SEARCH · Search PubMed

Results for “Botulinum Toxins”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

SourceResearch connectionFrom yearThrough year

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 19 recordsLinked to original sources

PubMed2006

Clinical use of non-A botulinum toxins: botulinum toxin type C and botulinum toxin type F.

Botulinum neurotoxin (BoNT) serotype A is commonly used in the treatment of focal dystonia, but some patients are primarily or become secondarily resistant to it. Consequently, other serotypes have to be used when immuno-resistance is proven. In the literature, patients with focal dystonia have been treated with BoNT serotype F with clinical benefit but with short lasting effects. Recently, BoNT serotype C has been used with positive clinical outcome. An update on the clinical use of BoNT serotype F and BoNT serotype C is provided.

Adult↗

PubMed2006

Clinical use of non-A botulinum toxins: botulinum toxin type B.

Botulinum neurotoxin type B (BT, BT-B) has been used as NeuroBloc/MyoBloc since 1999 for treatment of cervical dystonia, hyperhidrosis, spastic conditions, cerebral palsy, hemifacial spasm, bladder dysfunction, spasmodic dysphonia, sialorrhoea, anal fissures, piriformis syndrome, various pain conditions and cosmetic applications. Generally, its therapeutic effects are comparable to BT type A (BT-A). The adverse effect profiles of BT-B and BT-A, however, differ considerably. BT-B has been found to produce more regional as well as systemic anticholinergic adverse effects, such as dryness of mouth, accommodation difficulties, conjunctival irritation, reduced sweating, dysphagia, heartburn, constipation, bladder voiding difficulties and dryness of nasal mucosa. In BT-B the relationship between autonomic and motor effects known from BT-A is substantially shifted towards autonomic effects. BT-B, therefore, should be used carefully in patients with autonomic disorders and in patients with concomitant anticholinergic therapy. If NeuroBloc/MyoBloc is used to treat cervical dystonia patients with antibody-induced failure of BT-A therapy, 86% of those will develop complete secondary therapy failure after five applications. If NeuroBloc/MyoBloc used to treat cervical dystonia patients without prior exposure to BT, 44% of those will develop complete secondary therapy failure after nine applications. NeuroBloc/MyoBloc, therefore, is associated with substantial antigenicity problems originating from a particular low specific biological potency. Systemic anticholinergic adverse effects and high antigenicity limits the clinical use of NeuroBloc/MyoBloc considerably.

Animals↗

PubMed1999

Characterization of a vertebrate neuromuscular junction that demonstrates selective resistance to botulinum toxin.

Botulinum toxin blocks transmitter release by proceeding through a series of four steps: binding to cell surface receptors, penetration of the cell membrane by receptor-mediated endocytosis, penetration of the endosome membrane by pH-induced translocation, and intracellular proteolysis of substrates that govern exocytosis. Each of these steps is essential for toxin action on intact cells. Therefore, alterations in cell structure or cell function that impede any of these steps should confer resistance to toxin. In the present study, screening for susceptibility to four serotypes of botulinum toxin revealed that the cutaneous-pectoris nerve-muscle preparation of Rana pipiens is resistant to type B botulinum toxin. Resistance was demonstrated both by electrophysiologic techniques and by dye-staining techniques. In addition, resistance to serotype B was demonstrated at toxin concentrations that were 2 orders of magnitude higher than those associated with blockade produced by other serotypes. In experiments on broken cell preparations, type B toxin cleaved synaptobrevin from frog brain synaptosomes. However, the toxin did not bind to frog nerve membranes. These findings suggest that resistance is due to an absence of cell surface receptors for botulinum toxin type B. The fact that cutaneous-pectoris preparations were sensitive to other botulinum toxin serotypes (A, C, and D), as well as other neuromuscular blocking agents (alpha-latrotoxin, beta-bungarotoxin), indicates that botulinum toxin type B receptors are distinct.

Animals↗

PubMed2004

Pearls and pitfalls in the therapeutic use of botulinum toxin.

Botulinum toxin is a potent toxin and powerful therapeutic tool. Botulinum toxin has therapeutic application in the treatment of a host of neurological, ophthalmologic, gastroenterological, urologic, and dermatologic conditions. Although there are issues specific to each disorder for which botulinum toxin therapy is employed, there are several common principles. This article reviews several of these general principles by addressing common questions that arise in the therapeutic use of botulinum toxin. Areas of focus include patient selection, drug preparation and delivery, use of electromyography to guide injections, drug resistance, and organization of a therapeutic botulinum toxin clinic.

Botulinum Toxins↗

PubMed1997

Expression of neurotransmitter genes in rat spinal motoneurons after chemodenervation with botulinum toxin.

Botulinum toxin is widely used for the treatment of focal movement disorders, where chemodenervation is used to decrease hyperactivity in selected muscles. Beside a focal paresis, widespread effects on neuromuscular synaptic function have been demonstrated. However, reactions of motoneurons after neuromuscular chemodenervation without gross morphological lesions are largely unknown. Peripheral axotomy, in contrast, leads to profound changes in the expression of several genes, including those encoding neurotransmitters, in motoneurons. We therefore examined the expression of neurotransmitter genes in rat motoneurons six days after intramuscular botulinum toxin application in the right gastrocnemius muscle. Similar doses of botulinum toxin as used in human where injected. A focal bilateral increase in expression of the choline acetyltransferase gene and a widespread bilateral increase of the beta-calcitonin-gene-related peptide and the enkephalin genes was measured in motoneurons after botulinum toxin injection. Cholecystokinin had a lower expression after botulinum toxin injections. Growth-associated protein 43, nitric oxide synthase, somatostatin and proopiomelanocortin messenger RNA were not found in motoneurons of both groups. Our results demonstrate that changes in the expression of neurotransmitter genes in motoneurons also occur after chemodenervation but with different patterns to those found after mechanical nerve lesioning. These changes reflect focal and widespread modulative events. The knowledge of these events should lead to a better understanding of the focal paralysis and of the more widespread effects found in human after intramuscular injection of botulinum toxin.

Animals↗

PubMed2006

Update on botulinum toxin.

Botulinum toxin for facial enhancement is currently the most popular aesthetic procedure performed in the United States. New developments have occurred within the last few years. Patients prefer having multiple areas of the upper face treated which increases patient satisfaction. Treatment of the forehead is now being accomplished with fewer units of botulinum toxin. This helps preserve the natural look of some movement of the forehead. Men require more units of botulinum toxin than women. Combination therapy using botulinum toxin along with lasers or filler substances is ideal. Aesthetic medicine knowledge has progressed, contributing a greater understanding of botulinum treatment for advanced areas of the face. The orbicularis oris, mentalis, and depressor anguli oris are now routinely treated and help improve overall facial appearance. Other forms of botulinum toxins (additional type A or type B toxins) are available, each with advantages and disadvantages.

Botulinum Toxins, Type A↗

PubMed2006

[Potential antinociceptive mechanisms of botulinum toxin].

Botulinum toxin has been used in pain therapy for several years. Its application in migraine and headaches is particularly interesting. Clinical results have not yet been definitely conclusive, and a uniform model of the mode of action has not been established either. Apart from a purely muscular effect, a direct antinociceptive effect of botulinum toxin has been found in patients, in the preclinical model, and in a clinical pain model. This is contradicted by negative observations in the clinical model of pain, which might be related to methodological deficits. Further basics need to be worked out before arriving at any final result. Clinical studies with patients and pain models should then follow. Studying botulinum toxin within the context of pain will also provide many new insights into pain therapy in general. In which pain model botulinum toxin may play a role in the future, has to be awaited.

Analgesics, Non-Narcotic↗

PubMed2001

Botulinophilia: contraindication for therapy with botulinum toxin.

Botulinum toxin inhibits neuromuscular transmission and is one of the most potent toxins. It has proven to be effective in the treatment of hyperhidrosis and is being more frequently demanded for therapy. Patients with body dysmorphic disorder also seek costly treatment with botulinum toxin. This botulinophilia is a new venenophilia. Body dysmorphic disorder is defined as a preoccupation with an imagined defect in appearance. If a slight physical anomaly is present, the person's concern is markedly exessive. The patient's preoccupation causes clinically significant distress or impairment in socially, occupational, or other important areas of functioning. The sweat test according to Minor is negative. Patients with botulinophilia are among the most difficult patients managed by the dermatologist. They are demanding and time-consuming. In our clinic, 23.1% of a series of patients seeking treatment with botulinum toxin screened positive for body dysmorphic disorder. Botulinophilia is a contraindication for therapy with botulinum toxin but is an indication for psychotherapy.

Adult↗

PubMed1996

[Mechanism of action, clinical indication and results of treatment of botulinum toxin].

Botulinum toxin, the most potent of the neurotoxins, produces paralysis by blocking presynaptic release of the neurotransmitter (acetylcholine) at the neuromuscular junction, with reversible chemical denervation of the muscle fibre, thereby inducing partial paralysis and atrophy. Because chemical denervation is reversible, botulinum toxin has temporary effects, the muscle being progressively reinnervated by nerve sproutings. Type A botulinum toxin (Bix-A) is available under two dosage forms: Botox and Dysport. Although the initial clinical indication was strabismus, subsequent studies have demonstrated the efficacy of Btx-A, mainly in dystonia, hemifacial spasm and spasticity. However, botulinum toxin has been successfully used in various other clinical indications. In regard to spasticity associated with cerebral palsy, Btx-A is a promising treatment requiring a multidisciplinary approach. Btx-A injections lead to effective reduction of muscle hyperactivity with minor side-effects. They are painless, even though electromyographic guidance may be required for the injection of deep muscles. However, the production of antibodies to Btx-A may compromise the effect of long-term treatment.

Blepharospasm↗

PubMedDate not supplied

Synaptic transmission: inhibition of neurotransmitter release by botulinum toxins.

Botulinum toxin type A, a protein long used in the successful treatment of various dystonias, has a complex mechanism of action that results in muscle relaxation. At the neuromuscular junction, the presynaptic nerve ending is packed with synaptic vesicles filled with acetylcholine, and clustered at the tip of the folds of the postsynaptic muscle membrane are the acetylcholine receptors. Synaptic vesicles fuse with the membrane in response to an elevation of intraneuronal calcium concentration and undergo release of their transmitter by exocytosis. Intracellular proteins that contribute to the fusion of the vesicles with the plasma membrane during exocytosis include synaptosomal protein with a molecular weight of 25 kDa (SNAP-25); vesicle-associated membrane protein (VAMP), also known as synaptobrevin; and syntaxin. Through their proteolytic action on these proteins, botulinum toxins prevent exocytosis, thereby inhibiting the release of acetylcholine. There are 7 serotypes of this toxin-A, B, C1, D, E, F, and G-and each cleaves a different intracellular protein or the same target at distinct bonds. The separate cleavage sites in SNAP-25 for botulinum toxin types A and E contribute to their dissimilar durations of muscle relaxation. This report describes the molecular basis for the inhibition by botulinum toxins of neuroexocytosis and subsequent functional recovery at the neuromuscular junction.

Acetylcholine↗

PubMed1999

Evidence for calcium-dependent vesicular transmitter release insensitive to tetanus toxin and botulinum toxin type F.

Whether exocytosis evoked by a given releasing stimulus from different neuronal families or by different stimuli from one neuronal population occurs through identical mechanisms is unknown. We studied the release of [3H]noradrenaline, [3H]acetylcholine and [3H]dopamine induced by different stimuli from superfused rat brain synaptosomes pretreated with tetanus toxin or botulinum toxin F, known to block exocytosis by cleaving VAMP/synaptobrevin. The external Ca2(+)-dependent [3H]transmitter overflows evoked by KCl were similarly inhibited by tetanus toxin or botulinum toxin F; the toxins cleaved similar amounts of synaptosomal synaptobrevin, as determined by western blot analysis, suggesting prevalent involvement of synaptobrevin-II. GABA uptake-mediated release of the three [3H]transmitters was that differentially sensitive to the toxins: only the release of [3H]noradrenaline, which is dependent on external Ca2+, but not of [3H]acetylcholine and [3H]dopamine was blocked. Neither toxin affected the [3H]transmitter overflows evoked by the Ca2(+) ionophore ionomycin. Cadmium blocked the K(+)-evoked release of all [3H]transmitters and the GABA-evoked release of [3H]noradrenaline; the GABA-evoked releases of [3H]acetylcholine and [3H]dopamine and those elicited by ionomycin were insensitive to cadmium. The results suggest that tetanus toxin and botulinum toxin F selectively affect exocytosis linked to activation of voltage-sensitive Ca2(+) channels; the Ca2(+)-dependent, exocytotic-like release induced by stimuli not leading to activation of voltage-sensitive Ca2+ channels seems insensitive to these clostridial toxins.

Animals↗

PubMed1996

Repeatedly successful closure of the larynx for the treatment of chronic aspiration with the use of botulinum toxin A.

Botulinum toxin A was used preoperatively to temporarily paralyze the intrinsic laryngeal muscles to hinder movements during the healing period after operation. In addition, toxin was injected into the cricopharyngeal muscle to allow a better passive drainage of the saliva into the esophagus. We treated six patients. Three suffered from chronic aspiration problems after multiple lower cranial nerve lesions, and three patients were apallic (after stroke and major brain injury). Two weeks before scheduled operation, we injected the toxin into the posterior cricoarytenoid muscles, the aryepiglottic muscles, and the vocalis muscle on both sides, as well as the cricopharyngeal muscle. The amount of injected toxin varied between 1.0 and 1.4 mL, equal to 200 to 280 units of botulinum toxin A (Dysport). After a complete palsy of these muscles (controlled by direct electromyography), a closure of the larynx was performed. After laminotomy and exposure of the intralaryngeal structures, the false vocal cords were mobilized and adapted with sutures. Because involuntary movements of the intralaryngeal musculature were absent, primary healing without complications occurred in all cases. Aspiration and related complications disappeared in all patients. In addition, the intensity of patient care could be considerably reduced. Preoperative use of botulinum toxin A allows sufficient laryngeal closure. This procedure is especially useful in the treatment of children and young adults, preserving the ability of later speech rehabilitation because of the return of voluntary movements of the intrinsic laryngeal muscles 6 months after the injection. Furthermore, this technique, as minimal surgical intervention, can be performed in high-risk patients.

Adolescent↗

PubMed2005

Expanding use of botulinum toxin.

Botulinum toxin type A (BTX-A) is best known to neurologists as a treatment for neuromuscular conditions such as dystonias and spasticity and has recently been publicized for the management of facial wrinkles. The property that makes botulinum toxin type A useful for these various conditions is the inhibition of acetylcholine release at the neuromuscular junction. Although botulinum toxin types A and B (BTX-A and BTX-B) continue to find new uses in neuromuscular conditions involving the somatic nervous system, it has also been recognized that the effects of these medications are not confined to cholinergic neurons at the neuromuscular junction. Acceptors for BTX-A and BTX-B are also found on autonomic nerve terminals, where they inhibit acetylcholine release at glands and smooth muscle. This observation led to trials of botulinum neurotoxins in various conditions involving autonomic innervation. The article reviews the emerging use of botulinum neurotoxins in these and selected other conditions, including sialorrhea, primary focal hyperhidrosis, pathological pain and primary headache disorders that may be of interest to neurologists and related specialists.

Botulinum Toxins↗

PubMed1997

Therapeutic uses of botulinum toxin.

Botulinum toxin was introduced as a safe and effective treatment for strabismus and other disorders of the extraocular muscles in the early 1980s. Approved by the U.S. Food and Drug Administration for use in the treatment of strabismus, blepharospasm and seventh cranial nerve disorders, botulinum toxin has also been shown to be effective in the treatment of a wide range of disorders associated with involuntary muscle contraction and spasm, including focal dystonia, hemifacial spasm and spasmodic torticollis. Neurologic syndromes associated with excessive muscle contraction or involuntary movement, disturbances of sphincter function and musculoskeletal pain are other conditions that can be successfully treated with botulinum toxin.

Anti-Dyskinesia Agents↗

PubMed2001

The role of zinc binding in the biological activity of botulinum toxin.

Botulinum toxin is a zinc-dependent endoprotease that acts on vulnerable cells to cleave polypeptides that are essential for exocytosis. To exert this poisoning effect, the toxin must proceed through a complex sequence of events that involves binding, productive internalization, and intracellular expression of catalytic activity. Results presented in this study show that soluble chelators rapidly strip Zn(2+) from its binding site in botulinum toxin, and this stripping of cation results in the loss of catalytic activity in cell-free or broken cell preparations. Stripped toxin is still active against intact neuromuscular junctions, presumably because internalized toxin binds cytosolic Zn(2+). In contrast to soluble chelators, immobilized chelators have no effect on bound Zn(2+), nor do they alter toxin activity. The latter finding is because of the fact that the spontaneous loss of Zn(2+) from its coordination site in botulinum toxin is relatively slow. When exogenous Zn(2+) is added to toxin that has been stripped by soluble chelators, the molecule rebinds cation and regains catalytic and neuromuscular blocking activity. Exogenous Zn(2+) can restore toxin activity either when the toxin is free in solution on the cell exterior or when it has been internalized and is in the cytosol. The fact that stripped toxin can reach the cytosol means that the loss of bound Zn(2+) does not produce conformational changes that block internalization. Similarly, the fact that stripped toxin in the cytosol can be reactivated by ambient Zn(2+) or exogenous Zn(2+) means that productive internalization does not produce conformational changes that block rebinding of cation.

Animals↗

PubMed2002

Complications and adverse reactions with the use of botulinum toxin.

Botulinum toxins are the causative agents of the severe food-borne illness botulism. With lethal doses approximating 10(-9) g/kg body weight, these neurotoxins represent some of the most toxic naturally occurring substances. Regardless, botulinum toxin is considered a safe therapy for inappropriate muscle spasms with adverse effects being typically self-limited. This article deals with some of the complications that have occurred with these treatments. The greatest concern with the use of BOTOX is probably the formation of blocking antibodies leading to nonresponse of subsequent treatment. Prevalence of resistance is less than 5%. Most complications associated with its aesthetic use are few and anecdotal. Nevertheless, the common problems and pitfalls associated with aesthetic treatment of the various areas of the face and neck with botulinum toxin are discussed. Also included are recommendations as to how to avoid these very undesirable, yet common, problems.

Blepharoptosis↗

PubMed2001

Complications and adverse reactions with the use of botulinum toxin.

Blepharoptosis↗

PubMed2003

How to avoid brow ptosis after forehead treatment with botulinum toxin.

Botulinum toxin is primarily indicated on the upper third of face. The treatment of the forehead wrinkles has a limited number of side effects, but can lead to brow ptosis. Brow ptosis appears in many studies with a frequency of around 1-5%. This is caused, often, by using incorrect injection sites, too high dosages, and by an inappropriate selection of patients. In our experience, this side effect has occurred in less than 1% of cases. This paper will emphasize the technical methods we use in order to reduce to a minimum this unpleasant side effect. Understanding the side effects of botulinum toxin on forehead requires a thorough understanding of muscular anatomy. We emphasize the importance of the correct dilution, the use of adrenalin and a 30 U syringe, particularly for patients who have skin abundance (dermatocalasys) of forehead. Patients with dermatocalasys should usually be excluded, but if treated, it should be done in two different sessions, without overdosing and respecting the symmetry. Brow ptosis, the only real side effect of forehead treatment with botulinum toxin A, can be reduced to a minimum by using simple rules.

Botulinum Toxins, Type A↗