now recognized to inhibit acetylcholine release at autonomic cholinergic nerve terminals, as well as peripheral release of neurotransmitters involved in pain regulation. Thus, their use in neurology has been expanded to include headache and other pain syndromes, as well as hypersecretory disorders. This article highlights some of the common neurologic conditions currently improved by botulinum toxins and reviews the scientific evidence from research studies and clinical experience with these conditions. [ABSTRACT FROM AUTHOR]