Botulinum Toxin

Botulinum toxin is a neurotoxic protein produced by the bacterium Clostridium botulinum. Although botulinum toxin is the cause of the disease botulism and can be used in a terrorist attack, there are also many other uses for botulinum toxin. Botox, a derivative of botulinum toxin, is used for cosmetic purposes. Botulinum toxin is also used in medicines to control certain conditions marked by involuntary muscle contractions. The objective of this paper is to present a strong review of botulinum toxin so that one can see all the good and bad that is botulinum

Clinical Relevance of Botulinum Toxin Immunogenicity

Botulinum toxin type A is a 150 kD protein produced by Clostridium botulinum, which exists in a complex with up to six additional proteins. The ability of botulinum toxin to inhibit acetylcholine release at the neuromuscular junction has been exploited for use in medical conditions characterized by muscle hyperactivity. As such, botulinum toxin is widely recommended by international treatment guidelines for movement disorders and it has a plethora of other clinical and cosmetic indications. The chronic nature of these conditions requires repeated injections of botulinum toxin, usually every few months. Multiple injections can lead to secondary treatment failure in some patients that may be associated with the production of neutralizing antibodies directed specifically against the neurotoxin. However, the presence of such antibodies does not always render patients non-responsive. The reported prevalence of immunoresistance varies greatly, depending on factors such as study design and treated indication. This review presents what is currently known about the immunogenicity of botulinum toxin and how this impacts upon patient non-response to treatment. The complexing proteins may act as adjuvants and stimulate the immune response. Their role and that of neutralizing and non-neutralizing antibodies in the response to botulinum toxin is discussed, together with an assessment of current neutralizing antibody measurement techniques. Botulinum toxin preparations with different compositions and excipients have been developed. The major commercially available preparations of botulinum toxin are Botox® (onabotulinumtoxinA; Allergan, Inc., Ireland), Dysport® (abobotulinumtoxinA; Ipsen Ltd, UK), and Xeomin® (incobotulinumtoxinA; botulinum toxin type A [150 kD], free from complexing proteins; NT 201; Merz Pharmaceuticals GmbH, Germany). The new preparations of botulinum toxin aim to minimize the risk of immunoresistance in patients being treated for chronic clinical conditions

Use of Botulinum Toxin in Central Nervous System Disorders

Botulinum toxin is a neurotoxin that is produced by Clostridium botulinum. At one time, this toxin was only seen as a lethal substance, but now scientists have found many medical uses for it. There are eight distinctive toxins (A-H), but only A and B currently have clinical uses. Botulinum toxin A has three different versions that are U.S. Food and Drug Administration (FDA) approved: onabotulinumtoxinA (Botox®), abobotulinumtoxinA (Dysport®), incobotulinumtoxinA (Xeomin®). Botulinum toxin B is also FDA approved as rimabotulinumtoxinB (Myobloc®). The toxins work by inducing reversible, local, dose-dependent chemodenervation by inhibiting acetylcholine release from presynaptic terminals. These drugs are approved to treat many different types of disorders but have found significant use for the treatment of migraines, dystonias and cerebral palsy. Botulinum toxin has proven to be efficacious in prophylactically treating those patients with migraines who have failed other pharmacologic and nonpharmacologic treatments. Botulinum toxin is also FDA approved for the treatment of dystonias; more specifically, all three types of botulinum toxin A and the rimabotulinumtoxin B have FDA approval for the treatment of cervical dystonia. Perhaps the most important use for botulinum toxin is in patients with cerebral palsy. Botulinum toxin is efficacious in patients with upper limb spasticity who are not good surgical candidates. It also proves useful as an adjunct to physiotherapy in these patients. This can help reduce or slow progression in patients with cerebral palsy. Exercise has been shown to be an efficacious treatment in patients with migraines, dystonias and cerebral palsy. Further research is necessary to determine the potential benefits the combination of exercise and botulinum toxin can have in these patients. While the high cost of botulinum toxin might deter some patients, it is a good option for those that have exhausted other options or are not good candidates for surgery

Botulinum toxin treatment of urethral and bladder dysfunction.

Tremendous excitement has been generated by the use of botulinum toxin for the treatment of various types of urethral and bladder dysfunction over the past several years. Botulinum toxin is the most lethal naturally occurring toxin known to mankind. Why, then, would an urologist want to use this agent to poison the bladder or urethral sphincter? In this review article we will examine the mechanisms underlying the effects of botulinum toxin treatment. We will discuss the current use of this agent within the urologic community and will provide perspectives on future targets of botulinum toxin.</p

Diagnostic nerve block in prediction of outcome of botulinum toxin treatment for spastic equinovarus foot after stroke: A retrospective observational study

Objective: To evaluate the role of diagnostic nerve block in predicting the outcome of subsequent botulinum toxin type A treatment for spastic equinovarus foot due to chronic stroke. Design: Retrospective observational study. Patients: Fifty chronic stroke patients with spastic equinovarus foot. Methods: Each patient was given diagnostic tibial nerve block (lidocaine 2% perineural injection) assessment followed by botulinum toxin type A inoculation into the same muscles as had been targeted by the nerve block. All patients were evaluated before diagnostic nerve block, after the nerve block, and 4 weeks after botulinum toxin injection. Outcomes were ankle dorsiflexion passive range of motion of the affected side, and calf muscle spasticity, measured with the modified Ashworth scale and the Tardieu Scale. Results: Significant improvements were measured after diagnostic nerve block and botulinum toxin injection compared with the baseline condition. Diagnostic nerve block led to significantly greater improvements in all outcomes than botulinum toxin injection. Conclusion: This study confirmed diagnostic nerve block as a valuable screening tool in deciding whether to treat spastic equinovarus with botulinum toxin. However, the results support the evidence that diagnostic nerve block results in a greater reduction in muscle overactivity than does botulinum toxin type A in patients with spastic equinovarus due to stroke

Patient-Reported Side Effects of Intradetrusor Botulinum Toxin Type A for Idiopathic Overactive Bladder Syndrome

Objective: The aim of the study was a prospective assessment of patient-reported side effects in an open-label study after intradetrusor botulinum toxin injections for idiopathic overactive bladder (OAB). Patients and Methods: Botulinum toxin A injection was performed in 56 patients with idiopathic OAB. Patients were followed up for 6 months concerning side effects and patients' satisfaction. Results: Different types of side effects were assessed such as dry mouth (19.6%), arm weakness (8.9%), eyelid weakness (8.9%), leg weakness (7.1%), torso weakness (5.4%), impaired vision (5.4%) and dysphagia (5.4%). In all cases, symptoms were mild and transient. Urological complications such as gross hematuria (17.9%), acute urinary retention (8.9%) and acute urinary tract infection (7.1%) were noticed. In all cases, acute urinary retention was transient and treated with temporary intermittent self-catheterization. There was no statistically significant correlation between dosage and observed side effects. Patients' satisfaction rate was high (71.4%). Conclusion: Intradetrusor injection of botulinum toxin was associated with a high rate of neurourological side effects. In general, side effects were transient, mild and did not require special treatment. Copyright (C) 2010 S. Karger AG, Base

Botulinum toxin therapy: functional silencing of salivary disorders.

Botulinum toxin (BTX) is a neurotoxic protein produced by Clostridium botulinum, an anaerobic bacterium. BTX therapy is a safe and effective treatment when used for functional silencing of the salivary glands in disorders such as sialoceles and salivary fistulas that may have a post-traumatic or post-operative origin. BTX injections can be considered in sialoceles and salivary fistulas after the failure of or together with conservative treatments (e.g. antibiotics, pressure dressings, or serial aspirations). BTX treatment has a promising role in chronic sialadenitis. BTX therapy is highly successful in the treatment of gustatory sweating (Frey\u2019s syndrome), and could be considered the gold standard treatment for this neurological disorder

Current status and future directions of botulinum neurotoxins for targeting pain processing.

Current evidence suggests that botulinum neurotoxins (BoNTs) A1 and B1, given locally into peripheral tissues such as skin, muscles, and joints, alter nociceptive processing otherwise initiated by inflammation or nerve injury in animal models and humans. Recent data indicate that such locally delivered BoNTs exert not only local action on sensory afferent terminals but undergo transport to central afferent cell bodies (dorsal root ganglia) and spinal dorsal horn terminals, where they cleave SNAREs and block transmitter release. Increasing evidence supports the possibility of a trans-synaptic movement to alter postsynaptic function in neuronal and possibly non-neuronal (glial) cells. The vast majority of these studies have been conducted on BoNT/A1 and BoNT/B1, the only two pharmaceutically developed variants. However, now over 40 different subtypes of botulinum neurotoxins (BoNTs) have been identified. By combining our existing and rapidly growing understanding of BoNT/A1 and /B1 in altering nociceptive processing with explorations of the specific characteristics of the various toxins from this family, we may be able to discover or design novel, effective, and long-lasting pain therapeutics. This review will focus on our current understanding of the molecular mechanisms whereby BoNTs alter pain processing, and future directions in the development of these agents as pain therapeutics