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Sample records for botulinum toxin administered

  1. Botulinum toxin

    Directory of Open Access Journals (Sweden)

    Nigam P

    2010-01-01

    Full Text Available Botulinum toxin, one of the most poisonous biological substances known, is a neurotoxin produced by the bacterium Clostridium botulinum. C. botulinum elaborates eight antigenically distinguishable exotoxins (A, B, C 1 , C 2 , D, E, F and G. All serotypes interfere with neural transmission by blocking the release of acetylcholine, the principal neurotransmitter at the neuromuscular junction, causing muscle paralysis. The weakness induced by injection with botulinum toxin A usually lasts about three months. Botulinum toxins now play a very significant role in the management of a wide variety of medical conditions, especially strabismus and focal dystonias, hemifacial spasm, and various spastic movement disorders, headaches, hypersalivation, hyperhidrosis, and some chronic conditions that respond only partially to medical treatment. The list of possible new indications is rapidly expanding. The cosmetological applications include correction of lines, creases and wrinkling all over the face, chin, neck, and chest to dermatological applications such as hyperhidrosis. Injections with botulinum toxin are generally well tolerated and side effects are few. A precise knowledge and understanding of the functional anatomy of the mimetic muscles is absolutely necessary to correctly use botulinum toxins in clinical practice.

  2. Botulinum toxin in parkinsonism: The when, how, and which for botulinum toxin injections.

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    Cardoso, Francisco

    2018-06-01

    The aim of this article is to provide a review of the use of injections of botulinum toxin in the management of selected symptoms and signs of Parkinson's disease and other forms of parkinsonism. Sialorrhea is defined as inability to control oral secretions, resulting in excessive saliva in the oropharynx. There is a high level of evidence for the treatment of sialorrhea in parkinsonism with injections of different forms of botulinum toxin type A as well as botulinum toxin type B. Tremor can be improved by the use of botulinum toxin injections but improved tremor control often leads to concomitant motor weakness, limiting its use. Levodopa induced dyskinesias are difficult to treat with botulinum toxin injections because of their variable frequency and direction. Apraxia of eyelid opening, a sign more commonly seen in progressive supranuclear palsy and other tauopathies, often improves after botulinum toxin injections. Recent data suggest that regardless of the underlying mechanism, pain in parkinsonism can be alleviated by botulinum toxin injections. Finally, freezing of gait, camptocormia and Pisa syndrome in parkinsonism almost invariably fail to respond to botulinum toxin injections. Copyright © 2017 Elsevier Ltd. All rights reserved.

  3. Botulinum Toxin (Botox) for Facial Wrinkles

    Science.gov (United States)

    ... Stories Español Eye Health / Eye Health A-Z Botulinum Toxin (Botox) for Facial Wrinkles Sections Botulinum Toxin (Botox) ... Facial Wrinkles How Does Botulinum Toxin (Botox) Work? Botulinum Toxin (Botox) for Facial Wrinkles Leer en Español: La ...

  4. Topical botulinum toxin.

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    Collins, Ashley; Nasir, Adnan

    2010-03-01

    Nanotechnology is a rapidly growing discipline that capitalizes on the unique properties of matter engineered on the nanoscale. Vehicles incorporating nanotechnology have led to great strides in drug delivery, allowing for increased active ingredient stability, bioavailability, and site-specific targeting. Botulinum toxin has historically been used for the correction of neurological and neuromuscular disorders, such as torticollis, blepharospasm, and strabismus. Recent dermatological indications have been for the management of axillary hyperhydrosis and facial rhytides. Traditional methods of botulinum toxin delivery have been needle-based. These have been associated with increased pain and cost. Newer methods of botulinum toxin formulation have yielded topical preparations that are bioactive in small pilot clinical studies. While there are some risks associated with topical delivery, the refinement and standardization of delivery systems and techniques for the topical administration of botulinum toxin using nanotechnology is anticipated in the near future.

  5. Botulinum toxin: bioweapon & magic drug.

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    Dhaked, Ram Kumar; Singh, Manglesh Kumar; Singh, Padma; Gupta, Pallavi

    2010-11-01

    Botulinum neurotoxins, causative agents of botulism in humans, are produced by Clostridium botulinum, an anaerobic spore-former Gram positive bacillus. Botulinum neurotoxin poses a major bioweapon threat because of its extreme potency and lethality; its ease of production, transport, and misuse; and the need for prolonged intensive care among affected persons. A single gram of crystalline toxin, evenly dispersed and inhaled, can kill more than one million people. The basis of the phenomenal potency of botulinum toxin is enzymatic; the toxin is a zinc proteinase that cleaves neuronal vesicle associated proteins responsible for acetylcholine release into the neuromuscular junction. As a military or terrorist weapon, botulinum toxin could be disseminated via aerosol or by contamination of water or food supplies, causing widespread casualties. A fascinating aspect of botulinum toxin research in recent years has been development of the most potent toxin into a molecule of significant therapeutic utility . It is the first biological toxin which is licensed for treatment of human diseases. In the late 1980s, Canada approved use of the toxin to treat strabismus, in 2001 in the removal of facial wrinkles and in 2002, the FDA in the United States followed suit. The present review focuses on both warfare potential and medical uses of botulinum neurotoxin.

  6. Botulinum toxin injection - larynx

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    Injection laryngoplasty; Botox - larynx: spasmodic dysphonia-BTX; Essential voice tremor (EVT)-btx; Glottic insufficiency; Percutaneous electromyography - guided botulinum toxin treatment; Percutaneous indirect laryngoscopy - guided botulinum toxin treatment; ...

  7. [Intoxication of botulinum toxin].

    Science.gov (United States)

    Chudzicka, Aleksandra

    2015-09-01

    Botulinum toxin is an egzotoxin produced by Gram positive bacteria Clostridium botulinum. It is among the most potent toxins known. The 3 main clinical presentations of botulism are as follows: foodborne botulism, infant botulism and wound botulism. The main symptom of intoxication is flat muscles paralysis. The treatment is supportive care and administration of antitoxin. In prevention the correct preparing of canned food is most important. Botulinum toxin is accepted as a biological weapon. © 2015 MEDPRESS.

  8. Role of Botulinum Toxin in Depression.

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    Parsaik, Ajay K; Mascarenhas, Sonia S; Hashmi, Aqeel; Prokop, Larry J; John, Vineeth; Okusaga, Olaoluwa; Singh, Balwinder

    2016-03-01

    The goal of this review was to consolidate the evidence concerning the efficacy of botulinum toxin type A (onabotulinumtoxinA) in depression. We searched MEDLINE, EMBASE, Cochrane, and Scopus through May 5, 2014, for studies evaluating the efficacy of botulinum toxin A in depression. Only randomized controlled trials were included in the meta-analysis. A pooled mean difference in primary depression score, and pooled odds ratio for response and remission rate with 95% confidence interval (CI) were estimated using the random-effects model. Heterogeneity was assessed using Cochran Q test and χ statistic. Of the 639 articles that were initially retrieved, 5 studies enrolling 194 subjects (age 49±9.6 y) were included in the systematic review, and 3 randomized controlled trials enrolling 134 subjects were included in the meta-analysis. The meta-analysis showed a significant decrease in mean primary depression scores among patients who received botulinum toxin A compared with placebo (-9.80; 95% CI, -12.90 to -6.69) with modest heterogeneity between the studies (Cochran Q test, χ=70). Response and remission rates were 8.3 and 4.6 times higher, respectively, among patients receiving botulinum toxin A compared with placebo, with no heterogeneity between the studies. The 2 studies excluded from the meta-analysis also found a significant decrease in primary depression scores in patients after receiving botulinum toxin A. A few subjects had minor side effects, which were similar between the groups receiving botulinum toxin and those receiving placebo. This study suggests that botulinum toxin A can produce significant improvement in depressive symptoms and is a safe adjunctive treatment for patients receiving pharmacotherapy for depression. Future trials are needed to evaluate the antidepressant effect per se of botulinum toxin A and to further elucidate the underlying antidepressant mechanism of botulinum toxin A.

  9. Botulinum Toxin: Pharmacology and Therapeutic Roles in Pain States.

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    Patil, Shilpadevi; Willett, Olga; Thompkins, Terin; Hermann, Robert; Ramanathan, Sathish; Cornett, Elyse M; Fox, Charles J; Kaye, Alan David

    2016-03-01

    Botulinum toxin, also known as Botox, is produced by Clostridium botulinum, a gram-positive anaerobic bacterium, and botulinum toxin injections are among the most commonly practiced cosmetic procedures in the USA. Although botulinum toxin is typically associated with cosmetic procedures, it can be used to treat a variety of other conditions, including pain. Botulinum toxin blocks the release of acetylcholine from nerve endings to paralyze muscles and to decrease the pain response. Botulinum toxin has a long duration of action, lasting up to 5 months after initial treatment which makes it an excellent treatment for chronic pain patients. This manuscript will outline in detail why botulinum toxin is used as a successful treatment for pain in multiple conditions as well as outline the risks associated with using botulinum toxin in certain individuals. As of today, the only FDA-approved chronic condition that botulinum toxin can be used to treat is migraines and this is related to its ability to decrease muscle tension and increase muscle relaxation. Contraindications to botulinum toxin treatments are limited to a hypersensitivity to the toxin or an infection at the site of injection, and there are no known drug interactions with botulinum toxin. Botulinum toxin is an advantageous and effective alternative pain treatment and a therapy to consider for those that do not respond to opioid treatment. In summary, botulinum toxin is a relatively safe and effective treatment for individuals with certain pain conditions, including migraines. More research is warranted to elucidate chronic and long-term implications of botulinum toxin treatment as well as effects in pregnant, elderly, and adolescent patients.

  10. Botulinum toxin in trigeminal neuralgia.

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    Castillo-Álvarez, Federico; Hernando de la Bárcena, Ignacio; Marzo-Sola, María Eugenia

    2017-01-06

    Trigeminal neuralgia is one of the most disabling facial pain syndromes, with a significant impact on patients' quality of life. Pharmacotherapy is the first choice for treatment but cases of drug resistance often require new strategies, among which various interventional treatments have been used. In recent years a new therapeutic strategy consisting of botulinum toxin has emerged, with promising results. We reviewed clinical cases and case series, open-label studies and randomized clinical trials examining the use of botulinum toxin for drug-refractory trigeminal neuralgia published in the literature. The administration of botulinum toxin has proven to be a safe and effective therapeutic strategy in patients with drug-refractory idiopathic trigeminal neuralgia, but many questions remain unanswered as to the precise role of botulinum toxin in the treatment of this disease. Copyright © 2016 Elsevier España, S.L.U. All rights reserved.

  11. Botulinum toxin for the treatment of strabismus.

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    Rowe, Fiona J; Noonan, Carmel P

    2017-03-02

    The use of botulinum toxin as an investigative and treatment modality for strabismus is well reported in the medical literature. However, it is unclear how effective it is in comparison to other treatment options for strabismus. The primary objective was to examine the efficacy of botulinum toxin therapy in the treatment of strabismus compared with alternative conservative or surgical treatment options. This review sought to ascertain those types of strabismus that particularly benefit from the use of botulinum toxin as a treatment option (such as small angle strabismus or strabismus with binocular potential, i.e. the potential to use both eyes together as a pair). The secondary objectives were to investigate the dose effect and complication rates associated with botulinum toxin. We searched CENTRAL (which contains the Cochrane Eyes and Vision Trials Register) (2016, Issue 6), Ovid MEDLINE, Ovid MEDLINE In-Process and Other Non-Indexed Citations, Ovid MEDLINE Daily, Ovid OLDMEDLINE (January 1946 to July 2016), Embase (January 1980 to July 2016), Latin American and Caribbean Literature on Health Sciences (LILACS) (January 1982 to July 2016), the ISRCTN registry (www.isrctn.com/editAdvancedSearch), ClinicalTrials.gov (www.clinicaltrials.gov), and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en). We did not use any date or language restrictions in the electronic searches for trials. We last searched the electronic databases on 11 July 2016. We handsearched the British and Irish Orthoptic Journal, Australian Orthoptic Journal, proceedings of the European Strabismological Association (ESA), International Strabismological Association (ISA) and International Orthoptic Association (IOA) (www.liv.ac.uk/orthoptics/research/search.htm) and American Academy of Paediatric Ophthalmology and Strabismus meetings (AAPOS). We contacted researchers who are active in this field for information about further

  12. Botulinum toxin for the treatment of bruxism.

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    Tinastepe, Neslihan; Küçük, Burcu Bal; Oral, Koray

    2015-10-01

    Botulinum toxin, the most potent biological toxin, has been shown to be effective for a variety of disorders in several medical conditions, when used both therapeutically and cosmetically. In recent years, there has been a rising trend in the use of this pharmacological agent to control bruxing activity, despite its reported adverse effects. The aim of this review was to provide a brief overview to clarify the underlying essential ideas for the use of botulinum toxin in bruxism based on available scientific papers. An electronic literature search was performed to identify publications related to botulinum toxin and its use for bruxism in PubMed. Hand searching of relevant articles was also made to identify additional studies. Of the eleven identified studies, only two were randomized controlled trials, compared with the effectiveness of botulinum toxins on the reduction in the frequency of bruxism events and myofascial pain after injection. The authors of these studies concluded that botulinum toxin could be used as an effective treatment for reducing nocturnal bruxism and myofascial pain in patients with bruxism. Evidence-based research was limited on this topic. More randomized controlled studies are needed to confirm that botulinum toxin is safe and reliable for routine clinical use in bruxism.

  13. Botulinum toxin for vaginismus treatment.

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    Ferreira, Juliana Rocha; Souza, Renan Pedra

    2012-01-01

    Vaginismus is characterized by recurrent or persistent involuntary contraction of the perineal muscles surrounding the outer third of the vagina when penile, finger, tampon, or speculum penetration is attempted. Recent results have suggested the use of botulinum toxin for the treatment of vaginismus. Here, we assessed previously published data to evaluate the therapeutic effectiveness of botulinum toxin for vaginismus. We have carried out a systematic review followed by a meta-analysis. Our results indicate that botulinum toxin is an effective therapeutic option for patients with vaginismus (pooled odds ratio of 8.723 with 95% confidence interval limits of 1.942 and 39.162, p = 0.005). This may hold particularly true in treatment-refractory patients because most of the studies included in this meta-analysis have enrolled these subjects in their primary analysis. Botulinum toxin appears to bea reasonable intervention for vaginismus. However, this conclusion should be read carefully because of the deficiency of placebo-controlled randomized clinical trials and the quality issues presented in the existing ones.

  14. Treatment of displaced mandibular condylar fracture with botulinum toxin A.

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    Akbay, Ercan; Cevik, Cengiz; Damlar, Ibrahim; Altan, Ahmet

    2014-04-01

    The aim of this case report is to discuss the effect on condylar reduction of botulinum toxin A treatment used in a child with displaced fracture at condylar neck of mandible. A 3-years old boy was admitted to our clinic for incomplete fracture of mandibular symphysis and displaced condylar fracture at the left side. An asymmetrical occlusal splint with intermaxillary fixation was used instead of open reduction and internal fixation because of incomplete fracture of symphysis and possible complications of condyle surgery. However, it was observed that condylar angulation persisted despite this procedure. Thus, botulinum toxin A was administered to masseter, temporalis and pterygoideus medialis muscles. At the end of first month, it was seen that mandibular condyle was almost completely recovered and that fusion was achieved. In conclusion, Botulinum A toxin injection aiming the suppression of masticatory muscle strength facilitates the reduction in the conservative management of displaced condyle in pediatric patients. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  15. Botulinum toxin in pain treatment.

    Science.gov (United States)

    Colhado, Orlando Carlos Gomes; Boeing, Marcelo; Ortega, Luciano Bornia

    2009-01-01

    Botulinum toxin (BTX) is one of the most potent bacterial toxins known and its effectiveness in the treatment of some pain syndromes is well known. However, the efficacy of some of its indications is still in the process of being confirmed. The objective of this study was to review the history, pharmacological properties, and clinical applications of BTX in the treatment of pain of different origins. Botulinum toxin is produced by fermentation of Clostridium botulinum, a Gram-positive, anaerobic bacterium. Commercially, BTX comes in two presentations, types A and B. Botulinum toxin, a neurotoxin with high affinity for cholinergic synapses, blocks the release of acetylcholine by nerve endings without interfering with neuronal conduction of electrical signals or synthesis and storage of acetylcholine. It has been proven that BTX can selectively weaken painful muscles, interrupting the spasm-pain cycle. Several studies have demonstrated the efficacy and safety of BTX-A in the treatment of tension headaches, migraines, chronic lumbar pain, and myofascial pain. Botulinum toxin type A is well tolerated in the treatment of chronic pain disorders in which pharmacotherapy regimens can cause side effects. The reduction in the consumption of analgesics and length of action of 3 to 4 months per dose represent other advantages of its use. However, further studies are necessary to establish the efficacy of BTX-A in chronic pain disorders and its exact mechanism of action, as well as its potential in multifactorial treatments.

  16. Botulinum Toxin for Rhinitis.

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    Ozcan, Cengiz; Ismi, Onur

    2016-08-01

    Rhinitis is a common clinical entity. Besides nasal obstruction, itching, and sneezing, one of the most important symptoms of rhinitis is nasal hypersecretion produced by nasal glands and exudate from the nasal vascular bed. Allergic rhinitis is an IgE-mediated inflammatory reaction of nasal mucosa after exposure to environmental allergens. Idiopathic rhinitis describes rhinitis symptoms that occur after non-allergic, noninfectious irritants. Specific allergen avoidance, topical nasal decongestants, nasal corticosteroids, immunotherapy, and sinonasal surgery are the main treatment options. Because the current treatment modalities are not enough for reducing rhinorrhea in some patients, novel treatment options are required to solve this problem. Botulinum toxin is an exotoxin generated by Clostridium botulinum. It disturbs the signal transmission at the neuromuscular and neuroglandular junction by inhibiting the acetylcholine release from the presynaptic nerve terminal. It has been widely used in neuromuscular, hypersecretory, and autonomic nerve system disorders. There have been a lot of published articles concerning the effect of this toxin on rhinitis symptoms. Based on the results of these reports, intranasal botulinum toxin A administration appears to be a safe and effective treatment method for decreasing rhinitis symptoms in rhinitis patients with a long-lasting effect. Botulinum toxin type A will be a good treatment option for the chronic rhinitis patients who are resistant to other treatment methods.

  17. Diffusion of Botulinum Toxins

    Directory of Open Access Journals (Sweden)

    Matthew A. Brodsky

    2012-08-01

    Full Text Available Background: It is generally agreed that diffusion of botulinum toxin occurs, but the extent of the spread and its clinical importance are disputed. Many factors have been suggested to play a role but which have the most clinical relevance is a subject of much discussion.Methods: This review discusses the variables affecting diffusion, including protein composition and molecular size as well as injection factors (e.g., volume, dose, injection method. It also discusses data on diffusion from comparative studies in animal models and human clinical trials that illustrate differences between the available botulinum toxin products (onabotulinumtoxinA, abobotulinumtoxinA, incobotulinumtoxinA, and rimabotulinumtoxinB.Results: Neither molecular weight nor the presence of complexing proteins appears to affect diffusion; however, injection volume, concentration, and dose all play roles and are modifiable. Both animal and human studies show that botulinum toxin products are not interchangeable, and that some products are associated with greater diffusion and higher rates of diffusion-related adverse events than others.Discussion: Each of the botulinum toxins is a unique pharmacologic entity. A working knowledge of the different serotypes is essential to avoid unwanted diffusion-related adverse events. In addition, clinicians should be aware that the factors influencing diffusion may range from properties intrinsic to the drug to accurate muscle selection as well as dilution, volume, and dose injected.

  18. Botulinum toxin A for the Treatment of Overactive Bladder.

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    Hsieh, Po-Fan; Chiu, Hung-Chieh; Chen, Kuan-Chieh; Chang, Chao-Hsiang; Chou, Eric Chieh-Lung

    2016-02-29

    The standard treatment for overactive bladder starts with patient education and behavior therapies, followed by antimuscarinic agents. For patients with urgency urinary incontinence refractory to antimuscarinic therapy, currently both American Urological Association (AUA) and European Association of Urology (EAU) guidelines suggested that intravesical injection of botulinum toxin A should be offered. The mechanism of botulinum toxin A includes inhibition of vesicular release of neurotransmitters and the axonal expression of capsaicin and purinergic receptors in the suburothelium, as well as attenuation of central sensitization. Multiple randomized, placebo-controlled trials demonstrated that botulinum toxin A to be an effective treatment for patients with refractory idiopathic or neurogenic detrusor overactivity. The urinary incontinence episodes, maximum cystometric capacity, and maximum detrusor pressure were improved greater by botulinum toxin A compared to placebo. The adverse effects of botulinum toxin A, such as urinary retention and urinary tract infection, were primarily localized to the lower urinary tract. Therefore, botulinum toxin A offers an effective treatment option for patients with refractory overactive bladder.

  19. Botulinum Toxin in Management of Limb Tremor

    Directory of Open Access Journals (Sweden)

    Elina Zakin

    2017-11-01

    Full Text Available Essential tremor is characterized by persistent, usually bilateral and symmetric, postural or kinetic activation of agonist and antagonist muscles involving either the distal or proximal upper extremity. Quality of life is often affected and one’s ability to perform daily tasks becomes impaired. Oral therapies, including propranolol and primidone, can be effective in the management of essential tremor, although adverse effects can limit their use and about 50% of individuals lack response to oral pharmacotherapy. Locally administered botulinum toxin injection has become increasingly useful in the management of essential tremor. Targeting of select muscles with botulinum toxin is an area of active research, and muscle selection has important implications for toxin dosing and functional outcomes. The use of anatomical landmarks with palpation, EMG guidance, electrical stimulation, and ultrasound has been studied as a technique for muscle localization in toxin injection. Earlier studies implemented a standard protocol for the injection of (predominantly wrist flexors and extensors using palpation and EMG guidance. Targeting of muscles by selection of specific activators of tremor (tailored to each patient using kinematic analysis might allow for improvement in efficacy, including functional outcomes. It is this individualized muscle selection and toxin dosing (requiring injection within various sites of a single muscle that has allowed for success in the management of tremors.

  20. Botulinum Toxin and Muscle Atrophy: A Wanted or Unwanted Effect.

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    Durand, Paul D; Couto, Rafael A; Isakov, Raymond; Yoo, Donald B; Azizzadeh, Babak; Guyuron, Bahman; Zins, James E

    2016-04-01

    While the facial rejuvenating effect of botulinum toxin type A is well known and widespread, its use in body and facial contouring is less common. We first describe its use for deliberate muscle volume reduction, and then document instances of unanticipated and undesirable muscle atrophy. Finally, we investigate the potential long-term adverse effects of botulinum toxin-induced muscle atrophy. Although the use of botulinum toxin type A in the cosmetic patient has been extensively studied, there are several questions yet to be addressed. Does prolonged botulinum toxin treatment increase its duration of action? What is the mechanism of muscle atrophy and what is the cause of its reversibility once treatment has stopped? We proceed to examine how prolonged chemodenervation with botulinum toxin can increase its duration of effect and potentially contribute to muscle atrophy. Instances of inadvertent botulinum toxin-induced atrophy are also described. These include the "hourglass deformity" secondary to botulinum toxin type A treatment for migraine headaches, and a patient with atrophy of multiple facial muscles from injections for hemifacial spasm. Numerous reports demonstrate that muscle atrophy after botulinum toxin type A treatment occurs and is both reversible and temporary, with current literature supporting the notion that repeated chemodenervation with botulinum toxin likely responsible for both therapeutic and incidental temporary muscle atrophy. Furthermore, duration of response may be increased with subsequent treatments, thus minimizing frequency of reinjection. Practitioners should be aware of the temporary and reversible effect of botulinum toxin-induced muscle atrophy and be prepared to reassure patients on this matter. © 2016 The American Society for Aesthetic Plastic Surgery, Inc. Reprints and permission: journals.permissions@oup.com.

  1. Botulinum Toxin in Neurogenic Detrusor Overactivity

    Directory of Open Access Journals (Sweden)

    Carlos Arturo Levi D'Ancona

    2012-09-01

    Full Text Available Purpose To evaluate the effects of botulinum toxin on urodynamic parameters and quality of life in patients with neurogenic detrusor overactivity. Methods Thirty four adult patients with spinal cord injury and detrusor overactivity were selected. The patients received 300 units of botulinum toxin type A. The endpoints evaluated with the episodes of urinary incontinence and measured the maximum cystometric capacity, maximum amplitude of detrusor pressure and bladder compliance at the beginning and end of the study (24 weeks and evaluated the quality of life by applying the Qualiveen questionnaire. Results A significant decrease in the episodes of urinary incontinence was observed. All urodynamic parameters presented a significant improvement. The same was observed in the quality of life index and the specific impact of urinary problems scores from the Qualiveen questionnaire. Six patients did not complete the study, two due to incomplete follow-up, and four violated protocol and were excluded from the analyses. No systemic adverse events of botulinum toxin type A were reported. Conclusions A botulinum toxin type A showed a significantly improved response in urodynamics parameters and specific and general quality of life.

  2. Botulinum toxin in the treatment of vocal fold nodules.

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    Allen, Jacqui E; Belafsky, Peter C

    2009-12-01

    Promising new techniques in the management of vocal fold nodules have been developed in the past 2 years. Simultaneously, the therapeutic use of botulinum toxin has rapidly expanded. This review explores the use of botulinum toxin in treatment of vocal nodules and summarizes current therapeutic concepts. New microsurgical instruments and techniques, refinements in laser technology, radiosurgical excision and steroid intralesional injections are all promising new techniques in the management of vocal nodules. Botulinum toxin-induced 'voice rest' is a new technique we have employed in patients with recalcitrant nodules. Successful resolution of nodules is possible with this technique, without the risk of vocal fold scarring inherent in dissection/excision techniques. Botulinum toxin usage is exponentially increasing, and large-scale, long-term studies demonstrate its safety profile. Targeted vocal fold temporary paralysis induced by botulinum toxin injection is a new, well tolerated and efficacious treatment in patients with persistent vocal fold nodules.

  3. The resurgence of botulinum toxin injection for strabismus in children.

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    Mahan, Marielle; Engel, J Mark

    2017-09-01

    The present review discusses recent advances in the use of botulinum toxin for the management of strabismus in children. Botulinum toxin injection produces similar results compared to surgery for certain subtypes of strabismus, especially acute onset esotropia. It may be more effective in many subtypes of esotropia where surgery has been less reliable, including partially accommodative esotropia, esotropia associated with cerebral palsy, and thyroid eye disease. Small retrospective studies have demonstrated the efficacy of botulinum toxin in the treatment of many types of pediatric strabismus, providing some guidance for clinicians to determine which patients would benefit most from this intervention. Although administration of botulinum toxin is generally accepted as a reasonable option in select cases, many strabismus surgeons have not fully embraced the treatment, in part because of perceived disadvantages compared to surgery and difficulty in identifying subsets with the highest potential for therapeutic success. A recent study compared the administration of botulinum toxin in children with acute-onset esotropia to surgical correction and found botulinum toxin had a statistically equal success rate, but with the advantage of significantly less time under general anesthesia. In addition, botulinum toxin has been recently tried in patients with partially accommodative esotropia, esotropia associated with cerebral palsy, cyclic esotropia, and in patients with thyroid eye disease. The present review will discuss current clinical recommendations based on recent studies on the use of botulinum toxin in children with strabismus.

  4. Long-term outcomes of Botulinum toxin in the treatment of chronic anal fissure: 5 years of follow-up.

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    Barbeiro, Sandra; Atalaia-Martins, Catarina; Marcos, Pedro; Gonçalves, Cláudia; Canhoto, Manuela; Arroja, Bruno; Silva, Filipe; Cotrim, Isabel; Eliseu, Liliana; Santos, Antonieta; Vasconcelos, Helena

    2017-03-01

    Chronic anal fissure is a frequent and disabling disease, often affecting young adults. Botulinum toxin and lateral internal sphincterotomy are the main therapeutic options for refractory cases. Botulinum toxin is minimally invasive and safer compared with surgery, which carries a difficult post-operative recovery and fecal incontinence risk. The long-term efficacy of Botulinum toxin is not well known. The aim of this study was to evaluate the long-term efficacy and safety of Botulinum toxin in the treatment of chronic anal fissure. This was a retrospective study at a single center, including patients treated with Botulinum toxin from 2005 to 2010, followed over at least a period of 5 years. All patients were treated with injection of 25U of Botulinum toxin in the intersphincteric groove. The response was registered as complete, partial, refractory and relapse. Botulinum toxin was administered to 126 patients, 69.8% ( n  = 88) were followed over a period of 5 years. After 3 months, 46.6% ( n  = 41) had complete response, 23.9% ( n  = 21) had partial response and 29.5% ( n  = 26) were refractory. Relapse was observed in 1.2% ( n  = 1) at 6 months, 11.4% ( n  = 10) at 1 year, 2.3% ( n  = 2) at 3 years; no relapse at 5 years. The overall success rate was 64.8% at 5 years of follow-up. Botulinum toxin was well tolerated by all patients and there were no complications. The use of Botulinum toxin to treat patients with chronic anal fissure was safe and effective in long-term follow-up.

  5. Botulinum toxin for treatment of glandular hypersecretory disorders.

    LENUS (Irish Health Repository)

    Laing, T A

    2012-02-03

    SUMMARY: The use of botulinum toxin to treat disorders of the salivary glands is increasing in popularity in recent years. Recent reports of the use of botulinum toxin in glandular hypersecretion suggest overall favourable results with minimal side-effects. However, few randomised clinical trials means that data are limited with respect to candidate suitability, treatment dosages, frequency and duration of treatment. We report a selection of such cases from our own department managed with botulinum toxin and review the current data on use of the toxin to treat salivary gland disorders such as Frey\\'s syndrome, excessive salivation (sialorrhoea), focal and general hyperhidrosis, excessive lacrimation and chronic rhinitis.

  6. Treatment of Palatal Myoclonus with Botulinum Toxin Injection

    Directory of Open Access Journals (Sweden)

    Mursalin M. Anis

    2013-01-01

    Full Text Available Palatal myoclonus is a rare cause of pulsatile tinnitus in patients presenting to the otolaryngology office. Rhythmic involuntary contractions of the palatal muscles produce the pulsatile tinnitus in these patients. Treatment of this benign but distressing condition with anxiolytics, anticonvulsants, and surgery has been largely unsuccessful. A few investigators have obtained promising results with botulinum toxin injection into the palatal muscles. We present a patient with palatal myoclonus who failed conservative treatment with anxiolytics. Unilateral injection of botulinum toxin into her tensor veli palatini muscle under electromyographic guidance resolved pulsatile tinnitus in her ipsilateral ear and unmasked pulsatile tinnitus in the contralateral ear. A novel method of following transient postinjection symptoms using a diary is presented in this study. Botulinum toxin dose must be titrated to achieve optimal results in each individual patient, analogous to titrations done for spasmodic dysphonia. Knowledge of the temporal onset of postinjection side effects and symptomatic relief may aid physicians in dose titration and surveillance. We present suggestions on titrating the botulinum toxin dose to optimal levels. A review of the literature on the use of botulinum toxin for palatal myoclonus and some common complications are discussed.

  7. Endocardial botulinum toxin injection into ganglionated plexi in order to reduce atrial fibrillation inducibility

    Directory of Open Access Journals (Sweden)

    А. Г. Стрельников

    2016-01-01

    Full Text Available Objective. Prior animal studies suggest that botulinum toxin injection into the epicardial fat pads can suppress atrial fibrillation (AF inducibility. The purpose of the present study was to assess the efficacy and safety of endocardial botulinum toxin injection into epicardial fat pads and intramyocardial left atrial ganglionated plexi (GP for preventing AF.Methods. Twenty-four dogs were separated into 3 groups: endocardial approach for botulinum toxin (Xeomin, Germany injection into epicardial fat pads and intramyocardial GPs; endocardial approach for placebo injection (0.9% normal saline; control 1; n = 8 and epicardial approach for botulinum toxin injection (control 2; n = 8.Results. A mean of 6.9±1.7 intramyocardial injections (10 U/0.2 mL at each and 3 injections (50 U/1 mL at each were administered into each site exhibiting a positive vagal response and into each epicardial fat pad in all groups (p>0.05 between groups.The injections of botulinum toxin demonstrated dramatic prolongation of ERP in all PV-atrial junctions. This effect correlated with less pronounced ERP shortening in response to vagal nerve stimulation. Suppression of AF inducibility was observed at 7 days after endocardial botulinum toxin injections. The level of AF inducibility was: at 7 days – 57% (p<0.001 vs placebo; p<0.001 vs baseline; at 14 days – 61% (p<0.001 vs placebo; p<0.001 vs baseline; at 1 month – 38% (p<0.001 vs placebo; p<0.001 vs baseline; at 3 months – 23% (p = 0.003; p = 0.06 vs baseline. There were no differences between botulinum groups (p>0.05 for all. The effect of AF suppression disappeared at 3 months. No procedure-related complications occurred.Conclusion. Botulinum toxin injection into intramyocardial GPs and epicardial fat pads by an endocardial approach is feasible and safe. It provides complete removal of cardiac vagal responses and reliably reduces vulnerability to atrial fibrillation.

  8. Cosmetic Effect of Botulinum Toxin In Focal Hyperhydrosis

    Directory of Open Access Journals (Sweden)

    Jain S

    2005-01-01

    Full Text Available Hyperhydrosis of axillae, palm and sole is not a very uncommon problem. It leads to great embarrassment and considerable emotional stress to the individuals. Botulinum toxins prevent the release of acetylcholine at nerve terminals, therefore, reduces sweat secretion. Six patients of axillary and 4 patients of palmer and planter hyperhydrosis were treated with botulinum toxin. All patients experienced relatively satisfactory reduction of hyperhydrosis for period ranging between 4-7 months. No adverse effects were observed. Botulinum toxin therefore can be considered as an effective treatment in focal hyperhydrosis.

  9. Botulinum toxin type A versus botulinum toxin type B for cervical dystonia.

    Science.gov (United States)

    Duarte, Gonçalo S; Castelão, Mafalda; Rodrigues, Filipe B; Marques, Raquel E; Ferreira, Joaquim; Sampaio, Cristina; Moore, Austen P; Costa, João

    2016-10-26

    This is an update of a Cochrane review first published in 2003. Cervical dystonia is the most common form of focal dystonia and is a disabling disorder characterised by painful involuntary head posturing. There are two available formulations of botulinum toxin, with botulinum toxin type A (BtA) usually considered the first line therapy for this condition. Botulinum toxin type B (BtB) is an alternative option, with no compelling theoretical reason why it might not be as- or even more effective - than BtA. To compare the efficacy, safety and tolerability of botulinum toxin type A (BtA) versus botulinum toxin type B (BtB) in people with cervical dystonia. To identify studies for this review we searched the Cochrane Movement Disorders Group Trials Register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, reference lists of articles and conference proceedings. All elements of the search, with no language restrictions, were last run in October 2016. Double-blind, parallel, randomised, placebo-controlled trials (RCTs) comparing BtA versus BtB in adults with cervical dystonia. Two independent authors assessed records, selected included studies, extracted data using a paper pro forma, and evaluated the risk of bias. We resolved disagreements by consensus or by consulting a third author. We performed meta-analyses using the random-effects model, for the comparison BtA versus BtB to estimate pooled effects and corresponding 95% confidence intervals (95% CI). No prespecified subgroup analyses were carried out. The primary efficacy outcome was improvement on any validated symptomatic rating scale, and the primary safety outcome was the proportion of participants with adverse events. We included three RCTs, all new to this update, of very low to low methodological quality, with a total of 270 participants.Two studies exclusively enrolled participants with a known positive response to BtA treatment. This raises concerns of population enrichment

  10. Office-based endoscopic botulinum toxin injection in laryngeal movement disorders.

    Science.gov (United States)

    Kaderbay, A; Righini, C A; Castellanos, P F; Atallah, I

    2018-06-01

    Botulinum toxin injection is widely used for the treatment of laryngeal movement disorders. Electromyography-guided percutaneous injection is the technique most commonly used to perform intralaryngeal botulinum toxin injection. We describe an endoscopic approach for intralaryngeal botulinum toxin injection under local anaesthesia without using electromyography. A flexible video-endoscope with an operating channel is used. After local anaesthesia of the larynx by instillation of lidocaine, a flexible needle is inserted into the operating channel in order to inject the desired dose of botulinum toxin into the vocal and/or vestibular folds. Endoscopic botulinum toxin injection under local anaesthesia is a reliable technique for the treatment of laryngeal movement disorders. It can be performed by any laryngologist without the need for electromyography. It is easy to perform for the operator and comfortable for the patient. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

  11. Botulinum toxin treatment for facial palsy: A systematic review.

    Science.gov (United States)

    Cooper, Lilli; Lui, Michael; Nduka, Charles

    2017-06-01

    Facial palsy may be complicated by ipsilateral synkinesis or contralateral hyperkinesis. Botulinum toxin is increasingly used in the management of facial palsy; however, the optimum dose, treatment interval, adjunct therapy and performance as compared with alternative treatments have not been well established. This study aimed to systematically review the evidence for the use of botulinum toxin in facial palsy. The Cochrane central register of controlled trials (CENTRAL), MEDLINE(R) (1946 to September 2015) and Embase Classic + Embase (1947 to September 2015) were searched for randomised studies using botulinum toxin in facial palsy. Forty-seven studies were identified, and three included. Their physical and patient-reported outcomes are described, and observations and cautions are discussed. Facial asymmetry has a strong correlation to subjective domains such as impairment in social interaction and perception of self-image and appearance. Botulinum toxin injections represent a minimally invasive technique that is helpful in restoring facial symmetry at rest and during movement in chronic, and potentially acute, facial palsy. Botulinum toxin in combination with physical therapy may be particularly helpful. Currently, there is a paucity of data; areas for further research are suggested. A strong body of evidence may allow botulinum toxin treatment to be nationally standardised and recommended in the management of facial palsy. Copyright © 2017 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.

  12. Botulinum toxin for treatment of the focal dystonia.

    Science.gov (United States)

    Nakamura, Yusaku

    2017-07-29

    Dystonia is defined as a movement disorder characterized by sustained or intermittent muscles contraction causing abnormal, often repetitive, movements, postures, or both. Dystonic movements are typically patterned and twisting, and may be tremulous. The precis diagnosis of dystonia is difficult for physicians because neurological brain imaging does not provide enough practical information. The diagnosis is depend on clinical experience of physicians. Botulinum toxin treatment is the accepted standard of care for patients with focal dystonia. Botulinum toxin treatment results in significant improvement of decreasing the symptom of dystonia. The success of treatment is dependent on muscle selection for treating involved muscles. Usually performance of botulinum toxin treatment is injected according to clinical experience of surface anatomy or clinical location method. However, the benefit of guidance of botulinum toxin treatment is improve outcome in dystonia. Injection techniques with ultra sound echogram or EMG guidance to identify dystonic muscles can be more benefit for patients.

  13. Treatment of proctalgia fugax with botulinum A toxin.

    Science.gov (United States)

    Katsinelos, P; Kalomenopoulou, M; Christodoulou, K; Katsiba, D; Tsolkas, P; Pilpilidis, I; Papagiannis, A; Kapitsinis, I; Vasiliadis, I; Souparis, T

    2001-11-01

    Two recent studies described a temporal association between a high-amplitude and high-frequency myoelectrical activity of the anal sphincter and the occurrence of proctalgia, which suggest that paroxysmal hyperkinesis of the anus may cause proctalgia fugax. We describe a single case of proctalgia fugax responding to anal sphincter injection of Clostridium botulinum type A toxin. The presumed aetiology of proctalgia fugax is discussed and the possible mechanism of action of botulinum toxin (BTX) in this condition is outlined. Botulinum A toxin seems to be a promising treatment for patients with proctalgia fugax, and further trials appear to be worthwhile for this condition, which has been described as incurable.

  14. Treatment of Gastrointestinal Sphincters Spasms with Botulinum Toxin A

    Directory of Open Access Journals (Sweden)

    Giuseppe Brisinda

    2015-05-01

    Full Text Available Botulinum toxin A inhibits neuromuscular transmission. It has become a drug with many indications. The range of clinical applications has grown to encompass several neurological and non-neurological conditions. One of the most recent achievements in the field is the observation that botulinum toxin A provides benefit in diseases of the gastrointestinal tract. Although toxin blocks cholinergic nerve endings in the autonomic nervous system, it has also been shown that it does not block non-adrenergic non-cholinergic responses mediated by nitric oxide. This has promoted further interest in using botulinum toxin A as a treatment for overactive smooth muscles and sphincters. The introduction of this therapy has made the treatment of several clinical conditions easier, in the outpatient setting, at a lower cost and without permanent complications. This review presents current data on the use of botulinum toxin A in the treatment of pathological conditions of the gastrointestinal tract.

  15. Update on botulinum toxin and dermal fillers.

    Science.gov (United States)

    Berbos, Zachary J; Lipham, William J

    2010-09-01

    The art and science of facial rejuvenation is an ever-evolving field of medicine, as evidenced by the continual development of new surgical and nonsurgical treatment modalities. Over the past 10 years, the use of botulinum toxin and dermal fillers for aesthetic purposes has risen sharply. Herein, we discuss properties of several commonly used injectable products and provide basic instruction for their use toward the goal of achieving facial rejuvenation. The demand for nonsurgical injection-based facial rejuvenation products has risen enormously in recent years. Used independently or concurrently, botulinum toxin and dermal filler agents offer an affordable, minimally invasive approach to facial rejuvenation. Botulinum toxin and dermal fillers can be used to diminish facial rhytides, restore facial volume, and sculpt facial contours, thereby achieving an aesthetically pleasing, youthful facial appearance.

  16. Affinity chromatography of tetanus toxin, tetanus toxoid, and botulinum A toxin on synaptosomes, and differentiation of their acceptors

    Energy Technology Data Exchange (ETDEWEB)

    Habermann, E [Giessen Univ. (Germany, F.R.). Pharmakologisches Inst.

    1976-01-01

    /sup 125/I-labelled tetanus toxin and /sup 125/I-labelled botulinum A neurotoxin are known to be specifically bound to brain synaptosomes. In order to discriminate between active toxin and inactive admixtures present in the starting material or arising during iodination, synaptosome columns were prepared using bromacetylcellulose and/or kieselgur (Celite) as carriers. Both types of columns adsorb the toxins from low ionic strength medium and release them if the pH and ionic strength are raised. Botulinum toxin was eluted with lower ionic strength than tetanus toxin, and could be freed from nontoxic admixtures. Analysis by affinity chromatography disclosed partially toxoided tetanus toxin in both labelled and unlabelled toxin samples. High concentrations of formaldehyde (0.5%) destroyed both toxicity and affinity to the synaptosomes of tetanus toxin. Low concentrations of formaldehyde (0.05%) yielded a derivative of low toxicity which was still, however less firmly, bound to synaptosomes. Tetanus and botulinum toxin differ by their acceptors. Whereas unlabelled botulinum toxin is unable to compete with labelled tetanus toxin, unlabelled tetanus toxin slightly competes with botulinum toxin. Both labelled toxins display anomalous binding behaviour in that they cannot be displaced completely even with a large excess of unlabelled toxin.

  17. Affinity chromatography of tetanus toxin, tetanus toxoid, and botulinum A toxin on synaptosomes, and differentiation of their acceptors

    International Nuclear Information System (INIS)

    Habermann, E.

    1976-01-01

    125 I-labelled tetanus toxin and 125 I-labelled botulinum A neurotoxin are known to be specifically bound to brain synaptosomes. In order to discriminate between active toxin and inactive admixtures present in the starting material or arising during iodination, synaptosome columns were prepared using bromacetylcellulose and/or kieselgur (Celite) as carriers. Both types of columns adsorb the toxins from low ionic strength medium and release them if the pH and ionic strength are raised. Botulinum toxin was eluted with lower ionic strength than tetanus toxin, and could be freed from nontoxic admixtures. Analysis by affinity chromatography disclosed partially toxoided tetanus toxin in both labelled and unlabelled toxin samples. High concentrations of formaldehyde (0.5%) destroyed both toxicity and affinity to the synaptosomes of tetanus toxin. Low concentrations of formaldehyde (0.05%) yielded a derivative of low toxicity which was still, however less firmly, bound to synaptosomes. Tetanus and botulinum toxin differ by their acceptors. Whereas unlabelled botulinum toxin is unable to compete with labelled tetanus toxin, unlabelled tetanus toxin slightly competes with botulinum toxin. Both labelled toxins display anomalous binding behaviour in that they cannot be displaced completely even with a large excess of unlabelled toxin. (orig.) [de

  18. Achalasia in Pregnancy: Botulinum Toxin A Injection of Lower Esophageal Sphincter

    Directory of Open Access Journals (Sweden)

    Nicole Hooft

    2015-01-01

    Full Text Available Background. Achalasia, a rare esophageal motility disorder that may cause malnutrition during pregnancy, can result in fetal and maternal morbidity and mortality. Many medical treatment regimens are contraindicated or not tolerated during pregnancy, and surgery is generally avoided due to potential risks to the fetus. Case Report. Severe, medically refractory achalasia in a 23-year-old pregnant woman that caused malnutrition was successfully managed by administering a botulinum toxin A injection to the lower esophageal sphincter. The injection was performed at approximately 14 weeks’ gestation and the patient reported clinically significant relief from dysphagia. She gained weight and ultimately delivered a healthy baby girl at term, but her symptoms returned a few months postpartum. She underwent a second treatment of botulinum toxin A injection, but it offered only one month of relief. Roughly eight months after delivery, the patient underwent a laparoscopic extended Heller myotomy and Dor fundoplication. The patient resumed a normal diet one week postoperatively, and her baby has had no complications. Conclusion. This is only the second reported case of botulinum toxin A injection being used to treat achalasia in pregnancy. This treatment proved to be a safe temporary alternative without the risks of surgery and anesthesia during pregnancy.

  19. Efficacy of botulinum toxins on bruxism: an evidence-based review.

    Science.gov (United States)

    Long, Hu; Liao, Zhengyu; Wang, Yan; Liao, Lina; Lai, Wenli

    2012-02-01

    The objective of this study was to assess the efficacy of botulinum toxins on bruxism. Electronic databases (PubMed, Embase and Science Citation Index), websites (Cochrane Central Register of Controlled Trials and ClinicalTrials.gov) and the literature database of SIGLE (System for Information on Grey Literature in Europe) were searched from January 1990 to April 2011 for randomised controlled trials or nonrandomised studies assessing the efficacy of botulinum toxins on bruxism. There was no language restriction. Through a predefined search strategy, we retrieved 28 studies from PubMed, 94 from Embase, 60 from the Science Citation Index, two ongoing clinical trials and two from the Cochrane Central Register of Controlled Trials. Of these, only four studies met our inclusion criteria and were finally included. Of the four included studies, two were randomised controlled trials and two were controlled before-and-after studies. These studies showed that botulinum toxin injections can reduce the frequency of bruxism events, decrease bruxism-induced pain levels and satisfy patients' self-assessment with regard to the effectiveness of botulinum toxins on bruxism. In comparison with oral splint, botulinum toxins are equally effective on bruxism. Furthermore, botulinum toxin injections at a dosage of bruxism and are safe to use. Therefore, they can be used clinically for otherwise healthy patients with bruxism. © 2012 FDI World Dental Federation.

  20. Botulinum toxin therapy for limb dystonias.

    Science.gov (United States)

    Yoshimura, D M; Aminoff, M J; Olney, R K

    1992-03-01

    We investigated the effectiveness of botulinum toxin in 17 patients with limb dystonias (10 with occupational cramps, three with idiopathic dystonia unrelated to activity, and two each with post-stroke and parkinsonian dystonia) in a placebo-controlled, blinded study. We identified affected muscles clinically and by recording the EMG from implanted wire electrodes at rest and during performance of tasks that precipitated abnormal postures. There were three injections given with graded doses of toxin (average doses, 5 to 10, 10 to 20, and 20 to 40 units per muscle) and one with placebo, in random order. Subjective improvement occurred after 53% of injections of botulinum toxin, and this was substantial in 24%. Only one patient (7%) improved after placebo injection. Subjective improvement occurred in 82% of patients with at least one dose of toxin, lasting for 1 to 4 months. Response rates were similar between clinical groups. Objective evaluation failed to demonstrate significant improvement following treatment with toxin compared with placebo. The major side effect was transient focal weakness after 53% of injections of toxin.

  1. Bupivacaine and botulinum toxin to treat comitant strabismus

    Directory of Open Access Journals (Sweden)

    Luisa Moreira Hopker

    2012-04-01

    Full Text Available PURPOSE: To evaluate the change in ocular motility and muscle thickness measured with ultrasonography after intramuscular injection of bupivacaine and botulinum toxin A. METHODS: Eight patients (five female were enrolled to measure ocular motility prior and 1, 7, 30 and 180 days after one injection of 2 ml of 1.5% bupivacaine and 2.5 U of botulinum toxin A in agonist and antagonist muscles, respectively, of eight amblyopic eyes. Muscle thickness was measured prior and on days 1, 7 and 30 after injection using 10-MHz ultrasonography (eyelid technique. RESULTS: Mean change in alignment was 10 prism diopters after 180 days (n=6. An average increase of 1.01 mm in muscle thickness was observed after 30 days of bupivacaine injection and 0.28 mm increase was observed after botulinum toxin A injection, as measured by ultrasonography. Lateral rectus muscles injected with bupivacaine had a mean increase of 1.5 mm in muscle thickness. CONCLUSION: In this study, a change in ocular motility was observed after 180 days of intramuscular injection of bupivacaine and botulinum toxin in horizontal extraocular muscles. Overall, there was an increase of muscle thickness in both botulinum toxinum A and bupivacaine injected muscles after 30 days of injection when measured by ultrasonography. This change was more pronounced on lateral rectus muscles after bupivacaine injection.

  2. Topical Botulinum Toxin

    OpenAIRE

    Collins, Ashley; Nasir, Adnan

    2010-01-01

    Nanotechnology is a rapidly growing discipline that capitalizes on the unique properties of matter engineered on the nanoscale. Vehicles incorporating nanotechnology have led to great strides in drug delivery, allowing for increased active ingredient stability, bioavailability, and site-specific targeting. Botulinum toxin has historically been used for the correction of neurological and neuromuscular disorders, such as torticollis, blepharospasm, and strabismus. Recent dermatological indicati...

  3. Evaluation of the protective effect of Botulinum toxin type A injection on otitis media with effusion.

    Science.gov (United States)

    Çalım, Ömer Faruk; Yıldırım, Yavuz Selim; Doğan, Remzi; Tuğrul, Selhattin; Gedik, Özge; Özturan, Orhan

    2017-09-01

    This study makes an analysis of the effect of Botulinum toxin type A on otitis media with effusion in rats. As part of the study, 24 male Wistar Albino rats were divided into three groups: Group 1: Botulinum toxin Type A and Histamıne (intratympanic 0.2 ml = 20 unit BTA); Group 2: Saline and Histamine (intratympanic 0.2 ml 0.9%); Group 3: Histamine (intratympanic 0.2 ml). Histamine (intratympanic 0.2 ml) was administered into the right ear for all groups. DPOAE and ABR tests were carried out on days 5, 10, 15 and 20 from the beginning of the study. There was no significant difference between DPOAE and ABR scores of the groups. In each group, the DPOAE scores for the right ear significantly decreased on day 5 when compared to the basal scores. In each group, there was no significant difference between days 5, 10 and 15 for the right ear. Botulinum toxin type A blocked the secretion of glands in the middle ear and showed no effect to prevent the formation of serous otitis. In addition, it was found out that Botulinum toxin did not lead to any morphological change in the cochlea.

  4. Usefulness of intra-articular botulinum toxin injections. A systematic review.

    Science.gov (United States)

    Khenioui, Hichem; Houvenagel, Eric; Catanzariti, Jean François; Guyot, Marc Alexandre; Agnani, Olivier; Donze, Cécile

    2016-03-01

    Botulinum toxin is a proven and widely used treatment for numerous conditions characterized by excessive muscular contractions. Recent studies have assessed the analgesic effect of botulinum toxin in joint pain and started to unravel its mechanisms. We searched the international literature via the Medline database using the term "intraarticular botulinum toxin injection" combined with any of the following terms: "knee", "ankle", "shoulder", "osteoarthritis", "adhesive capsulitis of the shoulder". Of 16 selected articles about intraarticular botulinum toxin injections, 7 were randomized controlled trials done in patients with osteoarthritis, adhesive capsulitis of the shoulder, or chronic pain after joint replacement surgery. Proof of anti-nociceptive effects was obtained in some of these indications and the safety and tolerance profile was satisfactory. The studies are heterogeneous. The comparator was usually a glucocorticoid or a placebo; a single study used hyaluronic acid. Pain intensity was the primary outcome measure. The number of randomized trials and sample sizes are too small to provide a satisfactory level of scientific evidence or statistical power. Unanswered issues include the effective dosage and the optimal dilution and injection modalities of botulinum toxin. Copyright © 2015 Société française de rhumatologie. Published by Elsevier SAS. All rights reserved.

  5. Therapeutic Approaches of Botulinum Toxin in Gynecology

    OpenAIRE

    Marius Alexandru Moga; Oana Gabriela Dimienescu; Andreea Bălan; Ioan Scârneciu; Barna Barabaș; Liana Pleș

    2018-01-01

    Botulinum toxins (BoNTs) are produced by several anaerobic species of the genus Clostridium and, although they were originally considered lethal toxins, today they find their usefulness in the treatment of a wide range of pathologies in various medical specialties. Botulinum neurotoxin has been identified in seven different isoforms (BoNT-A, BoNT-B, BoNT-C, BoNT-D, BoNT-E, BoNT-F, and BoNT-G). Neurotoxigenic Clostridia can produce more than 40 different BoNT subtypes and, recently, a new BoNT...

  6. Botulinum toxin in medicine and cosmetology – two hundred years’ history and new perspectives

    Directory of Open Access Journals (Sweden)

    Małgorzata Zbrojkiewicz

    2018-04-01

    of coding genes and by the duration of the therapeutic effect. American physician Allan B. Scott was the first to demonstrate the use of botulinum toxin for medical purposes. Nowadays, botulinum toxin type A is widely used in medicine. Botulinum toxin injections are not only one of the most popular non-surgical aesthetic-cosmetic procedures, but are also widely used in neurology, ophthalmology and dermatology. The therapeutic potential of botulinum toxin has not been exhausted yet. Currently, many clinical trials are underway to extend the therapeutic indications of botulinum toxin and to improve its safety. Due to the huge development in medicine, botulinum toxin is today not only associated with aesthetic procedures and improvement in appearance, but also with raising the quality of life for people suffering from diseases with excessive muscle contraction and with other neuromuscular disorders.

  7. Evaluating the functional outcomes of ultrasound-guided botulinum toxin type A injections using the Euro-musculus approach for upper limb spasticity treatment in post-stroke patients; an observational study.

    Science.gov (United States)

    Buyukavci, Raikan; Akturk, Semra; Ersoy, Yüksel

    2018-02-07

    Ultrasound-guided botulinum toxin type A injection is an effective treatment for spasticity. Euro-musculus spasticity approach is a new method for administering injections to the correct point of the correct muscle. The clinical outcomes of this practical approach is not yet available in the literature. The purpose of this study was to evaluate the effects on spasticity and the functional outcomes of ultrasound guided botulinum toxin type A injections via the Euro-musculus spasticity approach to treat upper limb spasticity in post-stroke patients. An observational study. Inpatient post-stroke patients. Twenty five post-stroke patients with post-stroke upper limb spasticity were recruited. The ultrasound-guided botulinum toxin type A injections were administered into the spastic target muscles using the Euro-musculus spasticity approach, and all of the patients were enrolled in rehabilitation programmes after the injections. This research included the innervation zone and injection site figures and ultrasound images of each muscle in the upper limb. The degree of spasticity was assessed via the Modified Ashworth Scale and the upper limb motor function via the Fugl Meyer Upper Extremity Scale at the baseline and 4 and 12 weeks after the botulinum toxin type A injection. Significant decreases in the Modified Ashworth Scale scores of the upper limb flexor muscle tone measured 4 and 12 weeks after the botulinum toxin type A injection were found when compared to the baseline scores (pbotulinum toxin type A injection via the Euro- musculus spasticity approach is a practical and effective method for administering injections to the correct point of the correct muscle. Ultrasound-guided botulinum toxin type A injections combined with rehabilitation programmes decrease spasticity and improve the upper extremity motor functions in stroke patients. This new approach for ultrasound- guided botulinum toxin type A injection is very practical and effective method for upper

  8. Headache and botulinum toxin

    OpenAIRE

    Porta, M.; Camerlingo, M.

    2005-01-01

    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 tensiontype headache, migraine and chronic tension–type headache. In the present paper mechanisms of action and injection sites will also be discussed.

  9. [Bruxism, temporo-mandibular dysfunction and botulinum toxin].

    Science.gov (United States)

    Chikhani, L; Dichamp, J

    2003-07-01

    Tooth grinding and tooth clenching are unvoluntary mainly nocturnal habits that result in an hypertrophy of masseter and temporalis muscles with an unbalance between opening and closing muscles of the jaw and lead to an alteration of mandibular condyles movements and to hyper pressure in the temporo-mandibular joints (TMJ) which can generate severe pain. Intra muscular injections of botulinum toxin permit to restablish the balance between closing and opening muscles, to relieve pain, to treat masseteric hypertrophy with improvement of face outline and to recover a normal cinetic of temporo-mandibular joints. Moreover, botulinum toxin injections permit to quit habits of tooth grinding and clenching and one single session of injections is curative for 2/3 of the patients. There are no side effects apart from slight diffusion to superficial muscles of the face resulting in a "fixed" smile for about 6 to 8 weeks. So injections of botulinum toxin in masseter and temporalis muscles are an efficient treatment of bruxism and TMJ dysfunction, cheap with no lasting side effect.

  10. Failure of botulinum toxin injection for neurogenic detrusor overactivity: Switch of toxin versus second injection of the same toxin.

    Science.gov (United States)

    Peyronnet, Benoit; Castel-Lacanal, Evelyne; Manunta, Andréa; Roumiguié, Mathieu; Marque, Philippe; Rischmann, Pascal; Gamé, Xavier

    2015-12-01

    To evaluate the efficacy of a second injection of the same toxin versus switching to a different botulinum toxin A after failure of a first detrusor injection in patients with neurogenic detrusor overactivity. The charts of all patients who underwent detrusor injections of botulinum toxin A (either abobotulinumtoxinA or onabotulinumtoxinA) for the management of neurogenic detrusor overactivity at a single institution were retrospectively reviewed. Patients in whom a first detrusor injection had failed were included in the present study. They were managed by a second injection of the same toxin at the same dosage or by a new detrusor injection using a different botulinum toxin A. Success was defined as a resolution of urgency, urinary incontinence and detrusor overactivity in a patient self-catheterizing seven times or less per 24 h. A total of 58 patients were included for analysis. A toxin switch was carried out in 29 patients, whereas the other 29 patients received a reinjection of the same toxin at the same dose. The success rate was higher in patients who received a toxin switch (51.7% vs. 24.1%, P = 0.03). Patients treated with a switch from abobotulinumtoxinA to onabotulinumtoxinA and those treated with a switch from onabotulinumtoxinA to abobotulinumtoxinA had similar success rates (52.9% vs. 50%, P = 0.88). After failure of a first detrusor injection of botulinum toxin for neurogenic detrusor overactivity, a switch to a different toxin seems to be more effective than a second injection of the same toxin. The replacement of onabotulinumtoxin by abobotulinumtoxin or the reverse provides similar results. © 2015 The Japanese Urological Association.

  11. Botulinum toxin for motor and phonic tics in Tourette's syndrome.

    Science.gov (United States)

    Pandey, Sanjay; Srivanitchapoom, Prachaya; Kirubakaran, Richard; Berman, Brian D

    2018-01-05

    Gilles de la Tourette syndrome, or Tourette's syndrome, is defined as the presence of both motor and vocal (phonic) tics for more than 12 months, that manifest before the age of 18 years, in the absence of secondary causes. Treatment of motor and phonic tics is difficult and challenging. To determine the safety and effectiveness of botulinum toxin in treating motor and phonic tics in people with Tourette's syndrome, and to analyse the effect of botulinum toxin on premonitory urge and sensory tics. We searched the Cochrane Movement Disorders Group Trials Register, CENTRAL, MEDLINE, and two trials registers to 25 October 2017. We reviewed reference lists of relevant articles for additional trials. We considered all randomised, controlled, double-blind studies comparing botulinum toxin to placebo or other medications for the treatment of motor and phonic tics in Tourette's syndrome for this review. We sought both parallel group and cross-over studies of children or adults, at any dose, and for any duration. We followed standard Cochrane methods to select studies, assess risk of bias, extract and analyse data. All authors independently abstracted data onto standardized forms; disagreements were resolved by mutual discussion. Only one randomised placebo-controlled, double-blind cross-over study met our selection criteria. In this study, 20 participants with motor tics were enrolled over a three-year recruitment period; 18 (14 of whom had a diagnosis of Tourette's syndrome) completed the study; in total, 21 focal motor tics were treated. Although we considered most bias domains to be at low risk of bias, the study recruited a small number of participants with relatively mild tics and provided limited data for our key outcomes. The effects of botulinum toxin injections on tic frequency, measured by videotape or rated subjectively, and on premonitory urge, are uncertain (very low-quality evidence). The quality of evidence for adverse events following botulinum toxin was

  12. Survey of Botulinum Toxin Injections in Anticoagulated Patients: Korean Physiatrists' Preference in Controlling Anticoagulation Profile Prior to Intramuscular Injection.

    Science.gov (United States)

    Jang, Yongjun; Park, Geun-Young; Park, Jihye; Choi, Asayeon; Kim, Soo Yeon; Boulias, Chris; Phadke, Chetan P; Ismail, Farooq; Im, Sun

    2016-04-01

    To evaluate Korean physiatrists' practice of performing intramuscular botulinum toxin injection in anticoagulated patients and to assess their preference in controlling the bleeding risk before injection. As part of an international collaboration survey study, a questionnaire survey was administered to 100 Korean physiatrists. Physiatrists were asked about their level of experience with botulinum toxin injection, the safe international normalized ratio range in anticoagulated patients undergoing injection, their tendency for injecting into deep muscles, and their experience of bleeding complications. International normalized ratio injection by 41% of the respondents. Thirty-six respondents replied that the international normalized ratio should be lowered to sub-therapeutic levels before injection, and 18% of the respondents reported that anticoagulants should be intentionally withheld and discontinued prior to injection. In addition, 20%-30% of the respondents answered that they were uncertain whether they should perform the injection regardless of the international normalized ratio values. About 69% of the respondents replied that they did have any standardized protocols for performing botulinum toxin injection in patients using anticoagulants. Only 1 physiatrist replied that he had encountered a case of compartment syndrome. In accordance with the lack of consensus in performing intramuscular botulinum toxin injection in anticoagulated patients, our survey shows a wide range of practices among many Korean physiatrists; they tend to avoid botulinum toxin injection in anticoagulated patients and are uncertain about how to approach these patients. The results of this study emphasize the need for formulating a proper international consensus on botulinum toxin injection management in anticoagulated patients.

  13. Excellent response rate of anismus to botulinum toxin if rectal prolapse misdiagnosed as anismus ('pseudoanismus') is excluded.

    Science.gov (United States)

    Hompes, R; Harmston, C; Wijffels, N; Jones, O M; Cunningham, C; Lindsey, I

    2012-02-01

    Anismus causes obstructed defecation as a result of inappropriate contraction of the puborectalis/external sphincter. Proctographic failure to empty after 30 s is used as a simple surrogate for simultaneous electromyography/proctography. Botulinum toxin is theoretically attractive but efficacy is variable. We aimed to evaluate the efficacy of botulinum toxin to treat obstructed defecation caused by anismus. Botulinum toxin was administered, under local anaesthetic, into the puborectalis/external sphincter of patients with proctographic anismus. Responders (resolution followed by recurrence of obstructed defecation over a 1- to 2-month period) underwent repeat injection. Nonresponders underwent rectal examination under anaesthetic (EUA). EUA-diagnosed rectal prolapse was graded using the Oxford Prolapse Grade 1-5. Fifty-six patients were treated with botulinum toxin. Twenty-two (39%) responded initially and 21/22 (95%) underwent repeat treatment. At a median follow up of 19.2 (range, 7.0-30.4) months, 20/21 (95%) had a sustained response and required no further treatment. Isolated obstructed defecation symptoms (OR = 7.8, P = 0.008), but not proctographic or physiological factors, predicted response on logistic regression analysis. In 33 (97%) of 34 nonresponders, significant abnormalities were demonstrated at EUA: 31 (94%) had a grade 3-5 rectal prolapse, one had internal anal sphincter myopathy and one had a fissure. Exclusion of these alternative diagnoses revised the initial response rate to 96%. Simple proctographic criteria overdiagnose anismus and underdiagnose rectal prolapse. This explains the published variable response to botulinum toxin. Failure to respond should prompt EUA seeking undiagnosed rectal prolapse. A response to an initial dose of botulinum toxin might be considered a more reliable diagnosis of anismus than proctography. © 2011 The Authors. Colorectal Disease © 2011 The Association of Coloproctology of Great Britain and Ireland.

  14. Characterization of Hemagglutinin Negative Botulinum Progenitor Toxins

    Directory of Open Access Journals (Sweden)

    Suzanne R. Kalb

    2017-06-01

    Full Text Available Botulism is a disease involving intoxication with botulinum neurotoxins (BoNTs, toxic proteins produced by Clostridium botulinum and other clostridia. The 150 kDa neurotoxin is produced in conjunction with other proteins to form the botulinum progenitor toxin complex (PTC, alternating in size from 300 kDa to 500 kDa. These progenitor complexes can be classified into hemagglutinin positive or hemagglutinin negative, depending on the ability of some of the neurotoxin-associated proteins (NAPs to cause hemagglutination. The hemagglutinin positive progenitor toxin complex consists of BoNT, nontoxic non-hemagglutinin (NTNH, and three hemagglutinin proteins; HA-70, HA-33, and HA-17. Hemagglutinin negative progenitor toxin complexes contain BoNT and NTNH as the minimally functional PTC (M-PTC, but not the three hemagglutinin proteins. Interestingly, the genome of hemagglutinin negative progenitor toxin complexes comprises open reading frames (orfs which encode for three proteins, but the existence of these proteins has not yet been extensively demonstrated. In this work, we demonstrate that these three proteins exist and form part of the PTC for hemagglutinin negative complexes. Several hemagglutinin negative strains producing BoNT/A, /E, and /F were found to contain the three open reading frame proteins. Additionally, several BoNT/A-containing bivalent strains were examined, and NAPs from both genes, including the open reading frame proteins, were associated with BoNT/A. The open reading frame encoded proteins are more easily removed from the botulinum complex than the hemagglutinin proteins, but are present in several BoNT/A and /F toxin preparations. These are not easily removed from the BoNT/E complex, however, and are present even in commercially-available purified BoNT/E complex.

  15. [Botulinum toxin type A in headache treatment : Established and experimental indications].

    Science.gov (United States)

    Gaul, C; Holle-Lee, D; Straube, A

    2016-08-01

    In recent years botulinum toxin type A has been used increasingly more in the treatment of specific headache disorders. Especially regarding chronic migraine with and without combined medication overuse, convincing randomized studies have proven the efficacy of this treatment option and have led to approval for this indication. Regarding other headache entities, such as episodic migraine, tension-type headache, trigeminal autonomic cephalalgia (TAC), neuralgic, neuropathic and myofascial pain, currently available scientific data on the efficacy of botulinum toxin type A are scarce and often ambiguous. The exact underlying mechanisms of the influence of botulinum toxin type A on the pathophysiology of headache are not completely clear but an influence on the release of calcitonin gene-related peptide (CGRP) seems to play a crucial role. This article summarizes the most important studies as well as experiences of treatment with botulinum toxin type A regarding different headache entities.

  16. Use of intradermal botulinum toxin to reduce sebum production and facial pore size.

    Science.gov (United States)

    Shah, Anil R

    2008-09-01

    Review the safety profile and subjective efficacy of intradermal botulinum toxin type A in facial pore size and sebum production. Retrospective analysis of 20 patients. Twenty consecutive patients with a single application of intradermal botulinum toxin type A were examined: Patients (17/20) noted an improvement in sebum production and a decrease in pores size at 1 month after injection. No complications were observed, and 17/20 patients were satisfied with the procedure. Preliminary data suggests that intradermal botulinum toxin may play a role in decreasing sebum production. Further quantitive study may be necessary to determine effects of intradermal botulinum toxin on pore size.

  17. Botulinum toxin: The Midas touch.

    Science.gov (United States)

    Shilpa, P S; Kaul, Rachna; Sultana, Nishat; Bhat, Suraksha

    2014-01-01

    Botulinum Toxin (BT) is a natural molecule produced during growth and autolysis of bacterium called Clostridium botulinum. Use of BT for cosmetic purposes has gained popularity over past two decades, and recently, other therapeutic uses of BT has been extensively studied. BT is considered as a minimally invasive agent that can be used in the treatment of various orofacial disorders and improving the quality of life in such patients. The objective of this article is to review the nature, mechanism of action of BT, and its application in various head and neck diseases.

  18. Botulinum toxin in medicine and cosmetology – two hundred years’ history and new perspectives

    OpenAIRE

    Małgorzata Zbrojkiewicz; Agata Lebiedowska; Barbara Błońska-Fajfrowska Barbara Błońska-Fajfrowska

    2018-01-01

    It has been nearly 200 years since the discovery of the botulinum toxin and the strain responsible for its synthesis Clostridium botulinum. Over this period, the knowledge about botulism and the use of botulinum toxin in medicine has been significantly expanded. Currently, eight serotypes of botulinum toxin (A-H) are known and they differ from each other by molecular weight, antigenic structure, immunogenicity, receptors, localization of coding genes and by the duration of the therapeutic ...

  19. Botulinum toxin in bruxism treatment

    Directory of Open Access Journals (Sweden)

    Piotr Piech

    2017-07-01

    Full Text Available Introduction: Bruxism is defined as abnormal, fixed, unconscious chewing organ function, deviating qualitatively and quantitatively from normal function. Another definition speaks of motor dysfunction in the mouth, characterized by grinding and clenching of the teeth, occurring during sleep. The etiology of this disorder has not been explained until now, but it is believed to be related to localized, mental, nervous and neurotransmitter disorders. Purpose: The aim of the study is to review literature and knowledge about the use of botulinum toxin in the treatment of bruxism. Methods of treatment: The patient reports to the physician usually after a distressing, difficult to locate pain. The basis for proper treatment is to detect parafunctions and to make the patient aware of their existence. Diagnostic symptoms include dentinal lesions, recesses, enamel cracks and abfractive cavities, as well as changes in the mucosal area of the cheeks. Treatment begins with the use of an occlusive therapy to relax muscles, reduce parafunction and relieve pain. In the form of severe pain, NSAIDs are introduced and, if necessary, anxiolytics, sedatives and antidepressants. In the absence of response to the treatment used, botulinum toxin type A injections are used. The dose of the agent depends on the initial muscle tone and the effect of decrease in its activity is maintained for 4 to 6 months. Conclusions: The use of botulinum toxin makes it possible to selectively exclude overactive muscles, which is a great advantage over other techniques. An additional benefit of this therapy is achieved good cosmetic effect, reversible effect and minimal amount of side effects.

  20. Ultrasound-guided botulinum toxin injections

    Directory of Open Access Journals (Sweden)

    S. E. Khatkova

    2016-01-01

    Full Text Available One of the key conditions for achieving the desirable result during botulinum toxin therapy for muscular dystonia, spasticity, and other diseases accompanied by spasm, pain, and autonomic dysfunction (dystonias, spasticity, etc. is the proper administration of the agent into the muscles directly involved in the pathological process. The exact entry of botulinum toxin into the target muscles is essential for successful and safe treatment because its injection into a normal muscle may cause side effects. The most common errors are the incorrect depth and incorrect direction of a needle on insertion. Therefore, the exact injection of the agent particularly into the shallow and deep muscles is a difficult task even for an experienced specialist and requires the use of controlling methods.The European Consensus on Botulinum Toxin Therapy points out that various injection techniques are needed for the better identification of necessary muscles. However, there are currently no reports on the clear advantage of any technique. In our country, injections using palpation and anatomical landmarks have been widely used in routine practice so far; electromyographic monitoring and electrostimulation have been less frequently applied. In recent years, the new method ultrasound-guided injection has continued to grow more popular. This effective, accessible, and easy-to-use method makes it possible to manage a real-time injection process and to ensure the exact entry of the agent into the muscle. This paper is dedicated to a comparative analysis of different injection methods and to a description of the ultrasound-guided technique and its advantages over others. 

  1. Outcomes of Buccinator Treatment With Botulinum Toxin in Facial Synkinesis.

    Science.gov (United States)

    Patel, Priyesh N; Owen, Scott R; Norton, Cathey P; Emerson, Brandon T; Bronaugh, Andrea B; Ries, William R; Stephan, Scott J

    2018-05-01

    The buccinator, despite being a prominent midface muscle, has been previously overlooked as a target in the treatment of facial synkinesis with botulinum toxin. To evaluate outcomes of patients treated with botulinum toxin to the buccinator muscle in the setting of facial synkinesis. Prospective cohort study of patients who underwent treatment for facial synkinesis with botulinum toxin over multiple treatment cycles during a 1-year period was carried out in a tertiary referral center. Botulinum toxin treatment of facial musculature, including treatment cycles with and without buccinator injections. Subjective outcomes were evaluated using the Synkinesis Assessment Questionnaire (SAQ) prior to injection of botulinum toxin and 2 weeks after treatment. Outcomes of SAQ preinjection and postinjection scores were compared in patients who had at least 1 treatment cycle with and without buccinator injections. Subanalysis was performed on SAQ questions specific to buccinator function (facial tightness and lip movement). Of 84 patients who received botulinum toxin injections for facial synkinesis, 33 received injections into the buccinator muscle. Of the 33, 23 met inclusion criteria (19 [82.6%] women; mean [SD] age, 46 [10] years). These patients presented for 82 treatment visits, of which 44 (53.6%) involved buccinator injections and 38 (46.4%) were without buccinator injections. The most common etiology of facial paralysis included vestibular schwannoma (10 [43.5%] participants) and Bell Palsy (9 [39.1%] participants). All patients had improved posttreatment SAQ scores compared with prebotulinum scores regardless of buccinator treatment. Compared with treatment cycles in which the buccinator was not addressed, buccinator injections resulted in lower total postinjection SAQ scores (45.9; 95% CI, 38.8-46.8; vs 42.8; 95% CI, 41.3-50.4; P = .43) and greater differences in prebotox and postbotox injection outcomes (18; 95% CI, 16.2-21.8; vs 19; 95% CI, 14.2-21.8; P

  2. Treatment of anismus in intractable constipation with botulinum A toxin.

    Science.gov (United States)

    Hallan, R I; Williams, N S; Melling, J; Waldron, D J; Womack, N R; Morrison, J F

    1988-09-24

    In seven patients with anismus the striated sphincter muscle complex was selectively weakened by local injection of Clostridium botulinum type A toxin. Symptom scores improved significantly and correlated with a significant reduction in the maximum voluntary and canal squeeze pressure and a significant increase in the anorectal angle on straining. Botulinum A toxin seems to be promising treatment for some patients with anismus.

  3. Development of a quail embryo model for the detection of botulinum toxin type A activity

    Science.gov (United States)

    Clostridium botulinum is a ubiquitous microorganism which under certain anaerobic conditions can produce botulinum toxins. Due to concerns in regards to both food-borne illness and the potential use of botulinum toxin as a biological weapon, the capability to assess the amount of toxin in a food or...

  4. Botulinum toxin in the treatment of refractory vaginismus.

    Science.gov (United States)

    Ghazizadeh, Shirin; Nikzad, Masoomeh

    2004-11-01

    To investigate the efficacy of botulinum toxin injection to treat women with moderate and severe vaginismus. Twenty-four women referred to our clinic from February 2002 to February 2004 (mean age 25 years; range 19-34 years) with third- to fourth-degree vaginismus were recruited for this study. These women had previous unsuccessful treatments. Botulinum toxin (150-400 mIU) was injected into the puborectalis muscles in 3 sites on each side of the vagina. Twenty-three patients (95.8%) had vaginal examinations 1 week postoperatively that showed little or no vaginismus, 18 (75%) achieved satisfactory intercourse after the first injection, 4 (16.7%) had mild pain, 1 was cured after a second injection, 1 patient refused vaginal examination and did not attempt to have coitus, and another had no coitus as a result of her husband's secondary impotence. The women were followed up for a mean of 12.3 months (range 2-24 months), and there were no cases of recurrence. In refractory cases of vaginismus when conventional therapies have failed, local injection of botulinum toxin can be considered. III.

  5. Effect of Botulinum Toxin and Surgery among Spasmodic Dysphonia Patients.

    Science.gov (United States)

    van Esch, Babette F; Wegner, Inge; Stegeman, Inge; Grolman, Wilko

    2017-02-01

    Objective The effect of botulinum toxin among patients with adductor spasmodic dysphonia (AdSD) is temporary. To optimize long-term treatment outcome, other therapy options should be evaluated. Alternative treatment options for AdSD comprise several surgical treatments, such as thyroarytenoid myotomy, thyroplasty, selective laryngeal adductor denervation-reinnervation, laryngeal nerve crush, and recurrent laryngeal nerve resection. Here, we present the first systematic review comparing the effect of botulinum toxin with surgical treatment among patients diagnosed with AdSD. Data Sources MEDLINE (PubMed), EMBASE, and the Cochrane Library. Methods Articles were reviewed by 2 independent authors, and data were compiled in tables for analysis of the objective outcome (voice expert evaluation after voice recording), the subjective outcome (patient self-assessment scores), and voice-related quality of life (Voice Health Index scores). Results No clinical trials comparing both treatment modalities were identified. Single-armed studies evaluated either the effect of botulinum toxin or surgical treatment. Thirteen studies reported outcomes after botulinum toxin treatment (n = 419), and 9 studies reported outcomes after surgical treatment (n = 585 patients). A positive effect of bilateral botulinum toxin injections was found for the objective voice outcome, subjective voice outcome, and quality of life. The duration of the beneficial effect ranged from 15 to 18 weeks. Surgical treatment had an overall positive effect on objective voice improvement, subjective voice improvement, and quality of live. Conclusion No preference for one treatment could be demonstrated. Prospective clinical trials comparing treatment modalities are recommended to delineate the optimal outcomes by direct comparison.

  6. Contralateral botulinum toxin injection to improve facial asymmetry after acute facial paralysis.

    Science.gov (United States)

    Kim, Jin

    2013-02-01

    The application of botulinum toxin to the healthy side of the face in patients with long-standing facial paralysis has been shown to be a minimally invasive technique that improves facial symmetry at rest and during facial motion, but our experience using botulinum toxin therapy for facial sequelae prompted the idea that botulinum toxin might be useful in acute cases of facial paralysis, leading to improve facial asymmetry. In cases in which medical or surgical treatment options are limited because of existing medical problems or advanced age, most patients with acute facial palsy are advised to await spontaneous recovery or are informed that no effective intervention exists. The purpose of this study was to evaluate the effect of botulinum toxin treatment for facial asymmetry in 18 patients after acute facial palsy who could not be optimally treated by medical or surgical management because of severe medical or other problems. From 2009 to 2011, nine patients with Bell's palsy, 5 with herpes zoster oticus and 4 with traumatic facial palsy (10 men and 8 women; age range, 22-82 yr; mean, 50.8 yr) participated in this study. Botulinum toxin A (Botox; Allergan Incorporated, Irvine, CA, USA) was injected using a tuberculin syringe with a 27-gauge needle. The amount injected per site varied from 2.5 to 3 U, and the total dose used per patient was 32 to 68 U (mean, 47.5 +/- 8.4 U). After administration of a single dose of botulinum toxin A on the nonparalyzed side of 18 patients with acute facial paralysis, marked relief of facial asymmetry was observed in 8 patients within 1 month of injection. Decreased facial asymmetry and strengthened facial function on the paralyzed side led to an increased HB and SB grade within 6 months after injection. Use of botulinum toxin after acute facial palsy cases is of great value. Such therapy decreases the relative hyperkinesis contralateral to the paralysis, leading to greater symmetric function. Especially in patients with medical

  7. Treatment of chronic tension-type headache with botulinum toxin: a double-blind, placebo-controlled clinical trial

    NARCIS (Netherlands)

    Padberg, M.; de Bruijn, S. F. T. M.; de Haan, R. J.; Tavy, D. L. J.

    2004-01-01

    Botulinum toxin is increasingly advocated as effective treatment in chronic tension-type headache. We conducted a randomized, placebo-controlled clinical trial to prove efficacy of botulinum toxin in chronic tension-type headache. Patients were randomly assigned to receive botulinum toxin (maximum

  8. [Seniority of neurobladder and effectiveness of a first intradetrusor injection of botulinum toxin].

    Science.gov (United States)

    Lacout, M; Guinet-Lacoste, A; Popoff, M; Verollet, D; Lebreton, F; Amarenco, G

    2015-09-01

    Intradetrusor injection of botulinum toxin is one of the second-line therapy of neurologenic detrusor overactivity. In 26% to 66% of the cases, intradetrusor injection of botulinum toxin is inefficient in order to reduce overactive bladder symptoms and/or overactive detrusor. The objective of this study is to determine whether it exists a link between the efficacy of the first IDBT and the length of neurological detrusor overactivity symptoms. Retrospective study on 79 patients which have a first intradetrusor injection of botulinum toxin between January 2001 and December 2013. Inclusion criteria were patients older than 18 and having neurological detrusor overactivity. There is no significant difference of intradetrusor injection of botulinum toxin efficacy according to duration of urinary symptoms in the general neurologigal population (multiple sclerosis, spinal cord injury, spinal cord compression, ischemic pathology, infectious pathology) with the mean age being 46 years. On the contrary, the length of evolution of neurological detrusor overactivity symptoms before the intradetrusor botox injection therapy and the efficiency of the first intradetrusor injection of botulinum toxin seem to be correlated with negative results in patients with multiple sclerosis. The duration of urinary symptoms is a predictive factor of primary failure of intradetrusor injection of botulinum toxin in multiple sclerosis patients, in univariate analysis. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

  9. BOTULINUM TOXIN FOR THE TREATMENT OF CHRONIC HEADACHE

    Directory of Open Access Journals (Sweden)

    L. B. Zavaliy

    2015-01-01

    Full Text Available ABSTRACT. The article deals with the use of botulinum toxin in the treatment of chronic headache. We present four clinical cases of patients who sought treatment in the “Pain Clinic” of N.V. Sklifosovsky Research Institute for Emergency Medicine with a chronic severe cephalgic syndrome of different genesis (migraine, tension headache, dystonia, which had not responded to outpatient treatment for a long time. The paper shows the change of pain in patients with various forms of headache after treatment with botulinum toxin type A, indicating the effectiveness of the method in these patients. 

  10. Sphincter of Oddi botulinum toxin injection to prevent pancreatic fistula after distal pancreatectomy.

    Science.gov (United States)

    Hackert, Thilo; Klaiber, Ulla; Hinz, Ulf; Kehayova, Tzveta; Probst, Pascal; Knebel, Phillip; Diener, Markus K; Schneider, Lutz; Strobel, Oliver; Michalski, Christoph W; Ulrich, Alexis; Sauer, Peter; Büchler, Markus W

    2017-05-01

    Postoperative pancreatic fistula represents the most important complication after distal pancreatectomy. The aim of this study was to evaluate the use of a preoperative endoscopic injection of botulinum toxin into the sphincter of Oddi to prevent postoperative pancreatic fistula (German Clinical Trials Register number: DRKS00007885). This was an investigator-initiated, prospective clinical phase I/II trial with an exploratory study design. We included patients who underwent preoperative endoscopic sphincter botulinum toxin injection (100 units of Botox). End points were the feasibility, safety, and postoperative outcomes, including postoperative pancreatic fistula within 30 days after distal pancreatectomy. Botulinum toxin patients were compared with a control collective of patients undergoing distal pancreatectomy without botulinum toxin injection by case-control matching in a 1:1 ratio. Between February 2015 and February 2016, 29 patients were included. All patients underwent successful sphincter of Oddi botulinum toxin injection within a median of 6 (range 0-10) days before operation. One patient had an asymptomatic, self-limiting (48 hours) increase in serum amylase and lipase after injection. Distal pancreatectomy was performed in 24/29 patients; 5 patients were not resectable. Of the patients receiving botulinum toxin, 7 (29%) had increased amylase levels in drainage fluid on postoperative day 3 (the International Study Group of Pancreatic Surgery definition of postoperative pancreatic fistula grade A) without symptoms or need for reintervention. Importantly, no clinically relevant fistulas (International Study Group of Pancreatic Surgery grades B/C) were observed in botulinum toxin patients compared to 33% postoperative pancreatic fistula grade B/C in case-control patients (P botulinum toxin injection is a novel and safe approach to decrease the incidence of clinically relevant postoperative pancreatic fistula after distal pancreatectomy. The results of

  11. Cost-Effectiveness of Treating Upper Limb Spasticity Due to Stroke with Botulinum Toxin Type A: Results from the Botulinum Toxin for the Upper Limb after Stroke (BoTULS Trial

    Directory of Open Access Journals (Sweden)

    Nick Steen

    2012-11-01

    Full Text Available Stroke imposes significant burdens on health services and society, and as such there is a growing need to assess the cost-effectiveness of stroke treatment to ensure maximum benefit is derived from limited resources. This study compared the cost-effectiveness of treating post-stroke upper limb spasticity with botulinum toxin type A plus an upper limb therapy programme against the therapy programme alone. Data on resource use and health outcomes were prospectively collected for 333 patients with post-stroke upper limb spasticity taking part in a randomized trial and combined to estimate the incremental cost per quality adjusted life year (QALY gained of botulinum toxin type A plus therapy relative to therapy alone. The base case incremental cost-effectiveness ratio (ICER of botulinum toxin type A plus therapy was £93,500 per QALY gained. The probability of botulinum toxin type A plus therapy being cost-effective at the England and Wales cost-effectiveness threshold value of £20,000 per QALY was 0.36. The point estimates of the ICER remained above £20,000 per QALY for a range of sensitivity analyses, and the probability of botulinum toxin type A plus therapy being cost-effective at the threshold value did not exceed 0.39, regardless of the assumptions made.

  12. Vocal aging and adductor spasmodic dysphonia: Response to botulinum toxin injection

    Directory of Open Access Journals (Sweden)

    Michael P Cannito

    2008-03-01

    Full Text Available Michael P Cannito, Joel C Kahane, Lesya ChornaSchool of Audiology and Speech-Language Pathology, The University of Memphis, Memphis, TN, USAAbstract: Aging of the larynx is characterized by involutional changes which alter its biomechanical and neural properties and create a biological environment that is different from younger counterparts. Illustrative anatomical examples are presented. This natural, non-disease process appears to set conditions which may influence the effectiveness of botulinum toxin injection and our expectations for its success. Adductor spasmodic dysphonia, a type of laryngeal dystonia, is typically treated using botulinum toxin injections of the vocal folds in order to suppress adductory muscle spasms which are disruptive to production of speech and voice. A few studies have suggested diminished response to treatment in older patients with adductor spasmodic dysphonia. This retrospective study provides a reanalysis of existing pre-to-post treatment data as function of age. Perceptual judgments of speech produced by 42 patients with ADSD were made by two panels of professional listeners with expertise in voice or fluency of speech. Results demonstrate a markedly reduced positive response to botulinum toxin treatment in the older patients. Perceptual findings are further elucidated by means of acoustic spectrography. Literature on vocal aging is reviewed to provide a specific set of biological mechanisms that best account for the observed interaction of botulinum toxin treatment with advancing age.Keywords: vocal aging, adductor spasmodic dysphonia, botulinum toxin, voice quality, speech fluency

  13. Botulinum toxin as a therapeutic agent to prevent relapse in deep bite patients.

    Science.gov (United States)

    Mücke, Thomas; Löffel, Anja; Kanatas, Anastasios; Karnezi, Sandy; Rana, Majeed; Fichter, Andreas; Haarmann, Stephan; Wolff, Klaus-Dietrich; Loeffelbein, Denys John

    2016-05-01

    The etiology of deep bite is multifactorial. One of the causes is increased muscular activity. This makes the treatment of deep bite malocclusions difficult and often results in relapse in many cases. In this work we compared patients with surgical orthognathic treatment only and surgical orthognathic treatment with additional injections of botulinum toxin after mandibular advancement for class II division 2 malocclusion. This is a prospective study. Adult patients were assessed pretreatment (T1), posttreatment (T2), and long-term after 1 year (T3). In total, 32 patients (mean age, 30.7 years; 23 women and 9 men) reached the study end point (T3); 24 patients were treated without botulinum toxin and 8 patients received preoperative injections of botulinum toxin. Significant differences between both groups were observed, with a more stable result for the experimental group treated with botulinum toxin. In a selective group of adult patients with a class II division II incisor relationship and with a class II skeletal base, botulinum toxin injections can effectively prevent relapse. This may present an alternative to a conventional myotomy. Copyright © 2016 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved.

  14. Unilateral transient mydriasis and ptosis after botulinum toxin injection for a cosmetic procedure

    Directory of Open Access Journals (Sweden)

    Akkaya S

    2015-02-01

    Full Text Available Sezen Akkaya,1 Hatice Kübra Kökcen,1 Tuğba Atakan2 1Fatih Sultan Mehmet Education and Training Hospital, Ophthalmology Clinics, Bostanci, Istanbul, 2Aksaray Hospital, Ophthalmology Clinics, Konya, Turkey Abstract: We report a case of unilateral transient mydriasis and ptosis after botulinum toxin injection applied by a medical doctor for a cosmetic procedure. A 36-year-old nurse was referred to our eye clinic with unilateral mydriasis and ptosis in the right eye 3 days after botulinum toxin injection for a cosmetic procedure. Botulinum toxin was applied to her eye by a doctor at her hospital who was not an ophthalmologist. She was treated with topical apraclonidine 0.5% ophthalmic solution. Her ptosis decreased to 2 mm with apraclonidine and her visual axis improved. Mydriasis was present for 3 weeks and then disappeared. Mild ptosis continued for 3 months, then resolved completely. Patients seeking treatment with botulinum toxin A for cosmetic purposes should be warned about the possibility of ptosis and mydriasis after injection. If these side effects are seen, the patient must be referred to an ophthalmologist for appropriate management. Keywords: botulinum toxin, mydriasis, ptosis

  15. Effects of X-irradiation on axonal sprouting induced by botulinum toxin

    Energy Technology Data Exchange (ETDEWEB)

    Gomez, S; Duchen, L W [National Hospital, London (UK); Hornsey, S [Hammersmith Hospital, London (UK). M.R.C. Cyclotron Unit

    1982-01-01

    The effect of X-irradiation on axonal sprouting of motor nerves induced by botulinum toxin was examined. Muscles of one leg in the mouse were X-irradiated (15Gy) prior to the injection of a locally paralysing dose of botulinum toxin. It was found that axonal sprouting occurred as expected, but the sprouts remained unmyelinated and many degenerated. Fewer new end-plates were formed, muscles remained more severely atrophied and supersensitive to acetylcholine and recovery of neuromuscular transmission was greatly delayed when compared with the effects of botulinum toxin alone. X-irradiation did not prevent sprouting but, probably by impairing Schwann cell proliferation, altered axon-Schwann cell relationships and prevented the maturation of newly-formed axons and the differentiation of new end-plates.

  16. AbobotulinumtoxinA Efficacy and Safety in Children With Equinus Foot Previously Treated With Botulinum Toxin.

    Science.gov (United States)

    Dabrowski, Edward; Bonikowski, Marcin; Gormley, Mark; Volteau, Magali; Picaut, Philippe; Delgado, Mauricio R

    2018-05-01

    The effects of botulinum toxin are transient, and repeat injections are required in children with lower-limb spasticity. However, the efficacy of botulinum toxin in patients who have received previous injections has remained largely unexplored. We present subgroup analyses of a phase III study conducted in ambulatory children (aged two to 17) with spastic equinus foot. Patients were randomized to single doses of abobotulinumtoxinA 10 U/kg/leg, 15 U/kg/leg, or placebo injected into the gastrocnemius-soleus complex (one or both legs). The first analysis was prespecified to review the effect of abobotulinumtoxinA in children previously treated with botulinum toxin versus those children new to the treatment; a second post hoc analysis evaluated the effect of abobotulinumtoxinA in children who changed botulinum toxin formulation. Of the 241 randomized patients, 113 had previously received botulinum toxin, including 86 who had been treated with another formulation. In both analyses, muscle tone (Modified Ashworth Scale) and the Physicians Global Assessment, at week 4, improved with abobotulinumtoxinA treatment versus placebo, regardless of baseline botulinum toxin status. Placebo responses in patients new to treatment were consistently higher than in the previously treated group. These results demonstrate similar abobotulinumtoxinA efficacy and safety profiles in children with spasticity who are new to botulinum toxin treatment and those children who were previously treated. The efficacy and safety of abobotulinumtoxinA treatment in these previously treated patients were comparable with the overall trial population, indicating that doses of 10 and 15 U/kg/leg are suitable starting doses for children with spasticity regardless of the previous botulinum toxin preparation used. Copyright © 2018 Elsevier Inc. All rights reserved.

  17. Muscle selection for treatment of cervical dystonia with botulinum toxin : A systematic review

    NARCIS (Netherlands)

    Nijmeijer, S. W. R.; Koelman, J. H. T. M.; Kamphuis, D. J.; Tijssen, M. A. J.

    Rationale: Cervical dystonia, also called spasmodic torticollis, is the most common form of (primary) dystonia. Intramuscular injections with botulinum toxin are the first line of treatment for cervical dystonia. To optimise the treatment response to botulinum toxin correct muscles should be

  18. Muscle selection for treatment of cervical dystonia with botulinum toxin - A systematic review

    NARCIS (Netherlands)

    Nijmeijer, S. W. R.; Koelman, J. H. T. M.; Kamphuis, D. J.; Tijssen, M. A. J.

    2012-01-01

    Rationale: Cervical dystonia, also called spasmodic torticollis, is the most common form of (primary) dystonia. Intramuscular injections with botulinum toxin are the first line of treatment for cervical dystonia. To optimise the treatment response to botulinum toxin correct muscles should be

  19. Therapeutic Approaches of Botulinum Toxin in Gynecology.

    Science.gov (United States)

    Moga, Marius Alexandru; Dimienescu, Oana Gabriela; Bălan, Andreea; Scârneciu, Ioan; Barabaș, Barna; Pleș, Liana

    2018-04-21

    Botulinum toxins (BoNTs) are produced by several anaerobic species of the genus Clostridium and, although they were originally considered lethal toxins, today they find their usefulness in the treatment of a wide range of pathologies in various medical specialties. Botulinum neurotoxin has been identified in seven different isoforms (BoNT-A, BoNT-B, BoNT-C, BoNT-D, BoNT-E, BoNT-F, and BoNT-G). Neurotoxigenic Clostridia can produce more than 40 different BoNT subtypes and, recently, a new BoNT serotype (BoNT-X) has been reported in some studies. BoNT-X has not been shown to actually be an active neurotoxin despite its catalytically active LC, so it should be described as a putative eighth serotype. The mechanism of action of the serotypes is similar: they inhibit the release of acetylcholine from the nerve endings but their therapeutically potency varies. Botulinum toxin type A (BoNT-A) is the most studied serotype for therapeutic purposes. Regarding the gynecological pathology, a series of studies based on the efficiency of its use in the treatment of refractory myofascial pelvic pain, vaginism, dyspareunia, vulvodynia and overactive bladder or urinary incontinence have been reported. The current study is a review of the literature regarding the efficiency of BoNT-A in the gynecological pathology and on the long and short-term effects of its administration.

  20. The innovative therapeutic application of botulinum toxin type A in urology patients

    Directory of Open Access Journals (Sweden)

    Chrysoula Belai

    2016-06-01

    Full Text Available In the history of medical science the use of botulinum toxin was impressive. In the early 18th century it was defined as the neurotoxin implicated in the deadly disease botulism. Today, despite the toxic action finds application in the treatment of various diseases in a wide range of Medicine. Its use in urology was revolutionary in the treatment of neurogenic bladder, refractory idiopathic detrusor overactivity and other painful syndromes. The purpose of this review was to describe the treatment option of intravesical injection of botulinum toxin, in diseases of the urinary tract. The review showed that after many test applications under the experimental studies, the botulinum toxin type A has already established itself as the new treatment of choice after failure of conservative drug dealing in patients with neuro-urological symptoms of lower urinary tract. Cases of application of botulinum toxin in Urology are related to overactive bladder, neurogenic or idiopathic etiology, as bladder pain syndrome and chronic pelvic pain syndrome. According to the guidelines of the European Union directives Urology, the intravesical botulinum toxin injections are the most effective, minimally invasive treatment which results in reducing neurogenic hyperactivity of detrusor. In conclusion, this is a safe, easy and effective method that can be applied by health professionals, helping improve patients’ quality of life with neuro-urological diseases.

  1. Three-Dimensional Structure Determination of Botulinum Toxin

    National Research Council Canada - National Science Library

    Stevens, Ray

    1997-01-01

    ...) Based on the structure of the neurotoxin, understand the toxins mechanism of action. We have accomplished the first goal of determining the three-dimensional structure of the 150 kD botulinum neurotoxin serotype...

  2. Three-Dimensional Structure Determination of Botulinum Toxin

    National Research Council Canada - National Science Library

    Stevens, Ray

    1998-01-01

    ...) Based on the structure of the neurotoxin, understand the toxins mechanism of action. We have accomplished the first goal of determining the three-dimensional structure of the 150 kD botulinum neurotoxin serotype...

  3. Botulinum toxin therapy in Frey's syndrome: a retrospective study of 440 treatments in 100 patients.

    Science.gov (United States)

    Jansen, S; Jerowski, M; Ludwig, L; Fischer-Krall, E; Beutner, D; Grosheva, M

    2017-04-01

    Frey's syndrome is characterised as sweating, redness and warmth of the parotideal area and is often treated with botulinum toxin A. The objective of this retrospective study was to prove whether the toxin dosage and time-to-treatment intervals change after repeated botulinum toxin injections. The charts of patients, who were treated for Frey's syndrome during the last 16 years, were assessed. Three brands of botulinum toxin A were available for therapy. The Minor test was used to confirm the sweating before each treatment and to determine the toxin dosage. Constant amount of botulinum toxin was injected per cm 2 of the affected area. Patients consulted our department for the next treatment as soon as they felt disturbed by recurring sweating and when the sweating was objectively evident in the Minor test. Time intervals between treatments and injected toxin dosages were assessed. In total, 100 patients received 440 treatments in 16 years. Repeated injections, median 4.0, were carried out in 70.5% of patients. Median time interval to the first injection was 2.8 years. Median time interval between treatments was 12.0 months and showed to be steady (anova, P = .49, F = 1.01). Duration of effect of botulinum toxin on Frey's syndrome was long-lasting and stable with no significantly different time intervals between treatments. The extent of the sweating area did not vary significantly after repeated treatments and required a constant dose of botulinum toxin A. © 2016 John Wiley & Sons Ltd.

  4. Effectiveness of botulinum toxin A in treatment of refractory erythromelalgia

    Directory of Open Access Journals (Sweden)

    Kuan-Hsiang Lin

    2013-05-01

    Full Text Available Erythromelalgia is characterized by intense burning pain, erythema, and heat in affected areas after precipitating factors such as warm temperature or stress. It is refractory to treatment in some situations. We describe a woman with adenosquamous cell carcinoma of the lung and medically refractory erythromelalgia. The symptoms of erythromelalgia presented as refractory to any medical treatment. Due to the unresponsive nature of her condition, botulinum toxin type A (onabotulinumtoxin A was injected over both of her cheeks, periodically for six cycles. Her symptoms responded dramatically to subcutaneous and intradermal injection of botulinum toxin type A. Repetitive injection demonstrated consistent and reproducible responses, and the efficacy was maintained for approximately 1 month. No adverse effects or complications were noted. Botulinum toxin type A might be safe and effective as an alternative treatment for refractory erythromelalgia, but further large-scale studies are required.

  5. The Efficacy of Botulinum Toxin A Intramuscular Injections in After-Stroke Spasticity

    Directory of Open Access Journals (Sweden)

    Melek Karaçam

    2010-09-01

    Full Text Available OBJECTIVE: Spasticity is a common dysfunction in stroke patients. It hinders the performance of everyday living activities and lowers the quality of life. In this study, it was aimed to investigate the effects of botulinum toxin A therapy on various aspects, such as muscle tone, pain, daily living activities and disability. METHODS: Fifteen patients with stroke presenting with focal spasticity in the botulinum toxin outpatient unit were evaluated. Results before and after treatment were evaluated by applying different scales. Modified Ashworth Scale was applied for the severity of spasticity. The Medical Council Research Scale was used to test muscle power, and the disability scoring scale, Visual Analogue Pain Scale and Barthel index were the other measures tested. RESULTS: It was found that therapy with botulinum toxin A was effective in spasticity. The increased muscle tone and the disability scores decreased prominently after the treatment (p< 0.05. Lower values in pain scores (p< 0.05 also contributed to better functional outcome (p< 0.01. Along with the significantly good outcome according to the scales, the higher scores in quality of life, feeling of well-being, good performance during the physiotherapy sessions, and less medications needed for spasticity were also indications in commencing the therapy of botulinum toxin A in spasticity. CONCLUSION: Spasticity is a complicated condition causing serious disability. Botulinum toxin A is a preferred therapy when there is an increased motor activity. The effects of the agent are reversible and reliable. The duration of the treatment is long-lasting. Since botulinum toxin A is easily applied and the outcome in focal spasticity is favorable, it is recommended as the first-line choice in the treatment of focal spasticity

  6. Vocal aging and adductor spasmodic dysphonia: Response to botulinum toxin injection

    Science.gov (United States)

    Cannito, Michael P; Kahane, Joel C; Chorna, Lesya

    2008-01-01

    Aging of the larynx is characterized by involutional changes which alter its biomechanical and neural properties and create a biological environment that is different from younger counterparts. Illustrative anatomical examples are presented. This natural, non-disease process appears to set conditions which may influence the effectiveness of botulinum toxin injection and our expectations for its success. Adductor spasmodic dysphonia, a type of laryngeal dystonia, is typically treated using botulinum toxin injections of the vocal folds in order to suppress adductory muscle spasms which are disruptive to production of speech and voice. A few studies have suggested diminished response to treatment in older patients with adductor spasmodic dysphonia. This retrospective study provides a reanalysis of existing pre-to-post treatment data as function of age. Perceptual judgments of speech produced by 42 patients with ADSD were made by two panels of professional listeners with expertise in voice or fluency of speech. Results demonstrate a markedly reduced positive response to botulinum toxin treatment in the older patients. Perceptual findings are further elucidated by means of acoustic spectrography. Literature on vocal aging is reviewed to provide a specific set of biological mechanisms that best account for the observed interaction of botulinum toxin treatment with advancing age. PMID:18488884

  7. Vocal aging and adductor spasmodic dysphonia: response to botulinum toxin injection.

    Science.gov (United States)

    Cannito, Michael P; Kahane, Joel C; Chorna, Lesya

    2008-01-01

    Aging of the larynx is characterized by involutional changes which alter its biomechanical and neural properties and create a biological environment that is different from younger counterparts. Illustrative anatomical examples are presented. This natural, non-disease process appears to set conditions which may influence the effectiveness of botulinum toxin injection and our expectations for its success. Adductor spasmodic dysphonia, a type of laryngeal dystonia, is typically treated using botulinum toxin injections of the vocal folds in order to suppress adductory muscle spasms which are disruptive to production of speech and voice. A few studies have suggested diminished response to treatment in older patients with adductor spasmodic dysphonia. This retrospective study provides a reanalysis of existing pre-to-post treatment data as function of age. Perceptual judgments of speech produced by 42 patients with ADSD were made by two panels of professional listeners with expertise in voice or fluency of speech. Results demonstrate a markedly reduced positive response to botulinum toxin treatment in the older patients. Perceptual findings are further elucidated by means of acoustic spectrography. Literature on vocal aging is reviewed to provide a specific set of biological mechanisms that best account for the observed interaction of botulinum toxin treatment with advancing age.

  8. Plastic changes in spinal synaptic transmission following botulinum toxin A in patients with post-stroke spasticity.

    Science.gov (United States)

    Kerzoncuf, Marjorie; Bensoussan, Laurent; Delarque, Alain; Durand, Jacques; Viton, Jean-Michel; Rossi-Durand, Christiane

    2015-11-01

    The therapeutic effects of intramuscular injections of botulinum toxin-type A on spasticity can largely be explained by its blocking action at the neuromuscular junction. Botulinum toxin-type A is also thought to have a central action on the functional organization of the central nervous system. This study assessed the action of botulinum toxin-type A on spinal motor networks by investigating post-activation depression of the soleus H-reflex in post-stroke patients. Post-activation depression, a presynaptic mechanism controlling the synaptic efficacy of Ia-motoneuron transmission, is involved in the pathophysiology of spasticity. Eight patients with chronic hemiplegia post-stroke presenting with lower limb spasticity and requiring botulinum toxin-type A injection in the ankle extensor muscle. Post-activation depression of soleus H-reflex assessed as frequency-related depression of H-reflex was investigated before and 3, 6 and 12 weeks after botulinum toxin-type A injections in the triceps surae. Post-activation depression was quantified as the ratio between H-reflex amplitude at 0.5 and 0.1 Hz. Post-activation depression of soleus H-reflex, which is reduced on the paretic leg, was affected 3 weeks after botulinum toxin-type A injection. Depending on the residual motor capacity of the post-stroke patients, post-activation depression was either restored in patients with preserved voluntary motor control or further reduced in patients with no residual voluntary control. Botulinum toxin treatment induces synaptic plasticity at the Ia-motoneuron synapse in post-stroke paretic patients, which suggests that the effectiveness of botulinum toxin-type A in post-stroke rehabilitation might be partly due to its central effects.

  9. Therapeutic Approaches of Botulinum Toxin in Gynecology

    Directory of Open Access Journals (Sweden)

    Marius Alexandru Moga

    2018-04-01

    Full Text Available Botulinum toxins (BoNTs are produced by several anaerobic species of the genus Clostridium and, although they were originally considered lethal toxins, today they find their usefulness in the treatment of a wide range of pathologies in various medical specialties. Botulinum neurotoxin has been identified in seven different isoforms (BoNT-A, BoNT-B, BoNT-C, BoNT-D, BoNT-E, BoNT-F, and BoNT-G. Neurotoxigenic Clostridia can produce more than 40 different BoNT subtypes and, recently, a new BoNT serotype (BoNT-X has been reported in some studies. BoNT-X has not been shown to actually be an active neurotoxin despite its catalytically active LC, so it should be described as a putative eighth serotype. The mechanism of action of the serotypes is similar: they inhibit the release of acetylcholine from the nerve endings but their therapeutically potency varies. Botulinum toxin type A (BoNT-A is the most studied serotype for therapeutic purposes. Regarding the gynecological pathology, a series of studies based on the efficiency of its use in the treatment of refractory myofascial pelvic pain, vaginism, dyspareunia, vulvodynia and overactive bladder or urinary incontinence have been reported. The current study is a review of the literature regarding the efficiency of BoNT-A in the gynecological pathology and on the long and short-term effects of its administration.

  10. Botulinum toxin for treatment of Frey's syndrome: report of two cases

    Directory of Open Access Journals (Sweden)

    Teive Hélio A.G.

    2003-01-01

    Full Text Available Frey's syndrome is a phenomenon of hemifacial flushing and sweating after gustatory stimulus, usually secondary to surgical trauma over the parotid gland, although other injury mechanisms may be seen. It is accepted as a result of aberrant regeneration of facial autonomic nerve fibers. Treatment evolved from ineffective medical and surgical approaches to botulinum toxin. We evaluate the effectiveness and safety of botulinum toxin in the treatment of this complication in two patients.

  11. Retargeting the Clostridium botulinum C2 toxin to the neuronal cytosol.

    Science.gov (United States)

    Pavlik, Benjamin J; Hruska, Elizabeth J; Van Cott, Kevin E; Blum, Paul H

    2016-03-30

    Many biological toxins are known to attack specific cell types, delivering their enzymatic payloads to the cytosol. This process can be manipulated by molecular engineering of chimeric toxins. Using toxins with naturally unlinked components as a starting point is advantageous because it allows for the development of payloads separately from the binding/translocation components. Here the Clostridium botulinum C2 binding/translocation domain was retargeted to neural cell populations by deleting its non-specific binding domain and replacing it with a C. botulinum neurotoxin binding domain. This fusion protein was used to deliver fluorescently labeled payloads to Neuro-2a cells. Intracellular delivery was quantified by flow cytometry and found to be dependent on artificial enrichment of cells with the polysialoganglioside receptor GT1b. Visualization by confocal microscopy showed a dissociation of payloads from the early endosome indicating translocation of the chimeric toxin. The natural Clostridium botulinum C2 toxin was then delivered to human glioblastoma A172 and synchronized HeLa cells. In the presence of the fusion protein, native cytosolic enzymatic activity of the enzyme was observed and found to be GT1b-dependent. This retargeted toxin may enable delivery of therapeutics to peripheral neurons and be of use in addressing experimental questions about neural physiology.

  12. Drooling in Parkinson's disease: A randomized controlled trial of incobotulinum toxin A and meta-analysis of Botulinum toxins.

    Science.gov (United States)

    Narayanaswami, Pushpa; Geisbush, Thomas; Tarulli, Andrew; Raynor, Elizabeth; Gautam, Shiva; Tarsy, Daniel; Gronseth, Gary

    2016-09-01

    Botulinum toxins are a therapeutic option for drooling in Parkinson's Disease (PD). The aims of this study were to: 1. evaluate the efficacy of incobotulinum toxin A for drooling in PD. 2. Perform a meta-analysis of studies of Botulinum toxins for drooling in PD. 1. Primary study: Randomized, double blind, placebo controlled, cross over trial. Incobotulinum toxin (100 units) or saline was injected into the parotid (20 units) and submandibular (30 units) glands. Subjects returned monthly for three evaluations after each injection. Outcome measures were saliva weight and Drooling Frequency and Severity Scale. 2. Systematic review of literature, followed by inverse variance meta-analyses using random effects models. 1. Primary Study: Nine of 10 subjects completed both arms. There was no significant change in the primary outcome of saliva weight one month after injection in the treatment period compared to placebo period (mean difference, gm ± SD: -0.194 ± 0.61, range: -1.28 to 0.97, 95% CI -0.71 to 0.32). Secondary outcomes also did not change. 2. Meta-analysis of six studies demonstrated significant benefit of Botulinum toxin on functional outcomes (effect size, Cohen's d: -1.32, CI -1.86 to -0.78). The other studies used a higher dose of Botulinum toxin A into the parotid glands. This study did not demonstrate efficacy of incobotulinum toxin A for drooling in PD, but lacked precision to exclude moderate benefit. The parotid/submandibular dose-ratio may have influenced results. Studies evaluating higher doses of incobotulinum toxin A into the parotid glands may be useful. Copyright © 2016 Elsevier Ltd. All rights reserved.

  13. [Contribution of botulinum toxin to maxillo-facial surgery].

    Science.gov (United States)

    Batifol, D; de Boutray, M; Goudot, P; Lorenzo, S

    2013-04-01

    Botulinum toxin has a wide range of use in maxillo-facial surgery due to its action on muscles, on the glandular system, and against pain. It already has been given several market authorizations as indicated for: blepharospasm, spasmodic stiff neck, and glabellar lines. Furthermore, several studies are ongoing to prove its effectiveness and usefulness for many other pathologies: treatment of pain following cervical spine surgery; action on salivary glands after trauma, hypertrophy, or hyper-salivation; analgesic action (acknowledged but still being experimented) on neuralgia, articular pain, and keloids scars due to its anti-inflammatory properties. Botulinum toxin injections in the cervico-facial area are more and more used and should be to be correctly assessed. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

  14. Pneumothorax complicating botulinum toxin injection in the body of a dilated oesophagus in achalasia

    NARCIS (Netherlands)

    Weusten, Bas L. A. M.; Samsom, Melvin; Smout, André J. P. M.

    2003-01-01

    Botulinum toxin is used for an increasing number of indications in the field of gastroenterology. We report a case in which injection of botulinum toxin in the dilated tubular oesophagus in a patient with achalasia was complicated by a pneumothorax necessitating suction drainage

  15. Botulinum toxin in the management of sialorrhoea in acquired brain injury

    LENUS (Irish Health Repository)

    Carroll, A

    2016-06-01

    Sialorrhoea as a consequence of severe acquired brain injury can significantly negatively impact on quality of life. Medications used in its management have many side effects which can cause problems in the severely disabled. Botulinum toxin is an effective treatment of sialorrhoea in a number of neurological conditions but may also have a role to play in the management of sialorrhoea following severe ABI. We report on 4 cases of sialorrhoea following acquired brain injury causing a variety of problems, whose parotid glands were injected with Botulinum toxin type A (Dysport) 50mu each, under ultrasound guidance. All cases had a clinically and statistically significant reduction in drooling as measured by the teacher drooling scale (p=0.005) and carers Visual Analogue Scale (p=0.012). There were no side effects reported. Botulinum toxin is an effective treatment for sialorrhoea associated with acquired brain injury.

  16. Treatment diary for botulinum toxin spasticity treatment

    DEFF Research Database (Denmark)

    Biering-Sørensen, Bo; Iversen, Helle K; Frederiksen, Inge M S

    2017-01-01

    The aim of this study is to develop a treatment diary for patients receiving spasticity treatment including botulinum toxin injection and physiotherapy and/or occupational therapy. The diary focuses on problems triggered by skeletal muscle overactivity; agreed goals for treatment and the patient...

  17. Safety and efficacy of botulinum toxin injection therapy for esophageal achalasia in Japan.

    Science.gov (United States)

    Yamaguchi, Daisuke; Tsuruoka, Nanae; Sakata, Yasuhisa; Shimoda, Ryo; Fujimoto, Kazuma; Iwakiri, Ryuichi

    2015-11-01

    Botulinum toxin injection is an accepted treatment modality for esophageal achalasia in western countries. This pilot study aimed to clarify the effectiveness of botulinum toxin injection for esophageal achalasia in Japanese patients. We enrolled 10 patients diagnosed with esophageal achalasia between 2008 and 2014. A total of 100 U botulinum toxin A was divided into eight aliquots and injected around the esophagogastric junction. We compared the lower esophageal sphincter pressure before and 1 week after treatment. Scores of subjective symptoms for esophageal achalasia were assessed using a visual analog scale (VAS) before and after 1 week of follow-up of treatment. Barium passage was improved in barium esophagography and passage of contrast agent was also improved. Mean Eckardt score was reduced from 5.5 to 1.6 after treatment (ptreatment (p = 0.002). One week after treatment, mean VAS score was reduced from 10 to 3.9 (pachalasia was safe and effective with few complications. Therefore, botulinum toxin could be used as minimally invasive therapy for esophageal achalasia in Japan.

  18. A Beautician’s Dystonia: Long-Lasting Effect of Botulinum Toxin

    Directory of Open Access Journals (Sweden)

    Siria Di Martino

    2014-01-01

    Full Text Available Treatment options for dystonia are not curative but symptomatic; the treatment of choice for focal dystonias is repeated botulinum toxin injections. Here, we present the case of a 46-year-old beautician with focal dystonia in her left hand that affected her ability to work. Pharmacological treatment with clonazepam and gabapentin failed to resolve her symptoms and was discontinued due to side effects (sleepiness, gastrointestinal disorders. Intramuscular injection of botulinum toxin (incobotulinumtoxinA, Xeomin into the extensor digitorum communis (35 U, flexor carpi radialis (35 U, and flexor digitorum superficialis (30 U muscles resulted in complete resolution of symptoms at clinical assessments at 1, 3, 6, and 10 months after the injections, confirmed by the results of surface electromyography 10 months after treatment. The patient was able to work again 1 month after treatment. No reinjection has been necessary at the last evaluation (12 months after treatment. In conclusion, botulinum toxin is an effective treatment for focal dystonia that can have long-lasting effects and can improve patients’ ability to work and quality of life.

  19. Intralesional botulinum toxin-A injection for the treatment of multiple eccrine hidrocystomas.

    Science.gov (United States)

    Gheisari, Mehdi; Hamedani, Behnaz; Robati, RezaM; Mozafari, Nikoo

    2018-01-31

    Multiple eccrine hidrocystomas (MEH) are benign cystic lesions of the sweat gland ducts. They are characterized by translucent, skin-colored or bluish dome-shaped papules on the face, causing cosmetic concern. Recently, botulinum toxin-A, because of its antiperspirant properties, has been used to treat facial MEH. However, there are only some case reports in the literature. Here, we conducted a prospective study to assess the efficacy and safety of intralesional injection of botulinum toxin-A (Dysport) for the treatment of MEH. Twenty patients (3 men and 17 women), aged from 31 to 75 years old, participated in this study. A 300 unit vial of botulinum toxin-A (Dysport, Ipsenn Biopharm, United Kingdom) was diluted with 4 ml of saline solution without preservative to achieve a concentration of 7.5U/.1 ml. Up to 1.5 unit of botulinum toxin was injected intradermally at the base of each lesion to raise a visible wheal. The patients were evaluated 7 days later, and any clinical changes or adverse effects were recorded. In all patients, more than 75% of eccrine hidrocystoma lesions resolved without any scaring. The result sustained for 2-5 months. In two patients mild smile asymmetry and in one patient lagophthalmos were noted approximately 5-7 days after injection that gradually resolved in 3 weeks. Intralesional botulinum toxin-A for treatment of multiple hidrocystomas is a simple and well-tolerated procedure. It is accompanied by excellent results, a good postoperative course, and no risk of scarring. It can be considered in patients who did not respond to other treatment or even as the first line therapy.

  20. SPASTICITY PATTERNS OF HAND MUSCLES AND BOTULINUM TOXIN THERAPY APPLICATION IN PATIENTS WITH CEREBRAL PALSY WITH UPPER LIMB INVOLVEMENT

    Directory of Open Access Journals (Sweden)

    O. A. Klochkova

    2013-01-01

    Full Text Available Botulinum toxin therapy is an effective and safe method of treatment of local spasticity in patients with cerebral palsy (CP. Calculation of botulinum toxin A (BTA dosage based on the spasticity patterns and functional capabilities of the patient proved effective for the hypertonic lower limb muscle spasm treatment and is being applied to BTA injections in hand muscles more often. The article presents contemporary scientific data and results of the original study of BTA injections efficacy for pathologic tension reduction in hand muscles of 52 patients with CP. The authors give detailed description of the upper limb spasticity patterns, their frequency and role in the pathological movement pattern formation. The authors propose BTA dosage calculation for the functional segments of upper limbs, which allows minimizing the total amount of the administered drug and avoiding excessive weakness. The authors have also conducted a follow-up analysis of changes in hand muscle tone for the period of 6 months after the first BTA injection, compared results of botulinum toxin therapy at various clinical forms of CP and given recommendations on the optimum duration of the follow-up period.

  1. Botulinum Toxin for the Treatment of Tremor and Tics.

    Science.gov (United States)

    Lotia, Mitesh; Jankovic, Joseph

    2016-02-01

    The therapeutic applications of botulinum toxin (BoNT) have grown manifold since its initial approval in 1989 by the U.S. Food and Drug Administration for the treatment of strabismus, blepharospasm, and other facial spasms. Although it is the most potent biologic toxin known to man, long-term studies have established its safety in the treatment of a variety of neurologic and nonneurologic disorders. Despite a paucity of randomized controlled trials, BoNT has been found to be beneficial in treating a variety of tremors and tics when used by clinicians skilled in the administration of the drug for these hyperkinetic movement disorders. Botulinum toxin injections can provide meaningful improvement in patients with localized tremors and tics; in some cases, they may be an alternative to other treatments with more undesirable adverse effects. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

  2. Effect of Botulinum Toxin Type A on TGF-β/Smad Pathway Signaling: Implications for Silicone-Induced Capsule Formation.

    Science.gov (United States)

    Kim, Sena; Ahn, Moonsang; Piao, Yibo; Ha, Yooseok; Choi, Dae-Kyoung; Yi, Min-Hee; Shin, Nara; Kim, Dong Woon; Oh, Sang-Ha

    2016-11-01

    One of the most serious complications of breast surgery using implants is capsular contracture. Several preventive treatments have been introduced; however, the mechanism of capsule formation has not been resolved completely. The authors previously identified negative effects of botulinum toxin type A on capsule formation, expression of transforming growth factor (TGF)-β1, and differentiation of fibroblasts into myofibroblasts. Thus, the authors investigated how to prevent capsule formation by using botulinum toxin type A, particularly by means of TGF-β1 signaling, in human fibroblasts. In vitro, cultured human fibroblasts were treated with TGF-β1 and/or botulinum toxin type A. Expression of collagen, matrix metalloproteinase, and Smad was examined by Western blotting. The activation of matrix metalloproteinase was observed by gelatin zymography. In vivo, the effect of botulinum toxin type A on the phosphorylation of Smad2 in silicone-induced capsule formation was evaluated by immunocytochemistry. In vitro, the phosphorylation of Smad2 was inhibited by botulinum toxin type A treatment. The expression levels of collagen types 1 and 3 were inhibited by botulinum toxin type A treatment, whereas those of matrix metalloproteinase-2 and matrix metalloproteinase-9 were enhanced. Gelatin zymography experiments confirmed enhanced matrix metalloproteinase-2 activity in collagen degradation. In vivo, botulinum toxin type A treatment reduced capsule thickness and Smad2 phosphorylation in silicone-induced capsules. This study suggests that botulinum toxin type A plays an important role in the inhibition of capsule formation through the TGF-β/Smad signaling pathway. Therapeutic, V.

  3. [Botulinum toxin and rejuvenation of the eye].

    Science.gov (United States)

    Volpei, Ch; Miniconi, M-J; Brunner, C I; Besins, T; Braccini, F

    2013-01-01

    Treatments with botulinum toxin in the forehead and periorbital areas may induce disappointing or even paradoxical results. Our study, focused on this area aimed at refining injection techniques by analyzing muscular balances and comparing the effect according to injection doses and topography. This experimental study has been carried out in the form of 2 session workshops, with volunteers duly informed of the study contents and giving their informed consent. It was conducted by physicians and surgeons members of SAMCEP* (Société Avancée de Médecine et Chirurgie Esthétique et Plastique). The botulinum toxin was onabotulinumtoxin A. Results were evaluated 15 days after treatment, in regard to global eyebrow position, eyebrow head and tail position; muscle interactions; lines above the eyebrow. Eleven case reports and their results are shown and discussed. Our study underlines two important insights: muscle balances and "border areas", between orbicularis oculi and corrugator, key features for eyebrow head, and between frontalis and orbicularis oculifor eyebrow tail.

  4. USE OF BOTULINUM TOXIN TYPE A IN THE TREATMENT OF SPASTICITY IN CHILDREN WITH CEREBRAL PALSY

    Directory of Open Access Journals (Sweden)

    Ljiljana Lazić

    2011-06-01

    Full Text Available Cerebral palsy has an incidence of about 1-2 per 1000 live births, and in spite of the progress of neonatal medicine, it seems that the incidence will not subside in the near future. The most important characteristic of cerebral palsy is movement abnormality: spasticity, chorea, athetosis, ataxia, dystonia, as well as their different combinations. About 70% of children who suffer from cerebral palsy also suffer from some form of spasticity. Spasticity is a type of muscle hypertonicity characterized by rapid increase in resistance to passive stretching of muscles. The interest for botulinum toxin application in the treatment of spasticity has dramatically increased in the last 10 years. Botulinum toxin is the most powerful neurotoxin that is found in nature. It is produced by anaerobic bacteria – clostridium botulinum. It is produced in eight serotypes of which type A is the most commonly used. Botulinum toxin blocks neuromuscular transmission and causes irreversible weakness of the treated muscle. It has been used since 1993 in the treatment of cerebral palsy in children. The toxin effect is permanent and it results in irreversible denervation. Functional recovery is possible after 2-4 months, due to sprouting of nerve endings and the formation of new synaptic contacts. Treatment with botulinum toxin is safe. Adverse effects are rare, temporary and completely reversible. Application of botulinum toxin prevents or reduces contractures and deformities, and thus delays or avoids surgical treatment. Yet, physical therapy, which prolongs and improves the effects of botulinum toxin, remains an essential and most important form of therapy in the treatment of children with cerebral palsy.

  5. Review of botulinum toxin type A for the prophylactic treatment of chronic daily headache

    Directory of Open Access Journals (Sweden)

    Stefan Evers

    2007-05-01

    Full Text Available Stefan EversDepartment of Neurology, University of Münster, Münster, GermanyAbstract: Botulinum toxin A is increasingly used in the treatment of idiopathic and symptomatic headache disorders. However, only few controlled trials are available and many trials can hardly be compared to each other because of different endpoints and different trial designs. In particular chronic daily headache, which is defined as an idiopathic headache occurring on more than 15 days per month for at least 3 months and a daily duration of at least 4 hours, is considered as a headache disorder with possible efficacy of botulinum toxin A. For the prophylactic treatment of chronic tension-type headache and chronic migraine, no sufficient positive evidence for a successful treatment can be obtained from randomized, double-blind, and placebo-controlled trials to date. For the treatment of chronic daily headache including medication overuse headache, there is some positive evidence for efficacy in a subgroup of patients. To date, the majority of double-blind and placebo-controlled studies do not suggest that botulinum toxin A is efficacious in the treatment of chronic idiopathic headache disorders. However, it is possible that some subgroups of patients with chronic daily headache will benefit from a long-term treatment with botulinum toxin A.Keywords: botulinum toxin A, chronic daily headache, chronic tension-type headache, chronic migraine

  6. Attempts to identify Clostridium botulinum toxin in milk from three experimentally intoxicated Holstein cows

    Science.gov (United States)

    Moeller, R.B.; Puschner, B.; Walker, R.L.; Rocke, T.E.; Smith, S.R.; Cullor, J.S.; Ardans, A.A.

    2009-01-01

    Three adult lactating Holstein cows were injected in the subcutaneous abdominal vein with 175 ng/kg of body weight of Clostridium botulinum type C toxin (451 cow median toxic doses) to determine if this botulinum toxin crosses the blood–milk barrier. Whole blood (in sodium heparin) and clotted blood serum samples were taken at 0 min, 10 min, and 3, 6, 9, and 12 h postinoculation. Milk samples were taken at 0 min and at 3, 6, 9 and 12 h postinoculation. All samples were tested for the presence of the toxin using the mouse bioassay and immunostick ELISA test. The immunostick ELISA identified the toxin in whole blood and the mouse bioassay identified the toxin in serum at all times examined in all 3 animals. Toxin was not identified by either detection method in milk samples collected from the 3 animals. From these results, it appears that Clostridium botulinum type C toxin does not cross from the blood to the milk in detectable concentrations.

  7. Effects of botulinum toxin on strength-duration properties.

    Science.gov (United States)

    Yerdelen, Deniz; Koc, Filiz; Sarica, Yakup

    2007-10-01

    Axonal excitability studies have been used in several diseases to investigate the underlying pathophysiology. The threshold tracking technique was developed to measure noninvasively several indices of axonal excitability, such as strength-duration properties. This study investigated the possible effects of botulinum toxin on strength-duration time constant (SDTC) in patients with the symptoms and signs of botulism. The clinical and electrophysiological findings of 13 patients who were admitted to the authors' clinic with botulism signs and symptoms were evaluated in a 5-day period after exposure to the toxin prospectively. After routine diagnostic electroneuromyographic examinations and electromyogram with repetitive nerve stimulation at 20-50 Hz, SDTC was studied. The results were compared with 13 age- and sex-matched healthy volunteers. The SDTCs were 381 +/- 60 micros and 471 +/- 84 micros in patients and controls, respectively. There was a statistical difference between the two groups (p = .003, Mann Whitney U test). These findings suggest a possible effect of botulinum toxin, known to be effective at neuromuscular junction, on Na(+)/K(+) pump activity, and Na(+) or K(+) conductance.

  8. Cellular Entry of Clostridium perfringens Iota-Toxin and Clostridium botulinum C2 Toxin.

    Science.gov (United States)

    Takehara, Masaya; Takagishi, Teruhisa; Seike, Soshi; Oda, Masataka; Sakaguchi, Yoshihiko; Hisatsune, Junzo; Ochi, Sadayuki; Kobayashi, Keiko; Nagahama, Masahiro

    2017-08-11

    Clostridium perfringens iota-toxin and Clostridium botulinum C2 toxin are composed of two non-linked proteins, one being the enzymatic component and the other being the binding/translocation component. These latter components recognize specific receptors and oligomerize in plasma membrane lipid-rafts, mediating the uptake of the enzymatic component into the cytosol. Enzymatic components induce actin cytoskeleton disorganization through the ADP-ribosylation of actin and are responsible for cell rounding and death. This review focuses upon the recent advances in cellular internalization of clostridial binary toxins.

  9. Study on potential Clostridium botulinum growth and toxin production in Parma ham

    Directory of Open Access Journals (Sweden)

    Giuseppe Merialdi

    2016-04-01

    Full Text Available The objective of this study was to investigate Clostridium botulinum growth and toxin production in the industrially manufactured Italian Parma ham. The study focuses on the Parma ham production phase identified as maximum risk to C. botulinum proliferation, i.e. the transition from cold phase (salting and resting to a phase carried out at temperature between 15 and 23°C (drying. A preliminary in vitro test was carried out in order to verify the capability of 6 C. botulinum strains (1 type A, 4 type B, and 1 type E strains to grow in conditions of temperature, pH and NaCl concentration comparable to those of the beginning stage of ham drying. Five C. botulinum strains grew at 20°C and pH 6, four strains produced toxin when inoculated at a concentration equal to 103 cfu/mL at NaCl concentration of 4%, while when the inoculum concentration was 10 cfu/mL, NaCl concentration of 3% resulted the toxin-genesis limiting factor. An experimental contamination with a mixture of the 5 C. botulinum strains selected by the preliminary in vitro test was performed on 9 thighs inoculated at the end of the resting phase. The study was designed to evaluate the potential growth and toxin production in extremely favourable conditions for the bacterium. Type B proteolytic C. botulinum toxin was produced after 14 days of incubation at 20°C in 2 thighs characterised by high weight, low number of days of resting and anomalous physiochemical characteristics [one for very low NaCl concentration (1.59%, the other for elevated pH (6.27 and both for high water activity values (>0.970]. The results of this research confirm that the cold resting step is a critical phase in the production process of Parma ham for the investigated hazard. Based on the present study, the long resting phase adopted in the manufacturing of Parma ham is proven effective to prevent the growth of C. botulinum, an event which could not otherwise be excluded if the hams were processed under less

  10. Efficacy of Botulinum Toxin Injections in the Treatment of Various Types of Facial Region Disorders

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    Arzu Çoban

    2012-12-01

    Full Text Available OBJECTIVE: Local injection of botulinum toxin is a highly effective treatment option for a wide range of movement disorders and there are reliable sources of information on its indications, effects and safety in clinical practice. In this study, we report our experience with botulinum toxin in the treatment of facial region disorders. METHODS: Patients who had been followed in the Botulinum Toxin Outpatient Clinic of the Neurology Department were retrospectively evaluated. Two preparations of botulinum toxin type A (BT-A were used. The efficacy of BT-A injections was rated according to the improvement in symptoms as follows: marked - 75-100% improvement, good - 50-74%, moderate - 25-49%, and insufficient - less than 25% symptom relief. RESULTS: One hundred eighty-two patients (73 male, 109 female with various facial region disorders were included. The efficacy rates for patients who had very good and good improvement were high in the treatment of blepharospasm, hemifacial spasm, facial synkinesis, and Meige syndrome and moderate for oromandibular dystonia and hypersalivation. Ptosis was the most common side effect. CONCLUSION: According to our results, botulinum toxin was very effective treatment for blepharospasm, Meige syndrome, hemifacial spasm and facial synkinesis, whereas it demonstrated good efficacy in oromandibular dystonia and hypersalivation

  11. Botulinum toxin in preparation of oral cavity for microsurgical reconstruction.

    Science.gov (United States)

    Corradino, Bartolo; Di Lorenzo, Sara; Mossuto, Carmela; Costa, Renato Patrizio; Moschella, Francesco

    2010-01-01

    Infiltration of botulinum toxin in the major salivary glands allows a temporary reduction of salivation that begins 8 days afterwards and returns to normal within 2 months. The inhibition of salivary secretion, carried out before the oral cavity reconstructive surgery, could allow a reduction of the incidence of oro-cutaneous fistulas and local complications. Saliva stagnation is a risk factor for patients who have to undergo reconstructive microsurgery of the oral cavity, because of fistula formation and local complications in the oral cavity. The authors suggest infiltration of botulinum toxin in the major salivary glands to reduce salivation temporarily during the healing stage. During the preoperative stage, 20 patients with oral cavity carcinoma who were candidates for microsurgical reconstruction underwent sialoscintigraphy and a quantitative measurement of the salivary secretion. Injection of botulinum toxin was carried out in the salivary glands 4 days before surgery. The saliva quantitative measurement was repeated 3 and 8 days after infiltration, sialoscintigraphy after 15 days. In all cases, the saliva quantitative measurement revealed a reduction of 50% and 70% of the salivary secretion after 72 h and 8 days, respectively. A lower rate of local complications was observed.

  12. Use of botulinum A toxin for proctalgia fugax-a case report of successful treatment.

    Science.gov (United States)

    Grigoriou, Marios; Ioannidis, Aristeidis; Kofina, Konstantinia; Efthimiadis, Christoforos

    2017-11-01

    Proctalgia fugax is considered as intermittent anal pain of unknown etiology; a variety of treatments have been used, without, however, permanent results. Injection of botulinum A toxin is recently suggested as an alternative option. We present the case of a woman presenting proctalgia fugax that was untreatable through other current forms of treatment. After two administrations of botulinum A toxin, 80 units and 100 units each, the patient remained asymptomatic on 8-month follow-up control. Botulinum A toxin injection can reduce internal anal sphincter pressure, leading to relief of symptoms, and seems a promising option with minimal morbidity in cases on proctalgia fugax that does not respond to other current treatments.

  13. Use of botulinum A toxin for proctalgia fugax—a case report of successful treatment

    Science.gov (United States)

    Grigoriou, Marios; Ioannidis, Aristeidis; Efthimiadis, Christoforos

    2017-01-01

    Abstract Proctalgia fugax is considered as intermittent anal pain of unknown etiology; a variety of treatments have been used, without, however, permanent results. Injection of botulinum A toxin is recently suggested as an alternative option. We present the case of a woman presenting proctalgia fugax that was untreatable through other current forms of treatment. After two administrations of botulinum A toxin, 80 units and 100 units each, the patient remained asymptomatic on 8-month follow-up control. Botulinum A toxin injection can reduce internal anal sphincter pressure, leading to relief of symptoms, and seems a promising option with minimal morbidity in cases on proctalgia fugax that does not respond to other current treatments. PMID:29218214

  14. Toxin formation by Clostridium botulinum type B in radurized fish

    International Nuclear Information System (INIS)

    Suhadi, F.; Thayib, S.S.

    1981-01-01

    The relation between maximum storage life and earliest toxin formation by proteolytic and nonproteolytic strains of C. botulinum type B in irradiated and unirradiated raw fish was determinated. The fish species used were Rastrelliger sp., Euthynnus sp. and Scomberomorus sp. Uninoculated fish samples held under the same treatment conditions were evaluated for the estimation of storage life by untrained panelist. The results showed that a storage temperature at or lower than 5.6 0 C is recommended in order to avoid botulism hazard caused by nonproteolytic type B. When the samples were inoculated with spores of proteolytic strains, no toxic samples were found during the storage life in all treatments with storage temperatures at or lower than 10.2 0 C. Toxin formation by proteolytic strains of C. botulinum type B in boiled (''Pindang'') chub mackerel (Rastrelliger sp.) under storage at ambient temperatures (27-31 0 C) was also determinated. The results showed that in the samples which were inoculated before the process of ''Pindang'', the earliest toxin formations were detected after the samples were spoiled regardless of the irradiation dose, strain and inoculum level; while in control unsalted samples, toxin was detected before or after the samples were spoiled, depending on the strain and inoculum level. Salt content in ordinary ''Pindang'' fish plays a major role both in extension of the storage life and the delay in toxin formation. When the samples were inoculated after the process of ''Pindang'', toxin was detected before or after the samples were spoiled, depending on the strain, salt content, irradiation dose and inoculum level. Irradiation does not prevent the toxin formation in ''Pindang'' fish if the samples are heavily contaminated with proteolytic strains of C. botulinum type B after cooking. (author)

  15. [Spasm of the near reflex. Treatment with botulinum toxin].

    Science.gov (United States)

    Merino, P; Rojas, P; Gómez de Liaño, P; Franco Iglesias, G

    2015-05-01

    A 38-year old female with diplopia and esotropia, with limitation of ocular abduction in both eyes, with full abduction after doll's head rotation also being observed. She was diagnosed with spasm of the near reflex. Treatment with injections of botulinum toxin in both medial rectus has temporally resolved the convergence spasm. Near reflex spasm is characterized as miosis, pseudomyopia, and convergent strabismus that lead to diplopia, blurred vision, headache, and variable, progressive, and intermittent esotropia. As the spasm worsens there will be limited ocular versions and ductions simulating a sixth nerve palsy. Botulinum toxin may be effective in some cases. Copyright © 2013 Sociedad Española de Oftalmología. Published by Elsevier España, S.L.U. All rights reserved.

  16. Cellular Entry of Clostridium perfringens Iota-Toxin and Clostridium botulinum C2 Toxin

    Directory of Open Access Journals (Sweden)

    Masaya Takehara

    2017-08-01

    Full Text Available Clostridium perfringens iota-toxin and Clostridium botulinum C2 toxin are composed of two non-linked proteins, one being the enzymatic component and the other being the binding/translocation component. These latter components recognize specific receptors and oligomerize in plasma membrane lipid-rafts, mediating the uptake of the enzymatic component into the cytosol. Enzymatic components induce actin cytoskeleton disorganization through the ADP-ribosylation of actin and are responsible for cell rounding and death. This review focuses upon the recent advances in cellular internalization of clostridial binary toxins.

  17. Botulinum toxin for the management of bladder dysfunction.

    Science.gov (United States)

    Schurch, Brigitte

    2006-01-01

    This review highlights a recent innovation in the medical treatment of detrusor overactivity (DO). Anticholinergics are usually the gold standard to treat bladder overactivity. Adverse effects and lack of efficacy are the two main causes for considering alternative treatments. Until recently, invasive surgery (mainly bladder augmentation) was the only available treatment option for patients with intractable DO. This article considers botulinum toxin type A (BTX-A) injection as an alternative treatment to surgery in patients with DO who do not respond to anticholinergic therapy. To identify papers for inclusion in this review, we searched PubMed with the keywords 'botulinum toxin', 'overactive bladder', 'urinary incontinence' and 'neurogenic bladder' for the years 2000-5. Review articles were not included. Abstracts were cited only if they contained important new information. Experimental animal studies and articles or book chapters related to the use of botulinum toxin for other indications (such as achalasia and cervical dystonia) were analysed with regard to the mechanisms of action of botulinum toxin. From this review, it appears that BTX-A injection into the detrusor muscle is a very effective method for treating urinary incontinence secondary to neurogenic detrusor overactivity (NDO), as well as urinary incontinence due to idiopathic overactive bladder (IDO). In both conditions, the duration of effect seems to be at least 6 months. Overall success rates seem to be similar in both patient populations. For NDO, only one evidence-based medicine level 1 study is available, whereas for IDO, only evidence-based medicine level 3 or 4 studies have been published. Particularly in this latter indication, injection technique and outcome parameters vary from study to study and need to be standardised. Without randomised controlled studies aimed at comparing different techniques and dosages, it remains difficult to decide what technique is optimal for treating patients

  18. Treatment Efficacy of Electromyography versus Fiberscopy-Guided Botulinum Toxin Injection in Adductor Spasmodic Dysphonia Patients: A Prospective Comparative Study

    Science.gov (United States)

    Kim, Jae Wook; Park, Jae Hong; Park, Ki Nam; Lee, Seung Won

    2014-01-01

    Introduction. This study prospectively evaluates and compares the treatment efficacy of botulinum toxin injection under electromyography guidance (EMG group) and percutaneous botulinum toxin injection under flexible fiberscopic guidance (fiberscopy group). Methods. Thirty patients with adductor spasmodic dysphonia (ADSD), who had never received treatment, were randomly allocated into EMG- or fiberscopy-guided botulinum toxin injections between March 2008 and February 2010. We assessed acoustic and aerodynamic voice parameters, and the voice handicap index (VHI) before injection and at 1, 3, and 6 months after injection. Results. The mean total dosage of botulinum toxin was similar for both groups: 1.7 ± 0.5 U for the EMG group and 1.8 ± 0.4 U for the fiberscopy group (P > 0.05). There were no significant differences in outcomes between the two groups in either the duration of effectiveness or complications such as breathy voice and aspiration. Conclusion. Botulinum toxin injection under fiberscopic guidance is a viable alternative to EMG-guided botulinum toxin injection for the treatment of adductor spasmodic dysphonia when EMG equipment is unavailable. PMID:25383369

  19. Treatment Efficacy of Electromyography versus Fiberscopy-Guided Botulinum Toxin Injection in Adductor Spasmodic Dysphonia Patients: A Prospective Comparative Study

    Directory of Open Access Journals (Sweden)

    Jae Wook Kim

    2014-01-01

    Full Text Available Introduction. This study prospectively evaluates and compares the treatment efficacy of botulinum toxin injection under electromyography guidance (EMG group and percutaneous botulinum toxin injection under flexible fiberscopic guidance (fiberscopy group. Methods. Thirty patients with adductor spasmodic dysphonia (ADSD, who had never received treatment, were randomly allocated into EMG- or fiberscopy-guided botulinum toxin injections between March 2008 and February 2010. We assessed acoustic and aerodynamic voice parameters, and the voice handicap index (VHI before injection and at 1, 3, and 6 months after injection. Results. The mean total dosage of botulinum toxin was similar for both groups: 1.7 ± 0.5 U for the EMG group and 1.8 ± 0.4 U for the fiberscopy group (P>0.05. There were no significant differences in outcomes between the two groups in either the duration of effectiveness or complications such as breathy voice and aspiration. Conclusion. Botulinum toxin injection under fiberscopic guidance is a viable alternative to EMG-guided botulinum toxin injection for the treatment of adductor spasmodic dysphonia when EMG equipment is unavailable.

  20. Treatment efficacy of electromyography versus fiberscopy-guided botulinum toxin injection in adductor spasmodic dysphonia patients: a prospective comparative study.

    Science.gov (United States)

    Kim, Jae Wook; Park, Jae Hong; Park, Ki Nam; Lee, Seung Won

    2014-01-01

    This study prospectively evaluates and compares the treatment efficacy of botulinum toxin injection under electromyography guidance (EMG group) and percutaneous botulinum toxin injection under flexible fiberscopic guidance (fiberscopy group). Thirty patients with adductor spasmodic dysphonia (ADSD), who had never received treatment, were randomly allocated into EMG- or fiberscopy-guided botulinum toxin injections between March 2008 and February 2010. We assessed acoustic and aerodynamic voice parameters, and the voice handicap index (VHI) before injection and at 1, 3, and 6 months after injection. The mean total dosage of botulinum toxin was similar for both groups: 1.7 ± 0.5 U for the EMG group and 1.8 ± 0.4 U for the fiberscopy group (P > 0.05). There were no significant differences in outcomes between the two groups in either the duration of effectiveness or complications such as breathy voice and aspiration. Botulinum toxin injection under fiberscopic guidance is a viable alternative to EMG-guided botulinum toxin injection for the treatment of adductor spasmodic dysphonia when EMG equipment is unavailable.

  1. Comparative study of biological activity of four botulinum toxin type A preparations in mice.

    Science.gov (United States)

    Chung, Myung Eun; Song, Dae Heon; Park, Joo Hyun

    2013-01-01

    Units of available botulinum toxin preparations are not interchangeable, and the dose-conversion ratios between such preparations remain controversial. To compare the efficacy and safety of four botulinum toxin type A preparations. Murine gastrocnemius compound muscle action potentials (CMAPs) were recorded before and after injecting the four botulinum toxin preparations (onabotulinumtoxinA, abobotulinumtoxinA, new botulinum toxin, and incobotulinumtoxinA). In all preparations, CMAP amplitudes decreased until 4 days after receiving the injection and then gradually recovered. On postinjection day 84, the amplitudes returned to baseline in all groups except the high-dose groups. CMAP amplitude in the contralateral limb also decreased up to postinjection days 4 to 7 and then gradually returned to baseline by postinjection day 28. The dose-conversion ratio between onabotulinumtoxinA and abobotulinumtoxinA was determined to be 1:2.6; previous reports of 1:3 were considered too high. A dose-conversion ratio between onabotulinumtoxinA and new botulinum toxin of 1:1 was deemed appropriate. OnabotulinumtoxinA and incobotulinumtoxinA demonstrated a dose-conversion ratio of 1:1.07. The efficacy of incobotulinumtoxinA was slightly lower than that of onabotulinumtoxinA. These dose-conversion ratios are applicable solely from an efficacy standpoint and not for safety. This study was conducted in mice, so it may not translate perfectly to human applications. © 2012 by the American Society for Dermatologic Surgery, Inc. Published by Wiley Periodicals, Inc.

  2. Comparative effectiveness of botulinum toxin versus non-surgical treatments for treating lateral epicondylitis: a systematic review and meta-analysis.

    Science.gov (United States)

    Lin, Yu-Ching; Wu, Wei-Ting; Hsu, Yu-Chun; Han, Der-Sheng; Chang, Ke-Vin

    2018-02-01

    To explore the effectiveness of botulinum toxin compared with non-surgical treatments in patients with lateral epicondylitis. Data sources including PubMed, Scopus, Embase and Airity Library from the earliest record to February 2017 were searched. Study design, patients' characteristics, dosage/brand of botulinum toxin, injection techniques, and measurements of pain and hand grip strength were retrieved. The standardized mean differences (SMDs) in pain relief and grip strength reduction were calculated at the following time points: 2-4, 8-12, and 16 weeks or more after injection. Six randomized controlled trials (321 participants) comparing botulinum toxin with placebo or corticosteroid injections were included. Compared with placebo, botulinum toxin injection significantly reduced pain at all three time points (SMD, -0.729, 95% confidence interval [CI], -1.286 to -0.171; SMD, -0.446, 95% CI, -0.740 to -0.152; SMD, -0.543, 95% CI, -0.978 to -0.107, respectively). Botulinum toxin was less effective than corticosteroid at 2-4 weeks (SMD, 1.153; 95% CI, 0.568-1.737) and both treatments appeared similar in efficacy after 8 weeks. Different injection sites and dosage/brand did not affect effectiveness. Botulinum toxin decreased grip strength 2-4 weeks after injection, and high equivalent dose could extend its paralytic effects to 8-12 weeks. When treating lateral epicondylitis, botulinum toxin was superior to placebo and could last for 16 weeks. Corticosteroid and botulinum toxin injections were largely equivalent, except the corticosteroid injections were better at pain relief in the early stages and were associated with less weakness in grip in the first 12 weeks.

  3. Treatment of chronic pain associated with nocturnal bruxism with botulinum toxin. A prospective and randomized clinical study

    Science.gov (United States)

    Al-Wayli, Hessa

    2017-01-01

    Background To evaluate the role of botulinum toxin type A (BTX-A) in the treatment of pain associated with nocturnal bruxism. Material and Methods Fifty subjects reporting nocturnal bruxism were recruited for a randomized clinical trial. Twenty five bruxers were injected with botulinum toxin in both masseters, and twenty five were treated with traditional methods of treating bruxism. Patients were evaluated at 3rd week, 2nd and 6th month and one year after injection and then used to calculate bruxism events. Bruxism symptoms were investigated using questionnaires. Results Mean pain score due to Bruxism events in the masseter muscle decreased significantly in the botulinum toxin injection group A (P =0.000, highly significant). However, in the conventional treatment group, mean pain score does not show improvement with time (p>0.05). Conclusions Our results suggest that botulinum toxin injection reduced the mean pain score and number of bruxism events, most likely by decreasing the muscle activity of masseter rather than affecting the central nervous system. Key words:Temporomandibular pain, nocturnal bruxism, botulinum toxin. PMID:28149474

  4. Characterisation of botulinum toxins type A and B, by matrix-assisted laser desorption ionisation and electrospray mass spectrometry

    NARCIS (Netherlands)

    Baar, B.L.M. van; Hulst, A.G.; Jong, A.L. de; Wils, E.R.J.

    2002-01-01

    A method earlier developed for the mass spectrometric (MS) identification of tetanus toxin (TTx) was applied to botulinum toxins type A and B (BTxA and BTxB). Botulinum toxins are extremely neurotoxic bacterial toxins, likely to be used as biological warfare agent. Biologically active BTxA and BTxB

  5. Botulinum toxin injection for hypercontractile or spastic esophageal motility disorders: may high-resolution manometry help to select cases?

    Science.gov (United States)

    Marjoux, S; Brochard, C; Roman, S; Gincul, R; Pagenault, M; Ponchon, T; Ropert, A; Mion, F

    2015-01-01

    Endoscopic injections of botulinum toxin in the cardia or distal esophagus have been advocated to treat achalasia and spastic esophageal motility disorders. We conducted a retrospective study to evaluate whether manometric diagnosis using the Chicago classification in high-resolution manometry (HRM) would be predictive of the clinical response. Charts of patients with spastic and hypertensive motility disorders diagnosed with HRM and treated with botulinum toxin were retrospectively reviewed at two centers. HRM recordings were systematically reanalyzed, and a patient's phone survey was conducted. Forty-five patients treated between 2008 and 2013 were included. Most patients had achalasia type 3 (22 cases). Other diagnoses were jackhammer esophagus (8 cases), distal esophageal spasm (7 cases), esophagogastric junction outflow obstruction (5 cases), nutcracker esophagus (1 case), and 2 unclassified cases. Botulinum toxin injections were performed into the cardia only in 9 cases, into the wall of the distal esophagus in 19 cases, and in both locations (cardia and distal esophagus) in 17 cases. No complication occurred in 31 cases. Chest pain was noticed for less than 7 days in 13 cases. One death related to mediastinitis occurred 3 weeks after botulinum toxin injection. Efficacy was assessed in 42 patients: 71% were significantly improved 2 months after botulinum toxin, and 57% remained satisfied for more than 6 months. No clear difference was observed in terms of response according to manometric diagnosis; however, type 3 achalasia previously dilated and with normal integrated relaxation pressure (4s-integrated relaxation pressure botulinum toxin. Endoscopic injections of botulinum toxin may be effective in some patients with spastic or hypercontractile esophageal motility disorders. The manometric Chicago classification diagnosis does not seem to predict the results. Prospective randomized trials are required to identify patients most likely to benefit from

  6. Botulinum toxin type A as treatment of partially accommodative esotropia.

    Science.gov (United States)

    Flores-Reyes, E M; Castillo-López, M G; Toledo-Silva, R; Vargas-Ortega, J; Murillo-Correa, C E; Aguilar-Ruiz, A

    2016-03-01

    To determine the effectiveness of a botulinum toxin type A injection in both medial rectus muscles in patients with partially accommodative esotropia. Residual deviation and stability of strabismus were evaluated at 18 months follow up. A prospective, analytical, quasi-experimental study was conducted on a cohort of 21 patients who underwent total cycloplegic refraction and with a residual deviation of at least 14 DP. A botulinum toxin type A dose of 5 IU was injected into each medial rectus muscle for a residual deviation greater than 18 DP, with a dose of 2.5 IU being used for a deviation between 14 and 18 DP. Multivariate logistic regression analyses were performed to relate residual deviation to variables recorded as potential predictors. A total of 21 patients were included, 33.3% (n=7) males and 66.6% (n=14) females. Mean visual acuity was -.28±.25 logMAR for right eye (range 0 to -1) and -.42±.31 logMAR for left eye (range 0 to -1.3). Mean angle of residual deviation before application of botulinum toxin was 40.95±8.6DP without spectacles correction, and 22.3±7.99 DP with full cycloplegic refraction. Adverse effects were ptosis in 14.2% (n=3), diplopia 23.8% (n=5), and vertical deviation in 33% (n=7). One patient had a poor outcome, therefore required surgical treatment. At one year follow up, 85.71% of patients showed good results with esotropia of 12 DP or less, dropping to 71.43% at 18 months of follow up. Botulinum toxin type A is an effective long-term treatment with a good response in 71.43% of patients. No predictors of good response were demonstrated. Copyright © 2015 Sociedad Española de Oftalmología. Published by Elsevier España, S.L.U. All rights reserved.

  7. Botulinum toxin for treatment of restrictive strabismus.

    Science.gov (United States)

    Merino, Pilar S; Vera, Rebeca E; Mariñas, Laura G; Gómez de Liaño, Pilar S; Escribano, Jose V

    To study the types of acquired restrictive strabismus treated in a tertiary hospital and the outcome of treatment with botulinum toxin. We performed a 10-year retrospective study of patients with restrictive strabismus aged ≥18 years who were treated with botulinum toxin. Treatment was considered successful if the final vertical deviation was ≤5 PD, horizontal deviation ≤10 PD, with no head turn or diplopia. We included 27 cases (mean age, 61.9 years). Horizontal strabismus was diagnosed in 11.1%, vertical in 51.9%, and mixed in 37%. Strabismus was secondary to cataract surgery in 6 cases, high myopia in 6, orbital fractures in 5, retinal surgery in 5, Graves ophthalmopathy in 4, and repair of conjunctival injury in 1 case. Diplopia was diagnosed in all patients, head turn in 33.3%. The initial deviation was 14 PD (range, 2-40), the mean number of injections per patient was 1.6 (range, 1-3), and the mean dose was 9.5 IU (range, 2.5-22.5). At the end of follow-up, diplopia was recorded in 59.3%, head turn in 18.5%, surgical treatment in 51.9%, and need for prism glasses in 14.8%. Outcome was successful in 37% of patients (4 high myopia, 3 orbital fractures, 2 post-surgical retinal detachment, and 1 post-cataract surgery). Mean follow-up was 3±1.8 years. Vertical deviation was observed in half of the sample. The most frequent deviation was secondary to cataract surgery and high myopia. Treatment with botulinum toxin was successful in one-third of the patients at the end of follow-up. Copyright © 2016 Spanish General Council of Optometry. Published by Elsevier España, S.L.U. All rights reserved.

  8. Botulinum toxin detection using AlGaN /GaN high electron mobility transistors

    Science.gov (United States)

    Wang, Yu-Lin; Chu, B. H.; Chen, K. H.; Chang, C. Y.; Lele, T. P.; Tseng, Y.; Pearton, S. J.; Ramage, J.; Hooten, D.; Dabiran, A.; Chow, P. P.; Ren, F.

    2008-12-01

    Antibody-functionalized, Au-gated AlGaN /GaN high electron mobility transistors (HEMTs) were used to detect botulinum toxin. The antibody was anchored to the gate area through immobilized thioglycolic acid. The AlGaN /GaN HEMT drain-source current showed a rapid response of less than 5s when the target toxin in a buffer was added to the antibody-immobilized surface. We could detect a range of concentrations from 1to10ng/ml. These results clearly demonstrate the promise of field-deployable electronic biological sensors based on AlGaN /GaN HEMTs for botulinum toxin detection.

  9. Botulinum toxin type a for chronic migraine.

    Science.gov (United States)

    Ashkenazi, Avi

    2010-03-01

    Chronic migraine (CM) is the leading cause of chronic daily headache, a common and debilitating headache syndrome. The management of CM patients is challenging, with only limited benefit from available oral preventive medications. Botulinum neurotoxin (BoNT) has been used extensively to treat disorders associated with increased muscle tone. More recent scientific data support an analgesic effect of the toxin. The pharmacokinetic and pharmacodynamic profiles of BoNT make it an appealing candidate for migraine prevention. Results from older clinical trials on the efficacy of the toxin in CM were inconclusive. However, recent trials using more stringent inclusion criteria have shown positive results, supporting the use of the toxin in some patients with this disorder. This review summarizes the scientific data on the analgesic properties of BoNT, as well as the clinical data on the efficacy of the toxin in treating CM.

  10. Binding properties of Clostridium botulinum type C progenitor toxin to mucins.

    Science.gov (United States)

    Nakamura, Toshio; Takada, Noriko; Tonozuka, Takashi; Sakano, Yoshiyuki; Oguma, Keiji; Nishikawa, Atsushi

    2007-04-01

    It has been reported that Clostridium botulinum type C 16S progenitor toxin (C16S toxin) first binds to the sialic acid on the cell surface of mucin before invading cells [A. Nishikawa, N. Uotsu, H. Arimitsu, J.C. Lee, Y. Miura, Y. Fujinaga, H. Nakada, T. Watanabe, T. Ohyama, Y. Sakano, K. Oguma, The receptor and transporter for internalization of Clostridium botulinum type C progenitor toxin into HT-29 cells, Biochem. Biophys. Res. Commun. 319 (2004) 327-333]. In this study we investigated the binding properties of the C16S toxin to glycoproteins. Although the toxin bound to membrane blotted mucin derived from the bovine submaxillary gland (BSM), which contains a lot of sialyl oligosaccharides, it did not bind to neuraminidase-treated BSM. The binding of the toxin to BSM was inhibited by N-acetylneuraminic acid, N-glycolylneuraminic acid, and sialyl oligosaccharides strongly, but was not inhibited by neutral oligosaccharides. Both sialyl alpha2-3 lactose and sialyl alpha2-6 lactose prevented binding similarly. On the other hand, the toxin also bound well to porcine gastric mucin. In this case, neutral oligosaccharides might play an important role as ligand, since galactose and lactose inhibited binding. These results suggest that the toxin is capable of recognizing a wide variety of oligosaccharide structures.

  11. Safety of Ultrasound-Guided Botulinum Toxin Injections for Sialorrhea as Performed by Pediatric Otolaryngologists.

    Science.gov (United States)

    Shariat-Madar, Bahbak; Chun, Robert H; Sulman, Cecille G; Conley, Stephen F

    2016-05-01

    To evaluate incidence of complications and hospital readmission as a result of ultrasound-guided botulinum toxin injections to manage sialorrhea. Case series with chart review. Children's Hospital of Wisconsin. A case series with chart review was performed of all cases of ultrasound-guided injection of botulinum toxin by pediatric otolaryngologists from March 5, 2010, to September 26, 2014,. Primary outcomes included complications such as dysphagia, aspiration pneumonia, and motor paralysis. Secondary outcomes included hospitalization, intubation, and nasogastric tube placement. There were 48 patients, 111 interventions, and 306 intraglandular injections identified. Botulinum toxin type A and type B were utilized in 4 and 107 operative interventions, respectively. Type A was injected into 4 parotid and 4 submandibular glands, utilizing doses of 20 U per parotid and 30 U per submandibular gland. Type B was injected into 98 parotid and 200 submandibular glands, with average dosing of 923 U per parotid and 1170 U per submandibular gland, respectively. There were 2 instances of subjectively worsening of baseline dysphagia that self-resolved. No cases were complicated by aspiration pneumonia or motor paralysis. No patients required hospital readmission, intubation, or nasogastric tube placement. Prior published data indicated 16% complication incidence with ultrasound-guided injection of botulinum toxin. Our study found a low complication rate (0.6%) with ultrasound-guided injections of botulinum toxin to manage sialorrhea, without cases of aspiration pneumonia or motor paralysis. Of 306 intraglandular injections, there were 2 cases of worsening baseline subjective dysphagia that self-resolved. © American Academy of Otolaryngology—Head and Neck Surgery Foundation 2016.

  12. Serial Casting as an Adjunct to Botulinum Toxin Type A Treatment in Children With Cerebral Palsy and Spastic Paraparesis With Scissoring of the Lower Extremities.

    Science.gov (United States)

    Dai, Alper I; Demiryürek, Abdullah T

    2017-06-01

    The purpose of this study was to examine whether combination therapy of serial casting and botulinum toxin type A injection can further enhance the effects of botulinum toxin type A in children with cerebral palsy with scissoring of both legs. This study was a prospective and randomized trial. The children were divided into 2 groups, one of which received serial casting after botulinum toxin type A (n = 40), and the other which only received botulinum toxin type A (n = 40). Serial casting started 3 weeks after the botulinum toxin type A. Both groups received physiotherapy. Groups were assessed at baseline then compared at 6 and 12 weeks following the intervention. Significant improvements in Gross Motor Function Measure-66 and Caregiver Health Questionnaire were recorded in both groups ( P botulinum toxin type A in the serial casting group ( P botulinum toxin type A only group. These results suggest that serial casting after botulinum toxin type A can enhance the benefits of botulinum toxin type A in children with cerebral palsy.

  13. Optimal Dosing of Botulinum Toxin for Treatment of Chronic Anal Fissure: A Systematic Review and Meta-Analysis.

    Science.gov (United States)

    Lin, Jin Xin; Krishna, Sanjeev; Su'a, Bruce; Hill, Andrew G

    2016-09-01

    Chronic anal fissures are associated with significant morbidity and reduced quality of life. Studies have investigated the efficacy of botulinum toxin with variable results; thus, there is currently no consensus on botulinum toxin dose or injection sites. This study aimed to systematically analyze trials studying the efficacy of botulinum toxin for treatment of chronic anal fissure to identify an optimum dosage and injection regimen. A comprehensive review of the literature was conducted according to PRISMA guidelines. PubMed/Medline, Embase, Scopus, and the Cochrane Library were searched from inception to June 2015. All clinical trials that investigated the efficacy of botulinum toxin for chronic anal fissure were selected according to specific criteria. The interventions used were various doses of botulinum toxin. Clinical outcomes, dosage, and injection site data were evaluated with weighted pooled results for each dosage and 95% confidence intervals. There were 1158 patients, with 661 in botulinum toxin treatment arms, from 18 clinical trials included in this review. The outcomes of interest were 3-month healing, incontinence, and recurrence rates. Meta-regression analysis demonstrated a small decrease in healing rate (0.34%; 95% CI, 0-0.68; p = 0.048) with each increase in dosage, a small increase in incontinence rate (1.02 times; 95% CI, 1.0002-1.049; p = 0.048) with each increase in dosage and a small increase in recurrence rate (1.037 times; 95% CI, 1.018-1.057; p = 0.0002) with each increase in dosage. The optimum injection site could not be determined. This study was limited by weaknesses in the underlying evidence, such as variable quality, short follow-up, and a limited range of doses represented. Fissure healing with lower doses of botulinum toxin is as effective as with high doses. Lower doses also reduce the risk of incontinence and recurrence in the long term.

  14. Dramatic changes in muscle contractile and structural properties after 2 botulinum toxin injections.

    Science.gov (United States)

    Minamoto, Viviane B; Suzuki, Kentaro P; Bremner, Shannon N; Lieber, Richard L; Ward, Samuel R

    2015-10-01

    Botulinum toxin is frequently administered serially to maintain therapeutic muscle paralysis, but the effect of repeated doses on muscle function are largely unknown. This study characterized the muscle response to 2 onabotulinum toxin (BoNT) injections separated by 3 months. Animal subjects received a single toxin injection (n = 8), 2 BoNT injections separated by 3 months (n = 14), or 1 BoNT and 1 saline injection separated by 3 months (n = 8). The functional effect of 2 serial injections was exponentially greater than the effect of a single injection. While both groups treated with a single BoNT injection had decreased torque in the injected leg by approximately 50% relative to contralateral legs, the double BoNT injected group had decreased torque by over 95% relative to the preinjection level. Both single and double BoNT injections produced clear signs of fiber-type grouping. These experiments demonstrate a disproportionately greater effect of repeated BoNT injections. © 2015 Wiley Periodicals, Inc.

  15. Pneumatic dilation and botulinum toxin: when and why?

    Science.gov (United States)

    Bozzi, Rosamaria; Di Martino, Vincenzo; Inzirillo, Antonio; D'Avenia, Eugenio; Inzirillo, Maurizio; Cattaneo, Fabio; Cattaneo, Domenico

    2013-01-01

    Pneumatic dilation and botulinum toxin:when and why? The endoscopic treatment options of achalasia include botulinum toxin (BT) injection and pneumatic dilation (PD) of the lower esophageal sphincter (LES). BT can reduce the LES pressure by blocking the release of acetylcoline from presynaptic cholinergic nerve terminals in the myenteric plexus. Although the procedure is safe and good initial response is reported, there is a wide variability in the duration of the response and the effect tends to decrease over time. BT is usually recommended for elderly patients or patients with comorbid illnesses, who are poor candidates for more invasive procedures. PD aims at tearing the muscle fibers of the LES and is considered the most effective nonsurgical treatment for achalasia. Technical details of the procedure vary in different institutions and in many clinical settings the choice between PD or minimally invasive surgical myotomy depends upon local expertise in the procedures. Further endoscopic treatment options such as submucosal esophageal myotomy or self-expanding metallic stents are being studied.

  16. Botulinum toxin for conditions of the female pelvis.

    Science.gov (United States)

    El-Khawand, Dominique; Wehbe, Salim; Whitmore, Kristene

    2013-07-01

    Botulinum toxin has recently been approved by the Food and Drug Administration (FDA) for the treatment of urinary incontinence associated with neurogenic detrusor overactivity. However, it has also been used off-label for a multitude of other conditions in the female pelvis, including urological, gynecological, and colorectal. This article reviews the most recent data regarding its efficacy and safety, and administration techniques for those conditions. A literature review of the most relevant reports published between 1985 and 2012. Urinary incontinence related to neurogenic detrusor overactivity is currently the only approved indication in the female pelvis. Other supported off-label uses include: idiopathic detrusor overactivity, interstitial cystitis/bladder pain syndrome, detrusor sphincter dyssynergia, high-tone pelvic floor dysfunction, anal fissure, anismus, and functional anal pain. Botulinum toxin may effectively and safely be used in many conditions of the female pelvis. More high quality research is needed to better clarify its role in the therapeutic algorithm for those indications.

  17. Effect of a clown's presence at botulinum toxin injections in children: a randomized, prospective study

    DEFF Research Database (Denmark)

    Hansen, Lars Kjaersgaard; Kibæk, Maria; Martinussen, Torben

    2011-01-01

    The effect of the presence of a hospital clown during pediatric procedures has rarely been evaluated. In a pediatric ward, botulinum toxin injection is a painful procedure and a stressful experience for the child. We undertook a study of the effect of the presence of a hospital clown on children...... treated with botulinum toxin in an outpatient setting....

  18. Botulinum toxin (BoNT) and back pain.

    Science.gov (United States)

    Porta, Mauro; Maggioni, G

    2004-02-01

    Myofascial pain syndrome is defined as subacute or chronic pain with sensory, motor and autonomic symptoms referred from active trigger points with associated painful dysfunctions. Authors present the usefulness of botulinum toxin A or B (BoNT/A or BoNT/B) injected into target muscles since the toxin is capable of controlling not only the muscular spasm but mostly the pain by alternative mechanisms of action, which are discussed. Posology of BoNT, technical aspects and results are presented. BoNT represents an interesting and useful tool for an adequate management of patients with myofascial pain.

  19. Effect of sodium nitrite on toxin production by Clostridium botulinum in bacon.

    Science.gov (United States)

    Christiansen, L N; Tompkin, R B; Shaparis, A B; Kueper, T V; Johnston, R W; Kautter, D A; Kolari, O J

    1974-04-01

    Pork bellies were formulated to 0, 30, 60, 120, 170, or 340 mug of nitrite per g of meat and inoculated with Clostridium botulinum via pickle or after processing and slicing. Processed bacon was stored at 7 or 27 C and assayed for nitrite, nitrate, and botulinal toxin at different intervals. Nitrite levels declined during processing and storage. The rate of decrease was more rapid at 27 than at 7 C. Although not added to the system, nitrate was detected in samples during processing and storage at 7 and 27 C. The amount of nitrate found was related to formulated nitrite levels. No toxin was found in samples incubated at 7 C throughout the 84-day test period. At 27 C, via pickle, inoculated samples with low inoculum (210 C. botulinum per g before processing and 52 per g after processing) became toxic if formulated with 120 mug of nitrite per g of meat or less. Toxin was not detected in bacon formulated with 170 or 340 mug of nitrite per g of meat under these same conditions. Toxin was detected at all formulated nitrite levels in bacon inoculated via the pickle with 19,000 C. botulinum per g (4,300 per g after processing) and in samples inoculated after slicing. However, increased levels of formulated nitrite decreased the probability of botulinal toxin formation in bacon inoculated by both methods.

  20. The role of botulinum toxin in vasospastic disorders of the hand.

    Science.gov (United States)

    Neumeister, Michael W

    2015-02-01

    Raynaud phenomenon may be a primary disorder or associated with a variety of other autoimmune processes. Raynaud phenomenon produces digital vasospasm, which can lead to ischemia and ulceration. The treatment of Raynaud phenomenon has been difficult because multiple medical treatments have not provided uniform resolution of symptoms. Many patients have turned to surgery and sympathectomies for the treatment of unrelenting vasospasm. Botulinum toxin has been shown to be an effective alternative to surgery, with a single treatment being capable of resolving pain and healing ulcer. This article reviews the use of botulinum toxin for the treatment of Raynaud phenomenon. Copyright © 2015 Elsevier Inc. All rights reserved.

  1. Towards new uses of botulinum toxin as a novel therapeutic tool.

    Science.gov (United States)

    Pickett, Andy; Perrow, Karen

    2011-01-01

    The uses of botulinum toxin in the fields of neurology, ophthalmology, urology, rehabilitation medicine and aesthetic applications have been revolutionary for the treatment of patients. This non-invasive therapeutic has continually been developed since first discovered in the 1970s as a new approach to what were previously surgical treatments. As these applications develop, so also the molecules are developing into tools with new therapeutic properties in specific clinical areas. This review examines how the botulinum toxin molecule is being adapted to new therapeutic uses and also how new areas of use for the existing molecules are being identified. Prospects for future developments are also considered.

  2. Towards New Uses of Botulinum Toxin as a Novel Therapeutic Tool

    Directory of Open Access Journals (Sweden)

    Karen Perrow

    2011-01-01

    Full Text Available The uses of botulinum toxin in the fields of neurology, ophthalmology, urology, rehabilitation medicine and aesthetic applications have been revolutionary for the treatment of patients. This non-invasive therapeutic has continually been developed since first discovered in the 1970s as a new approach to what were previously surgical treatments. As these applications develop, so also the molecules are developing into tools with new therapeutic properties in specific clinical areas. This review examines how the botulinum toxin molecule is being adapted to new therapeutic uses and also how new areas of use for the existing molecules are being identified. Prospects for future developments are also considered.

  3. Bruxism secondary to brain injury treated with Botulinum toxin-A: a case report

    Science.gov (United States)

    El Maaytah, Mohammed; Jerjes, Waseem; Upile, Tahwinder; Swinson, Brian; Hopper, Colin; Ayliffe, Peter

    2006-01-01

    We report a successful treatment of bruxism in a patient with anoxic brain injury using botulinum toxin-A (BTX-A). On examination the mouth opening was 0 mm, no feeding was possible through the mouth. Botulinum toxin was injected into the masseter and temporalis; great improvement in trismus and bruxism was noted after 3 weeks. One further treatment improved the mouth opening on the following week and the patient was discharged from our care to be reviewed when required. PMID:17123443

  4. Regulation of Botulinum Neurotoxin Synthesis and Toxin Complex Formation by Arginine and Glucose in Clostridium botulinum ATCC 3502.

    Science.gov (United States)

    Fredrick, Chase M; Lin, Guangyun; Johnson, Eric A

    2017-07-01

    Botulinum neurotoxin (BoNT), produced by neurotoxigenic clostridia, is the most potent biological toxin known and the causative agent of the paralytic disease botulism. The nutritional, environmental, and genetic regulation of BoNT synthesis, activation, stability, and toxin complex (TC) formation is not well studied. Previous studies indicated that growth and BoNT formation were affected by arginine and glucose in Clostridium botulinum types A and B. In the present study, C. botulinum ATCC 3502 was grown in toxin production medium (TPM) with different levels of arginine and glucose and of three products of arginine metabolism, citrulline, proline, and ornithine. Cultures were analyzed for growth (optical density at 600 nm [OD 600 ]), spore formation, and BoNT and TC formation by Western blotting and immunoprecipitation and for BoNT activity by mouse bioassay. A high level of arginine (20 g/liter) repressed BoNT production approximately 1,000-fold, enhanced growth, slowed lysis, and reduced endospore production by greater than 1,000-fold. Similar effects on toxin production were seen with equivalent levels of citrulline but not ornithine or proline. In TPM lacking glucose, levels of formation of BoNT/A1 and TC were significantly decreased, and extracellular BoNT and TC proteins were partially inactivated after the first day of culture. An understanding of the regulation of C. botulinum growth and BoNT and TC formation should be valuable in defining requirements for BoNT formation in foods and clinical samples, improving the quality of BoNT for pharmaceutical preparations, and elucidating the biological functions of BoNTs for the bacterium. IMPORTANCE Botulinum neurotoxin (BoNT) is a major food safety and bioterrorism concern and is also an important pharmaceutical, and yet the regulation of its synthesis, activation, and stability in culture media, foods, and clinical samples is not well understood. This paper provides insights into the effects of critical

  5. The point-touch technique for botulinum toxin injection in adductor spasmodic dysphonia: quality of life assessment.

    Science.gov (United States)

    Morzaria, S; Damrose, E J

    2011-07-01

    Botulinum toxin injection under electromyographic guidance is the 'gold standard' for adductor spasmodic dysphonia treatment. The point-touch technique, an alternative injection method which relies on anatomical landmarks, is cheaper, quicker and more accessible, but has not yet gained widespread acceptance due to concerns about patient satisfaction. To assess swallowing and voice-related quality of life following point-touch botulinum toxin injection in adductor spasmodic dysphonia patients. Stanford University Voice and Swallowing Center. Prospective case series (evidence level four). Consecutive adductor spasmodic dysphonia patients with a stable botulinum toxin dose-response relationship were recruited prospectively. The Eating Assessment Tool and Voice-Related Quality of Life questionnaires were completed pre-treatment and at 10 and 30 per cent completion of the injection cycle, respectively. Thirty-seven patients completed follow up. The mean total botulinum toxin dose was 0.88 units. Pre-treatment Voice-Related Quality of Life questionnaire results reflected the burden of disease. Post-treatment Eating Assessment Tool and Voice-Related Quality of Life questionnaire results were collected at 2.53 and 7.84 weeks, respectively; the former showed an increase in dysphagia, albeit statistically insignificant, while the latter showed significantly improved scores (both domain and total). The point-touch technique is a viable alternative for botulinum toxin injection in the treatment of adductor spasmodic dysphonia.

  6. [Botulism: structure and function of botulinum toxin and its clinical application].

    Science.gov (United States)

    Oguma, Keiji; Yamamoto, Yumiko; Suzuki, Tomonori; Fatmawati, Ni Nengah Dwi; Fujita, Kumiko

    2012-08-01

    Clostridium botulinum produces seven immunological distinct poisonous neurotoxins, A to G, with molecular masses of approximately 150kDa. In acidic foods and culture fluid, the neurotoxins associate with non-toxic components, and form large complexes designated progenitor toxins. The progenitor toxins are found in three forms named LL, L, and M. These neurotoxins and progenitor toxins were purified, and whole nucleotide sequences of their structure genes were determined. In this manuscript, the structure and function of these toxins, and the application of these toxins to clinical usage have been described.

  7. Effect of Cultured Celery Juice, Temperature, and Product Composition on the Inhibition of Proteolytic Clostridium botulinum Toxin Production.

    Science.gov (United States)

    Golden, Max C; Wanless, Brandon J; David, Jairus R D; Kottapalli, Bala; Lineback, D Scott; Talley, Ryan J; Glass, Kathleen A

    2017-08-01

    Clostridium botulinum may be of concern in prepared refrigerated meals, for which strict cold chain management cannot be guaranteed. This study evaluated the effect of temperature, product composition, and cultured celery juice powder (CCJP) as a source of nitrite on the inhibition of botulinum toxin formation in two experimental (meat- and vegetable-based) prepared meals. Data obtained from the challenge study were compared with a published mathematical model to determine whether the model is fail-safe with regard to the tested meals. Treatments were inoculated with proteolytic C. botulinum, vacuum packaged, cooked at 90°C for 10 min, and assayed for botulinum toxin at appropriate intervals in samples stored at 10, 15, or 20°C for up to 8 weeks. None of the treatments stored at 10°C for 8 weeks supported toxin production by proteolytic C. botulinum. The addition of CCJP delayed toxin production by 1 and 3 weeks in cauliflower potatoes and in Dijon pork, respectively, stored at 15°C. Toxin production was delayed by 1 week at 20°C when CCJP was added to the cauliflower potatoes. This study found that the predictive model was fail-safe but was overly conservative for the experimental meals described. Finally, this study confirms that product composition, the addition of nitrite via CCJP, storage time, and temperature play important roles in the inhibition of toxin formation by proteolytic C. botulinum.

  8. [Treatment of proctalgia fugax with botulinum toxin: results in 5 patients].

    Science.gov (United States)

    Sánchez Romero, A M; Arroyo Sebastián, A; Pérez Vicente, F A; Serrano Paz, P; Candela Polo, F; Calpena Rico, R

    2006-03-01

    Proctalgia fugax can be defined as transitory but recurrent anal pain. Although its etiology remains unknown, an internal anal sphincter spasm seems to be the most likely, so that the different treatments focus on reducing the pressure of the internal anal sphincter. This study is aimed at evaluating the effectiveness of botulinum A toxin in the treatment of proctalgia fugax. Prospective clinical trial of patients with proctalgia fugax treated with botulinum A toxin at the Outpatient Clinic attached to the Coloproctogy Unit, University Hospital of Elche, from January 1999 to January 2002. The patients included in the study underwent rectal digital examination, anuscopy, rectoscopy, anal manometry and ultrasonography, barium enema and pelvic CT scan to rule out any organic cause for anal pain. The treatment consisted of 25 IU of botulinum A toxin, with a supplementary dose of 50 IU in those patients with persistence of anal pain episodes within the next two months. The patients were reviewed on the first week, second month, sixth month and first and second year. Anal pain was measured by the patients, using a linear analogue scale from 0 to 10, and continence was assessed at every visit using the Cleveland Continence Grading Scale. Five patients were recluted for the study, with a predominance of females (4 vs. 1). Mean age was 45 years. Length of symptoms prior to the treatment was 13 months (range: 6-18 months). Only one female patient required a second dose of botulinum A toxin to handle the anal pain. All the patients healed and remained free of pain up to finishing the follow-up. There were no local complications. Anal manometry showed an increased MRP (mean resting pressure) in comparison to a control group of patients (114 mmHg vs. 66 mmHg; p proctalgia fugax.

  9. Botulinum toxin injection causes hyper-reflexia and increased muscle stiffness of the triceps surae muscle in the rat

    DEFF Research Database (Denmark)

    Pingel, Jessica; Wienecke, Jacob; Lorentzen, Jakob

    2016-01-01

    Botulinum toxin is used to diminish spasticity and reduce the risk of development of contractures. Here, we investigated changes in muscle stiffness caused by reflex activity or elastic muscle properties following botulinum toxin injection in the triceps surae muscle in rats. Forty-four rats...... received injection of botulinum toxin in the left triceps surae muscle. Control measurements were performed on the non-injected contralateral side in all rats. Acute experiments were performed 1, 2, 4 and 8 weeks following injection. The triceps surae muscle was dissected free, the Achilles tendon was cut...... and attached to a muscle puller. The resistance of the muscle to stretches of different amplitudes and velocities was systematically investigated. Reflex mediated torque was normalized to the maximal muscle force (Mmax) evoked by supramaximal stimulation of the tibial nerve. Botulinum toxin injection caused...

  10. Use of botulinum A toxin for proctalgia fugax—a case report of successful treatment

    OpenAIRE

    Grigoriou, Marios; Ioannidis, Aristeidis; Kofina, Konstantinia; Efthimiadis, Christoforos

    2017-01-01

    Abstract Proctalgia fugax is considered as intermittent anal pain of unknown etiology; a variety of treatments have been used, without, however, permanent results. Injection of botulinum A toxin is recently suggested as an alternative option. We present the case of a woman presenting proctalgia fugax that was untreatable through other current forms of treatment. After two administrations of botulinum A toxin, 80 units and 100 units each, the patient remained asymptomatic on 8-month follow-up ...

  11. Calf muscle volume estimates: Implications for Botulinum toxin treatment?

    DEFF Research Database (Denmark)

    Bandholm, Thomas; Sonne-Holm, Stig; Thomsen, Carsten

    2007-01-01

    An optimal botulinum toxin dose may be related to the volume of the targeted muscle. We investigated the suitability of using ultrasound and anthropometry to estimate gastrocnemius and soleus muscle volume. Gastrocnemius and soleus muscle thickness was measured in 11 cadaveric human legs, using...

  12. Incidental Treatment of a Subclinical Chronic Tension-Type Headache by Cosmetic Use of Botulinum Toxin A: A Case Report

    Directory of Open Access Journals (Sweden)

    Iselin Saltvig

    2017-11-01

    Full Text Available Background: Headache is a common disorder of the nervous system; chronic headache in particular may affect quality of life negatively. The pathophysiology is multifactorial and not completely elucidated. Studies have demonstrated the beneficial effects of botulinum toxin A on chronic migraine headaches, but failed to show the same effect on chronic tension-type headaches. Methods: We present the case of a 32-year-old woman who after receiving cosmetic injections with botulinum toxin A for fine lines of the forehead experienced relief of subclinical tension-type headaches. Conclusions: Although the effect of botulinum toxin A on chronic tension-type headaches is limited, several studies demonstrate its pain-modulating effects, and as such it is worth paying attention to this potential beneficial effect when performing cosmetic injections with botulinum toxin A.

  13. Botulinum toxin injection causes hyper-reflexia and increased muscle stiffness of the triceps surae muscle in the rat.

    Science.gov (United States)

    Pingel, Jessica; Wienecke, Jacob; Lorentzen, Jakob; Nielsen, Jens Bo

    2016-12-01

    Botulinum toxin is used with the intention of diminishing spasticity and reducing the risk of development of contractures. Here, we investigated changes in muscle stiffness caused by reflex activity or elastic muscle properties following botulinum toxin injection in the triceps surae muscle in rats. Forty-four rats received injection of botulinum toxin in the left triceps surae muscle. Control measurements were performed on the noninjected contralateral side in all rats. Acute experiments were performed, 1, 2, 4, and 8 wk following injection. The triceps surae muscle was dissected free, and the Achilles tendon was cut and attached to a muscle puller. The resistance of the muscle to stretches of different amplitudes and velocities was systematically investigated. Reflex-mediated torque was normalized to the maximal muscle force evoked by supramaximal stimulation of the tibial nerve. Botulinum toxin injection caused severe atrophy of the triceps surae muscle at all time points. The force generated by stretch reflex activity was also strongly diminished but not to the same extent as the maximal muscle force at 2 and 4 wk, signifying a relative reflex hyperexcitability. Passive muscle stiffness was unaltered at 1 wk but increased at 2, 4, and 8 wk (P botulinum toxin causes a relative increase in reflex stiffness, which is likely caused by compensatory neuroplastic changes. The stiffness of elastic elements in the muscles also increased. The data are not consistent with the ideas that botulinum toxin is an efficient antispastic medication or that it may prevent development of contractures. Copyright © 2016 the American Physiological Society.

  14. Centrifugal microfluidic platform for ultrasensitive detection of Botulinum Toxin

    Science.gov (United States)

    Botulinum neurotoxin – a global public health threat and category A bioterrorism agent - is the most toxic substance known and one of the most challenging toxins to detect due to its lethality at extremely low concentrations. Hence the live-mouse bioassay because of its superior sensitivity, remains...

  15. [Medical care of patients with spasticity following stroke : Evaluation of the treatment situation in Germany with focus on the use of botulinum toxin].

    Science.gov (United States)

    Kerkemeyer, L; Lux, G; Walendzik, A; Wasem, J; Neumann, A

    2017-08-01

    Upper limb spasticity is a common complication following stroke. Cohort studies found 19% of post-stroke patients had upper limb spasticity at 3 months and 38% of patients at 12 months. For focal spasticity, intramuscular injections of botulinum toxin are indicated. In Germany, it is assumed that patients with the described indication are undersupplied with botulinum toxin. The aim of the present study is to evaluate the medical care of patients with upper limb spasticity post-stroke with the focus on the use of botulinum toxin as one treatment option. A standardized questionnaire was developed and a postal survey of a representative national random sample of 800 neurologists to capture the actual medical care situation. The response rate amounted to 37% (n = 292). 59% of the neurologists surveyed had never used botulinum toxin. In total, 87% of neurologists noticed barriers regarding the use of botulinum toxin, where the amount of the doctor's remuneration in 40% and the lack of reimbursement of costs in off-label use in 60% were the most commonly used answers. The achievement of an advanced training in using botulinum toxin was also stated as a general obstacle for resident neurologists. Due to a response rate of 37% for the postal survey a selection bias cannot be excluded. Although botulinum toxin is recommended in the national treatment guidelines, many neurologists do not use botulinum toxin. The reasons can be seen from the barriers described.

  16. Occlusion therapy of unilateral amblyopia with botulinum toxin induced ptosis.

    Science.gov (United States)

    Halkiadakis, Ioannis; Iliaki, Olga; Kalyvianaki, Maria I; Tsilimbaris, Miltiadis K

    2007-01-01

    In order to evaluate the role of botulinum toxin induced ptosis as an occlusion method to treat unilateral deep strabismic amblyopia in two uncooperative children, we injected 0.2 ml of diluted botulinum toxin in the levator palpaebrae; low sedation was necessary in one of the two children. In both cases a marked ptosis was achieved, which lasted about four weeks and then gradually resolved completely. The visual acuity of the ablyopic eye increased in both children, making patching easy thereafter. One child developed amblyopia in the injected eye, which was handled successfully using part-time occlusion. No other side effects were noted. Whether this new method could be a simple, safe and effective alternative method of occlusion for the treatment of deep amblyopia in uncooperative children needs to be proven with a larger series of children.

  17. Intramural injection with botulinum toxin significantly elongates the pig esophagus

    DEFF Research Database (Denmark)

    Larsen, Heidi Fhær; Jensen, Thorbjørn Søren Rønn; Rasmussen, Lars

    2013-01-01

    Surgical treatment of long-gap esophageal atresia (LGEA) is challenging. Methods which facilitate stretching of the esophageal pouches may allow primary anastomosis. Botulinum toxin type A (BTX-A) blocks acetylcholine release in neuromuscular junctions, thereby causing muscle relaxation. We...

  18. A pilot study to evaluate effectiveness of botulinum toxin in treatment of androgenetic alopecia in males

    Directory of Open Access Journals (Sweden)

    Sehdev Singh

    2017-01-01

    Full Text Available Introduction: Androgenetic alopecia is a common form of alopecia with multifactorial etiology. Finasteride and minoxidil are approved by the FDA for the treatment of androgenetic alopecia. Balding scalp is believed to have relative microvascular insufficiency. Blood vessels in the scalp travel through the intramuscular plane. Intramuscular injection of botulinum toxin relaxes muscles and thereby increases blood flow in balding scalp. We conducted a pilot study to evaluate the efficacy of botulinum toxin in androgenetic alopecia management. Material and Methods: The study was conducted in a tertiary care center. A total of 10 male patients with androgenetic alopecia meeting inclusion criteria of the study were included. In the scalp, 30 sites were injected with 5 U of botulinum toxin in each site. Preprocedure photograph taken and evaluation was done, which was repeated after 24 weeks. Efficacy was assessed by photography and self-assessment scoring was done by patients. Results: Of 10 patients, 8 had good to excellent response on photographic assessment. At the end of 24 weeks, 1 patient showed poor and 1 showed fair response to treatment. As per self-assessment, 7of 10 patients showed good to excellent response. Two patients had fair response and 1 patient showed poor response to treatment. Conclusion: Botulinum toxin was found to be safe and effective therapy for the management of androgenetic alopecia in this pilot study. Studies with larger sample size and randomized controlled trials are required to establish the role of botulinum toxin in the management of androgenetic alopecia.

  19. Primary hyperhidrosis: Implications on symptoms, daily life, health and alcohol consumption when treated with botulinum toxin.

    Science.gov (United States)

    Shayesteh, Alexander; Boman, Jens; Janlert, Urban; Brulin, Christine; Nylander, Elisabet

    2016-08-01

    Primary hyperhidrosis affects approximately 3% of the population and reduces quality of life in affected persons. Few studies have investigated the symptoms of anxiety, depression and hazardous alcohol consumption among those with hyperhidrosis and the effect of treatment with botulinum toxin. The first aim of this study was to investigate the effect of primary hyperhidrosis on mental and physical health, and alcohol consumption. Our second aim was to study whether and how treatment with botulinum toxin changed these effects. One hundred and fourteen patients answered questionnaires regarding hyperhidrosis and symptoms, including hyperhidrosis disease severity scale (HDSS), visual analog scale (VAS) 10-point scale for hyperhidrosis symptoms, hospital anxiety and depression scale (HADS), alcohol use disorder identification test (AUDIT) and short-form health survey (SF-36) before treatment with botulinum toxin and 2 weeks after. The age of onset of hyperhidrosis was on average 13.4 years and 48% described heredity for hyperhidrosis. Significant improvements were noted in patients with axillary and palmar hyperhidrosis regarding mean HDSS, VAS 10-point scale, HADS, SF-36 and sweat-related health problems 2 weeks after treatment with botulinum toxin. Changes in mean AUDIT for all participants were not significant. Primary hyperhidrosis mainly impairs mental rather than physical aspects of life and also interferes with specific daily activities of the affected individuals. Despite this, our patients did not show signs of anxiety, depression or hazardous alcohol consumption. Treatment with botulinum toxin reduced sweat-related problems and led to significant improvements in HDSS, VAS, HADS and SF-36 in our patients. © 2016 Japanese Dermatological Association.

  20. Assessing adverse effects of intra-articular botulinum toxin A in healthy Beagle dogs: A placebo-controlled, blinded, randomized trial.

    Science.gov (United States)

    Heikkilä, Helka M; Jokinen, Tarja S; Syrjä, Pernilla; Junnila, Jouni; Hielm-Björkman, Anna; Laitinen-Vapaavuori, Outi

    2018-01-01

    To investigate the clinical, cytological, and histopathological adverse effects of intra-articularly injected botulinum toxin A in dogs and to study whether the toxin spreads from the joint after the injection. A longitudinal, placebo-controlled, randomized clinical trial was conducted with six healthy laboratory Beagle dogs. Stifle joints were randomized to receive either 30 IU of onabotulinum toxin A or placebo in a 1:1 ratio. Adverse effects and spread of the toxin were examined by evaluating dynamic and static weight-bearing of the injected limbs, by assessing painless range of motion and pain on palpation of joints, and by performing synovial fluid analysis, neurological examination, and electrophysiological recordings at different examination time-points in a 12-week period after the injections. The dogs were then euthanized and autopsy and histopathological examination of joint structures and adjacent muscles and nerves were performed. Intra-articular botulinum toxin A did not cause local weakness or injection site pain. Instead, static weight-bearing and painless range of motion of stifle joints decreased in the placebo limbs. No clinically significant abnormalities associated with intra-articular botulinum toxin A were detected in the neurological examinations. Electrophysiological recordings showed low compound muscle action potentials in two dogs in the botulinum toxin A-injected limb. No significant changes were detected in the synovial fluid. Autopsy and histopathological examination of the joint and adjacent muscles and nerves did not reveal histopathological adverse effects of the toxin. Intra-articular botulinum toxin A does not produce significant clinical, cytological, or histopathological adverse effects in healthy dogs. Based on the electrophysiological recordings, the toxin may spread from the joint, but its clinical impact seems to be low.

  1. Botulinum toxin A for treatment of neurogenic detrusor overactivity and incontinence in patients with spinal cord lesions

    DEFF Research Database (Denmark)

    Bagi, Per; Biering-Sørensen, Fin

    2004-01-01

    To evaluate the efficacy of intravesical botulinum toxin A (BTA) in the treatment of severe neurogenic detrusor overactivity (NDO) with incontinence in patients with spinal cord lesions (SCLs).......To evaluate the efficacy of intravesical botulinum toxin A (BTA) in the treatment of severe neurogenic detrusor overactivity (NDO) with incontinence in patients with spinal cord lesions (SCLs)....

  2. Botulinum toxin injection in laryngeal dyspnea.

    Science.gov (United States)

    Woisard, Virginie; Liu, Xuelai; Bes, Marie Christine Arné; Simonetta-Moreau, Marion

    2017-02-01

    Data, regarding the use of botulinum toxin (BT-A) in laryngeal dyspnea, are scarce, coming from some cases reports in the literature, including Vocal fold paralysis, laryngeal dystonia, vocal cord dysfunction also called paradoxical motion of the vocal fold (PMVF), and post-neuroleptic laryngeal dyskinesia. There is no consensus regarding the muscles and the doses to inject. The aim of this study is to present a retrospective review of patients treated in our ENT Department by BT-A injection in this indication. This study is a retrospective study describing patients who underwent an injection of botulinum toxin for laryngeal dyspnea in the ENT Department from 2005 to 2015 years. The inclusion criteria were a dyspnea associated with a laryngeal dysfunction, confirmed by flexible fiberoptic nasopharyngolaryngoscopy. Information concerning the causes of the dyspnea, the botulinum toxin BT-A injections procedure, post-injection follow-up, and respiratory outcome were collected for all patients included. In the group of 13 patients included, the main cause identified as principal factor linked with the short breath was: a bilateral VF paralysis (Patel et al., Otolaryngol Head Neck Surg 130:686-689, 7), laryngeal dystonia (Balkissoon and Kenn, Semin Respir Crit Care Med 33:595-605, 2), Anxiety syndrome associated with unilateral vocal fold paralysis or asthma (Marcinow et al., Laryngoscope 124:1425-1430, 3), and an isolated asthma (Zwirner et al., Eur Arch Otorhinolaryngol 254:242-245, 1). Nine out of the thirteen patients were improved by the injections. A BT-A-induced stable benefit for four patients led them to stop the injections in the follow-up. Good outcome was observed in five other patients (main cause: bilateral VP paralysis), allowing a progressive lengthening of the delay between BT-A injections. Four patients did not report a positive risk/benefit ratio after BT-A injections; two of them (with bilateral VF paralysis), because of respiratory side effects and

  3. Longitudinal Phonatory Characteristics after Botulinum Toxin Type A Injection.

    Science.gov (United States)

    Fisher, Kimberly V.; And Others

    1996-01-01

    A study investigated the long-term effects of a Botulinum Toxin Type A injection on the glottal competency of a man with adductor spasmodic dysphonia. Results suggest that change in degree of glottal adduction over time can be observed even when vocal instability is present within each recording session. (CR)

  4. [Botulinum toxin: An important complement for facial rejuvenation surgery].

    Science.gov (United States)

    Le Louarn, C

    2017-10-01

    The improved understanding of the functional anatomy of the face and of the action of the botulinum toxin A leads us to determine a new injection procedure which consequently decreases the risk of eyebrow and eyelid ptosis and increases the toxin's injection possibilities and efficiencies. With less units of toxin, the technique herein described proposes to be more efficient on more muscles: variable toxin injections concentration adapted to each injected muscle are used. Thanks to a new procedure in the upper face, toxin A injection can be quite close to an endoscopic surgical action. In addition, interesting results are achievable to rejuvenate the lateral canthus with injection on the upper lateral tarsus, to rejuvenate the nose with injection at the alar base, the jawline and the neck region. Lastly, a smoothing effect on the skin (meso botox) is obtained by the anticholinergic action of the toxin A on the dermal receptors. Copyright © 2017. Published by Elsevier Masson SAS.

  5. Muscle disuse caused by botulinum toxin injection leads to increased central gain of the stretch reflex in the rat

    DEFF Research Database (Denmark)

    Pingel, Jessica; Hultborn, Hans; Naslund-Koch, Lui

    2017-01-01

    Botulinum toxin (Btx) is used in children with cerebral palsy and other neurological patients to diminish spasticity and reduce the risk of development of contractures. Here, we investigated changes in the central gain of the stretch reflex circuitry in response to botulinum toxin injection...

  6. The therapeutic use of botulinum toxin in cervical and maxillofacial conditions: an evidence-based review.

    Science.gov (United States)

    Ihde, Stefan K A; Konstantinovic, Vitomir S

    2007-08-01

    The role of botulinum toxin as a therapeutic agent for several conditions is expanding. We sought to determine if botulinum toxin is safe and effective in treating patients with cervical dystonia and maxillofacial conditions. Our purpose was to establish a safety and efficacy profile to determine whether or not this treatment may be used prophylactically in patients undergoing dental implant therapy. We performed a systematic search of the literature to identify randomized clinical trials evaluating patients treated with botulinum toxin as an adjunct to dental implant therapy, maxillofacial conditions including temporomandibular disorders (TMD), and cervical dystonia. Four randomized controlled trials (RCTs) met our search criteria in the area of cervical dystonia and chronic facial pain. No RCTs were identified evaluating dental implant therapy. Patients with cervical dystonia exhibited significant improvements in baseline functional, pain, and global assessments compared to placebo. Adverse events were mild and transient with numbers needed to harm (NNH) ranging from 12 to 17. Patients with chronic facial pain improved significantly from baseline in terms of pain compared to placebo. Rates of adverse events were less than 1%. Botulinum toxin appears relatively safe and effective in treating cervical dystonia and chronic facial pain associated with masticatory hyperactivity. No literature exists evaluating its use in dental implantology. Randomized clinical trials are warranted to determine its safety and efficacy in dental implantology and other maxillofacial conditions such as bruxism.

  7. Botulinum toxin in the treatment of orofacial tardive dyskinesia : A single blind study

    NARCIS (Netherlands)

    Slotema, Christina W.; van Harten, Peter N.; Bruggeman, Richard; Hoek, Hans W.

    2008-01-01

    Objective: Orofacial tardive dyskinesia (OTD) is difficult to treat and Botulinium Toxin A (BTA) may be an option. Methods: In a single blind (raters were blind) study (N= 12, duration 33 weeks) OTD was treated with Botulinum Toxin A in three consecutive sessions with increasing dosages. The

  8. Value of botulinum toxin injections preceding a comprehensive rehabilitation period for children with spastic cerebral palsy: A cost-effectiveness study.

    Science.gov (United States)

    Schasfoort, Fabienne; Dallmeijer, Annet; Pangalila, Robert; Catsman, Coriene; Stam, Henk; Becher, Jules; Steyerberg, Ewout; Polinder, Suzanne; Bussmann, Johannes

    2018-01-10

    Despite the widespread use of botulinum toxin in ambulatory children with spastic cerebral palsy, its value prior to intensive physiotherapy with adjunctive casting/orthoses remains unclear. A pragmatically designed, multi-centre trial, comparing the effectiveness of botulinum toxin + intensive physiotherapy with intensive physiotherapy alone, including economic evaluation. Children with spastic cerebral palsy, age range 4-12 years, cerebral palsy-severity Gross Motor Function Classification System levels I-III, received either botulinum toxin type A + intensive physiotherapy or intensive physiotherapy alone and, if necessary, ankle-foot orthoses and/or casting. Primary outcomes were gross motor func-tion, physical activity levels, and health-related quality-of-life, assessed at baseline, 12 (primary end-point) and 24 weeks (follow-up). Economic outcomes included healthcare and patient costs. Intention-to-treat analyses were performed with linear mixed models. There were 65 participants (37 males), with a mean age of 7.3 years (standard deviation 2.3 years), equally distributed across Gross Motor Function Classification System levels. Forty-one children received botulinum toxin type A plus intensive physio-therapy and 24 received intensive physiotherapy treatment only. At primary end-point, one statistically significant difference was found in favour of intensive physiotherapy alone: objectively measured percentage of sedentary behaviour (-3.42, 95% confidence interval 0.20-6.64, p=0.038). Treatment costs were significantly higher for botulinum toxin type A plus intensive physiotherapy (8,963 vs 6,182 euro, p=0.001). No statistically significant differences were found between groups at follow-up. The addition of botulinum toxin type A to intensive physiotherapy did not improve the effectiveness of rehabilitation for ambulatory children with spastic cerebral palsy and was also not cost-effective. Thus botulinum toxin is not recommended for use in improving gross

  9. Molecular Evolutionary Constraints that Determine the Avirulence State of Clostridium botulinum C2 Toxin.

    Science.gov (United States)

    Prisilla, A; Prathiviraj, R; Chellapandi, P

    2017-04-01

    Clostridium botulinum (group-III) is an anaerobic bacterium producing C2 toxin along with botulinum neurotoxins. C2 toxin is belonged to binary toxin A family in bacterial ADP-ribosylation superfamily. A structural and functional diversity of binary toxin A family was inferred from different evolutionary constraints to determine the avirulence state of C2 toxin. Evolutionary genetic analyses revealed evidence of C2 toxin cluster evolution through horizontal gene transfer from the phage or plasmid origins, site-specific insertion by gene divergence, and homologous recombination event. It has also described that residue in conserved NAD-binding core, family-specific domain structure, and functional motifs found to predetermine its virulence state. Any mutational changes in these residues destabilized its structure-function relationship. Avirulent mutants of C2 toxin were screened and selected from a crucial site required for catalytic function of C2I and pore-forming function of C2II. We found coevolved amino acid pairs contributing an essential role in stabilization of its local structural environment. Avirulent toxins selected in this study were evaluated by detecting evolutionary constraints in stability of protein backbone structure, folding and conformational dynamic space, and antigenic peptides. We found 4 avirulent mutants of C2I and 5 mutants of C2II showing more stability in their local structural environment and backbone structure with rapid fold rate, and low conformational flexibility at mutated sites. Since, evolutionary constraints-free mutants with lack of catalytic and pore-forming function suggested as potential immunogenic candidates for treating C. botulinum infected poultry and veterinary animals. Single amino acid substitution in C2 toxin thus provides a major importance to understand its structure-function link, not only of a molecule but also of the pathogenesis.

  10. Report of Allergic Reaction After Application of Botulinum Toxin.

    Science.gov (United States)

    Careta, Mariana Figueiroa; Delgado, Livia; Patriota, Régia

    2015-07-01

    Botulinum toxin is a widely used treatment with satisfactory results, and it is relatively safe in the doses used for cosmetic procedures. The authors report a case of allergic reaction to Chinese botulinum toxin serotype A (CBTX-A). Although this is a rare adverse event, it is nonetheless clinically relevant to healthcare professionals. A 44-year-old woman presented to the authors' hospital complaining of dynamic wrinkles. CBTX-A was used to treat her. Minutes after application, she developed urticarial plaques proximal to the injection site. The patient had an allergic reaction, as documented by a positive skin test, which was controlled by the administration of antihistamines and systemic corticosteroids. This report is intended to guide healthcare professionals faced with this type of adverse event regarding how to proceed without hindering the delivery and effectiveness of the treatment. When performed by a qualified health professional, this treatment brings excellent results in the vast majority of cases. 5 Risk. © 2015 The American Society for Aesthetic Plastic Surgery, Inc. Reprints and permission: journals.permissions@oup.com.

  11. Dysport: pharmacological properties and factors that influence toxin action.

    Science.gov (United States)

    Pickett, Andy

    2009-10-01

    The pharmacological properties of Dysport that influence toxin action are reviewed and compared with other botulinum toxin products. In particular, the subject of diffusion is examined and discussed based upon the evidence that currently exists, both from laboratory studies and from clinical data. Diffusion of botulinum toxin products is not related to the size of the toxin complex in the product since the complex dissociates under physiological conditions, releasing the naked neurotoxin to act. The active neurotoxin in Type A products is the same and therefore diffusion is equal when equal doses are administered.

  12. Structure-function discrepancy in Clostridium botulinum C3 toxin for its rational prioritization as a subunit vaccine.

    Science.gov (United States)

    Prathiviraj, R; Prisilla, A; Chellapandi, P

    2016-06-01

    Clostridium botulinum is anaerobic pathogenic bacterium causing food-born botulism in human and animals by producing botulinum neurotoxins A-H, C2, and C3 cytotoxins. Physiological group III strains (type C and D) of this bacterium are capable of producing C2 and C3 toxins in cattle and avian. Herein, we have revealed the structure-function disparity of C3 toxins from two different C. botulinum type C phage (CboC) and type D phage (CboD) to design avirulent toxins rationally. Structure-function discrepancy of the both toxins was computationally evaluated from their homology models based on the conservation in sequence-structure-function relationships upon covariation and point mutations. It has shown that 8 avirulent mutants were generated from CboC of 34 mutants while 27 avirulent mutants resulted from CboD mutants. No major changes were found in tertiary structure of these toxins; however, some structural variations appeared in the coiled and loop regions. Correlated mutation on the first residue would disorder or revolutionize the hydrogen bonding pattern of the coevolved pairs. It suggested that the residues coupling in the local structural environments were compensated with coevolved pairs so as to preserve a pseudocatalytic function in the avirulent mutants. Avirulent mutants of C3 toxins have shown a stable structure with a common blue print of folding process and also attained a near-native backrub ensemble. Thus, we concluded that selecting the site-directed mutagenesis sites are very important criteria for designing avirulent toxins, in development of rational subunit vaccines, to cattle and avian, but the vaccine specificity can be determined by the C3 toxins of C. botulinum harboring phages.

  13. Structural constraints-based evaluation of immunogenic avirulent toxins from Clostridium botulinum C2 and C3 toxins as subunit vaccines.

    Science.gov (United States)

    Prisilla, A; Prathiviraj, R; Sasikala, R; Chellapandi, P

    2016-10-01

    Clostridium botulinum (group-III) is an anaerobic bacterium producing C2 and C3 toxins in addition to botulinum neurotoxins in avian and mammalian cells. C2 and C3 toxins are members of bacterial ADP-ribosyltransferase superfamily, which modify the eukaryotic cell surface proteins by ADP-ribosylation reaction. Herein, the mutant proteins with lack of catalytic and pore forming function derived from C2 (C2I and C2II) and C3 toxins were computationally evaluated to understand their structure-function integrity. We have chosen many structural constraints including local structural environment, folding process, backbone conformation, conformational dynamic sub-space, NAD-binding specificity and antigenic determinants for screening of suitable avirulent toxins. A total of 20 avirulent mutants were identified out of 23 mutants, which were experimentally produced by site-directed mutagenesis. No changes in secondary structural elements in particular to α-helices and β-sheets and also in fold rate of all-β classes. Structural stability was maintained by reordered hydrophobic and hydrogen bonding patterns. Molecular dynamic studies suggested that coupled mutations may restrain the binding affinity to NAD(+) or protein substrate upon structural destabilization. Avirulent toxins of this study have stable energetic backbone conformation with a common blue print of folding process. Molecular docking studies revealed that avirulent mutants formed more favorable hydrogen bonding with the side-chain of amino acids near to conserved NAD-binding core, despite of restraining NAD-binding specificity. Thus, structural constraints in the avirulent toxins would determine their immunogenic nature for the prioritization of protein-based subunit vaccine/immunogens to avian and veterinary animals infected with C. botulinum. Copyright © 2016 Elsevier B.V. All rights reserved.

  14. Botulinum neurotoxin vaccines: Past history and recent developments.

    Science.gov (United States)

    Rusnak, Janice M; Smith, Leonard A

    2009-12-01

    Botulinum toxin may cause a neuroparalytic illness that may result in respiratory failure and require prolonged mechanical ventilation. As medical resources needed for supportive care of botulism in a bioterrorist event may quickly overwhelm the local healthcare systems, biodefense research efforts have been directed towards the development of a vaccine to prevent botulism. While human botulism has been caused only by toxin serotypes A, B, and E (rarely serotype F), all seven known immunologically distinct toxin serotypes (A - G) may potentially cause intoxication in humans from a bioterrorist event. A pentavalent (ABCDE) botulinum toxoid (PBT) has been administered as an investigation new drug (IND) to at-risk individuals for nearly 50 years. Due to declining immunogenicity of the PBT, research efforts have been directed at development of both improved (less local reactogenicity) botulinum toxoids and recombinant vaccines as potential vaccine candidates to replace the PBT.

  15. Channels Formed by Botulinum, Tetanus, and Diphtheria Toxins in Planar Lipid Bilayers: Relevance to Translocation of Proteins across Membranes

    Science.gov (United States)

    Hoch, David H.; Romero-Mira, Miryam; Ehrlich, Barbara E.; Finkelstein, Alan; Dasgupta, Bibhuti R.; Simpson, Lance L.

    1985-03-01

    The heavy chains of both botulinum neurotoxin type B and tetanus toxin form channels in planar bilayer membranes. These channels have pH-dependent and voltage-dependent properties that are remarkably similar to those previously described for diphtheria toxin. Selectivity experiments with anions and cations show that the channels formed by the heavy chains of all three toxins are large; thus, these channels could serve as ``tunnel proteins'' for translocation of active peptide fragments. These findings support the hypothesis that the active fragments of botulinum neurotoxin and tetanus toxin, like that of diphtheria toxin, are translocated across the membranes of acidic vesicles.

  16. Experience with botulinum toxin in the treatment of cerebral palsy

    African Journals Online (AJOL)

    Institute of Child Health, Red Cross War Memorial Children's. Hospital and University of .... A majority of the children in this study showed definite short- term benefit following botulinum toxin injection and this form of therapy constitutes ... repeated when necessary as long as the spasticity remains dynamic. Patients with ...

  17. Diagnosis and management with botulinum toxin in 11 cases of laryngeal synkinesis.

    Science.gov (United States)

    Lekue, Asier; García-López, Isabel; Santiago, Susana; Del Palacio, Antonio; Gavilán, Javier

    2015-09-01

    Laryngeal synkinesis is a vocal fold movement disorder produced by a misdirected reinnervation after a recurrent laryngeal nerve injury. Its symptoms differ greatly between patients, requiring diverse therapeutical approaches. We aim to describe our experience in the diagnosis and treatment of different laryngeal synkinesis presentations. 11 patients diagnosed between 2011 and 2014 in a tertiary referral center with laryngeal synkinesis confirmed by laryngeal electromyography were included in our study. All medical records and laryngoscopic and electromyographic data were reviewed retrospectively. Four patients had previous unilateral vocal fold palsy and seven had a bilateral palsy with different degrees of clinical involvement. All of them showed paradoxical movements during inhalation in videofibrolaryngoscopic examination. Laryngeal electromyography confirmed the diagnosis of laryngeal synkinesis. Dyspnea was the main presentation symptom. Three patients with mild symptoms were not treated. Patients with unilateral vocal fold immobility were successfully treated with periodic botulinum toxin injections. Patients with bilateral immobility had a good initial response to botulinum toxin, although in some of them, a posterior cordectomy had to be finally performed. In conclusion, laryngeal synkinesis is a heterogeneous clinic entity that appears in patients with unilateral or bilateral vocal fold paralysis. Videofibrolaryngoscopy and laryngeal electromyography are essential to a correct diagnosis. Botulinum toxin injections are the main treatment for symptomatic cases, even if in bilateral palsy cases more aggressive treatments are often required.

  18. Botulinum neurotoxin formulations: overcoming the confusion

    Directory of Open Access Journals (Sweden)

    Samizadeh S

    2018-05-01

    Full Text Available Souphiyeh Samizadeh,1 Koenraad De Boulle2 1Great British Academy of Aesthetic Medicine, London, UK; 2Aalst Dermatology Clinic, Aalst, Belgium Abstract: Botulinum toxin A is produced by anaerobic spore-forming bacteria and is used for various therapeutic and cosmetic purposes. Botulinum toxin A injections are the most popular nonsurgical procedure worldwide. Despite an increased demand for botulinum toxin A injections, the clinical pharmacology and differences in formulation of commonly available products are poorly understood. The various products available in the market are unique and vary in terms of units, chemical properties, biological activities, and weight, and are therefore not interchangeable. For safe clinical practice and to achieve optimal results, the practitioners need to understand the clinical issues of potency, conversion ratio, and safety issues (toxin spread and immunogenicity. In this paper, the basic clinical pharmacology of botulinum toxin A and differences between onabotulinum toxin A, abobotulinum toxin A, and incobotulinum toxin A are discussed. Keywords: botulinum toxin, botulinum neurotoxin, moiety, protein complexes

  19. The botulinum toxin legend of Reinhard Heydrich's death: The end of "Himmler's brain".

    Science.gov (United States)

    Tatu, Laurent; Jost, Wolfgang; Bogousslavsky, Julien

    2017-07-04

    The high-ranking German Nazi Reinhard Heydrich (1904-1942) was one of the main organizers of the mass murder of Jews during the Second World War. He died on June 4, 1942, in Prague after having been wounded in Operation Anthropoid planned by the British intelligence services. Since the 1970s and 1980s, Heydrich's death has been frequently presented in British, American, and French literature as the consequence of a bacteriologic attack. Botulinum toxin would have been used in the grenades or ammunition. We discuss the botulinum toxin hypothesis using the now declassified British archives of Operation Anthropoid and of the chemical and bacteriologic warfare centers to assess this hypothesis. © 2017 American Academy of Neurology.

  20. Botulinum toxin efficacy in the treatment of patients with spasmodic dysphonia

    Directory of Open Access Journals (Sweden)

    Svetel Marina

    2007-01-01

    Full Text Available Background/Aim. Spasmodic dysphonia (DS is a disabling speech disturbance appearing as the consequence of dystonic vocal folds contraction. Its intermittent appearance in the laryngeal muscles causes vocal function discontinuation. The quality of life of these patients is significantly disturbed. Surgical and a medical therapy appear to be inadequate and unsuccessful ones of no steady improvement. It is the botulinum toxin therapy that proved to be highly efficacious one, with the established improvement in 80−100% of patients. The aim of our study was to evaluate the efficacy of botulinum toxin therapy in patients with SD and to show our preliminary results. Methods. The study included 10 patients with adductor spasmodic dysphonia. After diagnostic procedures, botulinum toxin was applied either in one or both vocal folds, in doses of 12−16 units each. In our study we applied indirect technique originally developed by Hočevar and Pirtošek. Perceptive voice and speech analysis was performed prior to and after the instillation of botuline toxin as per structured Scale of pathological characteristics of voice and speech appearing in the spasmodic dysphonia. Results. The majority of our patients experienced both subjective improvement and the improvement in the terms of the quality of life, Voice Henolicap Index − (VHI that was rated as rather significant one (t = 3.562; p = 0.006. Conclusion. Regardless unquestionable improvement of definite phonation, further function restitution requires individual vocal therapy and psychotherapy. Vocal therapy includes structural vocal techniques which reduce degree of vocal tension and rapid changes in the power and the height of voice. Further investigations are necessary for the scope of the definition of a standardized therapeutically procedure for spasmodic dysphonia treatment which comprises multidisciplinary approach in diagnosis, therapy and treatment efficacy evaluation.

  1. A monoclonal antibody based capture ELISA for botulinum neurotoxin serotype B: toxin detection in food

    Science.gov (United States)

    Botulism is a serious foodborne neuroparalyic disease caused by botulinum neurotoxin (BoNT) produced by the anaerobic bacterium Clostridium botulinum. Seven toxin serotypes (A-H) have been described. The majority of human cases of botulism are caused by serotypes A and B followed by E and F. We repo...

  2. Treatment of hemifacial spasm with botulinum A toxin. Results and rationale.

    Science.gov (United States)

    Gonnering, R S

    1986-01-01

    Hemifacial spasm is characterized by unilateral, periodic, tonic contractions of facial muscles, thought to be caused by mechanical compression at the root-exit zone of the facial nerve. Electrophysiologic abnormalities such as ectopic excitation and synkinesis are typical. Although posterior fossa microsurgical nerve decompression is successful in bringing about relief of the spasm in most cases, it carries a risk to hearing. As an alternative treatment, 15 patients with hemifacial spasm were given a total of 41 sets of injections with botulinum A toxin, with a mean follow-up of 14.3 +/- 1.1 months. Relief of symptoms lasted a mean of 108.3 +/- 4.2 days. Mild transient lagophthalmos and ptosis were the only complications. Although the exact mechanism of its action and beneficial effect is speculative at this time, botulinum A toxin appears to offer an effective, safe alternative to more radical intracranial surgery for patients with hemifacial spasm.

  3. Temporomandibular Myofacial Pain Treated with Botulinum Toxin Injection

    Directory of Open Access Journals (Sweden)

    Niv Mor

    2015-07-01

    Full Text Available This article reviews the diagnoses and treatment of temporomandibular disorders (TMD and outlines of the role of botulinum toxin (BoNT in the treatment of myofacial TMD. This manuscript includes a brief history of the use of BoNT in the treatment of pain, the mechanism of action of BoNT, and the techniques for injections, adverse effects and contraindications when using BoNT to treat mayofacial pain caused by TMD.

  4. Botulinum toxin type A in children and adolescents with severe cerebral palsy: a retrospective chart review.

    Science.gov (United States)

    Mesterman, Ronit; Gorter, Jan Willem; Harvey, Adrienne; Lockhart, Julia; McEwen-Hill, Jenny; Margallo, Karen; Goldie, Nancy

    2014-02-01

    This retrospective cohort study reviewed set goals and their outcomes of children and adolescents with severe cerebral palsy who received botulinum toxin A in 2008 and 2009. Sixty children (36 male, mean age 9 years) were included. They received on average 4 (range 1-7) treatments, with the dosage varying between 20 and 400 units per treatment (3-21 U/kg/body weight). Mild transient side effects were reported in 12 of 242 treatments with botulinum toxin A. Treatment goals were related to lower limb function (82%), range of motion (68%), positioning (33%), upper limb function (33%), and facilitating ease of care in dressing (30%), toileting, and diapering (22%). The treatment goals were reached in 60% to 85% by report of the parent and child dyad. Our findings suggest that botulinum toxin A should be considered as a treatment option in patients with cerebral palsy within Gross Motor Function Classification System levels IV and V.

  5. Successful use of botulinum toxin type a in the treatment of refractory postoperative dyspareunia.

    Science.gov (United States)

    Park, Amy J; Paraiso, Marie Fidela R

    2009-08-01

    Refractory dyspareunia presents a challenging therapeutic dilemma. A woman with defecatory dysfunction and dyspareunia presented with stage 2 prolapse. She underwent laparoscopic and vaginal pelvic floor reconstruction with excision of endometriosis. The patient experienced increased dyspareunia and de novo vaginismus postoperatively that were refractory to trigger point injections, physical therapy, and medical and surgical management. She underwent botulinum toxin type A injections into her levator ani muscles, which allowed her to have sexual intercourse again after 2 years of apareunia with no recurrence of pain for 12 months. Injecting botulinum toxin into the levator ani muscles shows promise for postoperative patients who develop vaginismus and do not respond to conservative therapy.

  6. The use of botulinum toxin type A in cosmetic facial procedures

    NARCIS (Netherlands)

    Jaspers, G. W. C.; Pijpe, J.; Jansma, J.

    Over the past decade, facial cosmetic procedures have become more commonplace ill dentistry and oral and maxillofacial surgery. An increasing number of patients seek minimal invasive procedures. One of the most requested procedures is treatment with botulinum toxin type A (BoNTA). Treatment of

  7. The medicinal chemistry of botulinum, ricin and anthrax toxins.

    Science.gov (United States)

    Hicks, Rickey P; Hartell, Mark G; Nichols, Daniel A; Bhattacharjee, Apurba K; van Hamont, John E; Skillman, Donald R

    2005-01-01

    The potential use of weapons of mass destruction (nuclear, biological or chemical) by terrorist organizations represents a major threat to world peace and safety. Only a limited number of vaccines are available to protect the general population from the medical consequences of these weapons. In addition there are major health concerns associated with a pre-exposure mass vaccination of the general population. To reduce or eliminate the impact of these terrible threats, new drugs must be developed to safely treat individuals exposed to these agents. A review of all therapeutic agents under development for the treatment of the illnesses and injuries that result from exposure to nuclear, biological or chemical warfare agents is beyond the scope of any single article. The intent here is to provide a focused review for medicinal and organic chemists of three widely discussed and easily deployed biological warfare agents, botulinum neurotoxin and ricin toxins and the bacteria Bacillus anthracis. Anthrax will be addressed because of its similarity in both structure and mechanism of catalytic activity with botulinum toxin. The common feature of these three agents is that they exhibit their biological activity via toxin enzymatic hydrolysis of a specific bond in their respective substrate molecules. A brief introduction to the history of each of the biological warfare agents is presented followed by a discussion on the mechanisms of action of each at the molecular level, and a review of current potential inhibitors under investigation.

  8. Botulinum toxin and neuromodulation for overactive bladder treatment

    Directory of Open Access Journals (Sweden)

    Ramazan Yavuz Akman

    2013-03-01

    Full Text Available The overactive bladder (OAB is a symptom complex characterized by urgency with /without urge incontinence, and often associated with frequency and nocturia. First-line therapy for OAB includes behavioral therapies and anticholinergic drugs. Although a large number of patients respond to conservative or pharmacological therapy or a combination of the two, some patients are refractory and require additional options for intervention. Botulinum toxin therapy and neuromodulation are frequently used treatment options in refractory OAB patients.

  9. Muscle structure and stiffness assessment after botulinum toxin type A injection. A systematic review.

    Science.gov (United States)

    Mathevon, L; Michel, F; Decavel, P; Fernandez, B; Parratte, B; Calmels, P

    2015-12-01

    Botulinum toxin type A manages spasticity disorders in neurological central diseases. Some studies have reported that it might induce muscle changes. We present a literature review abiding by the PRISMA statement guidelines. The purpose was to explore the structural and passive biomechanical muscle properties after botulinum toxin type A injections in healthy and spastic limb muscles, on animals and humans, as well as methods for evaluating these properties. We searched the PubMed and Cochrane Library databases using the following keywords: "Botulinum toxin" AND ("muscle structure" OR "muscle atrophy") and, "Botulinum toxin" AND "muscle elasticity". From the 228 initially identified articles, 21 articles were included. Histological analyses were performed, especially on animals. A neurogenic atrophy systematically occurred. In humans, one year after a single injection, the histological recovery remained incomplete. Furthermore, 2D ultrasound analyses showed a reduction of the gastrocnemius thickness and pennation angle. MRI volumetric analysis evidenced muscular atrophy six months or one year after a single injection. Passive muscle stiffness depends on these structural changes. On the short term, the biomechanical analysis showed an elastic modulus increase in animals whereas no change was recorded in humans. On the short term, ultrasound elastography imaging showed a decreased elastic modulus. To date, few data are available, but all show a structural and mechanical muscle impact post injections, specifically muscle atrophy which can linger over time. Further studies are necessary to validate this element, and the possibility of change must be taken into account particularly with repeated injections. Thus, in clinical practice, 2D ultrasound and ultrasound elastography are two non-invasive techniques that will help physicians to develop an efficient long term monitoring. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

  10. Genetic homogeneity of Clostridium botulinum type A1 strains with unique toxin gene clusters.

    Science.gov (United States)

    Raphael, Brian H; Luquez, Carolina; McCroskey, Loretta M; Joseph, Lavin A; Jacobson, Mark J; Johnson, Eric A; Maslanka, Susan E; Andreadis, Joanne D

    2008-07-01

    A group of five clonally related Clostridium botulinum type A strains isolated from different sources over a period of nearly 40 years harbored several conserved genetic properties. These strains contained a variant bont/A1 with five nucleotide polymorphisms compared to the gene in C. botulinum strain ATCC 3502. The strains also had a common toxin gene cluster composition (ha-/orfX+) similar to that associated with bont/A in type A strains containing an unexpressed bont/B [termed A(B) strains]. However, bont/B was not identified in the strains examined. Comparative genomic hybridization demonstrated identical genomic content among the strains relative to C. botulinum strain ATCC 3502. In addition, microarray data demonstrated the absence of several genes flanking the toxin gene cluster among the ha-/orfX+ A1 strains, suggesting the presence of genomic rearrangements with respect to this region compared to the C. botulinum ATCC 3502 strain. All five strains were shown to have identical flaA variable region nucleotide sequences. The pulsed-field gel electrophoresis patterns of the strains were indistinguishable when digested with SmaI, and a shift in the size of at least one band was observed in a single strain when digested with XhoI. These results demonstrate surprising genomic homogeneity among a cluster of unique C. botulinum type A strains of diverse origin.

  11. Experience with botulinum toxin therapy for axillary hyperhidrosis and comparison to modelled data for endoscopic thoracic sympathectomy - A quality of life and cost effectiveness analysis.

    Science.gov (United States)

    Gibbons, John P; Nugent, Emmeline; O'Donohoe, Nollaig; Maher, Barry; Egan, Bridget; Feeley, Martin; Tierney, Sean

    2016-10-01

    To estimate cost-effectiveness of botulinum toxin therapy for axillary hyperhidrosis compared to the standard surgical intervention of endoscopic thoracic sympathectomy (ETS). The validated dermatology life quality index questionnaire was given to patients attending for treatment over a 4 month period, to assess their quality of life (QoL) over the preceding week (n = 44). Follow-up was performed 4-6 weeks later by telephone using the same questionnaire to validate the effectiveness of the treatment. The duration of effect of the botulinum toxin treatment was also recorded and this data was used as the basis for cost effectiveness analysis. Using HIPE data, the baseline cost for single intervention using botulinum toxin and ETS was retrieved. Using figures provided by HIPE and expert opinion of the costs of complications, a stochastic model for 10,000 patients was used to evaluate the total costs for ETS including the complications. The results from the QoL analysis show that botulinum toxin therapy is a successful therapy for improvement of symptoms. It was revealed that the mean interval before recurrence of original symptoms after botulinum toxin therapy was 5.6 months. The baseline cost for both treatments are €389 for botulinum toxin and €9389 for uncomplicated ETS. The stochastic model yields a mean cost of €11,390 for ETS including complications. Treatments reached cost equivalence after 13.3 years. However, given the efficacy of the botulinum toxin therapy and the low risk we propose that botulinum toxin therapy for hyperhidrosis should be considered the gold standard. Copyright © 2015 Royal College of Surgeons of Edinburgh (Scottish charity number SC005317) and Royal College of Surgeons in Ireland. Published by Elsevier Ltd. All rights reserved.

  12. A Medical Research and Evaluation Facility (MREF) and Studies Supporting the Medical Chemical Defense Program. Evaluation of the Passive Protection Against Five Serotypes of Botulinum Toxin Provided by Botulinum Human Immune Globulin in an Animal Model

    National Research Council Canada - National Science Library

    Olson, Carl

    1998-01-01

    Pentavalent (ABCDE) botulinum toxoid vaccine is intended for use as a prophylactic measure to protect combat troops against the lethal effects of botulinum toxins A-E, a group of toxins considered to be a serious biological warfare threat...

  13. Safety and efficacy of repeated injections of botulinum toxin A in peripheral neuropathic pain (BOTNEP): a randomised, double-blind, placebo-controlled trial.

    Science.gov (United States)

    Attal, Nadine; de Andrade, Daniel C; Adam, Frédéric; Ranoux, Danièle; Teixeira, Manoel J; Galhardoni, Ricardo; Raicher, Irina; Üçeyler, Nurcan; Sommer, Claudia; Bouhassira, Didier

    2016-05-01

    Data from previous studies suggest that botulinum toxin A has analgesic effects against peripheral neuropathic pain, but the quality of the evidence is low. We aimed to assess the safety and efficacy of repeated administrations of botulinum toxin A in patients with neuropathic pain. We did a randomised, double-blind, placebo-controlled trial at two outpatient clinics in France (Clinical Pain Centre, Ambroise Paré Hospital, APHP, Boulogne-Billancourt, and Neurological Centre, Hôpital Dupuytren, Limoges) and one in Brazil (Neurological Department, Hospital das Clínicas da FMUSP, São Paulo). Patients aged 18-85 years with peripheral neuropathic pain were randomly assigned (1:1) by block randomisation, according to a centralised schedule, to receive two subcutaneous administrations of botulinum toxin A (up to 300 units) or placebo, 12 weeks apart. All patients and investigators were masked to treatment assignment. The primary outcome was the efficacy of botulinum toxin A versus placebo, measured as the change from baseline in self-reported mean weekly pain intensity over the course of 24 weeks from the first administration. The primary efficacy analysis was a mixed-model repeated-measures analysis in the intention-to-treat population. This trial is registered with ClinicalTrials.gov, NCT01251211. Between Oct 2, 2010, and Aug 2, 2013, 152 patients were enrolled, of whom 68 were randomly assigned (34 per group), and 66 (37 [56%] men) were included in the primary analysis (34 in the botulinum toxin A group and 32 in the placebo group). Botulinum toxin A reduced pain intensity over 24 weeks compared with placebo (adjusted effect estimate -0·77, 95% CI -0·95 to -0·59; pbotulinum toxin A group and 17 (53%) of those in the placebo group (p=1·0). Severe pain was experienced by ten (29%) participants in the botulinum toxin A group and 11 (34%) in the placebo group (p=0·8). Two administrations of botulinum toxin A, each of which comprised several injections, have a

  14. Botulinum toxin injection causes hyper-reflexia and increased muscle stiffness of the triceps surae muscle in the rat

    OpenAIRE

    Pingel, Jessica; Wienecke, Jacob; Lorentzen, Jakob; Nielsen, Jens Bo

    2016-01-01

    This study demonstrates, for the first time, adaptive plastic changes in the stretch reflex circuitry following denervation induced by botulinum toxin injection. The study also demonstrates alterations of the elastic properties of the muscles following botulinum injection.

  15. Antagonism of botulinum toxin-induced muscle weakness by aminopyridines in rat phrenic nerve-hemidiaphragm preparations

    Energy Technology Data Exchange (ETDEWEB)

    Adler, M.; Scovill, J.; Deshpande, S.S.

    1993-05-13

    The effects of the potassium channel inhibitor and putative botulinum toxin antagonists 4-aminopyridine (4-AP) and 3,4-diaminopyridine (3,4-DAP) were investigated in vitro on the contractile and electrophysiological properties of rat diaphragm muscle. In the presence of 300 pM botulinum toxin A (BoTx A), twitches elicited by supramaximal nerve stimulation (0. 1 Hz) were reduced by over 80% in 3 hr. The time to block decreased with increases in temperature, toxin concentration and stimulation frequency. Addition of 4-AP or 3,4-DAP led to a prompt reversal of the BoTx A-induced depression of twitch tension. This reversal was concentration-dependent such that, in the presence of 1 mM 4-AP, reversal of the BoTx A-induced blockade was complete in 6.7 min. The beneficial effect of the APs were well maintained and persisted for up to 6 hr after addition. Application of 1 microns M neostigmine 1 hr after 3,4-DAP produced a further potentiation of twitch tensions, but this action lasted for < 5 min and led to the appearance of tetanic fade during repetitive stimulation. It is concluded that the APs are of benefit in antagonizing the muscle paralysis following exposure to botulinum toxin. Co-application of neostigmine, however, appears to confer no additional benefit.

  16. Effect of headspace CO2 concentration on toxin production by Clostridium botulinum in MAP, irradiated fresh pork

    International Nuclear Information System (INIS)

    Lambert, A.D.; Smith, J.P.; Dodds, K.L.

    1991-01-01

    The effects of five initial levels of CO2 (15, 30, 45, 60, and 75%) and three irradiation doses (0, 0.5, and 1.0 kGy) on toxin production by Clostridium botulinum in inoculated fresh pork were studied using factorial design experiments. Headspace CO2 levels increased in all samples during storage at 15 degrees C. In most treatments, spoilage preceded toxigenesis. Toxin production occurred faster in samples initially packaged with 15 to 30% of CO2 while higher levels of CO2 (45-75%) delayed toxin production. Low-dose irradiation delayed toxin production at all levels of CO2 in the package headspace. Contrary to expectations, including a CO2 absorbent in the package enhanced toxin production by C. botulinum. This was attributed to production of H2 by the CO2 absorbent, possibly resulting in a decrease in the oxido-reduction potential of the meat

  17. In situ detection of the Clostridium botulinum type C1 toxin gene in wetland sediments with a nested PCR assay

    Science.gov (United States)

    Williamson, Judy L.; Rocke, Tonie E.; Aiken, Judd M.

    1999-01-01

    A nested PCR was developed for detection of the Clostridium botulinum type C1 toxin gene in sediments collected from wetlands where avian botulism outbreaks had or had not occurred. The C1 toxin gene was detected in 16 of 18 sites, demonstrating both the ubiquitous distribution of C. botulinum type C in wetland sediments and the sensitivity of the detection assay.

  18. [Applications of botulinum toxin in Neurology].

    Science.gov (United States)

    Garcia-Ruiz, Pedro J

    2013-07-07

    At present, botulinum toxin (BT) is one of the most fundamental available drugs in Neurology, only comparable with levodopa. BT is currently used in those entities characterized by excessive muscle contraction, including dystonia and spasticity. In addition, BT has been used to control pain associated with increased muscle contraction in dystonia and spasticity, but also is useful to control chronic pain not associated with muscle contraction, such as chronic daily headache. Finally, BT is useful in sialorrhoea and bruxism. The mechanism of action is complex, mainly acting on terminal neuromuscular junction, but also exhibiting analgesic properties, probably through inhibition of pain neurotransmitters release. Copyright © 2012 Elsevier España, S.L. All rights reserved.

  19. Mass Spectrometric Identification and Differentiation of Botulinum Neurotoxins through Toxin Proteomics.

    Science.gov (United States)

    Kalb, Suzanne R; Barr, John R

    2013-08-01

    Botulinum neurotoxins (BoNTs) cause the disease botulism, which can be lethal if untreated. There are seven known serotypes of BoNT, A-G, defined by their response to antisera. Many serotypes are distinguished into differing subtypes based on amino acid sequence and immunogenic properties, and some subtypes are further differentiated into toxin variants. Toxin characterization is important as different types of BoNT can respond differently to medical countermeasures for botulism, and characterization of the toxin can aid in epidemiologic and forensic investigations. Proteomic techniques have been established to determine the serotype, subtype, or toxin variant of BoNT. These techniques involve digestion of the toxin into peptides, tandem mass spectrometric (MS/MS) analysis of the peptides, and database searching to identify the BoNT protein. These techniques demonstrate the capability to detect BoNT and its neurotoxin-associated proteins, and differentiate the toxin from other toxins which are up to 99.9% identical in some cases. This differentiation can be accomplished from toxins present in a complex matrix such as stool, food, or bacterial cultures and no DNA is required.

  20. In vitro reconstitution of the Clostridium botulinum type D progenitor toxin.

    Science.gov (United States)

    Kouguchi, Hirokazu; Watanabe, Toshihiro; Sagane, Yoshimasa; Sunagawa, Hiroyuki; Ohyama, Tohru

    2002-01-25

    Clostridium botulinum type D strain 4947 produces two different sizes of progenitor toxins (M and L) as intact forms without proteolytic processing. The M toxin is composed of neurotoxin (NT) and nontoxic-nonhemagglutinin (NTNHA), whereas the L toxin is composed of the M toxin and hemagglutinin (HA) subcomponents (HA-70, HA-17, and HA-33). The HA-70 subcomponent and the HA-33/17 complex were isolated from the L toxin to near homogeneity by chromatography in the presence of denaturing agents. We were able to demonstrate, for the first time, in vitro reconstitution of the L toxin formed by mixing purified M toxin, HA-70, and HA-33/17. The properties of reconstituted and native L toxins are indistinguishable with respect to their gel filtration profiles, native-PAGE profiles, hemagglutination activity, binding activity to erythrocytes, and oral toxicity to mice. M toxin, which contained nicked NTNHA prepared by treatment with trypsin, could no longer be reconstituted to the L toxin with HA subcomponents, whereas the L toxin treated with proteases was not degraded into M toxin and HA subcomponents. We conclude that the M toxin forms first by assembly of NT with NTNHA and is subsequently converted to the L toxin by assembly with HA-70 and HA-33/17.

  1. Effect of Equilibrated pH and Indigenous Spoilage Microorganisms on the Inhibition of Proteolytic Clostridium botulinum Toxin Production in Experimental Meals under Temperature Abuse.

    Science.gov (United States)

    Golden, Max C; Wanless, Brandon J; David, Jairus R D; Lineback, D Scott; Talley, Ryan J; Kottapalli, Bala; Glass, Kathleen A

    2017-08-01

    Clostridium botulinum is a foreseeable biological hazard in prepared refrigerated meals that needs to be addressed in food safety plans. The objective of this study was to evaluate the effect of product composition and storage temperature on the inhibition of botulinum toxin formation in nine experimental meals (meat, vegetable, or carbohydrate based). Treatments were inoculated with proteolytic C. botulinum, vacuum packaged, cooked at 90°C for 10 min, and assayed for botulinum toxin in samples stored at 25°C for up to 96 h for phase 1, or at 25°C for 12 h and then transferred to 12.5°C for up to 12 and 6 weeks in phases 1 and 2, respectively. For phase 1, none of the treatments (equilibrated pH 5.8) supported toxin production when stored at 25°C for 48 h, but toxin production was observed in all treatments at 72 h. For the remaining experiments with storage at 12.5°C, toxin production was dependent on equilibrated pH, storage time, and growth of indigenous spoilage microorganisms. In phase 1, no gross spoilage and no botulinum toxin was detected for any treatment (pH ≤5.8) stored at 12.5°C for 12 weeks. In phase 2, gross spoilage varied by commodity, with the brussels sprouts meal with pH 6.5 showing the most rapid spoilage within 2 weeks and botulinum toxin detected at 5 and 6 weeks for the control and cultured celery juice treatments, respectively. In contrast, spoilage microbes decreased the pH of a pH 5.9 beef treatment by 1.0 unit, potentially inhibiting C. botulinum through 6 weeks at 12.5°C. None of the other treatments with pH 5.8 or below supported toxin production or spoilage. This study provides validation for preventive controls in refrigerated meals. These include equilibrated product pH and storage temperature and time to inhibit toxin formation by proteolytic C. botulinum, but the impact of indigenous microflora on safety and interpretation of challenge studies is also highlighted.

  2. Diffusion, spread, and migration of botulinum toxin.

    Science.gov (United States)

    Ramirez-Castaneda, Juan; Jankovic, Joseph; Comella, Cynthia; Dashtipour, Khashayar; Fernandez, Hubert H; Mari, Zoltan

    2013-11-01

    Botulinum toxin (BoNT) is an acetylcholine release inhibitor and a neuromuscular blocking agent used for the treatment of a variety of neurologic and medical conditions. The efficacy and safety of BoNT depends on accurate selection and identification of intended targets but also may be determined by other factors, including physical spread of the molecule from the injection site, passive diffusion, and migration to distal sites via axonal or hematogenous transport. The passive kinetic dispersion of the toxin away from the injection site in a gradient-dependent manner may also play a role in toxin spread. In addition to unique properties of the various BoNT products, volume and dilution may also influence local and systemic distribution of BoNT. Most of the local and remote complications of BoNT injections are thought to be due to unwanted spread or diffusion of the toxin's biologic activity into adjacent and distal muscles. Despite widespread therapeutic and cosmetic use of BoNT over more than three decades, there is a remarkable paucity of published data on the mechanisms of distribution and its effects on clinical outcomes. The primary aim of this article is to critically review the available experimental and clinical literature and place it in the practical context. © 2013 International Parkinson and Movement Disorder Society.

  3. Influence of Botulinum Toxin Therapy on Postural Control and Lower Limb Intersegmental Coordination in Children with Spastic Cerebral Palsy

    Directory of Open Access Journals (Sweden)

    Bernard Dan

    2013-01-01

    Full Text Available Botulinum toxin injections may significantly improve lower limb kinematics in gait of children with spastic forms of cerebral palsy. Here we aimed to analyze the effect of lower limb botulinum toxin injections on trunk postural control and lower limb intralimb (intersegmental coordination in children with spastic diplegia or spastic hemiplegia (GMFCS I or II. We recorded tridimensional trunk kinematics and thigh, shank and foot elevation angles in fourteen 3–12 year-old children with spastic diplegia and 14 with spastic hemiplegia while walking either barefoot or with ankle-foot orthoses (AFO before and after botulinum toxin infiltration according to a management protocol. We found significantly greater trunk excursions in the transverse plane (barefoot condition and in the frontal plane (AFO condition. Intralimb coordination showed significant differences only in the barefoot condition, suggesting that reducing the degrees of freedom may limit the emergence of selective coordination. Minimal relative phase analysis showed differences between the groups (diplegia and hemiplegia but there were no significant alterations unless the children wore AFO. We conclude that botulinum toxin injection in lower limb spastic muscles leads to changes in motor planning, including through interference with trunk stability, but a combination of therapies (orthoses and physical therapy is needed in order to learn new motor strategies.

  4. Structure, Function and Evolution of Clostridium botulinum C2 and C3 Toxins: Insight to Poultry and Veterinary Vaccines.

    Science.gov (United States)

    Chellapandi, Paulchamy; Prisilla, Arokiyasamy

    2017-01-01

    Clostridium botulinum group III strains are able to produce cytotoxins, C2 toxin and C3 exotoxin, along with botulinum neurotoxin types C and D. C2 toxin and C3 exotoxin produced by this organism are the most important members of bacterial ADP-ribosyltransferase superfamily. Both toxins have distinct pathophysiological functions in the avian and mammalian hosts. The members of this superfamily transfer an ADP-ribose moiety of NAD+ to specific eukaryotic target proteins. The present review describes the structure, function and evolution aspects of these toxins with a special emphasis to the development of veterinary vaccines. C2 toxin is a binary toxin that consists of a catalytic subunit (C2I) and a translocation subunit (C2II). C2I component is structurally and functionally similar to the VIP2 and iota A toxin whereas C2II component shows a significant homology with the protective antigen from anthrax toxin and iota B. Unlike C2 toxin, C3 toxin is devoid of translocation/binding subunit. Extensive studies on their sequence-structure-function link spawn additional efforts to understand the catalytic mechanisms and target recognition. Structural and functional relationships with them are often determined by using evolutionary constraints as valuable biological measures. Enzyme-deficient mutants derived from these toxins have been used as drug/protein delivery systems in eukaryotic cells. Thus, current knowledge on their molecular diversity is a well-known perspective to design immunotoxin or subunit vaccine for C. botulinum infection. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  5. Combined Effect Of Botulinum Toxin And Splinting On Motor Components And Function Of People With Stroke

    Directory of Open Access Journals (Sweden)

    Aryan Shamili

    2017-02-01

    Full Text Available Background and objective: Spasticity is one of the problems following stroke. Due to this increase in muscle tone, patients are confronted to problems in motor control and difficulties in activities of daily living and complications such as shortness and contracture. The aim of this study was to examine the effects of Simultaneous use of both splint and botulinum toxin-A (BTX-A injection on spasticity, range of motion and upper extremity function in a 3-month period. Methods: The design of this study was a comparison between 3 groups of interventions, conducted in rehabilitation clinics in Tehran. Sixty people with chronic stroke were recruited. Based on the inclusion criteria, a total of 39 stroke patients after completing the consent forms were entered to intervention groups; splint or botulinum toxin injection or combined splint/botulinum toxin injection. They were followed up about 3 months and the evaluations were done monthly. Goniometry was the method to measure range of motion, and Modified Ashworth scale was used to examine the spasticity and the upper extremity function was scored based on Fugl-Meyer assessment.   Statistical analysis was done using SPSS 17. And ANOVAs was used for comparison between groups and times.  Significance was set at 0.05. Results: All outcome measures improved within each group but the differences between splint group and BTX-A group and the BTX-A-splint group was not significant in most outcomes during 3 periods (first evaluation until end of the first month, the end of first month until the end of second month, the end of second month until the end of the third month (p> 0 / 05. The results also showed that the changes in elbow`s spasticity {p= 0.05} and wrist`s spasticity {p= 0.007} and upper extremity function { p = 0.04} were obvious between the three groups over the 3-months and the difference in the group of combined use of botulinum toxin and splint was more than other groups. Conclusion: In this

  6. Thickened saliva after effective management of drooling with botulinum toxin A

    NARCIS (Netherlands)

    Erasmus, C.E.; van Hulst, K.; van den Hoogen, F.J.; van Limbeek, J.; Roeleveld, N.; Veerman, E.C.I.; Rotteveel, J.J.; Jongerius, P.H.

    2010-01-01

    Aim: The aim of this study was to evaluate the rheological properties of saliva after submandibular botulinum toxin type A (BoNT-A) injections. Method: We enrolled 15 children (11 males and six females; age range 3-17y, mean age 9y 10mo) diagnosed with spastic (n=9) or dyskinetic (n=6) quadriplegic

  7. Thickened saliva after effective management of drooling with botulinum toxin A.

    NARCIS (Netherlands)

    Erasmus, C.E.; Hulst, K. van; Hoogen, F.J.A. van den; Limbeek, J. van; Roeleveld, N.; Veerman, E.C.; Rotteveel, J.J.; Jongerius, P.H.

    2010-01-01

    AIM: The aim of this study was to evaluate the rheological properties of saliva after submandibular botulinum toxin type A (BoNT-A) injections. METHOD: We enrolled 15 children (11 males and six females; age range 3-17 y, mean age 9 y 10 mo) diagnosed with spastic (n=9) or dyskinetic (n=6)

  8. Association of toxin-producing Clostridium botulinum with the macroalga Cladophora in the Great Lakes.

    Science.gov (United States)

    Chun, Chan Lan; Ochsner, Urs; Byappanahalli, Muruleedhara N; Whitman, Richard L; Tepp, William H; Lin, Guangyun; Johnson, Eric A; Peller, Julie; Sadowsky, Michael J

    2013-03-19

    Avian botulism, a paralytic disease of birds, often occurs on a yearly cycle and is increasingly becoming more common in the Great Lakes. Outbreaks are caused by bird ingestion of neurotoxins produced by Clostridium botulinum, a spore-forming, gram-positive, anaerobe. The nuisance, macrophytic, green alga Cladophora (Chlorophyta; mostly Cladophora glomerata L.) is a potential habitat for the growth of C. botulinum. A high incidence of botulism in shoreline birds at Sleeping Bear Dunes National Lakeshore (SLBE) in Lake Michigan coincides with increasingly massive accumulations of Cladophora in nearshore waters. In this study, free-floating algal mats were collected from SLBE and other shorelines of the Great Lakes between June and October 2011. The abundance of C. botulinum in algal mats was quantified and the type of botulism neurotoxin (bont) genes associated with this organism were determined by using most-probable-number PCR (MPN-PCR) and five distinct bont gene-specific primers (A, B, C, E, and F). The MPN-PCR results showed that 16 of 22 (73%) algal mats from the SLBE and 23 of 31(74%) algal mats from other shorelines of the Great Lakes contained the bont type E (bont/E) gene. C. botulinum was present up to 15000 MPN per gram dried algae based on gene copies of bont/E. In addition, genes for bont/A and bont/B, which are commonly associated with human diseases, were detected in a few algal samples. Moreover, C. botulinum was present as vegetative cells rather than as dormant spores in Cladophora mats. Mouse toxin assays done using supernatants from enrichment of Cladophora containing high densities of C. botulinum (>1000 MPN/g dried algae) showed that Cladophora-borne C. botulinum were toxin-producing species (BoNT/E). Our results indicate that Cladophora provides a habitat for C. botulinum, warranting additional studies to better understand the relationship between this bacterium and the alga, and how this interaction potentially contributes to botulism

  9. Clostridium botulinum C2 toxin--new insights into the cellular up-take of the actin-ADP-ribosylating toxin.

    Science.gov (United States)

    Aktories, Klaus; Barth, Holger

    2004-04-01

    Clostridium botulinum C2 toxin is a member of the family of binary actin-ADP-ribosylating toxins. It consists of the enzyme component C2I, and the separated binding/translocation component C2II. Proteolytically activated C2II forms heptamers and binds to a carbohydrate cell surface receptor. After attachment of C2I, the toxin complex is endocytosed to reach early endosomes. At low pH of endosomes, C2II-heptamers insert into the membrane, form pores and deliver C2I into the cytosol. Here, C2I ADP-ribosylates actin at Arg177 to block actin polymerization and to induce depolymerization of actin filaments. The mini-review describes main properties of C2 toxin and discusses new findings on the involvement of chaperones in the up-take process of the toxin.

  10. Effect of botulinum toxin for eyelid retraction in dysthyroid ophthalmopathy as related to hypertrophy of intraorbital muscles

    International Nuclear Information System (INIS)

    Komoto, Noriko; Kozaki, Ai; Yu, Fumihiko; Inoue, Rishu; Maeda, Toshine; Inoue, Toyoko; Inoue, Yoichi

    2007-01-01

    The purpose of this study was to report the effect of botulinum toxin for eyelid retraction in dysthyroid ophthalmopathy with or without hypertrophy of intraorbital muscles. We reviewed 28 eyes of 23 cases who received injection of botulinum toxin for eyelid retraction. Eyelid retraction improved in 23 eyes (82%). The height of palpebral fissure ranged from 8 to 12 mm, average 10.8 mm, before treatment. It ranged from 5 to 12 mm, average 9.4 mm, 2 weeks after treatment. The difference was significant. By magnetic resonance imaging (MRI), hypertrophy of levator and/or superior rectus muscle was present in 19 eyes and absent in 9 eyes. Eyelid retraction improved in 2 eyes (11%) in the former group and in one eye (11%) in the latter. Dalrymple sign was present in 28 eyes before and disappeared in 14 eyes after treatment. Graefe sign was present in 28 eyes before and disappeared in one eye after treatment. Botulinum toxin is effective for eyelid retraction and not for Graefe sign in dysthyroid ophthalmopathy. (author)

  11. Effect of Botulinum Toxin and Surgery among Spasmodic Dysphonia Patients : A Systematic Review

    NARCIS (Netherlands)

    van Esch, Babette F; Wegner, Inge; Stegeman, Inge; Grolman, Wilko

    2017-01-01

    OBJECTIVE: The effect of botulinum toxin among patients with adductor spasmodic dysphonia (AdSD) is temporary. To optimize long-term treatment outcome, other therapy options should be evaluated. Alternative treatment options for AdSD comprise several surgical treatments, such as thyroarytenoid

  12. Office-based Electromyography-guided Botulinum Toxin Injection to the Cricopharyngeus Muscle: Optimal Patient Selection and Technique.

    Science.gov (United States)

    Kim, Min-Su; Kim, Go-Woon; Rho, Young-Soo; Kwon, Kee-Hwan; Chung, Eun-Jae

    2017-05-01

    This retrospective study was carried out to investigate the effectiveness and safety of office-based electromyography-guided injection of botulinum toxin in the cricopharyngeus muscle of patients who did not show upper esophageal sphincter passage in a swallowing study in spite of maximal swallowing rehabilitation. Thirty-six patients who showed no or limited ability to oral feed after maximum swallowing rehabilitation were enrolled. Video fluoroscopic swallowing study, flexible endoscopic evaluation of swallowing, disability rating scale, penetration aspiration score, and National Institutes of Health swallowing safety scale were used in the evaluation of dysphagia. Success was defined as nondependence on gastrostomy for patients who previously were dependent on gastrostomy and improvement in disability rating scale score after botulinum toxin injections. The total success rate was 63.9%. The complication rate was very low, with only 1 patient showing temporary unilateral vocal fold paralysis. Botulinum toxin injection was more effective in patients with cranial nerve IX or X palsy than in those without it ( P = .006). This procedure can be a simple, safe, and effective tool in patients with cricopharyngeal dysfunction after swallowing rehabilitation, especially for cranial nerve IX or X palsy.

  13. Evaluation of a quail embryo model for the detection of botulinum toxin type A activity

    Science.gov (United States)

    The quail embryo was evaluated for use as a bioassay to detect biologically active botulinum toxin serotype A (BoNT/A). Day 15 of incubation embryos were injected with decreasing dosages of BoNT/A from 250 to 0.5 ng of toxin. At 1 day post-injection, embryos receiving 20 ng of BoNT or higher had m...

  14. Botulinum Toxin A as an Adjunct to Abdominal Wall Reconstruction for Incisional Hernia

    DEFF Research Database (Denmark)

    Soltanizadeh, Sinor; Helgstrand, Frederik; Jorgensen, Lars N

    2017-01-01

    BACKGROUND: Repair of large incisional hernias remains a surgical and costly challenge. Temporary paralysis of the lateral abdominal wall muscles with topical administration of botulinum toxin A (BTA) is a new therapeutic concept, which may obviate the need for component separation technique (CST...

  15. The use of botulinum toxin in head and face medicine: An interdisciplinary field

    Directory of Open Access Journals (Sweden)

    Laskawi Rainer

    2008-03-01

    Full Text Available Abstract Background In this review article different interdisciplinary relevant applications of botulinum toxin type A (BTA in the head and face region are demonstrated. Patients with head and face disorders of different etiology often suffer from disorders concerning their musculature (example: synkinesis in mimic muscles or gland-secretion. This leads to many problems and reduces their quality of life. The application of BTA can improve movement disorders like blepharospasm, hemifacial spasm, synkinesis following defective healing of the facial nerve, palatal tremor, severe bruxism, oromandibular dystonias hypertrophy of the masseter muscle and disorders of the autonomous nerve system like hypersalivation, hyperlacrimation, pathological sweating and intrinsic rhinitis. Conclusion The application of botulinum toxin type A is a helpful and minimally invasive treatment option to improve the quality of life in patients with head and face disorders of different quality and etiology. Side effects are rare.

  16. Comparison of Efficacy and Side Effects of Oral Baclofen Versus Tizanidine Therapy with Adjuvant Botulinum Toxin Type A in Children With Cerebral Palsy and Spastic Equinus Foot Deformity.

    Science.gov (United States)

    Dai, Alper I; Aksoy, Sefika N; Demiryürek, Abdullah T

    2016-02-01

    This retrospective study aimed to compare the therapeutic response, including side effects, for oral baclofen versus oral tizanidine therapy with adjuvant botulinum toxin type A in a group of 64 pediatric patients diagnosed with static encephalopathy and spastic equinus foot deformity. Following botulinum toxin A treatment, clinical improvement led to the gradual reduction of baclofen or tizanidine dosing to one-third of the former dose. Gross Motor Functional Measure and Caregiver Health Questionnaire scores were markedly elevated post-botulinum toxin A treatment, with scores for the tizanidine (Gross Motor Functional Measure: 74.45 ± 3.72; Caregiver Health Questionnaire: 72.43 ± 4.29) group significantly higher than for the baclofen group (Gross Motor Functional Measure: 68.23 ± 2.66; Caregiver Health Questionnaire: 67.53 ± 2.67, P botulinum toxin A and a low dose of tizanidine in treating children with cerebral palsy appears to be more effective and has fewer side effects versus baclofen with adjuvant botulinum toxin A. © The Author(s) 2015.

  17. Treatment of severe drooling with botulinum toxin in amyotrophic lateral sclerosis and Parkinson's disease: Efficacy and possible mechanisms

    DEFF Research Database (Denmark)

    Møller, Eigild; Karlsborg, Merete; Jensen, Allan Bardow

    2011-01-01

    Drooling in neurodegenerative diseases is associated with social impediment. Previous treatments of drooling have little effect or are effective but with severe side effects. Therefore, there is a need to test new methods such as the use of botulinum toxin type A (BTX-A).......Drooling in neurodegenerative diseases is associated with social impediment. Previous treatments of drooling have little effect or are effective but with severe side effects. Therefore, there is a need to test new methods such as the use of botulinum toxin type A (BTX-A)....

  18. Use of anatomic measurement to guide injection of botulinum toxin for the management of chronic lateral epicondylitis: a randomized controlled trial

    Science.gov (United States)

    Espandar, Ramin; Heidari, Pedram; Rasouli, Mohammad Reza; Saadat, Soheil; Farzan, Mahmood; Rostami, Mohsen; Yazdanian, Shideh; Mortazavi, S.M. Javad

    2010-01-01

    Background When using botulinum toxin for the management of lateral epicondylitis, injection at a fixed distance from an anatomic landmark could result in inadequate paralysis of the intended muscle. We assessed the effectiveness of injection of botulinum toxin using precise anatomic measurement in individual patients. Methods In this randomized placebo-controlled trial, 48 patients with chronic refractory lateral epicondylitis were randomly assigned to receive a single injection of either botulinum toxin (60 units) or placebo (normal saline). The site of injection was chosen as a distance one-third the length of the forearm from the tip of the lateral epicondyle on the course of the posterior interosseus nerve. The primary outcome measure was intensity of pain at rest, measured with the use of a 100-mm visual analogue scale, at baseline and at 4, 8 and 16 weeks after injection. Results Compared with the placebo group, the group given botulinum toxin had significant reductions in pain at rest during follow-up (decrease at 4 weeks 14.1 mm, 95% confidence interval [CI] 5.8–22.3; at 8 weeks 11.5 mm, 95% CI 2.0–21.0; at 16 weeks 12.6 mm, 95% CI 7.7–17.8; p = 0.01). As for the secondary outcomes, the intensity of pain during maximum pinch decreased in the botulinum toxin group; there was no difference in pain during maximum grip or in grip strength between the two groups. All but one of the patients in the intervention group experienced weakness in the extension of the third and fourth fingers at week 4 that resolved by week 16. No serious adverse events were reported. Interpretation The use of precise anatomic measurement to guide injection of botulinum toxin significantly reduced pain at rest in patients with chronic refractory lateral epicondylitis. However, the transient extensor lag makes this method inappropriate for patients whose job requires finger extension. (ClinicalTrials.gov trial register no. NCT00497913.) PMID:20421357

  19. Kinetic and Reaction Pathway Analysis in the Application of Botulinum Toxin A for Wound Healing

    Directory of Open Access Journals (Sweden)

    Frank J. Lebeda

    2012-01-01

    Full Text Available A relatively new approach in the treatment of specific wounds in animal models and in patients with type A botulinum toxin is the focus of this paper. The indications or conditions include traumatic wounds (experimental and clinical, surgical (incision wounds, and wounds such as fissures and ulcers that are signs/symptoms of disease or other processes. An objective was to conduct systematic literature searches and take note of the reactions involved in the healing process and identify corresponding pharmacokinetic data. From several case reports, we developed a qualitative model of how botulinum toxin disrupts the vicious cycle of muscle spasm, pain, inflammation, decreased blood flow, and ischemia. We transformed this model into a minimal kinetic scheme for healing chronic wounds. The model helped us to estimate the rate of decline of this toxin's therapeutic effect by calculating the rate of recurrence of clinical symptoms after a wound-healing treatment with this neurotoxin.

  20. Botulinum as a Toxin for Treating Post-herpetic Neuralgia

    OpenAIRE

    DING, Xu-Dong; ZHONG, Jing; LIU, Yan-Ping; CHEN, Hua-Xian

    2017-01-01

    Background: We aimed to study the curative effects of botulinum A toxin (BTX-A) on the treatment of post-herpetic neuralgia (PNH). Methods: We enrolled 58 PNH patients and treated them with hypodermic injection of BTX-A in Xiangyang No.1 People?s Hospital, Hubei University of Medicine, Hubei, China. We measured and compared the Visual Analog Score (VAS), Neuropathy Pain Scale (NPS), Quality of Life Scale (SF-36) score, PNH seizure severity degree, seizure duration, frequency of attack and the...

  1. Botulinum toxin uses in strabismus: A review of the injections performed during one year in a general hospital.

    Science.gov (United States)

    Jarrín, E; Arranz Márquez, E; Yebra González, L; García Gil de Bernabé, J

    2016-03-01

    To analyse the indications, dosage and efficacy of botulinum toxin A injection performed in patients in a Strabismus Department. In this prospective study, botulinum toxin A was injected into 28 patients diagnosed with strabismus. Data was obtained from the records of patients that were evaluated during 2013 in the Strabismus Unit of Rey Juan Carlos Hospital (Móstoles, Madrid, Spain) in order to assess the indications and dosage of botulinum toxin A use in strabismus, as well as its clinical effect and differences in paediatric and adult patients. The outcomes in the last visit, at least 14 months after the injections, were analysed. An analysis was performed on the data from 11 children, 6 females (54.5%), and 17 adults, 11 males (64%). The mean age was 4.42±3.48 years and 58.71±18.07 years in the children and adult groups, respectively. The majority of cases in both groups were esotropia (81.8% in children and 47.1% in adults). However the pathologies in the adult group were quite heterogeneous, including 4 patients with exotropia (26.5%), 4 with hypertropia (26.5%), and one with isolated nystagmus (5.9%). The mean number of the botulinum toxin injections in children was 1.45±0.93, although 72.7% received a single injection. In the adult group, the mean number of injections was 3.27±1.41. There was a statistically significant difference between pre- and post-injection in the tropia and phoria measurements in children and adults group (Ptoxin injection, whereas 2 needed surgery for diplopia correction. Botulinum toxin is a very useful tool in the management of strabismus, obtaining better sensory and motor results in children, but it is also effective as a symptomatic treatment in some types of strabismus in adults. Copyright © 2015 Sociedad Española de Oftalmología. Published by Elsevier España, S.L.U. All rights reserved.

  2. Thickened Saliva after Effective Management of Drooling with Botulinum Toxin A

    Science.gov (United States)

    Erasmus, Corrie E.; van Hulst, Karen; van den Hoogen, Frank J. A.; van Limbeek, Jacques; Roeleveld, Nel; Veerman, Enno C. I.; Rotteveel, Jan J.; Jongerius, Peter H.

    2010-01-01

    Aim: The aim of this study was to evaluate the rheological properties of saliva after submandibular botulinum toxin type A (BoNT-A) injections. Method: We enrolled 15 children (11 males and six females; age range 3-17y, mean age 9y 10mo) diagnosed with spastic (n=9) or dyskinetic (n=6) quadriplegic cerebral palsy (CP); Gross Motor Function…

  3. A Monoclonal Antibody Based Capture ELISA for Botulinum Neurotoxin Serotype B: Toxin Detection in Food

    Directory of Open Access Journals (Sweden)

    Larry H. Stanker

    2013-11-01

    Full Text Available Botulism is a serious foodborne neuroparalytic disease, caused by botulinum neurotoxin (BoNT, produced by the anaerobic bacterium Clostridium botulinum. Seven toxin serotypes (A–H have been described. The majority of human cases of botulism are caused by serotypes A and B followed by E and F. We report here a group of serotype B specific monoclonal antibodies (mAbs capable of binding toxin under physiological conditions. Thus, they serve as capture antibodies for a sandwich (capture ELISA. The antibodies were generated using recombinant peptide fragments corresponding to the receptor-binding domain of the toxin heavy chain as immunogen. Their binding properties suggest that they bind a complex epitope with dissociation constants (KD’s for individual antibodies ranging from 10 to 48 × 10−11 M. Assay performance for all possible combinations of capture-detector antibody pairs was evaluated and the antibody pair resulting in the lowest level of detection (L.O.D., ~20 pg/mL was determined. Toxin was detected in spiked dairy samples with good recoveries at concentrations as low as 0.5 pg/mL and in ground beef samples at levels as low as 2 ng/g. Thus, the sandwich ELISA described here uses mAb for both the capture and detector antibodies (binding different epitopes on the toxin molecule and readily detects toxin in those food samples tested.

  4. A monoclonal antibody based capture ELISA for botulinum neurotoxin serotype B: toxin detection in food.

    Science.gov (United States)

    Stanker, Larry H; Scotcher, Miles C; Cheng, Luisa; Ching, Kathryn; McGarvey, Jeffery; Hodge, David; Hnasko, Robert

    2013-11-18

    Botulism is a serious foodborne neuroparalytic disease, caused by botulinum neurotoxin (BoNT), produced by the anaerobic bacterium Clostridium botulinum. Seven toxin serotypes (A-H) have been described. The majority of human cases of botulism are caused by serotypes A and B followed by E and F. We report here a group of serotype B specific monoclonal antibodies (mAbs) capable of binding toxin under physiological conditions. Thus, they serve as capture antibodies for a sandwich (capture) ELISA. The antibodies were generated using recombinant peptide fragments corresponding to the receptor-binding domain of the toxin heavy chain as immunogen. Their binding properties suggest that they bind a complex epitope with dissociation constants (KD's) for individual antibodies ranging from 10 to 48 × 10-11 M. Assay performance for all possible combinations of capture-detector antibody pairs was evaluated and the antibody pair resulting in the lowest level of detection (L.O.D.), ~20 pg/mL was determined. Toxin was detected in spiked dairy samples with good recoveries at concentrations as low as 0.5 pg/mL and in ground beef samples at levels as low as 2 ng/g. Thus, the sandwich ELISA described here uses mAb for both the capture and detector antibodies (binding different epitopes on the toxin molecule) and readily detects toxin in those food samples tested.

  5. Quantitative determination of biological activity of botulinum toxins utilizing compound muscle action potentials (CMAP), and comparison of neuromuscular transmission blockage and muscle flaccidity among toxins.

    Science.gov (United States)

    Torii, Yasushi; Goto, Yoshitaka; Takahashi, Motohide; Ishida, Setsuji; Harakawa, Tetsuhiro; Sakamoto, Takashi; Kaji, Ryuji; Kozaki, Shunji; Ginnaga, Akihiro

    2010-01-01

    The biological activity of various types of botulinum toxin has been evaluated using the mouse intraperitoneal LD(50) test (ip LD(50)). This method requires a large number of mice to precisely determine toxin activity, and so has posed a problem with regard to animal welfare. We have used a direct measure of neuromuscular transmission, the compound muscle action potential (CMAP), to evaluate the effect of different types of botulinum neurotoxin (NTX), and we compared the effects of these toxins to evaluate muscle relaxation by employing the digit abduction scoring (DAS) assay. This method can be used to measure a broad range of toxin activities the day after administration. Types A, C, C/D, and E NTX reduced the CMAP amplitude one day after administration at below 1 ip LD(50), an effect that cannot be detected using the mouse ip LD(50) assay. The method is useful not only for measuring toxin activity, but also for evaluating the characteristics of different types of NTX. The rat CMAP test is straightforward, highly reproducible, and can directly determine the efficacy of toxin preparations through their inhibition of neuromuscular transmission. Thus, this method may be suitable for pharmacology studies and the quality control of toxin preparations. Copyright 2009 Elsevier Ltd. All rights reserved.

  6. [Advantages of combined therapies in cosmetic medicine for the treatment of face aging: botulinum toxin, fillers and mesotherapy].

    Science.gov (United States)

    Braccini, F; Dohan Ehrenfest, D M

    2010-01-01

    Non surgical cosmetic medicine procedures for the face are developing considerably, as they deliver good results using simple, non invasive, atraumatic and reproducible techniques. Aesthetic mesotherapy, also known as anti-aging mesotherapy, uses intra-dermal injections of a nutritive and moisturizing solution to improve brightness, skin hydration and tonus, and also smooth out superficial wrinkles. Subcutaneous filler injections enable to fill wrinkles and folds; by using high density products it is also able to provide genuine facial volumetric reconstruction. Finally, botulinum toxin acts by reducing certain muscle contractions to smooth out expression lines and folds induced by facial dynamics. In this article, we explore the concept of combined therapy and describe our experience associating anti-aging mesotherapy (NCTF-135HA, Filorga, Paris, France), hyaluronic acid based fillers (X-HA3 and X-HA-Volume, Filorga, Paris, France) and botulinum toxin (Vistabel, Allergan, Irvine CA, USA). A therapy combining anti-aging mesotherapy, botulinum toxin and filler injections, offers full treatment of the 3 biological levels of the covering tissues. This non-invasive therapeutic strategy brings patient satisfaction through a global approach to facial aging.

  7. Anticholinergic versus botulinum toxin A comparison trial for the treatment of bothersome urge urinary incontinence: ABC trial.

    Science.gov (United States)

    Visco, Anthony G; Brubaker, Linda; Richter, Holly E; Nygaard, Ingrid; Paraiso, Marie Fidela; Menefee, Shawn A; Schaffer, Joseph; Wei, John; Chai, Toby; Janz, Nancy; Spino, Cathie; Meikle, Susan

    2012-01-01

    This trial compares the change in urgency urinary incontinence episodes over 6 months, tolerability and cost effectiveness between women receiving daily anticholinergic therapy plus a single intra-detrusor injection of saline versus a single intra-detrusor injection of 100 U of botulinum toxin A plus daily oral placebo tablets. We present the rationale and design of a randomized-controlled trial, Anticholinergic versus Botulinum Toxin, Comparison Trial for the Treatment of Bothersome Urge Urinary Incontinence: ABC trial, conducted by the NICHD-funded Pelvic Floor Disorders Network. We discuss the innovative nature of this trial and the challenges related to choice of patient population, maintaining masking, cost effectiveness, ethical considerations, measuring adherence, and placebo development and testing. Enrollment began in April, 2010. 242 participants will be randomized and primary outcome data analysis is anticipated to begin in mid 2012. Several challenges in the trial design are discussed. Randomization to placebo intra-detrusor injections may limit recruitment, potentially impacting generalizability. Other challenges included the heavy marketing of drugs for overactive bladder which could impact recruitment of drug-naïve women. In addition, anticholinergic medications often cause dry mouth, making masking difficult. Finally, adverse reporting of transient urinary retention is challenging as there is no standardized definition; yet this is the most common adverse event following intra-detrusor botulinum toxin injection. The ABC trial will help women with urgency urinary incontinence balance efficacy, side effects and cost of anticholinergic medication versus botulinum toxin intra-detrusor injection. The results have the potential to fundamentally change the therapeutic approach to this condition. Copyright © 2011 Elsevier Inc. All rights reserved.

  8. Botulinum toxin: An emerging therapy in female bladder outlet obstruction

    Directory of Open Access Journals (Sweden)

    Aditya A Pradhan

    2009-01-01

    Discussion: There is a gradual improvement in symptoms over time and the maximal effect occurred at 10-14 days. The duration of improvement was approximately 16.8 weeks. All patients were satisfied by the degree of improvement felt. Conclusions: Botulinum toxin proved successful in improving the voiding characteristics. It possibly acts at the zone of hypertonicity at the bladder neck or midurethra. The only disadvantage is the high cost of the drug.

  9. Sustained improvement of reading symptoms following botulinum toxin A injection for convergence insufficiency

    DEFF Research Database (Denmark)

    Saunte, Jon Peiter; Holmes, Jonathan M

    2014-01-01

    .008) at near, although 2 patients had a temporary intermittent esotropia in the distance with diplopia associated with difficulty driving. At 6 months, when the pharmacological effect of botulinum toxin had completely worn off, patients still maintained a small reduction of exodeviation (median 4 PD, p=0...

  10. Long-Term Resolution of Severe Ankle Contractures Using Botulinum Toxin, Serial Casting, Splinting, and Motor Retraining.

    Science.gov (United States)

    Leung, Joan; Stroud, Katarina

    2018-01-01

    Purpose: Serial casting for ankle contractures is traditionally performed in prone, a position that patients may not easily tolerate. Also, although serial casting is effective in correcting contracture, its effect dissipates quickly. This case report describes a procedure for performing casting for ankle contractures in a supine or sitting position. It also describes a process that enables the effect of serial casting to be maintained long term. Client Description: The client was an adult who had suffered traumatic brain injury and severe bilateral ankle contractures. Intervention: He received botulinum toxin and serial casting for his bilateral ankle contractures, one ankle at 8 months and the other at 13 months after the injury. He then underwent a programme of splinting and motor training. Measures and Outcome: The client gained more than 40° dorsiflexion for both ankles after receiving botulinum toxin injections and serial casting. The improvement in ankle range enabled him to progress to walking practice. Ankle splinting was gradually reduced. On discharge at 25 months post-injury, the ankle joint range was maintained. Implications: The use of botulinum toxin and serial casting, followed by an intensive programme of splinting and motor training, may be an option to consider for effective long-term resolution of severe contractures after acquired brain injury.

  11. The Role of Botulinum Toxin Type A in the Clinical Management of Refractory Anterior Knee Pain

    Directory of Open Access Journals (Sweden)

    Barbara J. Singer

    2015-08-01

    Full Text Available Anterior knee pain is a highly prevalent condition affecting largely young to middle aged adults. Symptoms can recur in more than two thirds of cases, often resulting in activity limitation and reduced participation in employment and recreational pursuits. Persistent anterior knee pain is difficult to treat and many individuals eventually consider a surgical intervention. Evidence for long term benefit of most conservative treatments or surgical approaches is currently lacking. Injection of Botulinum toxin type A to the distal region of vastus lateralis muscle causes a short term functional “denervation” which moderates the influence of vastus lateralis muscle on the knee extensor mechanism and increases the relative contribution of the vastus medialis muscle. Initial data suggest that, compared with other interventions for anterior knee pain, Botulinum toxin type A injection, in combination with an active exercise programme, can lead to sustained relief of symptoms, reduced health care utilisation and increased activity participation. The procedure is less invasive than surgical intervention, relatively easy to perform, and is time- and cost-effective. Further studies, including larger randomized placebo-controlled trials, are required to confirm the effectiveness of Botulinum toxin type A injection for anterior knee pain and to elaborate the possible mechanisms underpinning pain and symptom relief.

  12. Treating glabellar lines with botulinum toxin type A-hemagglutinin complex: A review of the science, the clinical data, and patient satisfaction

    Directory of Open Access Journals (Sweden)

    Koenraad De Boulle

    2010-04-01

    Full Text Available Koenraad De Boulle1, Steven Fagien2, Boris Sommer3, Richard Glogau41Aalst Dermatology Clinic, Aalst, Belgium; 2Aesthetic Eyelid Plastic, Surgery, Boca Raton, FL, USA; 3Aesthetic Dermatology, Frankfurt, Germany; 4University of California, San Francisco, USAAbstract: Botulinum toxin type A treatment is the foundation of minimally invasive aesthetic facial procedures. Clinicians and their patients recognize the important role, both negative and positive, that facial expression, particularly the glabellar frown lines, plays in self-perception, emotional well-being, and perception by others. This article provides up-to-date information on fundamental properties and mechanisms of action of the major approved formulations of botulinum toxin type A, summarizes recent changes in naming conventions (nonproprietary names mandated by the United States Food and Drug Administration, and describes the reasons for these changes. The request for these changes provides recognition that formulations of botulinum toxins (eg, onabotulinumtoxinA and abobotulinumtoxinA are not interchangeable and that dosing recommendations cannot be based on any one single conversion ratio. The extensive safety, tolerability, and efficacy data are summarized in detail, including the patient-reported outcomes that contribute to overall patient satisfaction and probability treatment continuation. Based on this in-depth review, the authors conclude that botulinum toxin type A treatment remains a cornerstone of facial aesthetic treatments, and clinicians must realize that techniques and dosing from one formulation cannot be applied to others, that each patient should undergo a full aesthetic evaluation, and that products and procedures must be selected in the context of individual needs and goals.Keywords: onabotulinumtoxinA, botulinum toxin type A, cosmetic, glabellar, patient satisfaction

  13. Computer-Aided Design/Computer-Assisted Manufacture-Derived Needle Guide for Injection of Botulinum Toxin into the Lateral Pterygoid Muscle in Patients with Oromandibular Dystonia.

    Science.gov (United States)

    Yoshida, Kazuya

    2018-01-01

    To evaluate the effectiveness and safety of botulinum toxin administration into the inferior head of the lateral pterygoid muscle of patients with jaw opening dystonia by using a computer-aided design/computer-assisted manufacture (CAD/CAM)-derived needle guide. A total of 17 patients with jaw opening dystonia were enrolled. After the patient's computed tomography (CT) scan was imported and fused with a scan of a plaster cast model of the maxilla, the optimal needle insertion site over the lateral pterygoid muscle was determined using the NobelClinician software. A total of 13 patients were injected both with and without the guide, and 4 patients underwent guided injection alone. The therapeutic effects of botulinum toxin injection and its associated complications were statistically compared between the guided and unguided procedures using paired t test. Botulinum toxin therapy was performed 42 and 32 times with and without the guides, respectively. The needle was easily inserted without any complications in all procedures. There was a significant difference (P < .001) between the mean comprehensive improvements observed with (66.3%) and without (54.4%) the guides. The findings suggest that the use of needle guides during the injection of botulinum toxin into the inferior head of the lateral pterygoid muscle is very useful for aiding the accurate and safe administration of botulinum toxin therapy for jaw opening dystonia.

  14. Investigation of inactivation of Clostridium botulinum toxin by nuclear radiation. Final report. Untersuchung zur Desaktivierung des Clostridium botulinum Toxins durch Kernstrahlung. Endbericht

    Energy Technology Data Exchange (ETDEWEB)

    Kaltenhaeuser, A.; Werner, K.H.

    1989-01-01

    The effect of nuclear radiation on the toxicity and the molecular structure of the toxin produced by the microorganism Clostridium botulinum type A was investigated. The radiation induced changes in the structure of the toxin molecule. This effect is influenced by the composition or the medium above the toxin solution as well as by the temperature during the irradiation. The results of the investigation indicate that with increasing irradiation dose a new molecule was formed with immunological properties similar to the properties of the original molecule however with a greater molecular weight. After exposure to a radiation dose of 3,4 Mrad at normal temperature in air, complete detoxification of the substance was found. Immunizing experiments with the toxoid with two guinea-pigs indicated a pronounced increase of the antibody titer in the serum after 4 weeks. Vaccination experiments with the toxoid on animals show, that the protection against the effect of the toxin corresponds to the demands of the European Pharmacopoeia. The efficiency of the toxoid shows a similar efficiency as toxoids produced by chemical methods. The production of a toxoid-viccine with the relatively simple method of nuclear radiation appears possible. (orig./MG) With 12 refs., 3 tabs., 11 figs.

  15. Botulinum Toxin Therapy: Is Syringe Type Related to Cost-Effectiveness?

    Science.gov (United States)

    Foglietti, Mark Anthony; Wright, Lauren; Foglietti-Fostyk, Alanna

    2018-03-01

    Clostridium botulinum toxin is effective through cleaving presynaptic proteins at the neuromuscular junction, which prevents the release of acetylcholine and inhibits muscle contraction. Several serotypes of botulinum toxin (BT) exist; however, only 2 types have been approved by the US Food and Drug Administration for commercial and medical use, A and B. Both types of BT must be administered intramuscularly with a syringe, but the type of syringe is the injector's preference. Which syringe type is most efficient in minimizing product waste and most cost-effective for the patient and provider? We performed a single-center, open-label, analytical study using BT therapy and 2 types of syringes for analytics of cost-effectiveness. OnabotulinumtoxinA was the neuromodulator used in this report. Vials (100 U) of BT A were each reconstituted with 2.5 mL of 0.9% sodium chloride, for a final concentration of 4 U/0.1 mL. High-dead-space syringes are compared with low-dead-space syringes: 1-mL tuberculin (TB) luer slip syringe with detachable 25-gauge needle and 1-mL ultrafine insulin syringe with an attached 31-gauge needle, respectively. After each syringe was evacuated, the TB syringe was noted to contain 0.05 mL of the remaining product in the hub. Providers are discarding approximately 2 U of BT per TB syringe product injection. If the physician uses 30 syringes per day, 3 days a week, for 1 year, it equals to a lost revenue of approximately $155,500 per year. To individualize the cost-effective analysis, average quantity of syringes used per patient and overall patient volume must be considered, with corresponding adjustment of cost and units discarded. The American Society of Plastic Surgeons reported that the use of neuromodulators has increased by approximately 797% from 2000 to 2016. During that period, the price of neuromodulators has also increased by approximately 85%. Considering these statistics, the type of syringe used for BT neuromodular injection is a

  16. Botulinum toxin for treating unilateral apraxia of eyelid opening in a patient with congenital myotonia

    Directory of Open Access Journals (Sweden)

    Estrella Fernández

    Full Text Available ABSTRACT A 37-year-old female presented with severe apraxia of lid opening (ALO affecting the right upper lid associated with Becker congenital myotonia (MC. The patient had a history of right upper lid ptosis for 25 years that was exacerbated over the previous month with severe incapacity to open her right eye. No other associated neurological or ophthalmic symptoms were observed. The patient was treated with botulinum toxin (BoNT-A injection into the pretarsal and lateral canthus region of the orbicularis oculi of the affected eyelid. Treatment with BoNT-A is an effective method of managing ALO in Becker MC. This is the first case of unilateral ALO in the course of Becker MC that was successfully treated with injections of botulinum toxin.

  17. The botulinum toxin as a therapeutic agent: molecular and pharmacological insights

    Directory of Open Access Journals (Sweden)

    Kukreja R

    2015-12-01

    Full Text Available Roshan Kukreja,1 Bal Ram Singh2 1Department of Chemistry and Biochemistry, University of Massachusetts, 2Botulinum Research Center, Institute of Advanced Sciences, Dartmouth, MA, USA Abstract: Botulinum neurotoxins (BoNTs, the most potent toxins known to mankind, are metalloproteases that act on nerve–muscle junctions to block exocytosis through a very specific and exclusive endopeptidase activity against soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE proteins of presynaptic vesicle fusion machinery. This very ability of the toxins to produce flaccid muscle paralysis through chemical denervation has been put to good use, and these potentially lethal toxins have been licensed to treat an ever expanding list of medical disorders and more popularly in the field of esthetic medicine. In most cases, therapeutic BoNT preparations are high-molecular-weight protein complexes consisting of BoNT, complexing proteins, and excipients. There is at least one isolated BoNT, which is free of complexing proteins in the market (Xeomin®. Each commercially available BoNT formulation is unique, differing mainly in molecular size and composition of complexing proteins, biological activity, and antigenicity. BoNT serotype A is marketed as Botox®, Dysport®, and Xeomin®, while BoNT type B is commercially available as Myobloc®. Nerve terminal intoxication by BoNTs is completely reversible, and the duration of therapeutic effects of BoNTs varies for different serotypes. Depending on the target tissue, BoNTs can block the cholinergic neuromuscular or cholinergic autonomic innervation of exocrine glands and smooth muscles. Therapeutic BoNTs exhibit a high safety and very limited adverse effects profile. Despite their established efficacy, the greatest concern with the use of therapeutic BoNTs is their propensity to elicit immunogenic reactions that might render the patient unresponsive to subsequent treatments, particularly in chronic

  18. Why do females use botulinum toxin injections?

    Directory of Open Access Journals (Sweden)

    Carter Singh

    2015-01-01

    Full Text Available Background: Botulinum toxin (BT use for enhancing the facial features has become a commonly accepted form of aesthetic intervention. This study conducted a self-report survey of female BT users in order to explore the motivating factors in its use (cost-benefit analysis. Settings and Design: This is a cross-sectional exploratory pilot study. Materials and Methods: Self-report questionnaires were administered to 41 consecutive clients attending an independent medical practice for BT injections for cosmetic purposes. All the participants were females and represented a range of age groups from the 20s to above 60s. Items in the nonstandardized questionnaire elicited questions relating to the reasons for and against BT use. Statistical Analysis Used: Descriptive analysis was used rather than inferential statistics, and involved ranking the responses according to the most likely reasons for using BT and disadvantages of its use. Results: In general, the primary motivating factor for BT use was to improve self-esteem, and the greatest disadvantage involved financial costs associated with the procedure. Conclusions: The main findings of this study suggest that females who use BT for aesthetic purposes are motivated by personal psychological gains (intrapersonal attributes rather than social gains (interpersonal factors. In other words, they do not believe that having BT will equate to being treated any better by other people but would rather provide them with confidence and satisfaction regarding their self-image.

  19. Efficacy of Repeated Botulinum Toxin Type A Injections for Spastic Equinus in Children with Cerebral Palsy-A Secondary Analysis of the Randomized Clinical Trial.

    Science.gov (United States)

    Hong, Bo Young; Chang, Hyun Jung; Lee, Sang-Jee; Lee, Soyoung; Park, Joo Hyun; Kwon, Jeong-Yi

    2017-08-21

    Botulinum toxin A is considered an important tool to control spasticity in children with cerebral palsy. Several factors are known to affect the efficacy of botulinum toxin, such as dosage, appropriate muscle selection and application, age, and accompanying therapy. A multicenter, double-blind, randomized, prospective phase III clinical trial of botulinum toxin A for the treatment of dynamic equinus in 144 children with cerebral palsy was performed to compare the efficacies of letibotulinumtoxin A and onabotulinumtoxin A. Secondary analyses were performed to evaluate factors that affected the outcome, focusing on the number of times injections were repeated. Effectiveness was defined as a change of 2 or more in the physician's rating scale. Multivariate regression analyses were performed with multiple variables. The first injection of botulinum toxin A significantly improved D subscale of Gross Motor Function Measure-88 scores at 3 months compared to repeated injections ( p < 0.05). After 6 months, patients who had one injection or none before the study showed significantly better outcomes than those who had more than one injection in terms of observational gait scores.

  20. Modulation of urinary bladder innervation: TRPV1 and botulinum toxin A.

    Science.gov (United States)

    Charrua, Ana; Avelino, António; Cruz, Francisco

    2011-01-01

    The persisting interest around neurotoxins such as vanilloids and botulinum toxin (BoNT) derives from their marked effect on detrusor overactivity refractory to conventional antimuscarinic treatments. In addition, both are administered by intravesical route. This offers three potential advantages. First, intravesical therapy is an easy way to provide high concentrations of pharmacological agents in the bladder tissue without causing unsuitable levels in other organs. Second, drugs effective on the bladder, but inappropriate for systemic administration, can be safely used as it is the case of vanilloids and BoNT. Third, the effects of one single treatment might be extremely longlasting, contributing to render these therapies highly attractive to patients despite the fact that the reasons to the prolonged effect are still incompletely understood. Attractive as it may be, intravesical pharmacological therapy should still be considered as a second-line treatment in patients refractory to conventional oral antimuscarinic therapy or who do not tolerate its systemic side effects. However, the increasing off-label use of these neurotoxins justifies a reappraisal of their pharmacological properties.

  1. Use of Botulinum toxin in 55 children with cerebral palsy

    Directory of Open Access Journals (Sweden)

    Mohammadi M

    2000-10-01

    Full Text Available Botulinum toxin A (BTA inhibits presynaptic release of acetylcholine at the neuromuscular junction and has reportedly been successful in the treatment of spastic disorders.To evaluate the effect of botulinum toxin on cerebral palsied children with spastic or mixed type of the disease, especially those patiens having spasticity as a cardinal symptom without joint contracture, we designed the following study. Ninety-one cases (55 of referred patients to pediatic Neurology outpatient clinics of children’s Medical Center were given BTA injections in affected muscles of the lower limb. They were reevaluating 3 to 5 weeks and 3 months later for type of walking and range of affected joints’ movement. The study showed a clinically significant gait improvement in 71.2% of patients (P<0.0005 and also an overall increased range of motion in affected limbs after BTA injection (P<0.04. Side effects occurred only in two cases as transient generalized weakness, gent recurvatum and ptosis. Drug effectiveness was time-limited, lasting abot 3 months in all patients ( a golden time for rehabilitation therapists to improve the patients’ condition. Overall, BTA has improved both the type of walking as well as the range of joints motion in our patients. So its’ administration is suggested in cerebral palsied children if the spasticity is a major and disabling sign

  2. Use of botulinum toxin-A for musculoskeletal pain in patients with whiplash associated disorders [ISRCTN68653575

    Directory of Open Access Journals (Sweden)

    Juan Francisco J

    2004-02-01

    Full Text Available Abstract Background Whiplash associated disorder is commonly linked to motor vehicle accidents and sports injuries. Cervical injury is attributed to rapid extension followed by neck flexion. The exact pathophysiology of whiplash is uncertain but probably involves some degree of aberrant muscle spasms and may produce a wide range of symptoms. The most commonly prescribed pharmacological agents for initial treatment of whiplash-associated pain are oral muscle relaxants and nonsteroidal anti-inflammatory drugs. However, potential systemic adverse effects limit these agents. Physical interventions such as mobilization, manipulation, and exercises have proved beneficial for pain and dysfunction but only on a time-limited basis. Little evidence suggests that physical therapy specifically aimed at the musculature (e.g., transcutaneous electrical nerve stimulation, ultrasonography, heat, ice, and acupuncture improves prognosis in acute whiplash associated disorder. A new approach to treatment is the use of botulinum toxin, which acts to reduce muscle spasms. Methods/design This is a prospective, randomized, controlled clinical trial and botulinum toxin-A (Botox® injections will be compared with placebo injections. The primary objective is to determine the efficacy of Botox® in the management of musculoskeletal pain in whiplash associated disorders. Discussion Botulinum toxin type-A toxin has been studied in small trials on whiplash associated disorder patients and has generally been found to relieve pain and improve range of motion. Specifically, we seek to assess the efficacy of Botox® in reducing pain and to improve the cervical spine range of movement, during the 6-month trial period.

  3. Dynamic Model of Applied Facial Anatomy with Emphasis on Teaching of Botulinum Toxin A

    Directory of Open Access Journals (Sweden)

    Ricardo Frota Boggio, MD, PhD

    2017-11-01

    Conclusion:. By making it possible to interrelate anatomy of a function, body painting is proposed in the present study as an innovative method, which in a demonstrative and highly didactic manner presents great potential as a teaching tool in the application of botulinum toxin A.

  4. Clinical Study of New Tetravalent (Type A, B, E, and F) Botulinum Toxoid Vaccine Derived from M Toxin in Japan.

    Science.gov (United States)

    Torii, Yasushi; Sugimoto, Nakaba; Kohda, Tomoko; Kozaki, Shunji; Morokuma, Kazunori; Horikawa, Yoshikane; Ginnaga, Akihiro; Yamamoto, Akihiko; Takahashi, Motohide

    2017-07-24

    Botulinum toxin is the most poisonous substance known, and is believed to be a highly lethal as a biological weapon; researchers of the toxin are exposed to this hazard. Botulinum toxoid vaccines have been produced and used in Japan. However, since clinical studies involving these vaccines were conducted before establishment of the Ethical Guidelines for Clinical Research in Japan, their immunogenicity and safety were not systematically assessed. In this study, we produced a new tetravalent (type A, B, E, and F) botulinum toxoid vaccine, the first ever to be derived from M toxin, and conducted quality control tests with reference to the Minimum Requirements in Japan for adsorbed tetanus toxoid vaccine. Subsequently, a clinical study using the new vaccine in 48 healthy adult volunteers was conducted according to the guidelines in Japan. No clinically serious adverse event was noted. Neutralizing antibody titers for each type of toxin in the participants' sera, 1 month after the 4th injection were more than 0.25 IU/mL, indicating sufficient protection. This study demonstrated that the vaccine has marked immunogenicity and is safe for use in humans.

  5. Treating glabellar lines with botulinum toxin type A-hemagglutinin complex: a review of the science, the clinical data, and patient satisfaction.

    Science.gov (United States)

    De Boulle, Koenraad; Fagien, Steven; Sommer, Boris; Glogau, Richard

    2010-04-26

    Botulinum toxin type A treatment is the foundation of minimally invasive aesthetic facial procedures. Clinicians and their patients recognize the important role, both negative and positive, that facial expression, particularly the glabellar frown lines, plays in self-perception, emotional well-being, and perception by others. This article provides up-to-date information on fundamental properties and mechanisms of action of the major approved formulations of botulinum toxin type A, summarizes recent changes in naming conventions (nonproprietary names) mandated by the United States Food and Drug Administration, and describes the reasons for these changes. The request for these changes provides recognition that formulations of botulinum toxins (eg, onabotulinumtoxinA and abobotulinumtoxinA) are not interchangeable and that dosing recommendations cannot be based on any one single conversion ratio. The extensive safety, tolerability, and efficacy data are summarized in detail, including the patient-reported outcomes that contribute to overall patient satisfaction and probability treatment continuation. Based on this in-depth review, the authors conclude that botulinum toxin type A treatment remains a cornerstone of facial aesthetic treatments, and clinicians must realize that techniques and dosing from one formulation cannot be applied to others, that each patient should undergo a full aesthetic evaluation, and that products and procedures must be selected in the context of individual needs and goals.

  6. Growth of and toxin production by nonproteolytic Clostridium botulinum in cooked puréed vegetables at refrigeration temperatures.

    Science.gov (United States)

    Carlin, F; Peck, M W

    1996-01-01

    Seven strains of nonproteolytic Clostridium botulinum (types B, E, and F) were each inoculated into a range of anaerobic cooked puréed vegetables. After incubation at 10 degrees C for 15 to 60 days, all seven strains formed toxin in mushrooms, five did so in broccoli, four did so in cauliflower, three did so in asparagus, and one did so in kale. Growth kinetics of nonproteolytic C. botulinum type B in cooked mushrooms, cauliflower, and potatoes were determined at 16, 10, 8, and 5 degrees C. Growth and toxin production occurred in cooked cauliflower and mushrooms at all temperatures and in potatoes at 16 and 8 degrees C. The C. botulinum neurotoxin was detected within 3 to 5 days at 16 degrees C, 11 to 13 days at 10 degrees C, 10 to 34 days at 8 degrees C, and 17 to 20 days at 5 degrees C. PMID:8702303

  7. Botulinum toxin to improve results in cleft lip repair: a double-blinded, randomized, vehicle-controlled clinical trial.

    Directory of Open Access Journals (Sweden)

    Chun-Shin Chang

    Full Text Available Most patients with facial scarring would value even a slight improvement in scar quality. Botulinum toxin A is widely used to alleviate facial dynamic rhytides but is also believed to improve scar quality by reducing wound tension during healing. The main objective was to assess the effect of Botulinum toxin on scars resultant from standardized upper lip wounds.In this double-blinded, randomized, vehicle-controlled, prospective clinical trial, 60 consecutive consenting adults undergoing cleft lip scar revision (CLSR surgery between July 2010 and March 2012 were randomized to receive botulinum toxin A (n = 30 or vehicle (normal saline; n = 30 injections into the subjacent orbicularis oris muscle immediately after wound closure. Scars were independently assessed at 6-months follow-up in blinded fashion using: Vancouver Scar Scale (VSS, Visual Analogue Scale (VAS and photographic plus ultrasound measurements of scar widths.58 patients completed the trial. All scar assessment modalities revealed statistically significantly better scars in the experimental than the vehicle-control group.Quality of surgical upper lip scars, which are oriented perpendicular to the direction of pull of the underlying orbicularis oris muscle, is significantly improved by its temporary paralysis during wound healing.ClinicalTrials.gov NCT01429402.

  8. Clostridium botulinum serotype D neurotoxin and toxin complex bind to bovine aortic endothelial cells via sialic acid.

    Science.gov (United States)

    Yoneyama, Tohru; Miyata, Keita; Chikai, Tomoyuki; Mikami, Akifumi; Suzuki, Tomonori; Hasegawa, Kimiko; Ikeda, Toshihiko; Watanabe, Toshihiro; Ohyama, Tohru; Niwa, Koichi

    2008-12-01

    Botulinum neurotoxin (BoNT) is produced as a large toxin complex (L-TC) associated with nontoxic nonhemagglutinin (NTNHA) and three hemagglutinin subcomponents (HA-70, -33 and -17). The binding properties of BoNT to neurons and L-TC to intestinal epithelial cells are well documented, while those to other tissues are largely unknown. Here, to obtain novel insights into the pathogenesis of foodborne botulism, we examine whether botulinum toxins bind to vascular endothelial cells. BoNT and 750 kDa L-TC (a complex of BoNT, NTNHA and HAs) of Clostridium botulinum serotype D were incubated with bovine aortic endothelial cells (BAECs), and binding to the cells was assessed using sodium dodecyl sulfate polyacrylamide gel electrophoresis and Western blot. Both BoNT and L-TC bound to BAECs, with L-TC showing stronger binding. Binding of BoNT and L-TC to BAECs was significantly inhibited by N-acetyl neuraminic acid in the cell culture medium or by treatment of the cells with neuraminidase. However, galactose, lactose or N-acetyl galactosamine did not significantly inhibit toxin binding to the cells. This is the first report demonstrating that BoNT and L-TC bind to BAECs via sialic acid, and this mechanism may be important in the trafficking pathway of BoNT in foodborne botulism.

  9. Botulinum toxin-induced acute anterior uveitis in a patient with Behçet's disease under infliximab treatment: a case report.

    Science.gov (United States)

    Sasajima, Hirofumi; Yagi, Syunsuke; Osada, Hiromu; Zako, Masahiro

    2017-05-04

    Injections of lipopolysaccharide in animal models generate acute anterior uveitis (also known as endotoxin-induced uveitis), but the effects of lipopolysaccharide injection are unknown in humans. We describe an unusual case in which acute anterior uveitis was dramatically activated subsequent to botulinum toxin injection in a patient with Behçet's disease but the acute anterior uveitis was satisfactorily attenuated by infliximab. A 53-year-old Japanese man had normal ocular findings at his regularly scheduled appointment. He had been diagnosed as having incomplete-type Behçet's disease 11 years before. Three years after the diagnosis he was given systemic infusions of 5 mg/kg infliximab every 8 weeks and he had not experienced a uveitis attack for 8 years with no treatment other than infliximab. Two days after the eye examination, he received intracutaneous botulinum toxin injections to treat axillary hyperhidrosis on both sides. Three hours after the injections, he noted rapidly increasing floaters in his right eye. Four days after the injections, his right eye showed severe acute anterior uveitis with deteriorated aqueous flare and anterior vitreous opacity. He received his scheduled infliximab injection, and the right acute anterior uveitis immediately attenuated. Botulinum toxin may have clinical effects similar to those of lipopolysaccharide in endotoxin-induced uveitis models. To the best of our knowledge, this is the first report to suggest that botulinum toxin may trigger acute anterior uveitis, although the precise mechanism is still unclear.

  10. Botulinum toxin A injection for chronic anal fissures and anal sphincter spasm improves quality of life in recessive dystrophic epidermolysis bullosa

    Directory of Open Access Journals (Sweden)

    Cassandra Chaptini, MBBS

    2015-12-01

    Full Text Available We report a 20-year-old female with generalized, severe, recessive dystrophic epidermolysis bullosa who developed secondary chronic anal fissures. This resulted in anal sphincter spasm and severe, disabling pain. She was treated with five botulinum toxin A injections into the internal anal sphincter over a period of 2 years and gained marked improvement in her symptoms. This case demonstrates the successful use of botulinum toxin A injections to relieve anal sphincter spasm and fissuring, with long-term improvement.

  11. Sensory integration in writer's cramp: comparison with controls and evaluation of botulinum toxin effect

    NARCIS (Netherlands)

    Contarino, M. F.; Kruisdijk, J. J. M.; Koster, L.; Ongerboer de Visser, B. W.; Speelman, J. D.; Koelman, J. H. T. M.

    2007-01-01

    OBJECTIVE: Abnormal temporal and spatial sensory integration have been described in mixed groups of dystonic patients. We tested somatosensory integration and the effect of botulinum toxin (BoNT) in patients with writer's cramp (WC). METHODS: Median and ulnar SEPs were recorded in 29 WC patients and

  12. Critical analysis of the use of onabotulinumtoxinA (botulinum toxin type A in migraine

    Directory of Open Access Journals (Sweden)

    Robertson CE

    2012-01-01

    Full Text Available Carrie E Robertson, Ivan GarzaDepartment of Neurology, Mayo Clinic, Rochester, MN, USAAbstract: OnabotulinumtoxinA, a neurotoxin, has been studied in numerous trials as a novel preventive therapy for migraine headache. The data would support that it may be effective at reducing headache days in patients suffering from chronic migraine (≥15 headache days/month, with eight or more of those migraine headache days. The mechanism by which onabotulinumtoxinA exerts its effects on migraine is not yet understood. It is known to inhibit acetylcholine release at the neuromuscular junction, but this probably does not explain the observed antinociceptive properties noted in preclinical and clinical trials. This review will discuss the known mechanisms of action of botulinum toxin type A, and will review the available randomized, placebo-controlled trials that have looked at its efficacy as a migraine preventative. We also describe the onabotulinumtoxinA injection sites used at our institution.Keywords: botulinum toxin, prophylaxis, onabotulinumtoxinA, mechanism, migraine, prevention

  13. The Structure of the Neurotoxin- Associated Protein HA33/A from Clostridium botulinum Suggests a Reoccurring Beta-Trefoil Fold in the Progenitor Toxin Complex

    National Research Council Canada - National Science Library

    Arndt, Joseph W; Gu, Jenny; Jaroszewski, Lukasz; Schwarzenbacher, Robert; Hanson, Michael A; Lebeda, Frank L; Stevens, Raymond C

    2004-01-01

    The hemagglutinating protein HA33 from Clostridium botulinum is associated with the large botulinum neurotoxin secreted complexes and is critical in toxin protection, internalization, and possibly activation...

  14. Neurorehabilitation with versus without resistance training after botulinum toxin treatment in children with cerebral palsy

    DEFF Research Database (Denmark)

    Bandholm, Thomas Quaade; Jensen, Bente Rona; Nielsen, Lone M

    2012-01-01

    Objective: To compare the effects of physical rehabilitation with (PRT) and without (CON) progressive resistance training following treatment of spastic plantarflexors with botulinum toxin type A (BoNT) in children with cerebral palsy (CP). Methods: Fourteen children with CP performed supervised...

  15. Case Report: Impact of Botulinum Toxin Injection on Function of Affected Upper Extremity in A Patient, 16 Years after Stroke

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    Malek Amini

    2012-10-01

    Full Text Available Objective: Case report Impact of Botulinum Toxin injection on function of affected upper extremity in a patient after 16 years since stroke (CVA. Botulinum toxin injection is one the treatments in spasticity reduction and consequently in recovery of upper limb function in stroke patients. The purpose of this case study is to report the effect of Botulinum toxin injection on upper extremity function after 16 years of stroke. Materials & Methods: The patient was a 63-year-old man who has had a cerebrovascular accident that happened in the left hemisphere about 16 years ago, and as a result, a paresis in dominant hand and arm. Although the patient was able to perform simple movements but he was complaining about the slowness and stiffness in the movements. To treat spasticity the Botulinum toxin type A was used. Injection into selected muscles of hemiparetic upper limb was done by a specialist physician and was between 50-150IU based on specific volume of each muscle. After injection, the patient was monitored for 3 months and at the end of each month, the assessments were reevaluated. During this period, although research team suggested the patient to continue the rehabilitation but for personal reasons he didn’t participate in any treatment and didn`t receive any other antispasmodic medications. Results: An increase in range of motion was seen in all joints but this improvement was not significant. The greatest improvement in passive and active range of motion was seen in Metacarpophalengeal joints. At the end of each month, compared to the first month the recovery of function in upper extremity was significant. Maximum recovery of upper extremity function was related to the hand section of fugl-meyer assessment. At the end of the first month, spasticity significantly decreased so that the patient was able to extend all his joints more easily than before injection. Although spasticity never reached zero. Conclusion: Botulinum toxin injection

  16. Botulinum Toxin for the Management of Sjögren Syndrome-Associated Recurrent Parotitis.

    Science.gov (United States)

    O'Neil, Luke M; Palme, Carsten E; Riffat, Faruque; Mahant, Neil

    2016-12-01

    Recurrent parotitis is a rare manifestation of Sjögren syndrome. The management of recurrent parotitis is challenging because conservative methods may be of limited efficacy and invasive approaches carry the risk of complications. Botulinum toxin has been shown to reduce salivary flow, and consequently, the results of its use in the management of recurrent parotitis have been encouraging. A 65-year-old female patient with recurrent parotitis due to Sjögren syndrome was referred to us, complaining of weekly bouts of inflammation. She required a course of antibiotics monthly to control bacterial superinfections. We treated her with onabotulinumtoxinA injections into both parotid glands at regular intervals. After her second injection cycle, she denied further inflammatory bouts, has not required antibiotics in more than 36 months, and denied any side effects. Botulinum toxin may be a safe and effective method of treating Sjögren syndrome-associated recurrent parotitis. Copyright © 2016 American Association of Oral and Maxillofacial Surgeons. Published by Elsevier Inc. All rights reserved.

  17. Botulinum Toxin as an Alternative to Treat the Spasm of the Near Reflex.

    Science.gov (United States)

    Laria, Carlos; Merino-Suárez, María L; Piñero, David P; Gómez-Hurtado, Arantxa; Pérez-Cambrodí, Rafael J

    2015-01-01

    We describe the case of an eight-year-old girl with complaints of headaches and blurred vision (uncorrected visual acuity: 0.1 decimal) that showed on examination miotic pupils, pseudomyopia, no ocular motility restrictions, and no associated neurological disease. After initial treatment with cyclopentolate for two months, pseudomyopia persisted with an intermittent and variable esotropia. Spectacles of +1 both eyes and atropine 1% one drop daily were then prescribed. The situation improved and remained stable for several weeks, with pseudomyopia and esotropia reappearing later. Finally, botulinum toxin (2.5 iu Botox) was injected in the medial rectus muscle on two occasions and a visual therapy program based on the stimulation of fusional divergence, diplopia, and stereopsis consciousness was recommended. This prescription was combined with the use of atropine during the first few weeks. Orthotropia and corrected distance visual acuity of 1.0 were found three months after treatment. The evolution and clinical results of this case report suggest that botulinum toxin in combination with other therapeutic alternatives may be useful in the treatment of spasm of the near reflex.

  18. Towards New Uses of Botulinum Toxin as a Novel Therapeutic Tool

    OpenAIRE

    Pickett, Andy; Perrow, Karen

    2011-01-01

    The uses of botulinum toxin in the fields of neurology, ophthalmology, urology, rehabilitation medicine and aesthetic applications have been revolutionary for the treatment of patients. This non-invasive therapeutic has continually been developed since first discovered in the 1970s as a new approach to what were previously surgical treatments. As these applications develop, so also the molecules are developing into tools with new therapeutic properties in specific clinical areas. This review ...

  19. Long-term effect of botulinum toxin on impairment and functional health in cervical dystonia

    NARCIS (Netherlands)

    Brans, J. W.; Lindeboom, R.; Aramideh, M.; Speelman, J. D.

    1998-01-01

    We investigated the long-term effect of botulinum toxin type A (BTA) on impairment as well as functional health in terms of disability, handicap, and quality of life in 64 patients with cervical dystonia. These patients, who first participated in a double-blind trial, were followed for another 12

  20. Multidose Botulinum Toxin A for Intralaryngeal Injection: A Cost Analysis.

    Science.gov (United States)

    Gilbert, Mark R; Young, VyVy N; Smith, Libby J; Rosen, Clark A

    2018-01-04

    Botulinum toxin A (BtxA) injection is the mainstay treatment for laryngeal dystonias. BtxA product labeling states that reconstituted toxin should be used within 4 hours on a single patient despite several studies that have demonstrated multidose BtxA to be safe and effective. Many insurance carriers mandate the use of an outside pharmacy which necessitates a single-use approach. This study compares the cost savings of multidose BtxA for laryngeal dystonia compared to single-use. This is a retrospective review and projected cost savings analysis. Records and billing information were reviewed for patients receiving BtxA for intralaryngeal injection at a single laryngology division in 2015. Inclusion criteria included CPT 64617 or J0585; exclusion criteria included CPT 64616. The price of BtxA 100 unit vial for calculation was $670. A total of 142 patients were seen for intralaryngeal BtxA injection resulting in 337 visits over 1 year. The average BtxA dose per visit was 2.86 units with an average of 3.06 procedure visits per year. The calculated cost of BtxA treatment using a single vial approach was found to be $2,050 per patient per year. If billed instead for $7/unit with 5 units wastage charge per visit, the yearly per patient charge is $168. Single vial-use of BtxA injection thus represents a 1,118% price increase versus multidose use. When estimated for yearly prevalence of spasmodic dysphonia, multidose BtxA use would save almost $100 million annually. Multidose botulinum toxin A application utilizing per unit billing is significantly less expensive than per single-use vial billing and would save the health-care system significant amount of money without any sacrifice in safety or effectiveness. Copyright © 2018. Published by Elsevier Inc.

  1. [Definition of botulinum toxin failure in neurogenic detrusor overactivity: Preliminary results of the DETOX survey].

    Science.gov (United States)

    Peyronnet, B; Sanson, S; Amarenco, G; Castel-Lacanal, E; Chartier-Kastler, E; Charvier, K; Damphousse, M; Denys, P; de Seze, M; Egon, G; Even, A; Forin, V; Karsenty, G; Kerdraon, J; le Normand, L; Loche, C-M; Manunta, A; Mouracade, P; Phe, V; Previnaire, J-G; Ruffion, A; Saussine, C; Schurch, B; Game, X

    2015-12-01

    There is currently no guideline regarding the management of neurogenic detrusor overactivity (NDO) refractory to intra-detrusor botulinum toxin injections. The primary objective of the present study was to find a consensus definition of failure of botulinum toxin intra-detrusor injections for NDO. The secondary objective was to report current trends in the managment of NDO refractory to botulinum toxin. A survey was created, based on data drawn from current literature, and sent via e-mail to all the experts form the Group for research in neurourology in french language (GENULF) and from the comittee of neurourology of the French urological association (AFU). The experts who did not answer to the first e-mail were contacted again twice. Main results from the survey are presented and expressed as numbers and proportions. Out of the 42 experts contacted, 21 responded to the survey. Nineteen participants considered that the definition of failure should be a combination of clinical and urodynamics criteria. Among the urodynamics criteria, the persistence of a maximum detrusor pressure>40 cm H2O was the most supported by the experts (18/21, 85%). According to the vast majority of participants (19/21, 90.5%), the impact of injections on urinary incontinence should be included in the definition of failure. Regarding the management, most experts considered that the first line treatment in case of failure of a first intra-detrusor injection of Botox(®) 200 U should be a repeat injection of Botox(®) at a higher dosage (300 U) (15/20, 75%), regardless of the presence or not of urodynamics risk factors of upper tract damage (16/20, 80%). This work has provided a first overview of the definition of failure of intra-detrusor injections of botulinum toxin in the management of NDO. For 90.5% of the experts involved, the definition of failure should be clinical and urodynamic and most participants (75%) considered that, in case of failure of a first injection of Botox(®) 200 U

  2. Studies on the irradiation of toxins of Clostridium botulinum and Staphylococcus aureus

    International Nuclear Information System (INIS)

    Rose, S.A.; Bailey, N.E.; Stringer, M.F.; Modi, N.K.; Tranter, H.S.; Hambleton, P.

    1989-01-01

    The effects of irradiation of Clostridium botulinum neutotoxin type A (BNTA) and staphylococcal enterotoxin A (SEA) in gelatin phosphate buffer and cooked mince beef slurries were investigated. Estimation of toxins by immunoassays showed that in buffer, toxins were destroyed by irradiation at 8.0 kGy; in mince slurries however, 45% of BTNA and 27-34% of SEA remained after this level of irradiation. At 23.7 kGy, over twice the dose of irradiation proposed for legal acceptance in the UK, 15% of BNTA and 16-26% of SEA still remained. Increasing concentrations of mince conferred increased protection against the effect of irradiation on both toxins. The biological activity of BNTA was more sensitive to irradiation than the immunological activity. Staphylococcal enterotoxin was more resistant to irradiation than BNTA. Irradiation should therefore only be used in conjunction with good manufacturing practices to prevent microbial proliferation and toxin production prior to irradiation. (author)

  3. Studies on the irradiation of toxins of Clostridium botulinum and Staphylococcus aureus

    Energy Technology Data Exchange (ETDEWEB)

    Rose, S A; Bailey, N E; Stringer, M F [Campden Food and Drink Research Association, Chipping Campden (UK); Modi, N K; Tranter, H S [Porton International plc., London (UK); Hambleton, P [Centre for Applied Microbiological Research, Porton Down (UK)

    1988-10-01

    The effects of irradiation of Clostridium botulinum neurotoxin type A (BNTA) and staphylococcal enterotoxin A (SEA) in gelatin phosphate buffer and cooked mince beef slurries were investigated. Estimation of toxins by immunoassays showed that in buffer, toxins were destroyed by irradiation at 8.0 kGy; in mince slurries however, 45% of BTNA and 27-34% of SEA remained after this level of irradiation. At 23.7 kGy, over twice the dose of irradiation proposed for legal acceptance in the UK, 15% of BNTA and 16-26% of SEA still remained. Increasing concentrations of mince conferred increased protection against the effect of irradiation on both toxins. The biological activity of BNTA was more sensitive to irradiation than the immunological activity. Staphylococcal enterotoxin was more resistant to irradiation than BNTA. Irradiation should therefore only be used in conjunction with good manufacturing practices to prevent microbial proliferation and toxin production prior to irradiation. (author).

  4. Studies on the irradiation of toxins of Clostridium botulinum and Staphylococcus aureus

    International Nuclear Information System (INIS)

    Rose, S.A.; Bailey, N.E.; Stringer, M.F.; Modi, N.K.; Tranter, H.S.; Hambleton, P.

    1988-01-01

    The effects of irradiation of Clostridium botulinum neurotoxin type A (BNTA) and staphylococcal enterotoxin A (SEA) in gelatin phosphate buffer and cooked mince beef slurries were investigated. Estimation of toxins by immunoassays showed that in buffer, toxins were destroyed by irradiation at 8.0 kGy; in mince slurries however, 45% of BTNA and 27-34% of SEA remained after this level of irradiation. At 23.7 kGy, over twice the dose of irradiation proposed for legal acceptance in the UK, 15% of BNTA and 16-26% of SEA still remained. Increasing concentrations of mince conferred increased protection against the effect of irradiation on both toxins. The biological activity of BNTA was more sensitive to irradiation than the immunological activity. Staphylococcal enterotoxin was more resistant to irradiation than BNTA. Irradiation should therefore only be used in conjunction with good manufacturing practices to prevent microbial proliferation and toxin production prior to irradiation. (author)

  5. Studies on the irradiation of toxins of Clostridium botulinum and Staphylococcus aureus

    Energy Technology Data Exchange (ETDEWEB)

    Rose, S.A.; Bailey, N.E.; Stringer, M.F. (Campden Food and Drink Research Association, Chipping Campden (UK)); Modi, N.K.; Tranter, H.S. (Centre for Applied Micobiological Research, Porton Down, (UK)); Hambleton, P. (Porton International plc, London (UK))

    1989-09-01

    The effects of irradiation of Clostridium botulinum neutotoxin type A (BNTA) and staphylococcal enterotoxin A (SEA) in gelatin phosphate buffer and cooked mince beef slurries were investigated. Estimation of toxins by immunoassays showed that in buffer, toxins were destroyed by irradiation at 8.0 kGy; in mince slurries however, 45% of BTNA and 27-34% of SEA remained after this level of irradiation. At 23.7 kGy, over twice the dose of irradiation proposed for legal acceptance in the UK, 15% of BNTA and 16-26% of SEA still remained. Increasing concentrations of mince conferred increased protection against the effect of irradiation on both toxins. The biological activity of BNTA was more sensitive to irradiation than the immunological activity. Staphylococcal enterotoxin was more resistant to irradiation than BNTA. Irradiation should therefore only be used in conjunction with good manufacturing practices to prevent microbial proliferation and toxin production prior to irradiation. (author).

  6. Paralysis of the orbicularis muscle of the eye using botulinum toxin type A in the treatment for dry eye.

    Science.gov (United States)

    Serna-Ojeda, Juan Carlos; Nava-Castaneda, Angel

    2017-03-01

    To evaluate the efficacy of botulinum toxin type A injection to cause orbicularis eyelid muscle paralysis to improve dry eye signs and symptoms. A prospective, randomized, comparative eye-to-eye and interventional study was performed. Patients with dry eye symptoms and positive fluorescein corneal staining were included. Randomly one eyelid received a subcutaneous injection of botulinum toxin in the medial orbicularis muscle portion of the lower eyelid, and the other eye received placebo. The subjective evaluation was achieved with a questionnaire assessing symptoms, quality of vision and ocular comfort level. The objective evaluation included the measurement of the tear film break-up time (TBUT), Schirmer's test and corneal and conjunctival staining. Twenty patients were included with a mean age of 59.5 years. Two weeks after the botulinum toxin injection, all patients showed a decrease in the horizontal movement of the lower eyelid when blinking. The eyes in the active treatment group showed better scores compared with the sham group in four symptoms 4 weeks after the treatment. The TBUT was higher at 1 and 3 months in the active treatment group. The corneal and conjunctival staining were significantly lower in the active treatment group at 1 and 3 months, and the Schirmer's test showed better measurements in the same group at 2 weeks, 1 month and 3 months. There were no adverse events reported. The injection of botulinum toxin A in the medial part of the lower eyelid is an effective and safe procedure that temporally improves some of the signs and symptoms of patients with dry eye. © 2016 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.

  7. Injection of Botulinum Toxin a to Upper Esophageal Sphincter for Oropharyngeal Dysphagia in Two Patients with Inclusion Body Myositis

    Directory of Open Access Journals (Sweden)

    Louis WC Liu

    2004-01-01

    Full Text Available Inclusion body myositis (IBM is a progressive degenerative skeletal muscle disease leading to weakening and atrophy of both proximal and distal muscles. Dysphagia is reported in up to 86% of IBM patients. Surgical cricopharyngeal myotomy may be effective for cricopharyngeal dysphagia and there is one published report that botulinum toxin A, injected into the cricopharyngeus muscle using a hypopharyngoscope under general anesthesia, relieved IBM-associated dysphagia. This report presents the first documentation of botulinum toxin A injection into the upper esophageal sphincter using a flexible esophagogastroduodenoscope under conscious sedation, to reduce upper esophageal sphincter pressure and successfully alleviate oropharyngeal dysphagia in two IBM patients.

  8. EGA Protects Mammalian Cells from Clostridium difficile CDT, Clostridium perfringens Iota Toxin and Clostridium botulinum C2 Toxin.

    Science.gov (United States)

    Schnell, Leonie; Mittler, Ann-Katrin; Sadi, Mirko; Popoff, Michel R; Schwan, Carsten; Aktories, Klaus; Mattarei, Andrea; Azarnia Tehran, Domenico; Montecucco, Cesare; Barth, Holger

    2016-04-01

    The pathogenic bacteria Clostridium difficile, Clostridium perfringens and Clostridium botulinum produce the binary actin ADP-ribosylating toxins CDT, iota and C2, respectively. These toxins are composed of a transport component (B) and a separate enzyme component (A). When both components assemble on the surface of mammalian target cells, the B components mediate the entry of the A components via endosomes into the cytosol. Here, the A components ADP-ribosylate G-actin, resulting in depolymerization of F-actin, cell-rounding and eventually death. In the present study, we demonstrate that 4-bromobenzaldehyde N-(2,6-dimethylphenyl)semicarbazone (EGA), a compound that protects cells from multiple toxins and viruses, also protects different mammalian epithelial cells from all three binary actin ADP-ribosylating toxins. In contrast, EGA did not inhibit the intoxication of cells with Clostridium difficile toxins A and B, indicating a possible different entry route for this toxin. EGA does not affect either the binding of the C2 toxin to the cells surface or the enzyme activity of the A components of CDT, iota and C2, suggesting that this compound interferes with cellular uptake of the toxins. Moreover, for C2 toxin, we demonstrated that EGA inhibits the pH-dependent transport of the A component across cell membranes. EGA is not cytotoxic, and therefore, we propose it as a lead compound for the development of novel pharmacological inhibitors against clostridial binary actin ADP-ribosylating toxins.

  9. EGA Protects Mammalian Cells from Clostridium difficile CDT, Clostridium perfringens Iota Toxin and Clostridium botulinum C2 Toxin

    Science.gov (United States)

    Schnell, Leonie; Mittler, Ann-Katrin; Sadi, Mirko; Popoff, Michel R.; Schwan, Carsten; Aktories, Klaus; Mattarei, Andrea; Tehran, Domenico Azarnia; Montecucco, Cesare; Barth, Holger

    2016-01-01

    The pathogenic bacteria Clostridium difficile, Clostridium perfringens and Clostridium botulinum produce the binary actin ADP-ribosylating toxins CDT, iota and C2, respectively. These toxins are composed of a transport component (B) and a separate enzyme component (A). When both components assemble on the surface of mammalian target cells, the B components mediate the entry of the A components via endosomes into the cytosol. Here, the A components ADP-ribosylate G-actin, resulting in depolymerization of F-actin, cell-rounding and eventually death. In the present study, we demonstrate that 4-bromobenzaldehyde N-(2,6-dimethylphenyl)semicarbazone (EGA), a compound that protects cells from multiple toxins and viruses, also protects different mammalian epithelial cells from all three binary actin ADP-ribosylating toxins. In contrast, EGA did not inhibit the intoxication of cells with Clostridium difficile toxins A and B, indicating a possible different entry route for this toxin. EGA does not affect either the binding of the C2 toxin to the cells surface or the enzyme activity of the A components of CDT, iota and C2, suggesting that this compound interferes with cellular uptake of the toxins. Moreover, for C2 toxin, we demonstrated that EGA inhibits the pH-dependent transport of the A component across cell membranes. EGA is not cytotoxic, and therefore, we propose it as a lead compound for the development of novel pharmacological inhibitors against clostridial binary actin ADP-ribosylating toxins. PMID:27043629

  10. Botulinum toxin type-A injection to treat patients with intractable anismus unresponsive to simple biofeedback training.

    Science.gov (United States)

    Zhang, Yong; Wang, Zhen-Ning; He, Lei; Gao, Ge; Zhai, Qing; Yin, Zhi-Tao; Zeng, Xian-Dong

    2014-09-21

    To evaluate the efficacy of botulinum toxin type A injection to the puborectalis and external sphincter muscle in the treatment of patients with anismus unresponsive to simple biofeedback training. This retrospective study included 31 patients suffering from anismus who were unresponsive to simple biofeedback training. Diagnosis was made by anorectal manometry, balloon expulsion test, surface electromyography of the pelvic floor muscle, and defecography. Patients were given botulinum toxin type A (BTX-A) injection and pelvic floor biofeedback training. Follow-up was conducted before the paper was written. Improvement was evaluated using the chronic constipation scoring system. BTX-A injection combined with pelvic floor biofeedback training achieved success in 24 patients, with 23 maintaining persistent satisfaction during a mean period of 8.4 mo. BTX-A injection combined with pelvic floor biofeedback training seems to be successful for intractable anismus.

  11. In Silico Analysis for the Study of Botulinum Toxin Structure

    Science.gov (United States)

    Suzuki, Tomonori; Miyazaki, Satoru

    2010-01-01

    Protein-protein interactions play many important roles in biological function. Knowledge of protein-protein complex structure is required for understanding the function. The determination of protein-protein complex structure by experimental studies remains difficult, therefore computational prediction of protein structures by structure modeling and docking studies is valuable method. In addition, MD simulation is also one of the most popular methods for protein structure modeling and characteristics. Here, we attempt to predict protein-protein complex structure and property using some of bioinformatic methods, and we focus botulinum toxin complex as target structure.

  12. Investigation of inactivation of Clostridium botulinum toxin by nuclear radiation

    International Nuclear Information System (INIS)

    Kaltenhaeuser, A.; Werner, K.H.

    1989-01-01

    The effect of nuclear radiation on the toxicity and the molecular structure of the toxin produced by the microorganism Clostridium botulinum type A was investigated. The radiation induced changes in the structure of the toxin molecule. This effect is influenced by the composition or the medium above the toxin solution as well as by the temperature during the irradiation. The results of the investigation indicate that with increasing irradiation dose a new molecule was formed with immunological properties similar to the properties of the original molecule however with a greater molecular weight. After exposure to a radiation dose of 3,4 Mrad at normal temperature in air, complete detoxification of the substance was found. Immunizing experiments with the toxoid with two guinea-pigs indicated a pronounced increase of the antibody titer in the serum after 4 weeks. Vaccination experiments with the toxoid on animals show, that the protection against the effect of the toxin corresponds to the demands of the European Pharmacopoeia. The efficiency of the toxoid shows a similar efficiency as toxoids produced by chemical methods. The production of a toxoid-viccine with the relatively simple method of nuclear radiation appears possible. (orig./MG) With 12 refs., 3 tabs., 11 figs [de

  13. The role of kinesiotaping combined with botulinum toxin to reduce plantar flexors spasticity after stroke.

    Science.gov (United States)

    Karadag-Saygi, Evrim; Cubukcu-Aydoseli, Koza; Kablan, Nilufer; Ofluoglu, Demet

    2010-01-01

    To evaluate the effect of kinesiotaping as an adjuvant therapy to botulinum toxin A (BTX-A) injection in lower extremity spasticity. This is a single-center, randomized, and double-blind study. Twenty hemiplegic patients with spastic equinus foot were enrolled into the study and randomized into 2 groups. The first group (n=10) received BTX-A injection and kinesiotaping, and the second group (n=10) received BTX-A injection and sham-taping. Clinical assessment was done before injection and at 2 weeks and 1, 3, and 6 months. Outcome measures were modified Ashworth scale (MAS), passive ankle dorsiflexion, gait velocity, and step length. Improvement was recorded in both kinesiotaping and sham groups for all outcome variables. No significant difference was found between groups other than passive range of motion (ROM), which was found to have increased more in the kinesiotaping group at 2 weeks. There is no clear benefit in adjuvant kinesiotaping application with botulinum toxin for correction of spastic equinus in stroke.

  14. Comparison of Pneumatic Dilation with Pneumatic Dilation Plus Botulinum Toxin for Treatment of Achalasia

    Directory of Open Access Journals (Sweden)

    Alireza Bakhshipour

    2010-03-01

    Full Text Available Among the therapeutic options for achalasia are pneumatic dilatation (PD, an appropriate long-term therapy, and botulinum toxin injection (BT that is a relatively short-term therapy. This study aimed to compare therapeutic effect of repetitive pneumatic dilation with a combined method (botulinum toxin injection and pneumatic dilation in a group of achalasia patients who are low responder to two initial pneumatic dilations. Thirty- four patients with documented primary achalasia that had low response to two times PD (<50% decrease in symptom score and barium height at 5 minute in timed esophagogram after 3month of late PD were randomized to receive pneumatic dilation (n=18 or botulinum toxin injection and pneumatic dilation by four weeks interval (n=16, PD and BT+PD groups respectively. Symptom scores were evaluated before and at 1, 6 and 12 months after treatment. Clinical remission was defined as a decrease in symptom score ≥ 50% of baseline. There were no significant differences between the two groups in gender, age and achalasia type. Remission rate of patients in BT-PD group in comparison with PD group were 87.5% vs. 67.1% (P = 0.7, 87.5% vs. 61.1% (P = 0.59 and 87.5% vs. 55.5% (P = 0.53 at 1, 6 and 12 months respectively .There were no major complications in either group. The mean symptom score decreased by 62.71% in the BT-PD group (P < 0.002 and 50.77% in the PD group (P < 0.01 at the end of the first year. Despite a better response rate in BT+PD group, a difference was not statistically significant. A difference may be meaningful if a large numbers of patients are included in the study.

  15. An overview of the cosmetic treatment of facial muscles with a new botulinum toxin.

    Science.gov (United States)

    Wiest, Luitgard G

    2009-01-01

    Botulinum toxin (BTX) is used nowadays in a much more differentiated way with a much more individualized approach to the cosmetic treatment of patients. To the well known areas of the upper face new indications in the mid and lower face have been added. Microinjection techniques are increasingly used besides the classic intramuscular injection technique. BTX injections of the mid and lower face require small and smallest dosages. The perioral muscles act in concert to achieve the extraordinarily complex movements that control facial expressions, eating, and speech. As the mouth has horizontal as well as vertical movements, paralysis of these perioral muscles has a greater effect on facial function and appearance than does paralysis of muscles of the upper face, which move primarily in vertical direction. It is essential that BTX injections should achieve the desired cosmetic result with the minimum dose without any functional discomfort. In this paper the three-year clinical experience with average dosages for an optimal outcome in the treatment of facial muscles with a newly developed botulinum toxin type A (Xeomin) free from complexing proteins is presented.

  16. Evidence to Use Botulinum Toxin Injections in Tension-Type Headache Management: A Systematic Review.

    Science.gov (United States)

    Wieckiewicz, Mieszko; Grychowska, Natalia; Zietek, Marek; Wieckiewicz, Gniewko; Smardz, Joanna

    2017-11-15

    Tension-type headache (TTH) is the most common type of chronic recurring head pain. It can occur twice as often in women as in men. It is the most common type of headache. Its lifetime prevalence is 30% to 78% in the general population. TTH treatment should be multilevel. It often consists of taking pain medication, muscle relaxants, antidepressants, using biofeedback therapy, acupuncture, and attending behavioral therapy. Several clinical trials also suggest that botulinum toxin (BTX) may be an effective treatment option for such patients. The aim of this study was to evaluate if BTX can be used as a treatment method in TTH in the light of current medical literature. The authors searched the PubMed, EBSCOhost, OVID, Web of Knowledge, Cochrane Library and CINAHL databases to identify relevant publications. The authors finally included 11 papers-prospective and retrospective cohort studies. Among most of the selected studies, there was a significant correlation between using BTX and reduction of TTH pain intensity and severity. By analyzing qualified studies, it can be concluded that botulinum toxin seems to be effective in TTH management.

  17. Botulinum toxin: yesterday, today, tomorrow

    Directory of Open Access Journals (Sweden)

    A. R. Artemenko

    2013-01-01

    Full Text Available Botulinum toxin (BoNT is a bacterial neurotoxin presented with seven serotypes that inhibit neurotransmitter release from nerve endings. The serotypes of BoNT are antigenically dissimilar, act via different, but interconnected mechanisms, and are not interchangeable. The activity of BoNT is associated with impaired neuroexocytosis occurring in several steps: from the binding of BoNT to its specific receptor on the axon terminal membrane to the proteolytic enzymatic cleavage of SNARE substrate. The effect of BoNT is considered to be restricted to the peripheral nervous system, but when given in particularly high doses, it has been recently shown to affect individual brain structures. In addition, by modulating peripheral afferentation, BoNT may influence the excitability of central neuronal structures at both spinal and cortical levels. Only BoNT serotypes A and B are used in clinical practice and aesthetic medicine. The type A has gained the widest acceptance as a therapeutic agent for more than 100 abnormalities manifesting themselves as muscular hyperactivity, hyperfunction of endocrine gland, and chronic pain. The effect of BoNT preparations shows itself 2-5 days after injection, lasts 3 months or more, and gradually decreases with as a result of pharmacokinetic and intracellular reparative processes. Biotechnology advances and potentialities allow purposefully modification of the protein molecular structure of BoNT, which expands the use and efficiency of performed therapy with neurotoxins. Recombinant technologies provide a combination of major therapeutic properties of each used BoNT serotype and expand indications for recombinant chimeric toxins.

  18. Botulinum toxin drugs: brief history and outlook.

    Science.gov (United States)

    Dressler, D

    2016-03-01

    The global botulinum toxin (BT) market is currently undergoing rapid changes: this may be the time to review the history and the future of BT drug development. Since the early 1990s Botox(®) and Dysport(®) dominated the international BT market. Later, Myobloc(®)/NeuroBloc(®), a liquid BT type B drug, came out, but failed. Xeomin(®) is the latest major BT drug. It features removal of complexing proteins and improved neurotoxin purity. Several new BT drugs are coming out of Korea, China and Russia. Scientific challenges for BT drug development include modification of BT's duration of action, its transdermal transport and the design of BT hybrid drugs for specific target tissues. The increased competition will change the global BT market fundamentally and a re-organisation according to large indication groups, such as therapeutic and cosmetic applications, might occur.

  19. Detection of botulinum toxin types A, B, E, and F activity using the quail embryo

    Science.gov (United States)

    We recently demonstrated an effective new model for the detection of botulinum toxin type A using quail embryos in place of the mouse model. These experiments demonstrated that the Japanese quail embryo at 15 days of incubation was an effective vertebrate animal model to detect the activity of botu...

  20. Effect of stimulation intensity and botulinum toxin isoform on rat bladder strip contractions.

    Science.gov (United States)

    Smith, Christopher P; Boone, Timothy B; de Groat, William C; Chancellor, Michael B; Somogyi, George T

    2003-07-15

    The present experiments compared the inhibitory effects of botulinum toxin A (BoNT-A) and botulinum toxin D (BoNT-D) on neurally evoked contractions of rat bladder strips. We examined the effect of fatigue (trains of 100 shocks at 20Hz every 20s for 10min) followed by non-fatigue stimulation (trains of 100 shocks at 20Hz every 100s for 20min) on the onset of effect and potency of the two toxins. For non-fatigue experiments, strips were untreated (n=4); or incubated with 1.36nM BoNT-A (n=4). During fatigue experiments, strips were untreated (n=5); or treated with either 1.36nM BoNT-A (n=6) or 0.8nM BoNT-D (n=6). In non-fatigue experiments, BoNT-A produced significant decreases in contractile area after 1h of stimulation compared to untreated strips (PD bladder strips, were statistically significant (PD-treated strips, as a significant reduction (PD) and untreated bladder strips responded similarly to atropine, suggesting that the effects of BoNT result from inhibition of both acetylcholine and ATP release. Our results demonstrate that BoNT-D may be a more effective agent to inhibit transmitter release from autonomic nerves of the rat lower urinary tract. Moreover, in our hands, non-fatigue stimulation is as effective as fatigue stimulation in inhibiting bladder strip contractions.

  1. Establishment of alternative potency test for botulinum toxin type A using compound muscle action potential (CMAP) in rats.

    Science.gov (United States)

    Torii, Yasushi; Goto, Yoshitaka; Nakahira, Shinji; Ginnaga, Akihiro

    2014-11-01

    The biological activity of botulinum toxin type A has been evaluated using the mouse intraperitoneal (ip) LD50 test. This method requires a large number of mice to precisely determine toxin activity, and, as such, poses problems with regard to animal welfare. We previously developed a compound muscle action potential (CMAP) assay using rats as an alternative method to the mouse ip LD50 test. In this study, to evaluate this quantitative method of measuring toxin activity using CMAP, we assessed the parameters necessary for quantitative tests according to ICH Q2 (R1). This assay could be used to evaluate the activity of the toxin, even when inactive toxin was mixed with the sample. To reduce the number of animals needed, this assay was set to measure two samples per animal. Linearity was detected over a range of 0.1-12.8 U/mL, and the measurement range was set at 0.4-6.4 U/mL. The results for accuracy and precision showed low variability. The body weight was selected as a variable factor, but it showed no effect on the CMAP amplitude. In this study, potency tests using the rat CMAP assay of botulinum toxin type A demonstrated that it met the criteria for a quantitative analysis method. Copyright © 2014 Elsevier Ltd. All rights reserved.

  2. Botulinum Neurotoxin Injections

    Science.gov (United States)

    ... botulinum neurotoxin as much art as it is science. It is in your best interest to locate the most well-trained and experienced doctor you can find. Before making an appointment to receive botulinum neuro toxin injections, ask the office personnel which doctor ...

  3. Efficacy of a potential trivalent vaccine based on Hc fragments of botulinum toxins A, B, and E produced in a cell-free expression system.

    Science.gov (United States)

    Zichel, R; Mimran, A; Keren, A; Barnea, A; Steinberger-Levy, I; Marcus, D; Turgeman, A; Reuveny, S

    2010-05-01

    Botulinum toxins produced by the anaerobic bacterium Clostridium botulinum are the most potent biological toxins in nature. Traditionally, people at risk are immunized with a formaldehyde-inactivated toxin complex. Second generation vaccines are based on the recombinant carboxy-terminal heavy-chain (Hc) fragment of the neurotoxin. However, the materialization of this approach is challenging, mainly due to the high AT content of clostridial genes. Herein, we present an alternative strategy in which the native genes encoding Hc proteins of botulinum toxins A, B, and E were used to express the recombinant Hc fragments in a cell-free expression system. We used the unique property of this open system to introduce different combinations of chaperone systems, protein disulfide isomerase (PDI), and reducing/oxidizing environments directly to the expression reaction. Optimized expression conditions led to increased production of soluble Hc protein, which was successfully scaled up using a continuous exchange (CE) cell-free system. Hc proteins were produced at a concentration of more than 1 mg/ml and purified by one-step Ni(+) affinity chromatography. Mice immunized with three injections containing 5 microg of any of the in vitro-expressed, alum-absorbed, Hc vaccines generated a serum enzyme-linked immunosorbent assay (ELISA) titer of 10(5) against the native toxin complex, which enabled protection against a high-dose toxin challenge (10(3) to 10(6) mouse 50% lethal dose [MsLD(50)]). Finally, immunization with a trivalent HcA, HcB, and HcE vaccine protected mice against the corresponding trivalent 10(5) MsLD(50) toxin challenge. Our results together with the latest developments in scalability of the in vitro protein expression systems offer alternative routes for the preparation of botulinum vaccine.

  4. Update on botulinum neurotoxin use in aesthetic dermatology.

    Science.gov (United States)

    Ibrahim, Omer; Keller, Emily C; Arndt, Kenneth A

    2014-12-01

    Botulinum toxins are among the most widely studied and versatile drugs in the medicinal market. Since their extraction from Clostridium botulinum, they have been harnessed and incorporated into different formulations with varied properties and actions. These products have been used to treat countless disorders such as musculoskeletal disorders, headaches, and eye disorders, among many others. In the realm of aesthetic cutaneous medicine, the evolution and creativity in the use of botulinum toxins has been swift and ever changing. Knowledge of the science and innovation behind this toxin enables the user to provide the patient with a variety of treatment options founded in evidence-based medicine. This review will highlight the properties and actions of the newer, more recent neurotoxin preparations, as well as some of the latest and novel therapeutic applications of botulinum toxins.

  5. Advances in Assays and Analytical Approaches for Botulinum Toxin Detection

    Energy Technology Data Exchange (ETDEWEB)

    Grate, Jay W.; Ozanich, Richard M.; Warner, Marvin G.; Bruckner-Lea, Cindy J.; Marks, James D.

    2010-08-04

    Methods to detect botulinum toxin, the most poisonous substance known, are reviewed. Current assays are being developed with two main objectives in mind: 1) to obtain sufficiently low detection limits to replace the mouse bioassay with an in vitro assay, and 2) to develop rapid assays for screening purposes that are as sensitive as possible while requiring an hour or less to process the sample an obtain the result. This review emphasizes the diverse analytical approaches and devices that have been developed over the last decade, while also briefly reviewing representative older immunoassays to provide background and context.

  6. Vitreous hemorrhage and Rhegmatogenous retinal detachment that developed after botulinum toxin injection to the extraocular muscle: case report.

    Science.gov (United States)

    Lee, Dong Hyun; Han, Jinu; Han, Sueng-Han; Lee, Sung Chul; Kim, Min

    2017-12-13

    The authors report a case of a rare complication that occurred after botulinum toxin injection to the extraocular muscle, which was easily overlooked and successfully corrected by surgery. A 34-year-old female patient visited our clinic for diplopia and ocular motility disorder after removal of an epidermoid tumor of the brain. At her initial visit, her best-corrected visual acuity (BCVA) was 20/20 for both eyes. An alternate cover test showed 45 prism-diopter esotropia and 3 prism-diopter hypertropia in the right eye. Following 6 months of observation, the deviation of the strabismus did not improve, and botulinum toxin was injected into the right medial rectus (RMR). After 6 days, she visited our clinic with decreased visual acuity of her right eye. The BCVA was found to be 20/50 for her right eye. Funduscopic examination presented a retinal tear inferonasal to the optic disc with preretinal hemorrhage. Subretinal fluid nasal to the fovea was seen on optical coherence tomography (OCT). Barrier laser photocoagulation was done around the retinal tear; however, her visual acuity continued to decrease, and vitreous hemorrhage and subretinal fluid at the lesion did not improve. In addition, a newly developed epiretinal membrane was seen on OCT. An alternate cover test presented 30 prism-diopter right esotropia. 19 weeks after RMR botulinum toxin injection, she received pars plana vitrectomy, membranectomy, endolaser barrier photocoagulation, and intravitreal bevacizumab (Avastin®) injection. After 4 months, her visual acuity improved to 20/20, and only 4 prism-diopter of right hypertropia and 3 prism-diopter of exotropia were noted. Vitreous opacity and the epiretinal membrane were completely removed, as confirmed by funduscopic and examination. Sudden loss of vision after injection of botulinum toxin into the extraocular muscle may suggest a serious complication, and a prompt, thorough ophthalmic examination should be performed. If improvements are not observed

  7. Channels formed by botulinum, tetanus, and diphtheria toxins in planar lipid bilayers: relevance to translocation of proteins across membranes.

    OpenAIRE

    Hoch, D H; Romero-Mira, M; Ehrlich, B E; Finkelstein, A; DasGupta, B R; Simpson, L L

    1985-01-01

    The heavy chains of both botulinum neurotoxin type B and tetanus toxin form channels in planar bilayer membranes. These channels have pH-dependent and voltage-dependent properties that are remarkably similar to those previously described for diphtheria toxin. Selectivity experiments with anions and cations show that the channels formed by the heavy chains of all three toxins are large; thus, these channels could serve as "tunnel proteins" for translocation of active peptide fragments. These f...

  8. Botulinum Toxin-A Dosing Trends for Adductor Spasmodic Dysphonia at a Single Institution Over 10 Years.

    Science.gov (United States)

    Bradley, Joseph P; Barrow, Emily M; Hapner, Edie R; Klein, Adam M; Johns, Michael M

    2017-05-01

    This study aimed to identify the changes in dosing of botulinum toxin-A for adductor spasmodic dysphonia (ADSD) over a prolonged period. This is a retrospective chart review. One hundred thirteen subjects treated for ADSD from 2003 to 2013 were identified from a clinical database. Subject age, gender, and total injection dose amount were all recorded for all subjects who had at least 10 injections. Fifty-four subjects met criteria for inclusion. There were no age or gender differences in the starting dose for subjects. Dosing decreased significantly compared with the second dose (5.05 ± 1.623 Units), by the sixth dose (4.26 ± 1.698 Units), and continued through the 10th dose (4.08 ± 2.019 Units) (P < 0.005 for all). Botulinum toxin-A dosing for ADSD decreases consistently over subsequent injections after the initial two dose titrations. Copyright © 2017. Published by Elsevier Inc.

  9. The use of botulinum toxin A in the treatment of functional epiphora.

    Science.gov (United States)

    Whittaker, Karl W; Matthews, Bethan N; Fitt, Alan W; Sandramouli, S

    2003-09-01

    The purpose of this study was to investigate the hitherto undescribed effects of botulinum toxin A injected into the lacrimal gland in patients with functional epiphora. A prospective non-comparative interventional case series study was designed to include patients with functional epiphora who presented to the Oculoplastic unit at the Wolverhampton and Midland Counties Eye Infirmary. Botulinum toxin A (2.5-5 units) was injected into the palpebral lobe of the lacrimal gland on the worst affected side via a transconjunctival approach under topical anaesthesia. Patients underwent a Schirmer test and provided a subjective evaluation of their epiphora symptoms, indoors and outdoors, at baseline and at 1, 4 and 13 weeks after injection. The mean score for symptoms indoors and outdoors was calculated. Fourteen patients agreed to take part in the study. Subjective epiphora scores improved in 8 out of the 11 patients (72.7%) who completed 13 weeks of follow-up. Schirmer test results showed objective reduction in tearing from baseline but did not strongly correlate with the subjective epiphora scores. Transient mild ptosis and diplopia were experienced by two patients. The results from this small pilot study are encouraging, although larger, controlled trials are needed to assess the optimal dose of BTX-A, its long-term efficacy and safety, and the role of multiple injections.

  10. Botulinum toxin A, brain and pain.

    Science.gov (United States)

    Matak, Ivica; Lacković, Zdravko

    2014-01-01

    Botulinum neurotoxin type A (BoNT/A) is one of the most potent toxins known and a potential biological threat. At the same time, it is among the most widely used therapeutic proteins used yearly by millions of people, especially for cosmetic purposes. Currently, its clinical use in certain types of pain is increasing, and its long-term duration of effects represents a special clinical value. Efficacy of BoNT/A in different types of pain has been found in numerous clinical trials and case reports, as well as in animal pain models. However, sites and mechanisms of BoNT/A actions involved in nociception are a matter of controversy. In analogy with well known neuroparalytic effects in peripheral cholinergic synapses, presently dominant opinion is that BoNT/A exerts pain reduction by inhibiting peripheral neurotransmitter/inflammatory mediator release from sensory nerves. On the other hand, growing number of behavioral and immunohistochemical studies demonstrated the requirement of axonal transport for BoNT/A's antinociceptive action. In addition, toxin's enzymatic activity in central sensory regions was clearly identified after its peripheral application. Apart from general pharmacology, this review summarizes the clinical and experimental evidence for BoNT/A antinociceptive activity and compares the data in favor of peripheral vs. central site and mechanism of action. Based on literature review and published results from our laboratory we propose that the hypothesis of peripheral site of BoNT/A action is not sufficient to explain the experimental data collected up to now. Copyright © 2014 Elsevier Ltd. All rights reserved.

  11. Botulinum toxin injections for new onset bilateral vocal fold motion impairment in adults.

    Science.gov (United States)

    Ekbom, Dale C; Garrett, C Gaelyn; Yung, Katherine C; Johnson, Felicia L; Billante, Cheryl R; Zealear, David L; Courey, Mark S

    2010-04-01

    Review of clinical experience and results using botulinum toxin type A (BTX) for the management of adult patients with respiratory compromise due to new onset bilateral vocal fold motion impairment (BVFMI). Retrospective case series. The records of 11 patients from two institutions with respiratory compromise due to bilateral vocal fold motion impairment were reviewed. Age, sex, etiology of motion impairment, subjective response to BTX injections, changes in pulmonary function studies pre- and postinjection when available, the dosage of botulinum toxin required to achieve response, the number of injections per patient, and complications were reported. All patients were over 18 years old. There were three male and eight female subjects. The etiology of BVFMI was due to previous anterior cervical surgery in nine patients and prolonged intubation in two. Ten patients reported symptomatic improvement and returned for an average of nine injections over the 10-year period of study. The most common interval between injections was 3 months. In all patients the dose required to achieve symptomatic improvement was at least 2.5 mouse units injected into each vocal fold. One patient without relief of symptoms had bilateral cricoarytenoid joint fixation. Complications were limited to moderate dysphagia in one patient and breathy dysphonia in all patients. BTX injection into the vocal folds provides temporary relief of symptoms in airway obstruction in adult patients with BVFMI. Patients require an average of 2.5 units of botulinum injection into each vocal fold and have an average length of response of 3 months. BTX injection may be used as a form of temporary relief of airway obstruction in patients wishing to avoid ablative surgery or tracheotomy.

  12. Off Label Use of Botulinum Toxin in Children under Two Years of Age: A Systematic Review

    Directory of Open Access Journals (Sweden)

    Claudia Druschel

    2013-01-01

    Full Text Available The treatment of children with cerebral palsy with Botulinum Toxin is considered safe and effective, but is only approved for children older than two years of age. The effect of BoNT-A injection on juvenile skeletal muscle especially on neuromuscular junction density, distribution and morphology is poorly delineated and concerns of irreversible damage to the motor endplates especially in young children exist. In contrast, earlier treatment could be appropriate to improve the attainment of motor milestones and general motor development. This review systematically analyzes the evidence regarding this hypothesis. A database search, including PubMed and Medline databases, was performed and all randomized controlled trials (RCTs comparing the efficacy of Botulinum Toxin in children younger than two years were identified. Two authors independently extracted the data and the methods of all identified trials were assessed. Three RCTs met the inclusion criteria. The results of the analysis revealed an improvement in spasticity of the upper and lower extremities as well as in the range of motion in the joints of the lower limbs. However, evidence of an improvement of general motor development could not be found, as the assessment of this area was not completely specified for this patient group. Based on available evidence it can not be concluded that Botulinum Toxin treatment in children younger than two years improves the achievement of motor milestones. However, there is evidence for the reduction of spasticity, avoiding contractures and delaying surgery. Due to some limitations, the results of this review should be cautiously interpreted. More studies, long-term follow up independent high-quality RCTs with effectiveness analyses are needed.

  13. A botulinum toxin A treatment algorithm for de novo management of torticollis and laterocollis

    Science.gov (United States)

    Kupsch, Andreas; Müngersdorf, Martina; Paus, Sebastian; Stenner, Andrea; Jost, Wolfgang

    2011-01-01

    Objectives Few studies have investigated the injection patterns for botulinum toxin type A for the treatment of heterogeneous forms of cervical dystonia (CD). This large, prospective, open-label, multicentre study aimed to evaluate the effectiveness and safety of 500 U botulinum toxin A for the initial treatment according to a standardised algorithm of the two most frequent forms of CD, predominantly torticollis and laterocollis. Design Patients (aged ≥18 years) with CD not previously treated with botulinum neurotoxin therapy were given one treatment with 500 U Dysport, according to a defined intramuscular injection algorithm based on clinical assessment of direction of head deviation, occurrence of shoulder elevation, occurrence of tremor (all evaluated using the Tsui rating scale) and hypertrophy of the sternocleidomastoid muscle. Results In this study, 516 patients were enrolled, the majority of whom (95.0%) completed treatment. Most patients had torticollis (78.1%). At week 4, mean Tsui scores had significantly decreased by −4.01, −3.76 and −4.09 points in the total, torticollis and laterocollis populations, respectively. Symptom improvement was equally effective between groups. Tsui scores remained significantly below baseline at week 12 in both groups. Treatment was well tolerated; the most frequent adverse events were muscular weakness (13.8%), dysphagia (9.9%) and neck pain (6.6%). Conclusions Dysport 500 U is effective and well tolerated for the de novo management of a range of heterogeneous forms of CD, when using a standardised regimen that allows tailored dosing based on individual symptom assessment. Clinical trials information (NCT00447772; clinicaltrials.gov) PMID:22021883

  14. Cutaneous cooling to manage botulinum toxin injection-associated pain in patients with facial palsy: A randomised controlled trial.

    Science.gov (United States)

    Pucks, N; Thomas, A; Hallam, M J; Venables, V; Neville, C; Nduka, C

    2015-12-01

    Botulinum toxin injections are an effective, well-established treatment to manage synkinesis secondary to chronic facial palsy, but they entail painful injections at multiple sites on the face up to four times per year. Cutaneous cooling has long been recognised to provide an analgesic effect for cutaneous procedures, but evidence to date has been anecdotal or weak. This randomised controlled trial aims to assess the analgesic efficacy of cutaneous cooling using a cold gel pack versus a room-temperature Control. The analgesic efficacy of a 1-min application of a Treatment cold (3-5 °C) gel pack versus a Control (room-temperature (20 °C)) gel pack prior to botulinum toxin injection into the platysma was assessed via visual analogue scale (VAS) ratings of pain before, during and after the procedure. Thirty-five patients received both trial arms during two separate clinic appointments. Cold gel packs provided a statistically significant reduction in pain compared with a room-temperature Control (from 26.4- to 10.2-mm VAS improvement (p injected or the order in which the Treatment or Control gel packs were applied. Cryoanalgesia using a fridge-cooled gel pack provides an effective, safe and cheap method for reducing pain at the botulinum toxin injection site in patients with facial palsy. Copyright © 2015 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.

  15. Identification of RNA species in the RNA-toxin complex and structure of the complex in Clostridium botulinum type E.

    Science.gov (United States)

    Kitamura, Masaru

    2002-02-15

    Clostridium botulinum type E toxin was isolated in the form of a complex with RNA(s) from bacterial cells. Characterization of the complexed RNA remains to be elucidated. The RNA is identified here as ribosomal RNA (rRNA) having 23S and 16S components. The RNA-toxin complexes were found to be made up of three types with different molecular sizes. The three types of RNA-toxin complex are toxin bound to both the 23S and 16S rRNA, toxin bound to the 16S rRNA and a small amount of 23S rRNA, and toxin bound only to the 16S rRNA. ©2002 Elsevier Science (USA).

  16. Use of botulinum toxin in musculoskeletal pain [v2; ref status: indexed, http://f1000r.es/16j

    Directory of Open Access Journals (Sweden)

    Jasvinder A Singh

    2013-07-01

    Full Text Available Chronic musculoskeletal pain is a common cause of chronic pain, which is associated with a total cost of $635 billion per year in the U.S. Emerging evidence suggests an anti-nociceptive action of botulinum toxin, independent of its muscle paralyzing action. This review provides a summary of data from both non-randomized and randomized clinical studies of botulinum toxin in back pain and various osteoarticular conditions, including osteoarthritis, tennis elbow, low back pain and hand pain. Three randomized controlled trials (RCTs of small sizes provide evidence of short-term efficacy of a single intra-articular injection of 100 units of botulinum toxin A (BoNT/A for the relief of pain and the improvement of both function and quality of life in patients with chronic joint pain due to arthritis. Three RCTs studied intramuscular BoNT/A for tennis elbow with one showing a significant improvement in pain relief compared with placebo, another one showing no difference from placebo, and the third finding that pain and function improvement with BoNT/A injection were similar to those obtained with surgical release. One RCT of intramuscular BoNT/A for low back pain found improvement in pain and function compared to placebo. Single RCTs using local injections of BoNT in patients with either temporomandibular joint (TMJ pain or plantar fasciitis found superior efficacy compared to placebo. One RCT of intramuscular BoNT/B in patients with hand pain and carpal tunnel syndrome found improvement in pain in both BoNT/B and placebo groups, but no significant difference between groups. Most evidence is based on small studies, but the use of BoNT is supported by a single, and sometimes up to three, RCTs for several chronic musculoskeletal pain conditions. This indicates that botulinum toxin may be a promising potential new treatment for chronic refractory musculoskeletal pain. Well-designed large clinical trials are needed.

  17. ADP-ribosylation of actins in fibroblasts and myofibroblasts by botulinum C2 toxin: Influence on microfilament morphology and migratory behavior

    DEFF Research Database (Denmark)

    Rønnov-Jessen, Lone; Petersen, Ole William

    1996-01-01

    botulinum C2 toxin. The substrate for C2 toxin is globular actin, which upon ribosylation cannot incorporate into microfilaments. The pattern of actin ADP-ribosylation in (myo)fibroblasts in the presence of [32P]NAD was analyzed by isoelectric focusing, fluorography and immunoblotting. The influence of C2...... toxin on microfilaments in intact cells was further assessed by immunofluorescence, and motility was measured in a mass migration assay and by computerized video time-lapse microscopy. We show here that C2 toxin specifically ribosylates - and -actin in both fibroblasts and myofibroblasts. Whereas...

  18. A comparative trial of ice application versus EMLA cream in alleviation of pain during botulinum toxin injections for palmar hyperhidrosis.

    Science.gov (United States)

    Alsantali, Adel

    2018-01-01

    Botulinum toxin is a safe and effective therapy for palmar hyperhidrosis, but the associated pain from injections limits the usefulness of this method of treatment. To evaluate the efficacy of Eutectic Mixture of Local Anesthetics (EMLA) cream versus ice application in alleviation of pain during botulinum toxin injections for palmar hyperhidrosis. In this prospective study, 23 patients underwent palm Botox injections to treat their excessive sweating. In each patient, EMLA cream was applied to one palm and ice was applied directly before the injections in the other palm. Pain was evaluated using a Visual Analog Scale. Statistically, there was a significant difference in pain control between EMLA cream group and ice application group ( p cream was applied was 8.9 (SD=0.81), whereas it was 4.8 (±0.9) in the ice group. In this study, the successful use of ice application in reducing pain by 40% in comparison to EMLA cream during Botox toxin injection for palmar hyperhidrosis is demonstrated.

  19. Botulinum toxin as treatment for focal dystonia : a systematic review of the pharmaco-therapeutic and pharmaco-economic value

    NARCIS (Netherlands)

    Zoons, E.; Dijkgraaf, M. G. W.; Dijk, J. M.; van Schaik, I. N.; Tijssen, M. A.

    2012-01-01

    Focal dystonia is a common, invalidating neurologic condition characterized by involuntary, sustained muscle contractions causing twisting movements and abnormal postures in one body part. Currently, botulinum toxin is the treatment of first choice. We performed a systematic review towards the

  20. Botulinum toxin as treatment for focal dystonia: a systematic review of the pharmaco-therapeutic and pharmaco-economic value

    NARCIS (Netherlands)

    Zoons, E.; Dijkgraaf, M. G. W.; Dijk, J. M.; van Schaik, I. N.; Tijssen, M. A.

    2012-01-01

    Focal dystonia is a common, invalidating neurologic condition characterized by involuntary, sustained muscle contractions causing twisting movements and abnormal postures in one body part. Currently, botulinum toxin is the treatment of first choice. We performed a systematic review towards the

  1. Analgesic Effects of Botulinum Toxin in Children with CP

    DEFF Research Database (Denmark)

    Sandahl Michelsen, Josephine; Normann, Gitte; Wong, Christian

    2018-01-01

    Experiencing pain is the greatest contributor to a reduced quality of life in children with cerebral palsy (CP). The presence of pain is quite common (~60%) and increases with age. This leads to missed school days, less participation, and reduced ambulation. Despite these alarming consequences...... of disorders and could potentially have an analgesic effect in children with CP as well. Even though most of the studies presented here show promising results, many also have limitations in their methodology as it is unlikely to capture all dimensions of pain in this heterogeneous group using only one...... assessment tool. In this review, we present a new way of examining the analgesic effect of botulinum toxin in children with CP using a variety of pain scores....

  2. The Effect of Intramural Botulinum Toxin Injections on the Elongation of the Piglet Oesophagus Is Time Dependent

    DEFF Research Database (Denmark)

    Bakholdt Dibbern, Christian; Rose, Morten; Ellebæk, Mark Bremholm

    2017-01-01

    Introduction One in 4,000 infants is born with oesophageal atresia. Approximately 15% of these have a long gap oesophageal atresia, where primary anastomosis is difficult or impossible. Previous studies have shown an effect of intramural botulinum toxin type A (BTX-A) injections on the elongation...

  3. Initial North American experience with botulinum toxin type A for treatment of anismus.

    Science.gov (United States)

    Joo, J S; Agachan, F; Wolff, B; Nogueras, J J; Wexner, S D

    1996-10-01

    Botulinum toxin type A (BTX-A), produced by Clostridium botulinum, is a potent neurotoxin. The purpose of this study was to evaluate the efficacy of BTX-A for treatment of anismus. All patients treated with BTX-A for anismus were evaluated. Eligibility criteria included a history of chronic assisted evacuation (laxatives, enemas, or suppositories), demonstration of anismus by cinedefecogram and electromyography, and failure of a minimum of three sessions of supervised biofeedback therapy (BF). Contingent on body mass, 6 to 15 units of BTX-A was injected bilaterally under electromyography guidance into the external sphincter or the puborectalis muscle. Treatment was repeated as necessary for a maximum of three sessions during a three-month period. Success was considered as discontinuation of evacuatory assistance and was evaluated between one and three months and again at up to one year. Between July 1994 and May 1995, four patients ranging from 29 to 82 years in age (2 females, 2 males) had anismus that failed to respond to between 3 and 15 biofeedback sessions. All patients improved between one and three months after BTX-A injection, and two had sustained improvement for a range of three months to one year. There was no morbidity or mortality associated with BTX-A injection. BTX-A is extremely successful for temporary treatment of anismus that is refractory to BF management. However, because the mechanism of action is short, longer term results are only 50 percent successful. Hopefully, modifications in the strain of BTX-A and dose administered will allow longer periods of success or a repeat trial of BF. Nonetheless, this preliminary report is very encouraging in offering a method of managing this recalcitrant condition.

  4. Efficacy and Safety of IncobotulinumtoxinA in Subjects Previously Treated with Botulinum Toxin versus Toxin-Naïve Subjects with Cervical Dystonia

    Directory of Open Access Journals (Sweden)

    Hubert Fernandez

    2013-05-01

    Full Text Available Background: To determine whether botulinum toxin treatment history affected the outcomes of a study comparing the safety and efficacy of incobotulinumtoxinA with placebo in subjects with cervical dystonia (CD.Methods: This was a prospective, double‐blind, randomized, placebo‐controlled, multicenter trial in botulinum toxin‐treated or toxin‐naïve CD subjects. Subjects received a fixed dose of either 120 U or 240 U of incobotulinumtoxinA or placebo. The primary outcome measure was change from baseline to Week 4 in the Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS total score. Treatment‐emergent adverse events (TEAEs were also evaluated. This report represents a subgroup analysis of botulinum toxin‐treated or toxin‐naïve subjects.Results: Participants (N = 233; 38.6% toxin‐naïve had a mean age of 52.8 years. IncobotulinumtoxinA significantly improved TWSTRS total scores from baseline to Week 4 in both dose groups versus placebo, and the improvement persisted through the end of the study (≤20 weeks. Both the previously toxin‐treated and toxin‐naïve subjects demonstrated significant improvements in TWSTRS total scores at Week 4 compared to baseline. The most frequent TEAEs in the incobotulinumtoxinA groups were dysphagia, neck pain, and muscular weakness, which were generally mild. TEAEs were more common in the 240 U group and toxin‐naïve subjects. Discussion: Overall, incobotulinumtoxinA was safe and effective in CD, regardless of toxin therapy history. A lower starting dose may be better tolerated among toxin‐naïve subjects without sacrificing efficacy.

  5. Crystallization and preliminary X-ray analysis of the HA3 component of Clostridium botulinum type C progenitor toxin

    Energy Technology Data Exchange (ETDEWEB)

    Nakamura, Toshio; Tonozuka, Takashi; Kotani, Mao; Obata, Kanae [Department of Applied Biological Science, Tokyo University of Agriculture and Technology, 3-5-8 Saiwai-cho, Fuchu-shi, Tokyo 183-8509 (Japan); Oguma, Keiji [Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Okayama 700-8558 (Japan); Nishikawa, Atsushi, E-mail: nishikaw@cc.tuat.ac.jp [Department of Applied Biological Science, Tokyo University of Agriculture and Technology, 3-5-8 Saiwai-cho, Fuchu-shi, Tokyo 183-8509 (Japan); CREST, Japan Science and Technology Agency (Japan)

    2007-12-01

    HA3, a 70 kDa haemagglutinating protein, is a precursor form of HA3a and HA3b, the subcomponents of Clostridium botulinum type C 16S progenitor toxin. In this report, recombinant HA3 protein was overexpressed in Escherichia coli, purified and crystallized. HA3, a 70 kDa haemagglutinating protein, is a precursor form of HA3a and HA3b, the subcomponents of Clostridium botulinum type C 16S progenitor toxin. In this report, recombinant HA3 protein was overexpressed in Escherichia coli, purified and crystallized. Diffraction data were collected to 2.6 Å resolution and the crystal belonged to the hexagonal space group P6{sub 3}. Matthews coefficient and self-rotation function calculations indicate that there is probably one molecule of HA3 in the asymmetric unit. A search for heavy-atom derivatives has been undertaken.

  6. Botulinum toxin type A injections for the management of muscle tightness following total hip arthroplasty: a case series

    Directory of Open Access Journals (Sweden)

    Delanois Ronald E

    2009-08-01

    Full Text Available Abstract Background Development of hip adductor, tensor fascia lata, and rectus femoris muscle contractures following total hip arthroplasties are quite common, with some patients failing to improve despite treatment with a variety of non-operative modalities. The purpose of the present study was to describe the use of and patient outcomes of botulinum toxin injections as an adjunctive treatment for muscle tightness following total hip arthroplasty. Methods Ten patients (14 hips who had hip adductor, abductor, and/or flexor muscle contractures following total arthroplasty and had been refractory to physical therapeutic efforts were treated with injection of botulinum toxin A. Eight limbs received injections into the adductor muscle, 8 limbs received injections into the tensor fascia lata muscle, and 2 limbs received injection into the rectus femoris muscle, followed by intensive physical therapy for 6 weeks. Results At a mean final follow-up of 20 months, all 14 hips had increased range in the affected arc of motion, with a mean improvement of 23 degrees (range, 10 to 45 degrees. Additionally all hips had an improvement in hip scores, with a significant increase in mean score from 74 points (range, 57 to 91 points prior to injection to a mean of 96 points (range, 93 to 98 at final follow-up. There were no serious treatment-related adverse events. Conclusion Botulinum toxin A injections combined with intensive physical therapy may be considered as a potential treatment modality, especially in difficult cases of muscle tightness that are refractory to standard therapy.

  7. Comparison of clinical marking and ultrasound-guided injection of Botulinum type A toxin into the masseter muscles for treating bruxism and its cosmetic effects.

    Science.gov (United States)

    Quezada-Gaon, Natacha; Wortsman, Ximena; Peñaloza, Osvaldo; Carrasco, Juan Eduardo

    2016-09-01

    Botulinum toxin type A has been used for treating the hypertrophy of the masseter muscles and its cosmetic effects. Ultrasound is increasingly used in dermatology, along with the guidance of mini-invasive procedures. To evaluate the role of ultrasound for guiding the application of Botulinum A toxin in patients with cosmetic alterations due to bruxism, correlate the clinical landmarks with the ultrasound findings, and study the effect on the symptoms, cosmetics, and quality of life. Twenty individuals with bruxism and cosmetic alterations underwent an ultrasound-guided injection of Botulinum toxin type A in each masseter muscle. Clinical and ultrasound marking of the procedure was compared. Clinical and sonographic evaluation was performed at the time of injection and 3 months later. Ten normal individuals underwent ultrasound of the masseter muscles as a control group. Up to 65% of individuals showed anatomical variants of the salivary glands. The method for clinically marking the skin showed a frequently erroneous location of the anterior point (up to 40% of cases) that was proven by ultrasound to be out of the muscle. In 20% of cases, ultrasound showed that the needle should be longer to enter the muscle. After injection, most of the patients demonstrated a decrease of the symptoms and cosmetic and quality of life improvements. Ultrasound can be a potent tool for guiding the injection of Botulinum toxin into the masseter muscles. It may contribute to a more personalized procedure, better cosmetic results, and help to avoid potential complications. © 2016 Wiley Periodicals, Inc.

  8. Effect of botulinum toxin A and nitroglycerin on random skin flap survival in rats.

    Science.gov (United States)

    Ghanbarzadeh, Kourosh; Tabatabaie, Omid Reza; Salehifar, Ebrahim; Amanlou, Massoud; Khorasani, Ghasemali

    2016-01-01

    A suitable pharmacological substitute for the well-established surgical delay technique for random skin flaps to increase viability has been elusive. To evaluate the effects of nitroglycerin and botulinum toxin type A on random flap survival in a rat model. The present controlled experimental study was performed in the four groups of rats. One week after intervention in each group, the flap was raised and kept in situ, and flap necrosis was evaluated through follow-up. Group 1 received intradermal botulinum toxin type A (BTX-A) and topical nitroglycerin 2%; group 2 received BTX-A and topical Vaseline (Unilever, USA); group 3 received topical nitroglycerin and intradermal normal saline; and group 4 received topical Vaseline and intradermal normal saline. BTX-A reduced the area of necrosis compared with control (24% versus 56% respectively; P<0.001). Nitroglycerin application was associated with a trend toward improved flap viability (42% versus 56%; P=0.059). The combination of topical nitroglycerin and BTX-A, compared with Vaseline and BTX-A, was associated with decreased flap necrosis (16.1% versus 24%, respectively), although it was not statistically significant (P=0.45). BTX-A was effective in reducing distal flap necrosis. The effect of BTX-A was significantly more pronounced than nitroglycerin ointment.

  9. Toxina botulínica y su empleo en la patología oral y maxilofacial Botulinum toxin and its use in oral and maxillofacial pathology

    Directory of Open Access Journals (Sweden)

    D. Martínez-Pérez

    2004-06-01

    Full Text Available Resumen: Las toxinas botulínicas son exotoxinas de la bacteria formadora de esporas Clostridim botulinum y los agentes causantes del botulismo. Cuando se inyecta en el músculo produce una parálisis flácida. El efecto clínico está directamente relacionado con la dosis y debe ajustarse para cada caso concreto. La Toxina botulínica ha demostrado en los más de veinte años en que se está utilizando que es un fármaco seguro. Las indicaciones de la toxina botulínica en la actualidad incluyen todas aquellas patologías que resultan de la hiperfunción muscular y la disfunción autonómica.Abstract: Botilinum toxins are exotoxins of the bacteria that form the Clostridium botulinum spores and the causative agents of botulism. When injected into the muscle flaccid paralysis is produced. The clinical effect is directly related with the dose and is should be adjusted for each particular case. over the last twenty years that it has been in use, the botulinum toxin has shown itself to be a reliable drug. Current indications for the use of botulinum toxin include all those pathologies which are the results of muscle hyperfunction and autonomic dysfunction.

  10. Botulinum Toxin Type A as Preoperative Treatment for Immediately Loaded Dental Implants Placed in Fresh Extraction Sockets for Full-Arch Restoration of Patients With Bruxism.

    Science.gov (United States)

    Mijiritsky, Eitan; Mortellaro, Carmen; Rudberg, Omri; Fahn, Miri; Basegmez, Cansu; Levin, Liran

    2016-05-01

    The aim of the present report was to describe the use of Botulinum toxin type A as preoperative treatment for immediately loaded dental implants placed in fresh extraction sockets for full-arch restoration of patients with bruxism. Patients with bruxism who were scheduled to receive immediately loaded full-arch implant supported fixed restorations were included in this retrospective clinical report. To reduce the occlusal forces applied in patients with bruxism, Botulinum toxin type A was introduced prior to the implant placement procedure. Patients were followed and implant survival as well as peri-implant bone level was assessed in each periodic follow-up visit. Adverse effects were also recorded. A control group with no use of Botulinum toxin was evaluated as well. A total of 26 patients (13 test and 13 control), with bruxism, aged 59.15 ± 11.43 years on average were included in this retrospective report and received immediately loaded dental implants placed in fresh extraction sockets for full-arch restoration. The test group treatment preceded by Botulinum toxin type A injection. Maxillary arches were supported by 8 to 10 implants while the mandibular arch was supported by 6 implants. All surgeries went uneventfully and no adverse effects were observed. The average follow-up time was 32.5 ± 10.4 months (range, 18-51). In the test group, no implant failures were recorded. One patient presented with 1 to 2 mm bone loss around 4 of the implants; the other implants presented with stable bone level. In the control group 1 patient lost 2 implants and another demonstrated 2 mm bone loss around 3 of the implants. The preoperative use of Botulinum toxin in patients with bruxism undergoing full-arch rehabilitation using immediately loaded dental implants placed in fresh extraction sockets seems to be a technique that deserves attention. Further long-term, large-scale randomized clinical trials will help to determine the additional benefit of this suggested

  11. A survey of traditional Iranian food products for contamination with toxigenic Clostridium botulinum

    Directory of Open Access Journals (Sweden)

    H.R. Tavakoli

    Full Text Available Summary: This study aimed to determine the rate of Clostridium botulinum contamination in some traditional Iranian food products (cheese, kashk and salted fish and evaluate the efficacy of the mouse bioassay method in detection of C. botulinum toxins in these foods. A total of 131 samples (57 cheese, 11 kashk and 63 salted fish were collected and examined to determine the rate of contamination by C. botulinum. Standard monovalent anti-toxins were used to determine the types of toxin. C. botulinum bacteria were detected in 4.58% of the examined samples (1.52% of cheese and 3.06% of salted fish samples. While no contamination was detected in the kashk samples, C. botulinum types A and E were found to be dominant in cheese and salted fish samples, respectively. These results indicate—some traditional Iranian foods may be contaminated with different types of C. botulinum, and the consumption of these products, either raw or cooked, may contribute to food-borne intoxications. Keywords: Clostridium botulinum, Botulinum toxin, Traditional foods

  12. Deeper than skin deep - The effect of botulinum toxin-A on emotion processing.

    Science.gov (United States)

    Baumeister, J-C; Papa, G; Foroni, F

    2016-08-01

    The effect of facial botulinum Toxin-A (BTX) injections on the processing of emotional stimuli was investigated. The hypothesis, that BTX would interfere with processing of slightly emotional stimuli and less with very emotional or neutral stimuli, was largely confirmed. BTX-users rated slightly emotional sentences and facial expressions, but not very emotional or neutral ones, as less emotional after the treatment. Furthermore, they became slower at categorizing slightly emotional facial expressions under time pressure. Copyright © 2016 Elsevier Ltd. All rights reserved.

  13. Treatment of hemifacial spasm with botulinum toxin type a: effective, long lasting and well tolerated

    Directory of Open Access Journals (Sweden)

    Jean Pierre Mette Batisti

    Full Text Available ABSTRACT Hemifacial spasm (HFS is a common movement disorder characterized by involuntary tonic or clonic contractions of the muscles innervated by the facial nerve. Objective To evaluate the long-term effect of botulinum toxin type A (BTX-A in the treatment of HFS. Methods A retrospective analysis of patients treated at the Movement Disorders Outpatient Clinic in the Neurology Service, Hospital de Clínicas, Federal University of Paraná, Curitiba, from 2009 to 2013 was carried out. A total of 550 BTX-A injections were administered to 100 HFS patients. Results Mean duration of improvement following each injection session was 3.1 months, mean latency to detection of improvement was 7.1 days and mean success rate was 94.7%. Patients were evaluated at an interval of 5.8 months after each application. Adverse effects, which were mostly minor, were observed in 37% of the patients at least once during follow-up. The most frequent was ptosis (35.1%. Conclusion Treatment of HFS with BTX-A was effective, sustainable and safe and had minimal, well-tolerated side effects.

  14. Adductor laryngeal breathing dystonia in NBIA treated with botulinum toxin-A

    Directory of Open Access Journals (Sweden)

    Vinod Rai

    2013-01-01

    Full Text Available We report a rare case of neurodegeneration with brain iron accumulation (NBIA presented with episodic inspiratory stridor. A 10-year-old boy presented with 3-year history of gradually progressive spastic gait and generalized dystonia (involving all four limbs, neck, jaw, and speech. MRI brain showed "Eye of Tiger" sign. He recently developed severe inspiratory stridor associated with almost gasping respiration. Direct video laryngoscopy showed paradoxical vocal cord closure during inspiration. He was treated with EMG-guided botulinum toxin-A injection given into bilateral thyroarytenoid muscles, resulting in dramatic response with complete disappearance of the stridor within a week. The effect lasted 18 months.

  15. GRIN: "GRoup versus INdividual physiotherapy following lower limb intra-muscular Botulinum Toxin-A injections for ambulant children with cerebral palsy: an assessor-masked randomised comparison trial": study protocol.

    Science.gov (United States)

    Thomas, Rachel E; Johnston, Leanne M; Boyd, Roslyn N; Sakzewski, Leanne; Kentish, Megan J

    2014-02-07

    Cerebral palsy is the most common cause of physical disability in childhood. Spasticity is a significant contributor to the secondary impairments impacting functional performance and participation. The most common lower limb spasticity management is focal intramuscular injections of Botulinum Toxin-Type A accompanied by individually-delivered (one on one) physiotherapy rehabilitation. With increasing emphasis on improving goal-directed functional activity and participation within a family-centred framework, it is timely to explore whether physiotherapy provided in a group could achieve comparable outcomes, encouraging providers to offer flexible models of physiotherapy delivery. This study aims to compare individual to group-based physiotherapy following intramuscular Botulinum Toxin-A injections to the lower limbs for ambulant children with cerebral palsy aged four to fourteen years. An assessor-masked, block randomised comparison trial will be conducted with random allocation to either group-based or individual physiotherapy. A sample size of 30 (15 in each study arm) will be recruited. Both groups will receive six hours of direct therapy following Botulinum Toxin-A injections in either an individual or group format with additional home programme activities (three exercises to be performed three times a week). Study groups will be compared at baseline (T1), then at 10 weeks (T2, efficacy) and 26 weeks (T3, retention) post Botulinum Toxin-A injections. Primary outcomes will be caregiver/s perception of and satisfaction with their child's occupational performance goals (Canadian Occupational Performance Measure) and quality of gait (Edinburgh Visual Gait Score) with a range of secondary outcomes across domains of the International Classification of Disability, Functioning and Health. This paper outlines the study protocol including theoretical basis, study hypotheses and outcome measures for this assessor-masked, randomised comparison trial comparing group versus

  16. Toxin production of non-proteolytic Cl. botulinum type B in radurized fish. Part of a coordinated programme on the wholesomeness of the process of food irradiation

    International Nuclear Information System (INIS)

    Suhadi, F.

    1981-02-01

    Toxin formation by proteolytic and nonproteolytic strains of C. botulinum type B in radurized raw fish and in radurized Pindang fish was investigated. In radurized Pindang fish samples, inoculation was done either before or after cooking. Radurization process with 2 and 3 kGy caused the extension of storage life of Rastrelliger sp., Euthynnus sp., and Scomberomorus sp. by factors of 2 and 2.5 at storage temperatures between 5 and 10 0 C. In general at 10.5 +- 0.3 0 C, no toxin was formed before the samples were spoiled both in irradiated and unirradiated samples. At 5.6 +- 0.5 0 C no toxin was formed until after the samples were spoiled. The earliest toxin formation in unirradiated Pindang samples stored at ambient temperature was detected after the samples were spoiled. In irradiated Pindang samples inoculated with C. botulinum spores after cooking and stored at ambient temperature the toxin formation was detected before the samples were spoiled. However, if the inoculation was done before the fish was processed into Pindang, the toxin was always detected after the samples were spoiled regardless of the irradiation dose, strain and inoculation level. As fish may be contaminated - if at all - with spores of C. botulinum in its raw state, processing of fish into Pindang and irradiation would not contribute to the health hazard concerning botulism even if the samples are stored at ambient temperature

  17. Analysis of the mechanisms that underlie absorption of botulinum toxin by the inhalation route.

    Science.gov (United States)

    Al-Saleem, Fetweh H; Ancharski, Denise M; Joshi, Suresh G; Elias, M; Singh, Ajay; Nasser, Zidoon; Simpson, Lance L

    2012-12-01

    Botulinum toxin is a highly potent oral and inhalation poison, which means that the toxin must have an efficient mechanism for penetration of epithelial barriers. To date, three models for toxin passage across epithelial barriers have been proposed: (i) the toxin itself undergoes binding and transcytosis; (ii) an auxiliary protein, HA35, transports toxin from the apical to the basal side of epithelial cells; and (iii) an auxiliary protein, HA35, acts on the basal side of epithelial cells to disrupt tight junctions, and this permits paracellular flux of toxin. These models were evaluated by studying toxin absorption following inhalation exposure in mice. Three types of experiments were conducted. In the first, the potency of pure neurotoxin was compared with that of progenitor toxin complex, which contains HA35. The results showed that the rate and extent of toxin absorption, as well as the potency of absorbed toxin, did not depend upon, nor were they enhanced by, the presence of HA35. In the second type of experiment, the potencies of pure neurotoxin and progenitor toxin complex were compared in the absence or presence of antibodies on the apical side of epithelial cells. Antibodies directed against the neurotoxin protected against challenge, but antibodies against HA35 did not. In the final type of experiment, the potency of pure neurotoxin and toxin complex was compared in animals pretreated to deliver antibodies to the basal side of epithelial cells. Once again, antibodies directed against the neurotoxin provided resistance to challenge, but antibodies directed against HA35 did not. Taken collectively, the data indicate that the toxin by itself is capable of crossing epithelial barriers. The data do not support any hypothesis in which HA35 is essential for toxin penetration of epithelial barriers.

  18. Electromyography-Guided Botulinum Toxin Injection Into the Cricothyroid Muscles in Bilateral Vocal Fold Abductor Paralysis

    OpenAIRE

    Sahin, Mustafa; Aydogdu, Ibrahim; Akyildiz, Serdar; Erdinc, Munevver; Ozturk, Kerem; Ogut, Fatih

    2016-01-01

    Objectives Bilateral vocal fold abductor paralysis (BVFAP) both deteriorates quality of life and may cause life-threatening respiratory problems. The aim of this study was to reduce respiratory symptoms in BVFAP patients using cricothyroid (CT) botulinum toxin (BTX) injection. Methods Before and 2 weeks and 4 months after bilateral BTX injection into the CT muscles under electromyography; alterations in respiratory, acoustic, aerodynamic and quality of life parameters were evaluated in BVFAP ...

  19. Single-fiber electromyography analysis of botulinum toxin diffusion in patients with fatigue and pseudobotulism.

    Science.gov (United States)

    Ruet, Alexis; Durand, Marie Christine; Denys, Pierre; Lofaso, Frederic; Genet, François; Schnitzler, Alexis

    2015-06-01

    To characterize electromyographic abnormalities according to symptoms (asymptomatic, fatigue, pseudobotulism) reported 1 month after botulinum toxin injection. Retrospective, single-center study comparing single-fiber electromyography (SFEMG) in the extensor digitorum communis (EDC) or orbicularis oculi (OO) muscles. Hospital. Four groups of adults treated for spasticity or neurologic bladder hyperactivity (N=55): control group (asymptomatic patients: n=17), fatigue group (unusual fatigue with no weakness: n=15), pseudobotulism group (muscle weakness and/or visual disturbance: n=20), and botulism group (from intensive care unit of the same hospital: n=3). Not applicable. Mean jitter, percentage of pathologic fibers, and percentage of blocked fibers were compared between groups. SFEMG was abnormal for 17.6% of control patients and 75% of patients in the pseudobotulism group. There were no differences between the control and fatigue groups. Mean jitter, percentage of pathologic fibers, and percentage of blocked fibers of the EDC muscle were significantly higher in the pseudobotulism group than in the fatigue and control groups. There were no differences between groups for the OO muscle. The SFEMG results in the botulism group were qualitatively similar to those of the pseudobotulism group. SFEMG of the EDC muscle confirmed diffusion of the toxin into muscles distant from the injection site in the pseudobotulism group. SFEMG in the OO muscle is not useful for the diagnosis of diffusion. No major signs of diffusion of botulinum toxin type A were found away from the injection site in patients with fatigue but no motor weakness. Such fatigue may be related to other mechanisms. Copyright © 2015 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.

  20. Value of botulinum toxin injections preceding a comprehensive rehabilitation period for children with spastic cerebral palsy: A cost-effectiveness study

    NARCIS (Netherlands)

    F.C. Schasfoort (Fabiënne); A.J. Dallmeijer (Annet); R.F. Pangalila (Robert); C. Catsman (Coriene); H.J. Stam (Henk); J.G. Becher (Jules); E.W. Steyerberg (Ewout W.); S. Polinder (Suzanne); J.B.J. Bussmann (Hans); H.L.D. Horemans (Herwin); E.M. Sneekes (E.); Bolster, E. (Eline); Viola, I. (Irma); Beek, K. (Karlijn) van; J.M.A. Verheijden (Johannes)

    2018-01-01

    textabstractObjective: Despite the widespread use of botulinum toxin in ambulatory children with spastic cerebral palsy, its value prior to intensive physiotherapy with adjunctive casting/orthoses remains unclear. Design: A pragmatically designed, multi-centre trial, comparing the effectiveness of

  1. Investigation of Clostridium botulinum group III's mobilome content.

    Science.gov (United States)

    Woudstra, Cédric; Le Maréchal, Caroline; Souillard, Rozenn; Anniballi, Fabrizio; Auricchio, Bruna; Bano, Luca; Bayon-Auboyer, Marie-Hélène; Koene, Miriam; Mermoud, Isabelle; Brito, Roseane B; Lobato, Francisco C F; Silva, Rodrigo O S; Dorner, Martin B; Fach, Patrick

    2018-02-01

    Clostridium botulinum group III is mainly responsible for botulism in animals. It could lead to high animal mortality rates and, therefore, represents a major environmental and economic concern. Strains of this group harbor the botulinum toxin locus on an unstable bacteriophage. Since the release of the first complete C. botulinum group III genome sequence (strain BKT015925), strains have been found to contain others mobile elements encoding for toxin components. In this study, seven assays targeting toxin genes present on the genetic mobile elements of C. botulinum group III were developed with the objective to better characterize C. botulinum group III strains. The investigation of 110 C. botulinum group III strains and 519 naturally contaminated samples collected during botulism outbreaks in Europe showed alpha-toxin and C2-I/C2-II markers to be systematically associated with type C/D bont-positive samples, which may indicate an important role of these elements in the pathogenicity mechanisms. On the contrary, bont type D/C strains and the related positive samples appeared to contain almost none of the markers tested. Interestingly, 31 bont-negative samples collected on farms after a botulism outbreak revealed to be positive for some of the genetic mobile elements tested. This suggests loss of the bont phage, either in farm environment after the outbreak or during laboratory handling. Copyright © 2017 Elsevier Ltd. All rights reserved.

  2. A Medical Research and Evaluation Facility (MREF) and Studies Supporting the Medical Chemical Defense Program: Task 95-39: Methods Development and Validation of Two Mouse Bioassays for Use in Quantifying Botulinum Toxins (A, B, C, D and E) and Toxin Antibody Titers

    National Research Council Canada - National Science Library

    Olson, Carl

    1997-01-01

    Ths task was conducted for the U.S. Army Medical Materiel Development Activity (USAMMDA) to validate two mouse bioassays for quantify botulinum toxin potency and neutralizing antibodies to botulimun toxins...

  3. Prevalence of toxin-producing Clostridium botulinum associated with the macroalga Cladophora in three Great Lakes: growth and management

    Science.gov (United States)

    Chun, Chan Lan; Kahn, Chase I.; Borchert, Andrew J.; Byappanahalli, Muruleedhara N.; Whitman, Richard L.; Peller, Julie R.; Pier, Christina; Lin, Guangyun; Johnson, Eric A.; Sadowsky, Michael J.

    2015-01-01

    The reemergence of avian botulism caused by Clostridium botulinum type E has been observed across the Great Lakes in recent years. Evidence suggests an association between the nuisance algae, Cladophoraspp., and C. botulinum in nearshore areas of the Great Lakes. However, the nature of the association between Cladophora and C. botulinum is not fully understood due, in part, to the complex food web interactions in this disease etiology. In this study, we extensively evaluated their association by quantitatively examining population size and serotypes of C. botulinum in algal mats collected from wide geographic areas in lakes Michigan, Ontario, and Erie in 2011–2012 and comparing them with frequencies in other matrices such as sand and water. A high prevalence (96%) of C. botulinum type E was observed inCladophora mats collected from shorelines of the Great Lakes in 2012. Among the algae samples containing detectable C. botulinum, the population size of C. Botulinum type E was 100–104 MPN/g dried algae, which was much greater (up to 103 fold) than that found in sand or the water column, indicating thatCladophora mats are sources of this pathogen. Mouse toxinantitoxin bioassays confirmed that the putativeC. botulinum belonged to the type E serotype. Steam treatment was effective in reducing or eliminating C. botulinum type E viable cells in Cladophora mats, thereby breaking the potential transmission route of toxin up to the food chain. Consequently, our data suggest that steam treatment incorporated with a beach cleaning machine may be an effective treatment of Cladophora-borne C. botulinum and may reduce bird mortality and human health risks.

  4. A Single-blind, Split-face, Randomized, Pilot Study Comparing the Effects of Intradermal and Intramuscular Injection of Two Commercially Available Botulinum Toxin A Formulas to Reduce Signs of Facial Aging

    Science.gov (United States)

    Sapra, Priya; Sapra, Sheetal; Khanna, Julie; Mraud, Kelli; Bonadonna, Jennifer

    2017-01-01

    Objective: To examine the effectiveness of intradermal botulinum toxin type A injection in improving skin texture and midface lift while reducing pore size and sebum production, as well as investigate the differences in effectiveness between onabotulinumtoxinA and abobotulinumtoxinA using intradermal and intramuscular injection methods. Design: A 16-week, single-blind, split-face, randomized study. Each patient served as their own control, receiving onabotulinumtoxinA and abobotulinumtoxinA randomized to either the left or right side of the face. Patients received intradermal botulinum toxin type A injections at Week 0 and intramuscular botulinum toxin type A injections at Week 2. Participants: Ten women aged 35 to 65 years who exhibited static rhytids in the glabellar and periorbital area. Measurements: The primary endpoint was efficacy of split-face treatment of intradermal and intramuscular onabotulinumtoxinA and abobotulinumtoxinA as assessed by a blinded evaluator using baseline and post-treatment photographs. The secondary endpoints included safety as assessed by adverse events and patient satisfaction measured by questionnaires completed at baseline and post-treatment. Results: Intradermal injection of botulinum toxin type A led to a statistically significant improvement in skin texture (p=0.004) while also resulting in mild midface lift (p=0.024), but did not provide a significant reduction of pore size and sebum production. There was no statistically significant difference between onabotulinumtoxinA and abobotulinumtoxinA when injected intradermally or intramuscularly. Conclusion: Intradermal injection of botulinum toxin type A appears to be a safe and effective therapy that provides an improvement in facial skin texture and midface lift. Registry: clinicaltrials.gov (ID#: NCT02907268). PMID:28367260

  5. Botulinum toxin type A for the treatment of sialorrhoea in amyotrophic lateral sclerosis: a clinical and neurophysiological study.

    Science.gov (United States)

    Gilio, Francesca; Iacovelli, Elisa; Frasca, Vittorio; Gabriele, Maria; Giacomelli, Elena; Picchiori, Floriana; Soldo, Pietro; Cipriani, Anna Maria; Ruoppolo, Giovanni; Inghilleri, Maurizio

    2010-08-01

    Botulinum toxin type A (BoNT/A) has been proposed as an alternative treatment for sialorrhoea in patients with amyotrophic lateral sclerosis (ALS). In an open-label prospective study, BoNT/A was injected into the parotid glands bilaterally using anatomic landmarks in 26 ALS patients with bulbar symptoms. Two weeks after injection the severity of sialorrhoea and the related disability were evaluated subjectively and objectively. A group of healthy subjects acted as controls for saliva production. Patients also underwent electrophysiological tests to evaluate possible toxin effects in the nearby non-injected muscles by comparing the amplitude of compound motor action potentials (cMAPs) elicited by electrical stimulation and recorded from the orbicularis oculi and masseter muscles. After BoNT/A injections, of the 26 patients treated, 23 reported that the severity of sialorrhoea improved and the disabling symptoms diminished. Cotton roll weight also decreased after BoNT/A injection, suggesting a reduction in saliva production. Two patients complained of dry mouth. BoNT/A injection left the cMAP amplitude unchanged, suggesting that botulinum toxin does not significantly affect the non-injected facial and masticatory muscles. In conclusion, intraparotid anatomically-guided BoNT/A injection is an effective, easy, and safe treatment for sialorrhoea in patients with bulbar symptoms related to ALS.

  6. Botulinum toxin in myotonia congenita: it does not help against rigidity and pain.

    Science.gov (United States)

    Dressler, Dirk; Adib Saberi, Fereshte

    2014-05-01

    Botulinum toxin (BT) is a potent local muscle relaxant with analgetic properties. Myotonia congenita (MC) is a genetic disorder producing muscle rigidity and pain. BT injected into the trapezius produced mild paresis, but no effect on rigidity and pain. There were no signs of systemic effects. Lack of BT efficacy on MC rigidity confirms its origin from muscle membrane dysfunction rather than from inappropriate neuromuscular activation. Lack of BT efficacy on pain could be caused by lack of anti-rigidity effect. It could also be due to separate non-muscular pain mechanisms unresponsive to BT.

  7. Botox facial slimming/facial sculpting: the role of botulinum toxin-A in the treatment of hypertrophic masseteric muscle and parotid enlargement to narrow the lower facial width.

    Science.gov (United States)

    Wu, Woffles T L

    2010-02-01

    Botulinum toxin A is a highly efficacious and cost-effective, nonsurgical option for reducing the width and shape of the lower face and jawline. The results can vary from the subtlest thinning of the face to an extremely thin, cachectic appearance. Many nuances can be achieved. The administration is simple, and the process takes barely 5 minutes in an office setting. Botulinum toxin A can also be effectively used to reduce the bulk of an enlarged parotid gland without affecting saliva production. Copyright 2010. Published by Elsevier Inc.

  8. The utility of EMG interference pattern analysis in botulinum toxin treatment of torticollis: A randomised, controlled and blinded study

    DEFF Research Database (Denmark)

    Werdelin, L; Dalager, T; Fuglsang-Frederiksen, Anders

    2011-01-01

    OBJECTIVE: The significance of electromyography (EMG) guidance in botulinum toxin (BT) treatment has been much debated. The aim of this study was to evaluate if EMG guidance in the treatment of torticollis in BT-naive patients had a better outcome than treatment after clinical evaluation alone...

  9. Bioterrorism: toxins as weapons.

    Science.gov (United States)

    Anderson, Peter D

    2012-04-01

    The potential for biological weapons to be used in terrorism is a real possibility. Biological weapons include infectious agents and toxins. Toxins are poisons produced by living organisms. Toxins relevant to bioterrorism include ricin, botulinum, Clostridium perfrigens epsilson toxin, conotoxins, shigatoxins, saxitoxins, tetrodotoxins, mycotoxins, and nicotine. Toxins have properties of biological and chemical weapons. Unlike pathogens, toxins do not produce an infection. Ricin causes multiorgan toxicity by blocking protein synthesis. Botulinum blocks acetylcholine in the peripheral nervous system leading to muscle paralysis. Epsilon toxin damages cell membranes. Conotoxins block potassium and sodium channels in neurons. Shigatoxins inhibit protein synthesis and induce apoptosis. Saxitoxin and tetrodotoxin inhibit sodium channels in neurons. Mycotoxins include aflatoxins and trichothecenes. Aflatoxins are carcinogens. Trichothecenes inhibit protein and nucleic acid synthesis. Nicotine produces numerous nicotinic effects in the nervous system.

  10. Sensation of Cold during the Ice Water Test Corresponds to the Perception of Pain during Botulinum Toxin Bladder Wall Injections.

    Science.gov (United States)

    Reitz, André; Hüsch, Tanja; Doggweiler, Regula; Buse, Stephan; Haferkamp, Axel

    2018-01-01

    To investigate the association of bladder cold sensation (BCS) during the ice water test (IWT) and pain perception when botulinum toxin injections (BTI) are administered into the bladder wall. In 86 patients with idiopathic overactive bladder, the BCS during the IWT was investigated. Patients were divided into 2 groups: with and without BCS. During subsequent administration of BTI, the number of perceived and painful injections as well as the pain levels on a 0-100 pain scale were compared in both groups using Student t test. Thirty-five patients reported a BCS, while 51 did not. After 10 BTI, the mean number of perceived injections was 7.9 in patients with and 2.4 in patients without BCS (p sensation (p perceptions of cold and pain in the urinary bladder may use similar receptors and neuronal pathways. © 2018 S. Karger AG, Basel.

  11. Botulinum toxin for treating muscular temporomandibular disorders: a systematic review

    Directory of Open Access Journals (Sweden)

    Eduardo Machado

    2012-12-01

    Full Text Available OBJECTIVE: This study, through a systematic literature review, aims to analyze the effectiveness of Botulinum Toxin as a treatment for masticatory myofascial pain and muscles temporomandibular disorders (TMD. METHODS: Survey in research bases: MEDLINE, Cochrane, EMBASE, Pubmed, Lilacs and BBO, between the years of 1966 and April 2011, with focus in randomized or quasi-randomized controlled clinical trials, blind or double-blind. RESULTS: After applying the inclusion criteria, 4 articles comprised the final sample: 3 were double-blind randomized controlled clinical trials and 1 was single-blind randomized controlled clinical trial. CONCLUSIONS: According to the literature, there is lack of evidence about the real effectiveness of botulinum toxin in the treatment of masticatory myofascial pain and muscular TMD. Thus, further randomized controlled clinical trials, with representative samples and longer follow-up time, to assess the real effectiveness of the technique are needed.OBJETIVO: este trabalho, por meio de uma revisão sistemática da literatura, teve como objetivo analisar a efetividade da toxina botulínica como tratamento para dor miofascial mastigatória e disfunções temporomandibulares (DTM musculares. MÉTODOS: pesquisa nas bases de dados Medline, Cochrane, Embase, Pubmed, Lilacs e BBO, no período entre 1966 e abril de 2011, com enfoque em estudos clínicos controlados randomizados ou quase-randomizados, cegos ou duplo-cegos. RESULTADOS: após a aplicação dos critérios de inclusão, chegou-se a 4 artigos, sendo que 3 eram estudos clínicos controlados randomizados duplo-cego e 1 era estudo clínico controlado randomizado simples-cego. CONCLUSÕES: pela análise da literatura, verificou-se um número reduzido de evidências significativas sobre a real efetividade da toxina botulínica no tratamento da dor miofascial e de DTM musculares. Assim, são necessários novos estudos clínicos controlados randomizados, com amostras

  12. Botulinum toxin type-A in therapy of patients with anismus.

    Science.gov (United States)

    Ron, Y; Avni, Y; Lukovetski, A; Wardi, J; Geva, D; Birkenfeld, S; Halpern, Z

    2001-12-01

    Anismus is a common cause of constipation and outlet obstruction. Standard therapy with laxatives or biofeedback has conflicting results. Surgical treatment gives poor results and has practically been abandoned. This study was designed to evaluate the efficacy of botulinum toxin type-A (Botox) injection to the puborectalis muscle in patients with anismus. Twenty-five patients (15 females; mean age, 23.2) with history of constipation and symptoms of outlet obstruction underwent anorectal perfusion manometry and video-proctography. All patients were found to have a nonrelaxing puborectalis muscle on both modalities. All have been unable to expel a rectal balloon. Each patient who participated in the study was randomly assigned to undergo local injection of Botox--10 units to each side of the puborectalis or 20 units to the posterior aspect of this muscle. Eight patients underwent further injections1-5 every 3 months in accordance with previous results. Follow-up was conducted 1, 4, 12, and 24 weeks after injection. Straining, anorectal pain, and overall satisfaction were assessed on a visual analog scale. Weekly evacuation, fecal incontinence, and complications were recorded. At the weekly meeting, each patient underwent anorectal manometry with a balloon expulsion test. Manometric relaxation was achieved after the first injection in 18 patients (75 percent). Once relaxation was achieved, it lasted throughout the follow-up. Nine patients (37.5 percent) expelled the rectal balloon after the first injection. Seven of 16 patients who failed the first injection had an additional one. In 2 patients it was successful (28.6 percent). Symptom improvement of 29.2 percent in straining index was recorded during follow-up. In 3 patients (12.5 percent) pain developed after injection. No other complications were observed. Overall satisfaction with Botox injection results was observed in 58.3 percent. Botox injection to the puborectalis muscle has been found to have a limited

  13. Patient Perceived Benefit in Facial Aesthetic Procedures: FACE-Q as a Tool to Study Botulinum Toxin Injection Outcomes.

    Science.gov (United States)

    Chang, Brian L; Wilson, Anthony J; Taglienti, Anthony J; Chang, Catherine S; Folsom, Nancy; Percec, Ivona

    2016-07-01

    There are numerous methods of assessing patient satisfaction with botulinum toxin type A neuromodulation of the glabellar rhytids. As the use of aesthetic neuromodulation increases both in breadth and number of procedures, there is a need for more comprehensive tools to evaluate patient-reported outcomes. The FACE-Q is a recently validated patient-reported outcome instrument that can be used to measure patient perceptions of botulinum toxin type A neuromodulation. This study used the FACE-Q to assess patient satisfaction following botulinum toxin type A neuromodulation of the glabellar rhytids. 57 female patients completed the FACE-Q, a survey that evaluates patients' satisfaction with their facial appearance. After this baseline survey, the patients received injections of one of onabotulinumtoxinA (Botox, Allergan, Dublin, Ireland), abobotulinumtoxinA (Dysport, Galderma, Lausanne, Switzerland), or incobotulinumtoxinA (Xeomin, Merz Pharmaceuticals, Frankfurt am Main, Germany) in the glabella. Two weeks post-injection, the patients completed the FACE-Q again. The percentage changes in patient responses were tabulated to determine how neuromodulation affects patient satisfaction with their facial appearance. The percentage changes for each of the neurotoxin groups were compared to determine if patient satisfaction with neuromodulation varies with the type of neurotoxin. Patient satisfaction with their overall facial appearance increased by 28% following neuromodulation. Patients stated that they believe they look an average of 5.6 years younger post-neuromodulation. There were no significant differences among the treatment groups. The FACE-Q demonstrates that patients are more satisfied by their overall facial appearance and age appearance following neuromodulation of their glabellar rhytids. Patients are equally satisfied with the improvement of their facial appearance regardless of which neurotoxin they received. LEVEL OF EVIDENCE 2: Therapeutic. © 2016 The

  14. Minimal Essential Domains Specifying Toxicity of the Light Chains of Tetanus Toxin and Botulinum Neurotoxin Type A

    NARCIS (Netherlands)

    Kurazono, Hisao; Mochida, Sumiko; Binz, Thomas; Eisel, Ulrich; Quanz, Martin; Grebenstein, Oliver; Wernars, Karel; Poulain, Bernard; Tauc, Ladislav; Niemann, Heiner

    1992-01-01

    To define conserved domains within the light (L) chains of clostridial neurotoxins, we determined the sequence of botulinum neurotoxin type B (BoNT/B) and aligned it with those of tetanus toxin (TeTx) and BoNT/A, BoNT/Cl, BoNT/D, and BoNT/E. The L chains of BoNT/B and TeTx share 51.6% identical

  15. Epidemiologic Overview of Synkinesis in 353 Patients with Longstanding Facial Paralysis under Treatment with Botulinum Toxin for 11 Years.

    Science.gov (United States)

    Salles, Alessandra Grassi; da Costa, Eduardo Fernandes; Ferreira, Marcus Castro; Remigio, Adelina Fatima do Nascimento; Moraes, Luciana Borsoi; Gemperli, Rolf

    2015-12-01

    Patients with longstanding facial paralysis often exhibit synkinesis. Few reports describe the prevalence and factors related to the development of synkinesis after facial paralysis. Botulinum toxin type A injection is an important adjunct treatment for facial paralysis-induced asymmetry and synkinesis. The authors assessed the clinical and epidemiologic characteristics of patients with sequelae of facial paralysis treated with botulinum toxin type A injections to evaluate the prevalence of synkinesis and related factors. A total of 353 patients (age, 4 to 84 years; 245 female patients) with longstanding facial paralysis underwent 2312 botulinum toxin type A injections during an 11-year follow-up. Doses used over the years, previous treatments (electrical stimulation, operations), and how they correlated to postparalysis and postreanimation synkinesis were analyzed. There was a significant association between cause and surgery. Most patients with facial paralysis caused by a congenital defect, trauma, or a tumor underwent reanimation. There were no sex- or synkinesis-related differences in the doses used, but the doses were higher in the reanimation group than in the no-surgery group. Synkinesis was found in 196 patients; 148 (41.9 percent) presented with postparalysis synkinesis (oro-ocular, oculo-oral) and 58 (16.4 percent) presented with postreanimation synkinesis. Ten patients presented with both types. This study determined the high prevalence (55.5 percent) of synkinesis in patients with longstanding facial paralysis. Postparalysis synkinesis was positively associated with infectious and idiopathic causes, electrical stimulation, facial nerve decompression, and no requirement for surgery. Postreanimation synkinesis was present in 28.2 percent of reanimated patients and was significantly associated with microsurgical flaps, transfacial nerve grafting, masseteric-facial anastomosis, and temporalis muscle transfers.

  16. Alternative Approach to Traumatic Stensen’s Duct Injuries Accompanied by Glandular Involvement: Botulinum Toxin Injection to the Gland in Conjunction with Microsurgical Repair of the Duct in an Acute Setting

    OpenAIRE

    Mert Çalış; Zeynep Öz; Hakan Uzun; Burçe Özgen; Alp Çetin3; Ali Emre Aksu

    2017-01-01

    Objective: The aim of this study was to evaluate the long-term results of a simultaneous application of botulinum toxin to the parotid gland in conjunction with the microsurgical repair of the duct in an acute setting and to encourage using botulinum toxin as a first-line option to prevent future complications associated with glandular involvement. Material and Methods: Three patients who were referred to the Plastic Surgery Clinic by the emergency room of the Hacettepe University Hospita...

  17. Botulinum Toxin in Secondarily Nonresponsive Patients with Spasmodic Dysphonia.

    Science.gov (United States)

    Mor, Niv; Tang, Christopher; Blitzer, Andrew

    2016-09-01

    Chemodenervation with botulinum toxin (BoNT) has been effective and well tolerated for all types of dystonia for >30 years. We reviewed outcomes of our patients treated with BoNT serotype A (BoNT-A) for spasmodic dysphonia (SD) who became secondarily nonresponsive. We found that 8 of 1400 patients became nonresponsive to BoNT-A (0.57%), which is lower than the secondary nonresponse rate in other dystonias. After a cessation period, 4 of our patients resumed BoNT-A injections, and recurrence of immunoresistance was not seen in any of them. When compared with patients with other dystonias, patients with SD receive extremely low doses of BoNT. Small antigen challenge may explain the lower rate of immunoresistance and long-lasting efficacy after BoNT-A is restarted among secondary nonresponsive patients with SD. © American Academy of Otolaryngology—Head and Neck Surgery Foundation 2016.

  18. Fatal Clostridium botulinum toxicosis in eleven Holstein cattle fed round bale barley haylage.

    Science.gov (United States)

    Kelch, W J; Kerr, L A; Pringle, J K; Rohrbach, B W; Whitlock, R H

    2000-09-01

    Twenty-two lactating Holstein cattle in Tennessee had clinical signs of intoxication with preformed Clostridium botulinum toxin. These signs included weakness, paralysis of the tongue and chest muscles, abdominal breathing, and, in 11 of the 22 cows, death. Differential diagnoses included hypocalcemia, hypomagnesemia, carbohydrate overload, and several toxicoses including mycotoxin, lead, nitrate, organophosphate, atropine or atropine-like alkaloid, and botulism. A diagnosis of botulism by the ingestion of preformed C. botulinum type B toxin was made by eliminating these other diseases, by finding C. botulinum type B spores in 3 bales of round bale barley haylage fed to these cattle, and by isolating preformed type B toxin from 1 of the 3 bales. Confirmation of the toxin type was made by demonstrating mouse lethality by intraperitoneal injection of specimen extracts with neutralization by C. botulinum type B antitoxin. The haylage, harvested green and encased in black plastic bags to facilitate fermentation, was presumably contaminated by the botulinum toxin when fermentation failed to produce enough acid to lower the pH to 4.5, the pH below which C. botulinum growth is inhibited. Farmers and ranchers who use round hay balers to produce haylage should be alert to this potential problem.

  19. The Use of Botulinum Toxin for the Treatment of Muscle Spasticity in the First 2 Years of Life

    Science.gov (United States)

    Bakheit, Abdel Magid

    2010-01-01

    Although there are sound theoretical reasons for the use of botulinum toxin (Btx) as early as possible in the management of severe childhood muscle spasticity, the experience with its safety in children younger than 2 years of age is limited and information about its possible effects on the development and maturation of the human motor system…

  20. Botulinum Toxin Type A as a Therapeutic Agent against Headache and Related Disorders

    Science.gov (United States)

    Luvisetto, Siro; Gazerani, Parisa; Cianchetti, Carlo; Pavone, Flaminia

    2015-01-01

    Botulinum neurotoxin A (BoNT/A) is a toxin produced by the naturally-occurring Clostridium botulinum that causes botulism. The potential of BoNT/A as a useful medical intervention was discovered by scientists developing a vaccine to protect against botulism. They found that, when injected into a muscle, BoNT/A causes a flaccid paralysis. Following this discovery, BoNT/A has been used for many years in the treatment of conditions of pathological muscle hyperactivity, like dystonias and spasticities. In parallel, the toxin has become a “glamour” drug due to its power to ward off facial wrinkles, particularly frontal, due to the activity of the mimic muscles. After the discovery that the drug also appeared to have a preventive effect on headache, scientists spent many efforts to study the potentially-therapeutic action of BoNT/A against pain. BoNT/A is effective at reducing pain in a number of disease states, including cervical dystonia, neuropathic pain, lower back pain, spasticity, myofascial pain and bladder pain. In 2010, regulatory approval for the treatment of chronic migraine with BoNT/A was given, notwithstanding the fact that the mechanism of action is still not completely elucidated. In the present review, we summarize experimental evidence that may help to clarify the mechanisms of action of BoNT/A in relation to the alleviation of headache pain, with particular emphasis on preclinical studies, both in animals and humans. Moreover, we summarize the latest clinical trials that show evidence on headache conditions that may obtain benefits from therapy with BoNT/A. PMID:26404377

  1. Sugar-binding sites of the HA1 subcomponent of Clostridium botulinum type C progenitor toxin.

    Science.gov (United States)

    Nakamura, Toshio; Tonozuka, Takashi; Ide, Azusa; Yuzawa, Takayuki; Oguma, Keiji; Nishikawa, Atsushi

    2008-02-22

    Clostridium botulinum type C 16S progenitor toxin contains a hemagglutinin (HA) subcomponent, designated HA1, which appears to play an important role in the effective internalization of the toxin in gastrointestinal epithelial cells and in creating a broad specificity for the oligosaccharide structure that corresponds to various targets. In this study, using the recombinant protein fused to glutathione S-transferase, we investigated the binding specificity of the HA1 subcomponent to sugars and estimated the binding sites of HA1 based on X-ray crystallography and soaking experiments using various sugars. N-Acetylneuraminic acid, N-acetylgalactosamine, and galactose effectively inhibited the binding that occurs between glutathione S-transferase-HA1 and mucins, whereas N-acetylglucosamine and glucose did not inhibit it. The crystal structures of HA1 complex with N-acetylneuraminic acid, N-acetylgalactosamine, and galactose were also determined. There are two sugar-binding sites, sites I and II. Site I corresponds to the electron densities noted for all sugars and is located at the C-terminal beta-trefoil domain, while site II corresponds to the electron densities noted only for galactose. An aromatic amino acid residue, Trp176, at site I has a stacking interaction with the hexose ring of the sugars. On the other hand, there is no aromatic residue at site II; thus, the interaction with galactose seems to be poor. The double mutant W176A at site I and D271F at site II has no avidity for N-acetylneuraminic acid but has avidity for galactose. In this report, the binding specificity of botulinum C16S toxin HA1 to various sugars is demonstrated based on its structural features.

  2. Molecular scaffold reorganization at the transmitter release site with vesicle exocytosis or botulinum toxin C1.

    Science.gov (United States)

    Stanley, Elise F; Reese, Tom S; Wang, Gary Z

    2003-10-01

    Neurotransmitter release sites at the freeze-fractured frog neuromuscular junction are composed of inner and outer paired rows of large membrane particles, the putative calcium channels, anchored by the ribs of an underlying protein scaffold. We analysed the locations of the release site particles as a reflection of the scaffold structure, comparing particle distributions in secreting terminals with those where secretion was blocked with botulinum toxin A, which cleaves a small segment off SNAP-25, or botulinum toxin C1, which cleaves the cytoplasmic domain of syntaxin. In the idle terminal the inner and outer paired rows were located approximately 25 and approximately 44 nm, respectively, from the release site midline. However, adjacent to vesicular fusion sites both particle rows were displaced towards the midline by approximately 25%. The intervals between the particles along each row were examined by a nearest-neighbour approach. In control terminals the peak interval along the inner row was approximately 17 nm, consistent with previous reports and the spacing of the scaffold ribs. While the average distance between particles in the outer row was also approximately 17 nm, a detailed analysis revealed short 'linear clusters' with a approximately 14 nm interval. These clusters were enriched at vesicle fusion sites, suggesting an association with the docking sites, and were eliminated by botulinum C1, but not A. Our findings suggest, first, that the release site scaffold ribs undergo a predictable, and possibly active, shortening during exocytosis and, second, that at the vesicle docking site syntaxin plays a role in the cross-linking of the rib tips to form the vesicle docking sites.

  3. Factors affecting growth and toxin production by Clostridium botulinum type E on irradiated (0.3 Mrad) chicken skins

    International Nuclear Information System (INIS)

    Firstenberg-Eden, R.; Rowley, D.B.; Shattuck, G.E.

    1982-01-01

    A model system (chicken skins with chicken exudate) was used to determine if Clostridium botulinum type E (Beluga) spores, stressed by low dose irradiation, would develop and produce toxin at abuse temperatures of 10 and 30 0 C in the absence of characteristic spoilage. Unstressed spores germinated, multiplied, and produced toxin on vacuum-packed chicken skins, stored at either 30 or 10 0 C. Cell numbers increased faster and toxin was evident sooner at 30 0 C than at 10 0 C. At 30 0 C, growth occurred and toxin was produced more slowly when samples were incubated aerobically than anaerobically. When samples were incubated aerobically at 10 0 C, no toxin was detected within a test period of 14 days. An irradiation dose of 0.3 Mrad at 5 0 C reduced a spore population on vacuum-sealed chicken skins by about 90%. The surviving population produced toxin at 30 0 C under either aerobic or anaerobic conditions, at 10 0 C no toxin was detected even on skins incubated anaerobically. Under the worst conditions (30 0 C, vacuum packed) toxin was not detected prior to characteristic spoilage caused by the natural flora surviving 0.3 Mrad

  4. Botulinum Toxin Type a Injection, Followed by Home-Based Functional Training for Upper Limb Hemiparesis after Stroke

    Science.gov (United States)

    Takekawa, Toru; Kakuda, Wataru; Taguchi, Kensuke; Ishikawa, Atsushi; Sase, Yousuke; Abo, Masahiro

    2012-01-01

    Botulinum toxin type A (BoNT-A) has been reported to be an effective treatment for limb spasticity after stroke. However, the reduction in the spasticity after BoNT-A injection alone does not ensure an improvement in the active motor function of the affected limb. The aim of this study was to clarify the clinical effects of a BoNT-A injection,…

  5. Comparing two botulinum toxin type A formulations using manufacturers' product summaries.

    Science.gov (United States)

    Wenzel, R; Jones, D; Borrego, J A

    2007-08-01

    Because of the unique pharmacology and clinical versatility of botulinum toxin (BoNT), particularly BoNT serotype A (BoNTA), a need exists for discussion of the current data on similarities and differences between two BoNTA products, BOTOX and Dysport. We compared the physiochemical and pharmacological properties of BOTOX and Dysport using information from the Summary of Product Characteristics (SmPC) documents from a number of countries around the world. Our analysis based on the SmPC documents demonstrated distinct differences in physical characteristics, breadth of approved indications, dosing and administration, and the incidence and severity of adverse events. BOTOX and Dysport are not bioequivalent. Many of the differences between BOTOX and Dysport discussed within are probably related to the differences in their physical characteristics.

  6. Reconstituting botulinum toxin drugs: shaking, stirring or what?

    Science.gov (United States)

    Dressler, Dirk; Bigalke, Hans

    2016-05-01

    Most botulinum toxin (BT) drugs are stored as powders which need to be reconstituted with normal saline before clinical use. As botulinum neurotoxin (BNT), the therapeutically active ingredient, is a large double-stranded protein the process of reconstitution should be performed with special attention to mechanical stress applied. We wanted to test the mechanical stability of BNT during the reconstitution process. For this, 100 MU onabotulinumtoxinA (Botox(®), Irvine, CA, USA) was reconstituted with 2.0 ml of NaCl/H2O. Gentle reconstitution (GR) was performed with a 5 ml syringe, a 0.90 × 70 mm injection needle, one cycle of injection-aspiration-injection and two gentle shakes of the vial. Aggressive reconstitution (AR) was performed with a 5 ml syringe, a 0.40 × 40 mm injection needle, ten injection-aspiration-injection cycles and 30 s of continuous shaking of the vial. AR increased the time to paralysis in the mouse hemidiaphragm assay (HDA) from 72.0 ± 4.6 to 106.0 ± 16.0 min (*p = 0.002, two-tailed t test after Kolmogorov-Smirnova test with Lilliefors correction for normal distribution). Construction of a calibration curve revealed that the increase in the time to paralysis was correlated with a loss of potency of from 100 to 58 MU (-42 %). BT users should use large diameter injection needles for reconstitution, apply two or three injection-aspiration-injection cycles and, maybe, shake the vials a few times to rinse the entire glass wall. Aggressive reconstitution with small diameter needles, prolonged injection-aspiration-injection and violent shaking should be avoided.

  7. Botulinum toxin treatment for limb spasticity in childhood cerebral palsy

    Directory of Open Access Journals (Sweden)

    Vito ePavone

    2016-02-01

    Full Text Available CP is the most common cause of chronic disability in childhood occurring in 2 to 2.5/1000 births. It is a severe disorder and a significant number of patients present cognitive delay and difficulty in walking. The use of botulinum toxin (BTX has become a popular treatment for CP especially for spastic and dystonic muscles while avoiding deformity and pain. Moreover, the combination of physiotherapy, casting, orthotics and injection of BTX may delay or decrease the need for surgical intervention while reserving single-event, multi-level surgery for fixed musculotendinous contractures and bony deformities in older children. This report highlights the utility of BTX in the treatment of cerebral palsy in children. We include techniques for administration, side effects and possible resistance as well as specific use in the upper and lower limbs muscles

  8. Alternative Approach to Traumatic Stensen’s Duct Injuries Accompanied by Glandular Involvement: Botulinum Toxin Injection to the Gland in Conjunction with Microsurgical Repair of the Duct in an Acute Setting

    Directory of Open Access Journals (Sweden)

    Mert Çalış

    2017-12-01

    Full Text Available Objective: The aim of this study was to evaluate the long-term results of a simultaneous application of botulinum toxin to the parotid gland in conjunction with the microsurgical repair of the duct in an acute setting and to encourage using botulinum toxin as a first-line option to prevent future complications associated with glandular involvement. Material and Methods: Three patients who were referred to the Plastic Surgery Clinic by the emergency room of the Hacettepe University Hospital after maxillofacial trauma are reviewed in this study. Exploration of the facial nerve and Stensen’s duct was planned for all patients within the first 72 hours after their injuries. After intraoral catheterization of the Stensen’s duct through the papilla using an epidural catheter, microsurgical end-to-end anastomosis was performed. Concurrently, 100 units of botulinum toxin A was injected at standardized eight points to the parotid gland. Results: Postoperative magnetic resonance (MR sialography revealed patency in all patients at the end of postoperative first year. The mean postoperative parotid volume of the injured and non-injured sides were 19.82±10.55 cm3 and 17.79±10.98 cm3, respectively, and the results were found to be comparable. Fibrillation potentials in the postoperative electromyography recordings and clinical examination demonstrated nerve regeneration. Conclusion: Botulinum toxin A appears to be effective in treating duct injuries accompanied by glandular involvement in an acute setting, as well as in preventing long-term complications.

  9. A comparative trial of ice application versus EMLA cream in alleviation of pain during botulinum toxin injections for palmar hyperhidrosis

    Directory of Open Access Journals (Sweden)

    Alsantali A

    2018-04-01

    Full Text Available Adel Alsantali Department of Dermatology, King Fahd Armed Forces Hospital, Jeddah, Saudi Arabia Background: Botulinum toxin is a safe and effective therapy for palmar hyperhidrosis, but the associated pain from injections limits the usefulness of this method of treatment. Purpose: To evaluate the efficacy of Eutectic Mixture of Local Anesthetics (EMLA cream versus ice application in alleviation of pain during botulinum toxin injections for palmar hyperhidrosis. Methods: In this prospective study, 23 patients underwent palm Botox injections to treat their excessive sweating. In each patient, EMLA cream was applied to one palm and ice was applied directly before the injections in the other palm. Pain was evaluated using a Visual Analog Scale. Results: Statistically, there was a significant difference in pain control between EMLA cream group and ice application group (p<0.05. The average pain score on the hands where EMLA cream was applied was 8.9 (SD=0.81, whereas it was 4.8 (±0.9 in the ice group. Conclusion: In this study, the successful use of ice application in reducing pain by 40% in comparison to EMLA cream during Botox toxin injection for palmar hyperhidrosis is demonstrated.Keywords: ice, local anesthetics, EMLA, palmar hyperhidrosis, Botox injection, pain reduction

  10. Crystal structure of the HA3 subcomponent of Clostridium botulinum type C progenitor toxin.

    Science.gov (United States)

    Nakamura, Toshio; Kotani, Mao; Tonozuka, Takashi; Ide, Azusa; Oguma, Keiji; Nishikawa, Atsushi

    2009-01-30

    The Clostridium botulinum type C 16S progenitor toxin contains a neurotoxin and several nontoxic components, designated nontoxic nonhemagglutinin (HA), HA1 (HA-33), HA2 (HA-17), HA3a (HA-22-23), and HA3b (HA-53). The HA3b subcomponent seems to play an important role cooperatively with HA1 in the internalization of the toxin by gastrointestinal epithelial cells via binding of these subcomponents to specific oligosaccharides. In this study, we investigated the sugar-binding specificity of the HA3b subcomponent using recombinant protein fused to glutathione S-transferase and determined the three-dimensional structure of the HA3a-HA3b complex based on X-ray crystallography. The crystal structure was determined at a resolution of 2.6 A. HA3b contains three domains, domains I to III, and the structure of domain I resembles HA3a. In crystal packing, three HA3a-HA3b molecules are assembled to form a three-leaved propeller-like structure. The three HA3b domain I and three HA3a alternate, forming a trimer of dimers. In a database search, no proteins with high structural homology to any of the domains (Z score >10) were found. Especially, HA3a and HA3b domain I, mainly composed of beta-sheets, reveal a unique fold. In binding assays, HA3b bound sialic acid with high affinity, but did not bind galactose, N-acetylgalactosamine, or N-acetylglucosamine. The electron density of liganded N-acetylneuraminic acid was determined by crystal soaking. In the sugar-complex structure, the N-acetylneuraminic acid-binding site was located in the cleft formed between domains II and III of HA3b. This report provides the first determination of the three-dimensional structure of the HA3a-HA3b complex and its sialic acid binding site. Our results will provide useful information for elucidating the mechanism of assembly of the C16S toxin and for understanding the interactions with oligosaccharides on epithelial cells and internalization of the botulinum toxin complex.

  11. Kinematic aiming task: measuring functional changes in hand and arm movements after botulinum toxin-A injections in children with spastic hemiplegia.

    NARCIS (Netherlands)

    Rameckers, E.A.A.; Speth, L.A.; Duysens, J.E.J.; Vles, J.S.; Smits-Engelsman, B.C.M.

    2007-01-01

    OBJECTIVE: To describe different aspects of a kinematic aiming task (KAT) as a quantitative way to assess changes in arm movements within 2 wks after botulinum toxin-A (BTX-A) injections in children with spastic hemiplegia. DESIGN: Intervention study randomized clinical trial; follow-up within 4 wks

  12. Botulinum Toxin Type A as a Therapeutic Agent against Headache and Related Disorders

    Directory of Open Access Journals (Sweden)

    Siro Luvisetto

    2015-09-01

    Full Text Available Botulinum neurotoxin A (BoNT/A is a toxin produced by the naturally-occurring Clostridium botulinum that causes botulism. The potential of BoNT/A as a useful medical intervention was discovered by scientists developing a vaccine to protect against botulism. They found that, when injected into a muscle, BoNT/A causes a flaccid paralysis. Following this discovery, BoNT/A has been used for many years in the treatment of conditions of pathological muscle hyperactivity, like dystonias and spasticities. In parallel, the toxin has become a “glamour” drug due to its power to ward off facial wrinkles, particularly frontal, due to the activity of the mimic muscles. After the discovery that the drug also appeared to have a preventive effect on headache, scientists spent many efforts to study the potentially-therapeutic action of BoNT/A against pain. BoNT/A is effective at reducing pain in a number of disease states, including cervical dystonia, neuropathic pain, lower back pain, spasticity, myofascial pain and bladder pain. In 2010, regulatory approval for the treatment of chronic migraine with BoNT/A was given, notwithstanding the fact that the mechanism of action is still not completely elucidated. In the present review, we summarize experimental evidence that may help to clarify the mechanisms of action of BoNT/A in relation to the alleviation of headache pain, with particular emphasis on preclinical studies, both in animals and humans. Moreover, we summarize the latest clinical trials that show evidence on headache conditions that may obtain benefits from therapy with BoNT/A.

  13. Physical therapies as an adjunct to Botulinum toxin-A injection of the upper or lower limb in adults following neurological impairment

    Directory of Open Access Journals (Sweden)

    Kinnear Bianca Z

    2012-06-01

    Full Text Available Abstract Background Spasticity of muscles is a common consequence of central nervous system impairment. Traditionally, neurological rehabilitation for spasticity has involved occupational and physical therapy; however, increasingly Botulinum toxin–A injections may be provided. Injection effects are temporary. Consequently, understanding the effect of adjunct physical therapies will help inform multimodal rehabilitation decisions. Presently, these effects are not known. This systematic review will identify and summarize evidence on physical therapies used after Botulinum toxin-A injection to improve motor function in adults with neurological impairments. Method Systematic searching of seven electronic databases will occur to identify relevant randomized trials. Available trial data will be extracted into a list of pre-defined primary outcomes, including range of movement, spasticity and functional limb use. Pre-defined secondary outcomes will also be reviewed where trials have these data available for reporting. Effects will be expressed as mean differences or standardized mean differences with 95% confidence intervals (CI. Where possible, comparable results will be meta-analyzed, and a summary of the available pool of evidence produced. All randomized controlled trials will be rated using the PEDro methodological quality scale. Where possible, study data will be meta-analyzed using RevMan 5 Software. The protocol was registered in PROSPERO international prosepective register of systematic reviews (PROSPERO 2011:CRD42011001491. Discussion Review results will be the most comprehensive answer available to the following question: Are physical therapies clinically effective after Botulinum toxin-A injections in adults with neurological spasticity? Results will inform healthcare providers and managers who determine who gets access to and provision of Botulinum toxin-A injection and whether this is done with or without physical therapies. Results

  14. Toxin production by Clostridium Botulinum type B (proteolitic) in radurized raw fish

    International Nuclear Information System (INIS)

    Suhadi, F.

    1978-01-01

    The earliest toxin production by three proteolytic strains of Cl. botulinum type B was determined in irradiated and unirradiated raw fish (Rastrelliger sp., Euthynnus sp., and Scomberomorus sp.) under the storage temperatures of 20, 10, and 5degC. The estimation of maximum storage life was evaluated by an untrained panel on uninoculated fish samples and in parellel the total bacterial counts were also determined. Percentage data of the toxic samples were analyzed according to a fully randomized design involving factorial treatments. In unirradiated samples with inoculum levels of 10 2 -10 6 spores per gram and stored at 20degC, the earliest toxin production was detected after the samples were spoiled. While in irradiated samples toxin were detected before the end of the storage life or after the samples were spoiled, depending on the levels of inoculum. In general, both in unirradiated and irradiated samples inoculated with 10 2 -10 6 spores per gram and stored at 10degC, the earlieast toxin production was detected after the samples were spoiled. While the samples were stored at 5degC, no toxic samples were found up to 30 days of storage when the experiment were terminated. The percentage of toxic samples was shown highly effected by type B strains, fish species, inoculum levels and storage time, when the storage temperature is 20degC. But no significant difference was found after treatment with irradiation doses. In general the interaction effects between those treatments on the percentage of toxic samples showed no significant difference. (author)

  15. Botox® after Botox® - a new approach to treat diplopia secondary to cosmetic botulinic toxin use: case reports

    Directory of Open Access Journals (Sweden)

    Cassiano Rodrigues Isaac

    2012-06-01

    Full Text Available A new technique for the treatment of diplopia secondary to cosmetic botulinum toxin A use is described. In this interventional case reports, two consecutive patients who developed diplopia after periocular cosmetic use of botulinum toxin A were treated with intramuscular botulinum toxin A injection into the antagonist extraocular muscle. Diplopia resolved in both patients in less than 1 week with no side effects or complications. In conclusion, the injection of intramuscular botulinum toxin A is an encouraging option for treatment of diplopia secondary to botulinum toxin A use for facial lifting.

  16. Progress on Botulinum Toxin Type A-Induced Pain Relief in the Field of Plastics.

    Science.gov (United States)

    Lu, Xiaona; Chen, Guocheng; Ren, Pengjie; Yang, Yan; Fan, Fei

    2017-11-01

    To retrospectively evaluate the effectiveness of Botulinum Toxin Type A (BTX-A) injections relieve pain in the field of plastic surgery and postoperative rehabilitation, and discuss the analgesic mechanism of BTX- A in plastics and related research progress. From appearance to September 1, 2016, PUBMED, EMBASE, and Web of Science were searched, using the key words related to "Botulinum Toxin Type A" and "Pain." Furtherly, nonplastic surgery-related literature was excluded by manual screening. Eleven literatures met the inclusion criteria, including 6 prospective controlled cohorts, 4 patient series, and 1 retrospective cohort. These studies involved Lower Limb, Breast, Hallux, Amputees, and Temporomandibular joint disk disfigurement and enrolled 402 patients. Among the patients, 360 received intraoperative BTX-A injection at the time of the main surgical procedure, 16 injected postoperatively and 26 did not undergo surgery. And 85.32% reported pain alleviation and 69.96% got favorable side effects and no one occurred major adverse effects. But 1.83% accepted injections more than once. Mechanism analysis explained these studies' results and demonstrated the analgesic effectiveness of BTX-A in plastics with nociceptive pain, inflammatory pain, and neuropathic pain. The results suggest that BTX-A may induce postoperative pain associated with plastic surgeries relief. But the available data of outcome assessment involved in this review are inconsistent and failed to meet methodological rigor. And pain alleviations are influenced by many factors. So further randomized controlled clinical trials with large sample sizes are needed to support this practice, determine standard usage methods, and establish corresponding specification systems.

  17. Isosorbide dinitrate ointment vs botulinum toxin A (Dysport®) as the primary treatment for chronic anal fissure: a randomized multicentre study

    NARCIS (Netherlands)

    Berkel, A.E.M.; Rosman, C.; Koop, R.; van Duijvendijk, P.; van der Palen, Jacobus Adrianus Maria; Klaase, J.M.

    2014-01-01

    Aim Nitric oxide donors, such as isosorbide dinitrate ointment (ISDN), are considered as first-choice agents in the treatment of chronic anal fissure. Injection with botulinum toxin A in the internal anal sphincter is often used as a second-line therapy, although it may give better results and fewer

  18. Historical Perspectives and Guidelines for Botulinum Neurotoxin Subtype Nomenclature

    Directory of Open Access Journals (Sweden)

    Michael W. Peck

    2017-01-01

    Full Text Available Botulinum neurotoxins are diverse proteins. They are currently represented by at least seven serotypes and more than 40 subtypes. New clostridial strains that produce novel neurotoxin variants are being identified with increasing frequency, which presents challenges when organizing the nomenclature surrounding these neurotoxins. Worldwide, researchers are faced with the possibility that toxins having identical sequences may be given different designations or novel toxins having unique sequences may be given the same designations on publication. In order to minimize these problems, an ad hoc committee consisting of over 20 researchers in the field of botulinum neurotoxin research was convened to discuss the clarification of the issues involved in botulinum neurotoxin nomenclature. This publication presents a historical overview of the issues and provides guidelines for botulinum neurotoxin subtype nomenclature in the future.

  19. Is Botulinum Toxin Type A a Valuable Adjunct During Femoral Lengthening? A Randomized Trial.

    Science.gov (United States)

    Park, Hoon; Shin, Soowan; Shin, Han Sol; Kim, Hyun Woo; Kim, Dong Wook; Lee, Dong Hoon

    2016-12-01

    Reduced joint ROM and distraction-induced pain are common complaints of patients who have undergone gradual femoral lengthening. Attempts to reduce the effects of lengthening on joint motion have included the use of botulinum toxin to reduce the muscle forces that restrict motion. The benefits of this approach during femoral lengthening, however, have not been conclusively established. We wished to evaluate the effects of botulinum toxin type A (BtX-A) injection in the anterior thigh muscles during femoral distraction osteogenesis on adjacent joint ROM and distraction-induced pain. We asked: (1) Does injection of BtX-A in the quadriceps muscles lead to improved knee and hip motion during femoral lengthening? (2) Does injection of BtX-A reduce pain during femoral lengthening? A single-center, double-blind, randomized placebo-controlled trial was conducted. Forty-four patients (88 femurs) undergoing bilateral femoral lengthening for familial short stature were included in the study. BtX-A (200 IU) was injected intraoperatively in the quadriceps muscles of one thigh. An equal volume of sterile normal saline was injected in the other thigh as a control. Selection of the limb receiving the toxin was randomized. Clinical evaluation included a VAS score for pain measurement, ROM evaluation of the hips and knees, and measurement of thigh circumference. Side-to-side differences were analyzed throughout the entire consolidation phase. No patients were lost to followup, leaving 44 patients (88 femurs). The mean followup was 26 months (range, 14-40 months). The distraction rate and final length of gain were similar between treated and control limbs. A priori power analysis suggested that 44 legs were required in each group to achieve statistical significance of 0.05 with 90% power to detect a 50% difference in treatment effect between treatment and control groups. There were no differences in hip ROM, knee ROM, or maximal thigh circumference between the two lower extremities

  20. Identification of the factors that govern the ability of therapeutic antibodies to provide postchallenge protection against botulinum toxin: a model for assessing postchallenge efficacy of medical countermeasures against agents of bioterrorism and biological warfare.

    Science.gov (United States)

    Al-Saleem, Fetweh H; Nasser, Zidoon; Olson, Rebecca M; Cao, Linsen; Simpson, Lance L

    2011-08-01

    Therapeutic antibodies are one of the major classes of medical countermeasures that can provide protection against potential bioweapons such as botulinum toxin. Although a broad array of antibodies are being evaluated for their ability to neutralize the toxin, there is little information that defines the circumstances under which these antibodies can be used. In the present study, an effort was made to quantify the temporal factors that govern therapeutic antibody use in a postchallenge scenario. Experiments were done involving inhalation administration of toxin to mice, intravenous administration to mice, and direct application to murine phrenic nerve-hemidiaphragm preparations. As part of this study, several pharmacokinetic characteristics of botulinum toxin and neutralizing antibodies were measured. The core observation that emerged from the work was that the window of opportunity within which postchallenge administration of antibodies exerted a beneficial effect increased as the challenge dose of toxin decreased. The critical factor in establishing the window of opportunity was the amount of time needed for fractional redistribution of a neuroparalytic quantum of toxin from the extraneuronal space to the intraneuronal space. This redistribution event was a dose-dependent phenomenon. It is likely that the approach used to identify the factors that govern postchallenge efficacy of antibodies against botulinum toxin can be used to assess the factors that govern postchallenge efficacy of medical countermeasures against any agent of bioterrorism or biological warfare.

  1. Three-dimensional CT might be a potential evaluation modality in correction of asymmetrical masseter muscle hypertrophy by botulinum toxin injection.

    Science.gov (United States)

    No, Yeon A; Ahn, Byeong Heon; Kim, Beom Joon; Kim, Myeung Nam; Hong, Chang Kwon

    2016-01-01

    For correction of this asymmetrical hypertrophy, botulinum toxin type A (BTxA) injection is one of convenient treatment modalities. Unfortunately, physical examination of masseter muscle is not enough to estimate the exact volume of muscle hypertrophy difference. Two Koreans, male and female, of bilateral masseter hypertrophy with asymmetricity were evaluated. BTxA (NABOTA(®), Daewoong, Co. Ltd., Seoul, Korea) was injected at master muscle site with total 50 U (25 U at each side) and volume change was evaluated with three-dimensional (3D) CT image analysis. Maximum reduction of masseter hypertrophy was recognized at 2-month follow-up and reduced muscle size started to restore after 3 months. Mean reduction of masseter muscle volume was 36% compared with baseline. More hypertrophied side of masseter muscle presented 42% of volume reduction at 2-month follow-up but less hypertrophied side of masseter muscle showed 30% of volume shrinkage. In conclusion, 3D CT image analysis might be the exact evaluation tool for correction of asymmetrical masseter hypertrophy by botulinum toxin injection.

  2. Phospholipase C produced by Clostridium botulinum types C and D: comparison of gene, enzymatic, and biological activities with those of Clostridium perfringens alpha-toxin.

    Science.gov (United States)

    Fatmawati, Ni Nengah Dwi; Sakaguchi, Yoshihiko; Suzuki, Tomonori; Oda, Masataka; Shimizu, Kenta; Yamamoto, Yumiko; Sakurai, Jun; Matsushita, Osamu; Oguma, Keiji

    2013-01-01

    Clostridium botulinum type C and D strains recently have been found to produce PLC on egg yolk agar plates. To characterize the gene, enzymatic and biological activities of C. botulinum PLCs (Cb-PLCs), the cb-plc genes from 8 strains were sequenced, and 1 representative gene was cloned and expressed as a recombinant protein. The enzymatic and hemolytic activities of the recombinant Cb-PLC were measured and compared with those of the Clostridium perfringens alpha-toxin. Each of the eight cb-plc genes encoded a 399 amino acid residue protein preceded by a 27 residue signal peptide. The protein consists of 2 domains, the N- and C-domains, and the overall amino acid sequence identity between Cb-PLC and alpha-toxin was greater than 50%, suggesting that Cb-PLC is homologous to the alpha-toxin. The key residues in the N-domain were conserved, whereas those in the C-domain which are important in membrane interaction were different than in the alpha-toxin. As expected, Cb-PLC could hydrolyze egg yolk phospholipid, p-nitrophenylphosphorylcholine, and sphingomyelin, and also exhibited hemolytic activity;however, its activities were about 4- to over 200-fold lower than those of alpha-toxin. Although Cb-PLC showed weak enzymatic and biological activities, it is speculated that Cb-PLC might play a role in the pathogenicity of botulism or for bacterial survival.

  3. Scientific skepticism and new discoveries: an analysis of a report of zinc/phytase supplementation and the efficacy of botulinum toxins in treating cosmetic facial rhytides, hemifacial spasm and benign essential blepharospasm.

    Science.gov (United States)

    Cohen, Joel L

    2014-10-01

    A recent paper in the Journal of Drugs in Dermatology by Koshy and colleagues (2012, 11( 4 ):507-512) report on "Effect of Dietary Zinc and Phytase Supplementation on Botulinum Toxin Treatments" and conclude by claiming the discovery of "a potentially meaningful role for zinc and/or phytase supplementation in increasing the degree and duration of botulinum toxin effect in the treatment of cosmetic facial rhytids, benign essential blepharospasm, and hemifacial spasm". The purpose of this paper is to examine these published claims for possible methodological and design errors and potential sources of bias. The authors evaluated the published results in comparison to the published literature on zinc deficiency, the role of phytase, prior reports of an effect of zinc on activity of botulinum toxin, issues of study design and execution and if the reported results of the study supported the study's conclusions. Multiple issues are present in the reported study, which appear to invalidate its conclusions. These areas include lack of direct evidence for the presence of clinical or subclinical zinc deficiency in the study population or for the level of phytate in the study population sufficient to interfere with zinc absorption in these subjects. Additionally, there is ambiguity as to the actual dose of zinc used as well as in the study design itself. Also there is a failure of the study through the "unmasking" of the crossover design. There is potential financial conflict of interest in the study execution that may have biased the reported results. Finally there is inadequate data presented to evaluate the claims made of a "new discovery" as to the three disease entities reported on and the various botulinum toxins used in each of the three treatment arms of the study. Based on this evaluation, it appears that a high level of clinical and scientific skepticism is warranted concerning any claim of a beneficial effect of zinc and phytase supplementation on the efficacy or

  4. Effects of botulinum toxin type A on healing of injured skeletal muscles

    Directory of Open Access Journals (Sweden)

    Shokravi Ramin

    2007-01-01

    Full Text Available Objectives: (1 Evaluation of microscopic healing of skeletal muscle fibers after injuries, especially the arrangement of new muscle fibers and scar tissue diameter in the injury region. (2 Evaluation of alterations in microscopy of the healing procedure within skeletal muscles after injury following botulinum toxin type A (BTX -A induced muscle immobilization. Materials and Methods: The study was done on 12 white lab rabbits of either sex in a 6-month period. Results: The immobilization of skeletal muscle fibers as a result of the use of BTX-A after injury caused a qualitative increase in fibrous tissue formation in the area of injury, and the BTX-A-induced immobilization for a period of 6 months led to muscle atrophy.

  5. The efficiency of botulinum toxin type A for the treatment of masseter muscle pain in patients with temporomandibular joint dysfunction and tension-type headache.

    Science.gov (United States)

    Pihut, Malgorzata; Ferendiuk, Ewa; Szewczyk, Michal; Kasprzyk, Katarzyna; Wieckiewicz, Mieszko

    2016-01-01

    Temporomandibular joint dysfunction are often accompanied by symptoms of headache such as tension-type headache which is the most frequent spontaneous primary headache. Masseter muscle pain is commonly reported in this group. The purpose of the study was to assess the efficiency of intramuscular botulinum toxin type A injections for treating masseter muscle pain in patients with temporomandibular joint dysfunction and tension-type headache. This prospective outcome study consisted of 42 subjects of both genders aged 19-48 years diagnosed with masseter muscle pain related to temporomandibular joint dysfunction and tension-type headache. The subjects were treated by the intramuscular injection of 21 U (mice units) of botulinum toxin type A (Botox, Allergan) in the area of the greatest cross-section surface of both masseter bellies. Pain intensity was evaluated using visual analogue scale (VAS) and verbal numerical rating scale (VNRS) 1 week before the treatment and 24 weeks after the treatment. The obtained data were analyzed using the Wilcoxon matched pairs test (p ≤ 0,005). The results of this study showed a decrease in the number of referred pain episodes including a decrease in pain in the temporal region bilaterally, a reduction of analgesic drugs intake as well as a decrease in reported values of VAS and VNRS after injections (p = 0,000). The intramuscular botulinum toxin type A injections have been an efficient method of treatment for masseter muscle pain in patients with temporomandibular joint dysfunction and tension-type headache.

  6. Investigation of Clostridium botulinum group III's mobilome content

    NARCIS (Netherlands)

    Woudstra, Cédric; Maréchal, Le Caroline; Souillard, Rozenn; Anniballi, Fabrizio; Auricchio, Bruna; Bano, Luca; Bayon-Auboyer, Marie Hélène; Koene, Miriam; Mermoud, Isabelle; Brito, Roseane B.; Lobato, Francisco C.F.; Silva, Rodrigo O.S.; Dorner, Martin B.; Fach, Patrick

    2018-01-01

    Clostridium botulinum group III is mainly responsible for botulism in animals. It could lead to high animal mortality rates and, therefore, represents a major environmental and economic concern. Strains of this group harbor the botulinum toxin locus on an unstable bacteriophage. Since the release of

  7. Effect of initial O2 and CO2 and low-dose irradiation on toxin production by Clostridium botulinum in MAP fresh pork

    International Nuclear Information System (INIS)

    Lambert, A.D.; Smith, J.P.; Dodds, K.L.

    1991-01-01

    The effects of irradiation, initial O2, initial CO2 and the presence of an O2 and CO2 absorbent on toxin production by Clostridium botulinum in inoculated pork stored at 15 degrees C were studied using a factorial experiment. Toxin production occurred faster in samples initially packaged with 20% O2, compared to samples packaged with 100% N2. The presence of CO2 in the package headspace was not a significant factor affecting time until toxin detection. Irradiation was significant in delaying the time until toxin detection in samples initially packaged with 20% O2 but not in other treatments. Sensory rejection, based primarily on discoloration, occurred within 7 to 14 d, irrespective of treatment. All samples were spoiled before they became toxic

  8. Alterations in CNS Activity Induced by Botulinum Toxin Treatment in Spasmodic Dysphonia: An H[subscript 2][superscript 15]O PET Study

    Science.gov (United States)

    Ali, S. Omar; Thomassen, Michael; Schulz, Geralyn M.; Hosey, Lara A.; Varga, Mary; Ludlow, Christy L.; Braun, Allen R.

    2006-01-01

    Speech-related changes in regional cerebral blood flow (rCBF) were measured using H[subscript 2][superscript 15]O positron-emission tomography in 9 adults with adductor spasmodic dysphonia (ADSD) before and after botulinum toxin (BTX) injection and 10 age- and gender-matched volunteers without neurological disorders. Scans were acquired at rest…

  9. Injection of high dose botulinum-toxin A leads to impaired skeletal muscle function and damage of the fibrilar and non-fibrilar structures

    DEFF Research Database (Denmark)

    Pingel, Jessica; Nielsen, Mikkel Schou; Lauridsen, Torsten

    2017-01-01

    Botulinum-toxin A (BoNT/A) is used for a wide range of conditions. Intramuscular administration of BoNT/A inhibits the release of acetylcholine at the neuromuscular junction from presynaptic motor neurons causing muscle-paralysis. The aim of the present study was to investigate the effect of high...

  10. Focal myositis of lower extremity responsive to botulinum A toxin.

    Science.gov (United States)

    Mitrovic, Josko; Prka, Zeljko; Zic, Rado; Marusic, Srecko; Morovic-Vergles, Jadranka

    2014-01-01

    Focal myositis is a rare, mostly benign disease (pseudotumor) of skeletal muscle, histopathologically characterized by interstitial myositis and tumorous enlargement of a single muscle. The etiology of focal myositis remains unknown; however, localized myopathy has been postulated to be caused by denervation lesions. This case report describes a patient that presented with clinical, laboratory, electromyoneurography, and magnetic resonance imaging features of focal myositis complicated with intervertebral disk protrusion in the lumbosacral spine affected with radicular distress. In most cases, focal myositic lesions show spontaneous regression, relapses are rare, and long-term prognosis is good. There is a wide spectrum of therapeutic options, from no therapy at all through nonsteroidal antirheumatics and glucocorticoids to radiotherapy, surgical excision, and immunosuppressants. In the patient presented, treatment with glucocorticoids, methotrexate, and surgical excision failed to produce satisfactory results. Clinical improvement, pain relief, and reduction in lower leg volume were only achieved by local infiltration of botulinum A toxin.

  11. Effect of chitosan-N-acetylcysteine conjugate in a mouse model of botulinum toxin B-induced dry eye.

    Science.gov (United States)

    Hongyok, Teeravee; Chae, Jemin J; Shin, Young Joo; Na, Daero; Li, Li; Chuck, Roy S

    2009-04-01

    To evaluate the effect of a thiolated polymer lubricant, chitosan-N-acetylcysteine conjugate (C-NAC), in a mouse model of dry eye. Eye drops containing 0.5% C-NAC, 0.3% C-NAC, a vehicle (control group), artificial tears, or fluorometholone were applied in a masked fashion in a mouse model of induced dry eye from 3 days to 4 weeks after botulinum toxin B injection. Corneal fluorescein staining was periodically recorded. Real-time reverse transcriptase-polymerase chain reaction and immunofluorescence staining were performed at the end of the study to evaluate inflammatory cytokine expressions. Mice treated with C-NAC, 0.5%, and fluorometholone showed a downward trend that was not statistically significant in corneal staining compared with the other groups. Chitosan-NAC formulations, fluorometholone, and artificial tears significantly decreased IL-1beta (interleukin 1beta), IL-10, IL-12alpha, and tumor necrosis factor alpha expression in ocular surface tissues. The botulinum toxin B-induced dry eye mouse model is potentially useful in evaluating new dry eye treatment. Evaluation of important molecular biomarkers suggests that C-NAC may impart some protective ocular surface properties. However, clinical data did not indicate statistically significant improvement of tear production and corneal staining in any of the groups tested. Topically applied C-NAC might protect the ocular surface in dry eye syndrome, as evidenced by decreased inflammatory cytokine expression.

  12. Comparison of toxin production by clostridium botulinum type E in irradiated vacuum-packed trout (Salmo gairdneri)

    International Nuclear Information System (INIS)

    Hussain, A.M.; Ehlermann, D.; Diehl, J.F.

    1977-01-01

    Trouts obtained from a nearby Fish farm were slaughtered, gutted, cut into 100 g samples and inoculated with 10 1 , 10 3 and 10 5 spores per g of Clostridium botulinum type E. The vacuum-packed samples were stored under melting ice (0 0 C) and at temperatures of 5 0 and 10 0 C for periods of up to 8 weeks. At weekly intervals, occurrence of spoilage and toxin production were determined. Only at 10 0 C storage, the irradiated samples showed toxin production before spoilage was observed. When the fishes were stored at 5 0 C, no toxicity occurred before spoilage was observed even in samples treated with doses as high as 200 krad. Samples stored under melting ice, irradiated or unirradiated, never showed toxin production. It is concluded that the radurization of fish at doses of about 100 or 200 krad and at storage temperatures of melting ice or up to 5 0 C is safe with regard to a possible botulism risk. (orig.) [de

  13. The Prediction of Botulinum Toxin Structure Based on in Silico and in Vitro Analysis

    Science.gov (United States)

    Suzuki, Tomonori; Miyazaki, Satoru

    2011-01-01

    Many of biological system mediated through protein-protein interactions. Knowledge of protein-protein complex structure is required for understanding the function. The determination of huge size and flexible protein-protein complex structure by experimental studies remains difficult, costly and five-consuming, therefore computational prediction of protein structures by homolog modeling and docking studies is valuable method. In addition, MD simulation is also one of the most powerful methods allowing to see the real dynamics of proteins. Here, we predict protein-protein complex structure of botulinum toxin to analyze its property. These bioinformatics methods are useful to report the relation between the flexibility of backbone structure and the activity.

  14. Clostridium botulinum in irradiated fish

    International Nuclear Information System (INIS)

    Hobbs, G.

    1977-01-01

    The properties of the Cl. botulinum resp. its toxin are described with a view to a combined heat and radiation treatment for fish conservation. The method is tested in several laboratories on 10 different fish products. It is found that the spore former Cl. botulinum is a critical factor in this type of preservation which can hardly be overcome although this method has organoleptic advantages over heat pasteurization of fish. At a storage temperatue over 5 0 C, there is a strong increase in toxin; the same applies to fish with a high fat content. Under poor hygienic conditions, the risk is markedly increased. The author recommends strict control measures in the production and distribution of fish, i.e. cooling and salt treatment. (AJ) [de

  15. Extra- and intramuscular nerve supply of the muscles of the anterior antebrachial compartment: applications for selective neurotomy and for botulinum toxin injection.

    Science.gov (United States)

    Lepage, D; Parratte, B; Tatu, L; Vuiller, F; Monnier, G

    2005-12-01

    Hypertonia of the upper limb due to spasticity causes pronation of the forearm and flexion of wrist and fingers. Nowadays this spasticity is often treated with injections of botulinum toxin and sometimes with selective fascicular neurotomy. To correctly perform this microsurgical technique, it is necessary to get precise knowledge of the extramuscular nerve branching in order to be better able to select the motor branches which supply the muscles involved in spasticity. The same knowledge is required for botulinum toxin injections which must be made as near as possible to the zones where intramuscular nerve endings are the densest, which is also where neuromuscular junctions are the most numerous. Thus, it is necessary to better know these zones, but their knowledge remains today imprecise. The muscles of the anterior compartment of 30 forearms were dissected, first macroscopically, then microscopically, to study the extra- and intramuscular nerve supply and the distribution of terminal nerve ramifications. The results were then linked to surface topographical landmarks to indicate the precise location of motor branches for each muscle with the aim of proposing appropriate surgical approaches for selective neurotomies. Then for each muscle, the zones with the highest density of nerve endings were divided into segments, thus determining the optimal zones for botulinim toxin injections.

  16. EFEKTIFITAS TOXIN BOTULLINUM UNTUK MANAJEMEN BLEFAROSPASME ESSENSIAL DAN SPASME HEMIFASIAL

    Directory of Open Access Journals (Sweden)

    Hendriati Hendriati

    2010-09-01

    Full Text Available AbstrakUntuk mengukur efektifikas toxin Botullinum pada kasus-kasus okuloplastik (blefarospasme essensial dan spasme hemifasial.Laporan kasus 16 pasien yang terdiri dari 14 kasus spasme hemifasial dan 2 kasus blefarospasme essensial. Digunakan 6 vial toxin Botullinum. Vial pertama digunakan untuk pasien spasme hemifasial dan 1 pasien blefasrospasme di minggu berikutnya. vial kedua dan ketiga masing-masing digunakan untuk 2 pasien spasme hemifasial. Vial keempat digunakan untuk pasien blefarospasme yang menggunakan vial pertama (setelah 6 bulan, dan 1 pasien spasme hemifasial yang menggunakan vial kedua ( setelah 4 bulan dan 1 pasien spasme hemifasial baru. Setelah 1 minggu, toxin Botullinum vial keempat digunakan untuk 6 pasien spasme hemifasial dan 1 pasien blefarospasme essensial yang menggunakan vial pertama 8 hari berikutnya (setelah 7 bulan.Terdapat 16 pasien pada studi ini ; 14 spasme hemifasial dan 2 blefarospasme essensial. Pada 5 pasien dilakukan injeksi ulangan dengan jangka waktu yang berbeda. Tidak ditemukan efek samping pada pasien-pasien ini.Toxin Botulinum efektif untuk manajemen spasme hemifasial dan blefarospasme essensial tetapi efeknya temporer. Pada studi ini, jangka waktu injeksi ulangan bervariasi sekitar 4 – 7 bulan pada 5 pasien.Kata Kunci : Toxin Botulinum toxin, spasme hemifasial, blefarospasmeAbstractTo asses Botulinum Toxin efficacy in oculoplastic cases (blepharospasm and hemifacial spasm.A case report on 16 patients consisted of 14 hemifacial spasms and 2 essential blepharospasm. Six vials of botulinum toxin were used. First vial was used for two patients of hemifacial spasm and one blepharospasm patient one week later. Second and third vials were used each for two patients of hemifacial spasms. Fourth vial was used for one blepharospasm patient from first vial user (after six month, one hemifacial spasm from second vial user (after four months and one new hemifacial spasm. After one week, Botulinum toxin from

  17. Botulinum toxin, a new treatment modality for chronic idiopathic constipation in children: long-term follow-up of a double-blind randomized trial.

    Science.gov (United States)

    Keshtgar, Alireza S; Ward, Harry C; Sanei, Ahmad; Clayden, Graham S

    2007-04-01

    Myectomy of the internal anal sphincter (IAS) has been performed on some children after failure of medical treatment to treat idiopathic constipation. The aim of this study was to compare botulinum toxin injection with myectomy of the IAS in the treatment of chronic idiopathic constipation and soiling in children. This was a double-blind randomized trial. Patients between 4 and 16 years old were included in the study if they had failed to respond to laxative treatment and anal dilatation for chronic idiopathic constipation. All study patients had anorectal manometry and anal endosonography under ketamine anesthesia. Outcome was measured using a validated symptom severity (SS) scoring system, with scores ranging from 0 to 65. Of 42 children, 21 were randomized to the botulinum group and 21 were randomized to the myectomy group. At the 3-month follow-up, the median preoperative SS score improved from 34 (range = 19-47) to 20 (range = 2-43) in the botulinum group (P 41) for the botulinum group and the myectomy group, respectively (P IAS for chronic idiopathic constipation and fecal incontinence in children.

  18. Molecular diversity of Clostridium botulinum and phenotypically similar strains.

    Science.gov (United States)

    Grenda, T; Kukier, E; Sieradzki, Z; Goldsztejn, M; Kwiatek, K

    2016-12-01

    This study was undertaken to examine phenotypic and genetic features of strains preliminary classified as Clostridium botulinum species. The phenotypic characteristics were assessed with different culture media and biochemical tests. The genetic characterization included detection of botulinum toxin genes by PCR and macrorestriction analysis with SmaI, XhoI and SacII by PFGE (Pulsed-field Gel Electrophoresis). Despite similar biochemical properties of all analysed strains, only 47% of them contained genes determining toxicity specific to C. botulinum species. The most valuable differentiation of C. botulinum and C. botulinum-like strains was obtained after SmaI digestion. The highest affinity was observed among C. botulinum type B profiles which was even up to 100%. It was found 100% of affinity between C. botulinum and C. botulinum-like strains, however, the similarity among C. botulinum and C. botulinum-like was generally lower than 80%.

  19. The Profile of Patients and Current Practice of Treatment of Upper Limb Muscle Spasticity with Botulinum Toxin Type A: An International Survey

    Science.gov (United States)

    Bakheit, Abdel Magid

    2010-01-01

    To document the current practice in relation with the treatment of patients with upper limb spasticity with botulinum toxin type A to inform future research in this area. We designed an international, cross-sectional, noninterventional survey of current practice. Nine hundred and seventy-four patients from 122 investigational centres in 31…

  20. Botulinum toxin a can positively impact first impression.

    Science.gov (United States)

    Dayan, Steven H; Lieberman, Elliot D; Thakkar, Nirav N; Larimer, Karen A; Anstead, Amy

    2008-06-01

    BACKGROUND First impression is influenced by facial appearance and improved by cosmetic surgery. OBJECTIVE We wanted to determine if treatment with botulinum toxin A (BTxnA) would improve first impression. MATERIALS AND METHODS Women received BTxnA in the forehead. Photos were taken prior to, and 1 week after, final BTxnA injection in smiling and relaxed poses. Photos were divided into books with each subject represented only once. Evaluators completed a survey rating first impression on various measures of success for each photo. RESULTS No differences were seen for social skills, financial, or relationship success scales. A significant decrease in first impression scores between treatment photos was seen for academic performance and occupational success. However, analysis of between-subject effects found that "smile/relax" accounted for the decreased score in both scales. Significant increases in first impression scores were seen for dating success, attractiveness, and athletic success scales where smile/relax and BTxnA contributed significantly to the improved scores. CONCLUSIONS BTxnA improved first impression scores for dating success, attractiveness, and athletic success scales. Academic performance and occupational success scores were not affected by BTxnA when the smile/relax variable was included. The smile/relax variable was a more important predictor for academic performance and occupational success scores.

  1. An Accelerated Multi-Modality Rehabilitation Protocol Combined with Botulinum Toxin-A Injection in Adult Idiopathic Toe Walking: Case Report

    Science.gov (United States)

    Yavuz, Ferdi; Balaban, Birol

    2016-01-01

    Diagnosis of Adult Idiopathic Toe Walking (AITW) is very rare in clinical practice. High quality studies regarding AITW and its treatment options have not been conducted previously. A 28-year-old male patient complaining of lower leg pain was referred to outpatient rehabilitation clinic. Physical examination revealed a gait abnormality of insufficient heel strike at initial contact. The aetiology was investigated and the patient’s walking parameters were assessed using a computerized gait analysis system. The AITW was diagnosed. Botulinum toxin-A (Dysport®) was injected to the bilateral gastrocnemius muscles. A combined 10-days rehabilitation program was designed, including a daily one-hour physiotherapist supervised exercise program, ankle dorsiflexion exercises using an EMG-biofeedback unit assisted virtual rehabilitation system (Biometrics) and virtual gait training (Rehawalk) every other day. After treatment, the patient was able to heel strike at the initiation of the stance phase of the gait. Ankle dorsiflexion range of motions increased. The most prominent improvement was seen in maximum pressure and heel force. In addition center of pressure evaluations were also improved. To the best of our knowledge this is the first case, of AITW treated with combined botulinum toxin, exercise and virtual rehabilitation systems. This short report demonstrates the rapid effect of this 10-days combined therapy. PMID:27504395

  2. RNA aptasensor for rapid detection of natively folded type A botulinum neurotoxin.

    Science.gov (United States)

    Janardhanan, Pavithra; Mello, Charlene M; Singh, Bal Ram; Lou, Jianlong; Marks, James D; Cai, Shuowei

    2013-12-15

    A surface plasmon resonance based RNA aptasensor for rapid detection of natively folded type A botulinum neurotoxin is reported. Using detoxified recombinant type A botulinum neurotoxin as the surrogate, the aptasensor detects active toxin within 90 min. The detection limit of the aptasensor in phosphate buffered saline, carrot juice, and fat free milk is 5.8 ng/ml, 20.3 ng/ml and 23.4 ng/ml, respectively, while that in 5-fold diluted human serum is 22.5 ng/ml. Recovery of toxin from disparate sample matrices are within 91-116%. Most significant is the ability of this aptasensor to effectively differentiate the natively folded toxin from denatured, inactive toxin, which is important for homeland security surveillance and threat assessment. The aptasensor is stable for more than 30 days and over 400 injections/regeneration cycles. Such an aptasensor holds great promise for rapid detection of active botulinum neurotoxin for field surveillance due to its robustness, stability and reusability. © 2013 Elsevier B.V. All rights reserved.

  3. Severity of cerebral palsy and likelihood of adverse events after botulinum toxin A injections.

    Science.gov (United States)

    Swinney, Caitlyn M; Bau, Karen; Burton, Karen L Oakley; O'Flaherty, Stephen J; Bear, Natasha L; Paget, Simon P

    2018-05-01

    To determine the incidence of common adverse events after botulinum toxin A (BoNT-A) injections in children with cerebral palsy (CP) and to identify whether the severity of CP influences the incidence of adverse events. This was an observational study of patients attending a BoNT-A clinic at a tertiary paediatric hospital (2010-2014). Data examined included procedural adverse events at the time of injection and at follow-up. Systemic adverse events were defined as lower respiratory tract illnesses, generalized weakness, dysphagia, and death. Severity of CP was categorized by the Gross Motor Function Classification System (GMFCS). The relationships between GMFCS and adverse events were analysed using negative binomial regression models. In total, 591 children underwent 2219 injection episodes. Adverse events were reported during the procedure (130 [6%] injection episodes) and at follow-up (492 [22%] injection episodes). There were significantly increased rates of systemic adverse events in injection episodes involving children in GMFCS level IV (incidence rate ratio [IRR] 3.92 [95% confidence interval] 1.45-10.57]) and GMFCS level V (IRR 7.37 [95% confidence interval 2.90-18.73]; p<0.001). Adverse events after BoNT-A injections are common but mostly mild and self-limiting. Children in GMFCS levels IV and V are at increased risk of systemic adverse events. The relationship between CP severity and BoNT-A adverse events is complex and further research is required to better understand this relationship. Adverse events reported at the time of botulinum toxin A injection occurred in 6% of injection episodes. Adverse events were reported at follow-up in 22% of injection episodes. Children in Gross Motor Function Classification System (GMFCS) levels IV and V have increased rates of systemic adverse events. Children in GMFCS levels IV and V report less local weakness and pain. © 2018 Mac Keith Press.

  4. Clostridium botulinum Spores Found in Honey from Small Apiaries in Poland

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    Wojtacka Joanna

    2016-12-01

    Full Text Available A total of 102 honey samples collected from small apiaries (≤ 20 hives in Poland were analysed for the presence of Clostridium botulinum spores. The samples were prepared using the dilution centrifugation method and cultured in parallel in cooked meat medium (CMM and tripticase peptone glucose yeast (TPGY enrichment broths. Identification of toxin types A, B, and E of Clostridium botulinum strains was performed with the use of the multiplex PCR method. Positive samples were also subjected to quantitative analysis with the use of Clostridium botulinum Isolation Agar Base (CBAB. The prevalence analysis showed 22 (21.6% samples contaminated with C. botulinum spores. The major serotype detected was botulin neurotoxin type A – 16 (72.7% whereas type B was found in 3 (13.6% honey samples and type E also only in 3 (13.6% honey samples. Dual-toxin-producing strains were noted. The average quantity of spores in PCR - C. botulinum positive samples was 190 in 1 gram of honey.

  5. Treatment of Chronic Migraine with Focus on Botulinum Neurotoxins

    Directory of Open Access Journals (Sweden)

    Sara M. Schaefer

    2015-07-01

    Full Text Available Migraine is the most common neurological disorder, and contributes to disability and large healthcare costs in the United States and the world. The treatment of migraine until recently has focused on medications, both abortive and prophylactic, but treatment of chronic migraine has been revolutionized with the introduction of botulinum toxin injection therapy. In this review, we explore the current understanding of migraine pathophysiology, and the evolution of the use of botulinum toxin therapy including proposed pathophysiological mechanisms through animal data. We also discuss the similarities and differences between three injection techniques.

  6. A randomized controlled trial of botulinum toxin A for treating neuropathic pain in patients with spinal cord injury.

    Science.gov (United States)

    Li, Gang; Lv, Chang-An; Tian, Li; Jin, Lian-Jin; Sun, Ping; Zhao, Wei

    2017-05-01

    To assess the effect of botulinum toxin A (BTA) for treating neuropathic pain in patients with spinal cord injury (SCI). A total of 44 patients with SCI with neuropathic pain were randomly divided into the intervention group and the placebo group, each group 21 patients. The subjects in the intervention group received BTA (200 U subcutaneous injection, once daily) at the painful area, whereas those in the placebo group were administered a saline placebo. This study was conducted from December 2014 to November 2016. The primary outcome was measured using the visual analog scale (VAS). The secondary outcomes were measured using the short-form McGill Pain Questionnaire (SF-MPQ), and World Health Organization quality of life (WHOQOL-BREF) questionnaire. All outcome measurements were performed before and after 4 and 8 weeks of intervention. Forty-one participants completed the study. The intervention with BTA showed greater efficacy than placebo in decreasing the VAS score after week 4 and week 8 of treatment. Significant differences in the SF-MPQ and WHOQOL-BREF were also found between the 2 groups. The results of this study demonstrated that BTA might decrease intractable neuropathic pain for patients with SCI.

  7. Efficacy of botulinum toxin in treating myofascial pain in bruxers: a controlled placebo pilot study.

    Science.gov (United States)

    Guarda-Nardini, Luca; Manfredini, Daniele; Salamone, Milena; Salmaso, Luigi; Tonello, Stefano; Ferronato, Giuseppe

    2008-04-01

    The present investigation is a preliminary double-blind, controlled placebo, randomized clinical trial with a six month follow-up period. The study aimed to assess the efficacy of type A botulinum toxin (Botox, Allergan, Inc. Irvine, CA) to treat myofascial pain symptoms and to reduce muscle hyperactivity in bruxers. Twenty patients (ten males, ten females; age range 25-45) with a clinical diagnosis of bruxism and myofascial pain of the masticatory muscles were enrolled in a double-blind, controlled placebo, randomized clinical trial, with a treatment group (ten subjects treated with botulinum toxin injections- BTX-A) and a control group (ten subjects treated with saline placebo injections). A number of objective and subjective clinical parameters (pain at rest and during chewing; mastication efficiency; maximum nonassisted and assisted mouth opening, protrusive and laterotrusive movements; functional limitation during usual jaw movements; subjective efficacy of the treatment; tolerance of the treatment) were assessed at baseline time and at one week, one month, and six months follow-up appointments. Descriptive analysis showed that improvements in both objective (range of mandibular movements) and subjective (pain at rest; pain during chewing) clinical outcome variables were higher in the Botox treated group than in the placebo treated subjects. Patients treated with BTX-A had a higher subjective improvement in their perception of treatment efficacy than the placebo subjects. Differences were not significant in some cases due to the small sample size. Results from the present study supported the efficacy of BTX-A to reduce myofascial pain symptoms in bruxers, and provided pilot data which need to be confirmed by further research using larger samples.

  8. Amino acid residues involved in membrane insertion and pore formation of Clostridium botulinum C2 toxin.

    Science.gov (United States)

    Lang, Alexander E; Neumeyer, Tobias; Sun, Jianjun; Collier, R John; Benz, Roland; Aktories, Klaus

    2008-08-12

    The actin-ADP-ribosylating Clostridium botulinum C2 toxin consists of the enzymatic component C2I and the binding component C2II. C2II forms heptameric channels involved in translocation of the enzymatic component into the target cell. On the basis of the heptameric toxin channel, we studied functional consequences of mutagenesis of amino acid residues probably lining the lumen of the toxin channel. Substitution of glutamate-399 of C2II with alanine blocked channel formation and cytotoxicity of the holotoxin. Although cytotoxicity and rounding up of cells by C2I were completely blocked by exchange of phenylalanine-428 with alanine, the mutation increased potassium conductance caused by C2II in artificial membranes by about 2-3-fold over that of wild-type toxin. In contrast to its effects on single-channel potassium conductance in artificial membranes, the F428A mutation delayed the kinetics of pore formation in lipid vesicles and inhibited the activity of C2II in promoting (86)Rb (+) release from preloaded intact cells after pH shift of the medium. Moreover, F428A C2II exhibited delayed and diminished formation of C2II aggregates at low pH, indicating major changes of the biophysical properties of the toxin. The data indicate that phenylalanine-428 of C2II plays a major role in conformational changes occurring during pore formation of the binding component of C2II.

  9. The use of botulinum toxin in the treatment of the consequences of bruxism on cervical spine musculature.

    Science.gov (United States)

    Finiels, P J; Batifol, D

    2014-03-01

    Hypertonia and hyperactivity of masticatory muscles are involved in pain and contractions of the cervical spine musculature, but their pathophysiology remains nonetheless unknown and its treatment far to be codified. In this study, 8 patients, showing disabling posterior neck muscle contractures linked with bruxism were prospectively treated and followed for an average 15 months period, after having received Injections of botulinum toxin A essentially in masticatory muscles. Injections were made every 3 months, varying from 10 to 100 U Botox* by muscles, without administrating more than 300 U Botox* in the same patient. The angle of cervical lordosis were calculated on lateral sitting radiographs in neutral position, good results being considered to be achieved in the case of a 2 point diminution of VAS score as well as at least a 5° positive gain in the curve. 7 patients out of 8 showed a real improvement in their symptoms after an average of 3 injections, showing a decrease of 4.5 points on the VAS score and an average increment of 15° in cervical lordosis. Although the follow-up period of patients was relatively short and the sample quite small, the general impression, confirmed by the patients' experience, seems to suggest a potential place for the use of botulinum toxin amongst the array of treatments which can be offered in certain selected cases which associate bruxism and posterior cervical contractions. Copyright © 2014 Elsevier Ltd. All rights reserved.

  10. Application of Local Injection of Botulinum Toxin A in Cosmetic Patients with Congenital Drooping Mouth Corner.

    Science.gov (United States)

    Qian, Wei; Zhang, Yan-Kun; Lv, Wei; Hou, Ying; Cao, Qian; Fan, Ju-Feng

    2016-12-01

    This study aimed to investigate the clinical application and efficacy of local injection of botulinum toxin A (BTX-A) at the depressor anguli oris in patients with congenital drooping mouth corner. From September 2013 to March 2015, 36 cosmetic patients received local injections of botulinum toxin A at the depressor anguli oris, with 1-3 injection sites in the moving region of the depressor anguli oris on each side. At each injection site, 2-4 U of BTX-A was injected, and the total dose for any unilateral treatment did not exceed 8 U. The change in the degree of drooping of the mouth corner before and after the injection was analyzed using statistical methods. The clinical efficacy, preservation time, and adverse reactions were observed. The degree of drooping of the mouth corners of the cosmetic patients before the treatment was compared with that at 1 month after using a paired t test, and the difference was statistically significant, with P injection. The local injection of BTX-A at the depressor anguli oris can effectively lift a drooping mouth corner, thereby improving the depressed, stern, and aged appearance of the face. The performance of this treatment is simple, safe, and easy to perform in clinical applications. This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

  11. Feasibility of a Day-Camp Model of Modified Constraint-Induced Movement Therapy with and without Botulinum Toxin A Injection for Children with Hemiplegia

    Science.gov (United States)

    Eliasson, Ann-Christin; Shaw, Karin; Ponten, Eva; Boyd, Roslyn; Krumlinde-Sundholm, Lena

    2009-01-01

    The objective of the study was to investigate the feasibility of modified constraint-induced (CI) therapy provided in a 2-week day-camp model with and without intramuscular botulinum toxin type A (BoNT-A) injections for children with congenital cerebral palsy. Sixteen children with congenital hemiplegia, Manual Ability Classification System (MACS)…

  12. Influence of botulinum toxin on rabbit jaw muscle activity and anatomy.

    Science.gov (United States)

    Korfage, J A M; Wang, Jeffrey; Lie, S H J T J; Langenbach, Geerling E J

    2012-05-01

    Muscles can adapt their fiber properties to accommodate to new conditions. We investigated the extent to which a decrease in muscle activation can cause an adaptation of fiber properties in synergistic and antagonistic jaw muscles. Three months after the injection of botulinum toxin type A in one masseter (anterior or posterior) muscle changes in fiber type composition and fiber cross-sectional areas in jaw muscles were studied at the microscopic level. The injected masseter showed a steep increase in myosin type IIX fibers, whereas fast fibers decreased by about 50% in size. Depending on the injection site, both synergistic and antagonistic muscles showed a significant increase in the size of their fast IIA fibers, sometimes combined with an increased number of IIX fibers. Silencing the activity in the masseter not only causes changes in the fibers of the injected muscle but also leads to changes in other jaw muscles. Copyright © 2012 Wiley Periodicals, Inc.

  13. Long-Term Effects of Botulinum Toxin Complex Type A Injection on Mechano- and Metabo-Sensitive Afferent Fibers Originating from Gastrocnemius Muscle.

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    Guillaume Caron

    Full Text Available The aim of the present study was to investigate long term effects of motor denervation by botulinum toxin complex type A (BoNT/A from Clostridium Botulinum, on the afferent fibers originating from the gastrocnemius muscle of rats. Animals were divided in 2 experimental groups: 1 untreated animals acting as control and 2 treated animals in which the toxin was injected in the left muscle, the latter being itself divided into 3 subgroups according to their locomotor recovery with the help of a test based on footprint measurements of walking rats: i no recovery (B0, ii 50% recovery (B50 and iii full recovery (B100. Then, muscle properties, metabosensitive afferent fiber responses to potassium chloride (KCl and lactic acid injections and Electrically-Induced Fatigue (EIF, and mechanosensitive responses to tendon vibrations were measured. At the end of the experiment, rats were killed and the toxin injected muscles were weighted. After toxin injection, we observed a complete paralysis associated to a loss of force to muscle stimulation and a significant muscle atrophy, and a return to baseline when the animals recover. The response to fatigue was only decreased in the B0 group. The responses to KCl injections were only altered in the B100 groups while responses to lactic acid were altered in the 3 injected groups. Finally, our results indicated that neurotoxin altered the biphasic pattern of response of the mechanosensitive fiber to tendon vibrations in the B0 and B50 groups. These results indicated that neurotoxin injection induces muscle afferent activity alterations that persist and even worsen when the muscle has recovered his motor activity.

  14. Long-Term Effects of Botulinum Toxin Complex Type A Injection on Mechano- and Metabo-Sensitive Afferent Fibers Originating from Gastrocnemius Muscle.

    Science.gov (United States)

    Caron, Guillaume; Marqueste, Tanguy; Decherchi, Patrick

    2015-01-01

    The aim of the present study was to investigate long term effects of motor denervation by botulinum toxin complex type A (BoNT/A) from Clostridium Botulinum, on the afferent fibers originating from the gastrocnemius muscle of rats. Animals were divided in 2 experimental groups: 1) untreated animals acting as control and 2) treated animals in which the toxin was injected in the left muscle, the latter being itself divided into 3 subgroups according to their locomotor recovery with the help of a test based on footprint measurements of walking rats: i) no recovery (B0), ii) 50% recovery (B50) and iii) full recovery (B100). Then, muscle properties, metabosensitive afferent fiber responses to potassium chloride (KCl) and lactic acid injections and Electrically-Induced Fatigue (EIF), and mechanosensitive responses to tendon vibrations were measured. At the end of the experiment, rats were killed and the toxin injected muscles were weighted. After toxin injection, we observed a complete paralysis associated to a loss of force to muscle stimulation and a significant muscle atrophy, and a return to baseline when the animals recover. The response to fatigue was only decreased in the B0 group. The responses to KCl injections were only altered in the B100 groups while responses to lactic acid were altered in the 3 injected groups. Finally, our results indicated that neurotoxin altered the biphasic pattern of response of the mechanosensitive fiber to tendon vibrations in the B0 and B50 groups. These results indicated that neurotoxin injection induces muscle afferent activity alterations that persist and even worsen when the muscle has recovered his motor activity.

  15. Novel Botulinum Neurotoxins: Exploring Underneath the Iceberg Tip.

    Science.gov (United States)

    Tehran, Domenico Azarnia; Pirazzini, Marco

    2018-05-10

    Botulinum neurotoxins (BoNTs), the etiological agents of botulism, are the deadliest toxins known to humans. Yet, thanks to their biological and toxicological features, BoNTs have become sophisticated tools to study neuronal physiology and valuable therapeutics for an increasing number of human disorders. BoNTs are produced by multiple bacteria of the genus Clostridium and, on the basis of their different immunological properties, were classified as seven distinct types of toxin. BoNT classification remained stagnant for the last 50 years until, via bioinformatics and high-throughput sequencing techniques, dozens of BoNT variants, novel serotypes as well as BoNT-like toxins within non-clostridial species have been discovered. Here, we discuss how the now “booming field” of botulinum neurotoxin may shed light on their evolutionary origin and open exciting avenues for future therapeutic applications.

  16. Novel Botulinum Neurotoxins: Exploring Underneath the Iceberg Tip

    Directory of Open Access Journals (Sweden)

    Domenico Azarnia Tehran

    2018-05-01

    Full Text Available Botulinum neurotoxins (BoNTs, the etiological agents of botulism, are the deadliest toxins known to humans. Yet, thanks to their biological and toxicological features, BoNTs have become sophisticated tools to study neuronal physiology and valuable therapeutics for an increasing number of human disorders. BoNTs are produced by multiple bacteria of the genus Clostridium and, on the basis of their different immunological properties, were classified as seven distinct types of toxin. BoNT classification remained stagnant for the last 50 years until, via bioinformatics and high-throughput sequencing techniques, dozens of BoNT variants, novel serotypes as well as BoNT-like toxins within non-clostridial species have been discovered. Here, we discuss how the now “booming field” of botulinum neurotoxin may shed light on their evolutionary origin and open exciting avenues for future therapeutic applications.

  17. Yesterday and Today: The Impact of Research Conducted at Camp Detrick on Botulinum Toxin.

    Science.gov (United States)

    Lebeda, Frank J; Adler, Michael; Dembek, Zygmunt F

    2018-05-01

    This review summarizes the research conducted on botulinum toxin (BoTx) from 1943 to 1956 by a small group of Camp Detrick investigators and their staff. A systematic, cross-disciplinary approach was used to develop effective vaccines against this biological warfare threat agent. In response to the potential need for medical countermeasures against BoTx during World War II, the refinement of isolation and purification techniques for BoTx successfully led to the large-scale production of botulinum toxoid vaccines. In addition, the work at Camp Detrick provided the foundation for the subsequent use of BoTx as a tool for studying the trophic regulation of skeletal muscle within motor neuron terminals and, more recently, for elucidation of the intricate details of neurotransmitter release at the molecular level. Indirectly, Camp Detrick investigators also played a significant role in studies that culminated in the use of BoTx as a pharmaceutical product that has been approved by the U.S. Food and Drug Administration for treating movement disorders, autonomic dysfunctions, and other conditions. Online literature searches were performed with Google, Google Scholar, PubMed, the bibliography from the Camp Detrick technical library, and at the Defense Technical Information Center. Reference lists in some of the primary research publications and reviews also provided source material. Search terms included botulinum, botulinus, and Camp Detrick. References related to the subsequent impacts of the Camp Detrick results were selected and cited from reviews and primary references in the more recent literature. Notes on toxin nomenclature and potential sources of error in this study are presented. The literature searches returned 27 citations of Camp Detrick authors, 24 of which were articles in peer-reviewed journals. The publications by these investigators included several disciplines such as biochemistry, immunology, pharmacology, physiology, and toxicology. A fundamental

  18. Comparison of toxin production by clostridium botulinum type E in irradiated and unirradiated vacuum-packed trout (Salmo gairdneri)

    International Nuclear Information System (INIS)

    Hussain, M.; Ehlermann, D.; Diehl, J.F.

    1977-01-01

    Trouts obtained from a nearby Fish farm were slaughtered, gutted, cut into 100g samples and inoculated with 10 1 , 10 3 and 10 5 spores per g of Clostridium botulinum type E. The vacuum-packed samples were stored under melting ice (0 0 C) and at temperatures of 5 0 and 10 0 C for periods of up to 8 weeks. At weekly intervals, occurrence of spoilage and toxin production were determined. Only at 10 0 C storage, the irradiated samples showed toxin production before spoilage was observed. When the fishes were stored at 5 0 C, no toxicity occured before spoilage was observed even in samples treated with doses as high as 200 krad. Samples stored under melting ice, irradiated or unirradiated, never showed toxin production. It is concluded that the radurization of fish at doses of about 100 or 200 krad and at storage temperatures of melting ice or up to 5 0 C is safe with regard to a possible botulism risk. (orig.) [de

  19. Comparison of toxin production by clostridium botulinum type E in irradiated and unirradiated vacuum-packed trout (Salmo gairdneri)

    International Nuclear Information System (INIS)

    Hussain, A.M.; Ehlermann, D.; Diehl, J.F.

    1977-01-01

    Trouts obtained from a nearby fish farm were slaughtered, gutted, cut into 100 g samples and inoculated with 10 1 , 10 3 and 10 5 spores per g of Clostridium botulinum type E. The vacuum-packed samples were stored under melting ice (0 0 C) and at temperatures of 5 0 and 10 0 C for periods of up to 8 weeks. At weekly intervals, occurrence of spoilage and toxin production were determined. Only at 10 0 C storage, the irradiated samples showed toxin production before spoilage was observed. When the fishes were stored at 5 0 C, no toxicity occurred before spoilage was observed even in samples treated with doses as high as 200 krad. Samples stored under melting ice, irradiated or unirradiated, never showed toxin production. It is concluded that the radurization of fish at doses of about 100 or 200 krad and at storage temperatures of melting ice or up to 5 0 C is safe with regard to a possible botulism risk. (orig.) [de

  20. Structure and action of the binary C2 toxin from Clostridium botulinum.

    Science.gov (United States)

    Schleberger, Christian; Hochmann, Henrike; Barth, Holger; Aktories, Klaus; Schulz, Georg E

    2006-12-08

    C2 toxin from Clostridium botulinum is composed of the enzyme component C2-I, which ADP-ribosylates actin, and the binding and translocation component C2-II, responsible for the interaction with eukaryotic cell receptors and the following endocytosis. Three C2-I crystal structures at resolutions of up to 1.75 A are presented together with a crystal structure of C2-II at an appreciably lower resolution and a model of the prepore formed by fragment C2-IIa. The C2-I structure was determined at pH 3.0 and at pH 6.1. The structural differences are small, indicating that C2-I does not unfold, even at a pH value as low as 3.0. The ADP-ribosyl transferase activity of C2-I was determined for alpha and beta/gamma-actin and related to that of Iota toxin and of mutant S361R of C2-I that introduced the arginine observed in Iota toxin. The substantial activity differences between alpha and beta/gamma-actin cannot be explained by the protein structures currently available. The structure of the transport component C2-II at pH 4.3 was established by molecular replacement using a model of the protective antigen of anthrax toxin at pH 6.0. The C-terminal receptor-binding domain of C2-II could not be located but was present in the crystals. It may be mobile. The relative orientation and positions of the four other domains of C2-II do not differ much from those of the protective antigen, indicating that no large conformational changes occur between pH 4.3 and pH 6.0. A model of the C2-IIa prepore structure was constructed based on the corresponding assembly of the protective antigen. It revealed a surprisingly large number of asparagine residues lining the pore. The interaction between C2-I and C2-IIa and the translocation of C2-I into the target cell are discussed.

  1. Quantitative analysis of the pendulum test: application to multiple sclerosis patients treated with botulinum toxin.

    Science.gov (United States)

    Bianchi, L; Monaldi, F; Paolucci, S; Iani, C; Lacquaniti, F

    1999-01-01

    The aim of this study was to develop quantitative analytical methods in the application of the pendulum test to both normal and spastic subjects. The lower leg was released by a torque motor from different starting positions. The resulting changes in the knee angle were fitted by means of a time-varying model. Stiffness and viscosity coefficients were derived for each half-cycle oscillation in both flexion and extension, and for all knee starting positions. This method was applied to the assessment of the effects of Botulinum toxin A (BTX) in progressive multiple sclerosis patients in a follow-up study. About half of the patients showed a significant decrement in stiffness and viscosity coefficients.

  2. Study design and methods of the BoTULS trial: a randomised controlled trial to evaluate the clinical effect and cost effectiveness of treating upper limb spasticity due to stroke with botulinum toxin type A

    Directory of Open Access Journals (Sweden)

    Graham Laura

    2008-10-01

    Full Text Available Abstract Background Following a stroke, 55–75% of patients experience upper limb problems in the longer term. Upper limb spasticity may cause pain, deformity and reduced function, affecting mood and independence. Botulinum toxin is used increasingly to treat focal spasticity, but its impact on upper limb function after stroke is unclear. The aim of this study is to evaluate the clinical and cost effectiveness of botulinum toxin type A plus an upper limb therapy programme in the treatment of post stroke upper limb spasticity. Methods Trial design : A multi-centre open label parallel group randomised controlled trial and economic evaluation. Participants : Adults with upper limb spasticity at the shoulder, elbow, wrist or hand and reduced upper limb function due to stroke more than 1 month previously. Interventions : Botulinum toxin type A plus upper limb therapy (intervention group or upper limb therapy alone (control group. Outcomes : Outcome assessments are undertaken at 1, 3 and 12 months. The primary outcome is upper limb function one month after study entry measured by the Action Research Arm Test (ARAT. Secondary outcomes include: spasticity (Modified Ashworth Scale; grip strength; dexterity (Nine Hole Peg Test; disability (Barthel Activities of Daily Living Index; quality of life (Stroke Impact Scale, Euroqol EQ-5D and attainment of patient-selected goals (Canadian Occupational Performance Measure. Health and social services resource use, adverse events, use of other antispasticity treatments and patient views on the treatment will be compared. Participants are clinically reassessed at 3, 6 and 9 months to determine the need for repeat botulinum toxin type A and/or therapy. Randomisation : A web based central independent randomisation service. Blinding : Outcome assessments are undertaken by an assessor who is blinded to the randomisation group. Sample size : 332 participants provide 80% power to detect a 15% difference in treatment

  3. Treatment of cervical dystonia with botulinum toxin in a patient with myasthenia gravis Tratamento de distonia cervical com toxina botulínica em uma paciente com miastenia gravis

    Directory of Open Access Journals (Sweden)

    MARCIA RUBIA R. GONÇALVES

    1999-09-01

    Full Text Available We report the case of a 49-year-old woman who has the rare combination of myasthenia gravis and cervical dystonia. She was treated with botulinum toxin type A with good response and no evidence of deterioration of the myasthenic symptoms. We therefore conclude that it is possible to use botulinum toxin in the presence of defective neuromuscular transmission.Relatamos o caso de uma mulher de 49 anos com rara combinação de miastenia gravis e distonia cervical tratada com toxina botulínica tipo A, apresentando boa resposta e nenhuma evidência de piora do quadro miastênico. A partir dessas observações concluimos que é possível o uso de toxina botulínica na presença de doença da transmissão neuromuscular.

  4. Effects of Botulinum Toxin on Reducing the Co-contraction of Antagonists in Birth Brachial Plexus Palsy

    Science.gov (United States)

    Shin, Yong Beom; Chang, Jae Hyeok; Cha, Young Sun; Ko, Hyun-Yoon

    2014-01-01

    Birth brachial plexus palsy (BBPP) is usually caused by plexus traction during difficult delivery. Although the possibility of complete recovery is relatively high, 5% to 25% of BBPP cases result in prolonged and persistent disability. In particular, muscle imbalance and co-contraction around the shoulder and elbow cause abnormal motor performance, osseous deformities, and joint contracture. Physical and occupational therapies have most commonly been used, but these conventional therapeutic strategies have often been inadequate, in managing the residual muscle imbalance and muscle co-contraction. Therefore, we attempted to improve the functional movements, by using botulinum toxin type A, to reduce the abnormal co-contraction of the antagonist muscles. PMID:24639937

  5. Effects of irradiation on growth and toxigenicity of Clostridium botulinum types A and B inoculated onto chicken skins

    International Nuclear Information System (INIS)

    Dezfulian, M.; Bartlett, J.G.

    1987-01-01

    This study was conducted to examine the effects of 0.3-Mrad irradiation on growth and toxigenicity of Clostridum botulinum types A and B on chicken skins. Irradiation followed by aerobic or anaerobic incubation at 30 0 C extended the shelf life of skin samples and delayed growth and toxin production by C. botulinum. During 2 weeks of incubation at 10 0 C, the irradiated and nonirradiated C. botulinum spores failed to grow or produce toxin

  6. Discovery of novel bacterial toxins by genomics and computational biology.

    Science.gov (United States)

    Doxey, Andrew C; Mansfield, Michael J; Montecucco, Cesare

    2018-06-01

    Hundreds and hundreds of bacterial protein toxins are presently known. Traditionally, toxin identification begins with pathological studies of bacterial infectious disease. Following identification and cultivation of a bacterial pathogen, the protein toxin is purified from the culture medium and its pathogenic activity is studied using the methods of biochemistry and structural biology, cell biology, tissue and organ biology, and appropriate animal models, supplemented by bioimaging techniques. The ongoing and explosive development of high-throughput DNA sequencing and bioinformatic approaches have set in motion a revolution in many fields of biology, including microbiology. One consequence is that genes encoding novel bacterial toxins can be identified by bioinformatic and computational methods based on previous knowledge accumulated from studies of the biology and pathology of thousands of known bacterial protein toxins. Starting from the paradigmatic cases of diphtheria toxin, tetanus and botulinum neurotoxins, this review discusses traditional experimental approaches as well as bioinformatics and genomics-driven approaches that facilitate the discovery of novel bacterial toxins. We discuss recent work on the identification of novel botulinum-like toxins from genera such as Weissella, Chryseobacterium, and Enteroccocus, and the implications of these computationally identified toxins in the field. Finally, we discuss the promise of metagenomics in the discovery of novel toxins and their ecological niches, and present data suggesting the existence of uncharacterized, botulinum-like toxin genes in insect gut metagenomes. Copyright © 2018. Published by Elsevier Ltd.

  7. Botulinum toxin in the management of facial paralysis.

    Science.gov (United States)

    Cabin, Jonathan A; Massry, Guy G; Azizzadeh, Babak

    2015-08-01

    Complete flaccid facial paralysis, as well as the synkinetic and hyperkinetic sequelae of partial recovery, has significant impact on quality of life. Patients suffer from functional deficiencies, cosmetic deformity, discomfort and social consequences leading to emotional distress. Despite an extensive and sophisticated array of available interventions for facial reanimation, most patients have persistent issues that require consistent follow-up. In long-term management, botulinum toxin (BT) injection remains a critical tool in the treatment of the facial paralysis patient, particularly in the case of synkinesis, hyperkinesis and imbalance. We review the recent scientific literature and highlight key principles and developments in the use of BT in the management of facial paralysis, including less common applications for acute facial paralysis, hyperlacrimation and pseudoptosis. We reviewed the literature for the latest advances in the use of BT in facial paralysis, including applications and technique, as well as measurement tools and adjunct exercises. We also share our experience in treating our own patient population. BT continues to be a well tolerated and effective tool in the long-term management of facial paralysis, specifically in treating synkinesis, imbalance and hyperkinesis, as well as hyperlacrimation and pseudoptosis. Consistent measurement tools and adjunct neuromuscular retraining are crucial in the successful deployment of BT. Controversy exists as to whether BT should be used to manage facial paralysis during the acute phase, and whether BT application to the nonparalyzed face can improve long-term recovery in the paralyzed side.

  8. Considerations on patient-related outcomes with the use of botulinum toxins: is switching products safe?

    Directory of Open Access Journals (Sweden)

    Fraint A

    2016-02-01

    Full Text Available 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

  9. Effects of treadmill running on rat gastrocnemius function following botulinum toxin A injection.

    Science.gov (United States)

    Tsai, Sen-Wei; Chen, Chun-Jung; Chen, Hsiao-Lin; Chen, Chuan-Mu; Chang, Yin-Yi

    2012-02-01

    Exercise can improve and maintain neural or muscular function, but the effects of exercise in physiological adaptation to paralysis caused by botulinum toxin A has not been well studied. Twenty-four rats were randomly assigned into control and treadmill groups. The rats assigned to the treadmill group were trained on a treadmill three times per week with the running speed set at 15 m/min. The duration of training was 20 min/session. Muscle strength, nerve conduction study and sciatic functional index (SFI) were used for functional analysis. Treadmill training improved the SFI at 2, 3, and 4 weeks (p = 0.01, 0.004, and 0.01, respectively). The maximal contraction force of the gastrocnemius muscle in the treadmill group was greater than in the control group (p properties of muscle contraction strength, CMAP amplitude, and the recovery of SFI. Copyright © 2011 Orthopaedic Research Society.

  10. The Botulinum Toxin as a Therapeutic Agent: Molecular Structure and Mechanism of Action in Motor and Sensory Systems.

    Science.gov (United States)

    Kumar, Raj; Dhaliwal, Harkiran Preet; Kukreja, Roshan Vijay; Singh, Bal Ram

    2016-02-01

    Botulinum neurotoxin (BoNT) produced by Clostridium botulinum is the most potent molecule known to mankind. Higher potency of BoNT is attributed to several factors, including structural and functional uniqueness, target specificity, and longevity. Although BoNT is an extremely toxic molecule, it is now increasingly used for the treatment of disorders related to muscle hyperactivity and glandular hyperactivity. Weakening of muscles due to peripheral action of BoNT produces a therapeutic effect. Depending on the target tissue, BoNT can block the cholinergic neuromuscular or cholinergic autonomic innervation of exocrine glands and smooth muscles. In recent observations of the analgesic properties of BoNT, the toxin modifies the sensory feedback loop to the central nervous system. Differential effects of BoNT in excitatory and inhibitory neurons provide a unique therapeutic tool. In this review the authors briefly summarize the structure and mechanism of actions of BoNT on motor and sensory neurons to explain its therapeutic effects and future potential. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

  11. Two horizontal rectus eye muscle surgery combined with botulinum toxin for the treatment of very large angle esotropia. A pilot study.

    Science.gov (United States)

    Khan, Arif O

    2005-01-01

    To evaluate the effectiveness of a proposed new protocol for the primary treatment for very large angle esotropia: two muscle horizontal rectus muscle surgery with simultaneous botulinum toxin A injection in a small pilot study. Eight patients who had esotropia at near (ET') greater than 60 prism diopters (in actuality 70 to 100 prism diopters ET') underwent 2 muscle horizontal rectus surgery with simultaneous botulinum toxin A injection of the medial rectus intraoperatively. This was the only surgical procedure for all patients included in this report. Seven patients underwent bilateral medial rectus recession and bilateral injection, and one patient underwent a unilateral medial rectus recession / lateral rectus resection procedure with unilateral medial rectus injection. Postoperatively, 6 of the 8 patients demonstrated residual esotropia at near of less than 10 prism diopters and were considered "successful" by the conventional criteria of binocular alignment within 8 prism diopters of orthotropia. Two undercorrections occurred in patients with 100 and 85 prism diopters of preop ET' respectively. But 3 other patients with such large deviations had satisfactory results. All patients and families were satisfied with postoperative binocular alignment, so no further surgery was undertaken. The patient who underwent unilateral surgery had the least surgical effect and was the largest undercorrection, probably because only one medial rectus received a Botox injection. Considering only the bilateral cases, results were "successful" in 6 of 7 cases. Most patients suffered an extended period of Botox induced exotropia in the postop' period before recovery from the paresis. One patient had a transient, successfully treated, postoperative strabismic amblyopia while exotropic. Bilateral medial rectus recession with simultaneous botulinum injection is a safe and effective primary surgical procedure for very large angle esotropia. A more extensive study is indicated to

  12. Botulinum toxin type A products are not interchangeable: a review of the evidence

    Directory of Open Access Journals (Sweden)

    Brin MF

    2014-10-01

    Full Text Available Mitchell F Brin,1,2 Charmaine James,3 John Maltman1 1Allergan, Inc., Irvine, CA, USA; 2Department of Neurology, University of California, Irvine, CA, USA; 3Allergan, Marlow, UKAbstract: Botulinum toxin type A (BoNTA products are injectable biologic medications derived from Clostridium botulinum bacteria. Several different BoNTA products are marketed in various countries, and they are not interchangeable. Differences between products include manufacturing processes, formulations, and the assay methods used to determine units of biological activity. These differences result in a specific set of interactions between each BoNTA product and the tissue injected. Consequently, the products show differences in their in vivo profiles, including preclinical dose response curves and clinical dosing, efficacy, duration, and safety/adverse events. Most, but not all, published studies document these differences, suggesting that individual BoNTA products act differently depending on experimental and clinical conditions, and these differences may not always be predictable. Differentiation through regulatory approvals provides a measure of confidence in safety and efficacy at the specified doses for each approved indication. Moreover, the products differ in the amount of study to which they have been subjected, as evidenced by the number of publications in the peer-reviewed literature and the quantity and quality of clinical studies. Given that BoNTAs are potent biological products that meet important clinical needs, it is critical to recognize that their dosing and product performance are not interchangeable and each product should be used according to manufacturer guidelines.Keywords: onabotulinumtoxinA, abobotulinumtoxinA, incobotulinumtoxinA, glabellar lines, non-interchangeability

  13. [Botulinum toxin injection techniques in the lower third and middle of the face, the neck and the décolleté: the "Nefertiti lift"].

    Science.gov (United States)

    Gassia, V; Beylot, C; Béchaux, S; Michaud, T

    2009-05-01

    Although correction of the dynamic wrinkles of the upper part of the face is the major indication for botulinum toxin, there are also many possibilities for the middle and lower thirds of the face and neck. However, these injections are more delicate and require an experienced operator who has excellent knowledge of the muscles of these regions, their functions, the antagonist actions exercised on other muscles, particularly in terms of the complex equilibrium of the mouth. An excessive dose, an inappropriate injection point, or a centering mistake can all easily be responsible for undesirable side effects. However, the results obtained, often with lower doses than in the superior part of the face, can be highly satisfactory, notably in erasing bunny lines, improvement of marionette lines, peau d'orange chin, attenuation of peribuccal lines, melomental folds, correction of a gummy smile, and facial asymmetries. In the neck it is possible to reduce platysmal bands, horizontal lines, and diagonal lines of the neck and décolleté. The face contours can also be improved by the Nefertiti lift. In the mid and lower regions of the face, botulinum toxin is often a complement to other esthetic techniques, particularly filling procedures.

  14. Critical analysis of the use of onabotulinumtoxinA (botulinum toxin type A) in migraine.

    Science.gov (United States)

    Robertson, Carrie E; Garza, Ivan

    2012-01-01

    OnabotulinumtoxinA, a neurotoxin, has been studied in numerous trials as a novel preventive therapy for migraine headache. The data would support that it may be effective at reducing headache days in patients suffering from chronic migraine (≥15 headache days/month, with eight or more of those migraine headache days). The mechanism by which onabotulinumtoxinA exerts its effects on migraine is not yet understood. It is known to inhibit acetylcholine release at the neuromuscular junction, but this probably does not explain the observed antinociceptive properties noted in preclinical and clinical trials. This review will discuss the known mechanisms of action of botulinum toxin type A, and will review the available randomized, placebo-controlled trials that have looked at its efficacy as a migraine preventative. We also describe the onabotulinumtoxinA injection sites used at our institution.

  15. Botulinum toxin's axonal transport from periphery to the spinal cord.

    Science.gov (United States)

    Matak, Ivica; Riederer, Peter; Lacković, Zdravko

    2012-07-01

    Axonal transport of enzymatically active botulinum toxin A (BTX-A) from periphery to the CNS has been described in facial and trigeminal nerve, leading to cleavage of synaptosomal-associated protein 25 (SNAP-25) in central nuclei. Aim of present study was to examine the existence of axonal transport of peripherally applied BTX-A to spinal cord via sciatic nerve. We employed BTX-A-cleaved SNAP-25 immunohistochemistry of lumbar spinal cord after intramuscular and subcutaneous hind limb injections, and intraneural BTX-A sciatic nerve injections. Truncated SNAP-25 in ipsilateral spinal cord ventral horns and dorsal horns appeared after single peripheral BTX-A administrations, even at low intramuscular dose applied (5 U/kg). Cleaved SNAP-25 appearance in the spinal cord after BTX-A injection into the sciatic nerve was prevented by proximal intrasciatic injection of colchicine (5 mM, 2 μl). Cleaved SNAP-25 in ventral horn, using choline-acetyltransferase (ChAT) double labeling, was localized within cholinergic neurons. These results extend the recent findings on BTX-A retrograde axonal transport in facial and trigeminal nerve. Appearance of truncated SNAP-25 in spinal cord following low-dose peripheral BTX-A suggest that the axonal transport of BTX-A occurs commonly following peripheral application. Copyright © 2012 Elsevier Ltd. All rights reserved.

  16. Botulinum toxin type A for neuropathic pain in patients with spinal cord injury.

    Science.gov (United States)

    Han, Zee-A; Song, Dae Heon; Oh, Hyun-Mi; Chung, Myung Eun

    2016-04-01

    To evaluate the analgesic effect of botulinum toxin type A (BTX-A) on patients with spinal cord injury-associated neuropathic pain. The effect of BTX-A on 40 patients with spinal cord injury-associated neuropathic pain was investigated using a randomized, double-blind, placebo-controlled design. A 1-time subcutaneous BTX-A (200U) injection was administered to the painful area. Visual analogue scale (VAS) scores (0-100mm), the Korean version of the short-form McGill Pain Questionnaire, and the World Health Organization WHOQOL-BREF quality of life assessment were evaluated prior to treatment and at 4 and 8 weeks after the injection. At 4 and 8 weeks after injection, the VAS score for pain was significantly reduced by 18.6 ± 16.8 and 21.3 ± 26.8, respectively, in the BTX-A group, whereas it was reduced by 2.6 ± 14.6 and 0.3 ± 19.5, respectively, in the placebo group. The pain relief was associated with preservation of motor or sensory function below the neurological level of injury. Among the responders in the BTX-A group, 55% and 45% reported pain relief of 20% or greater at 4 and 8 weeks, respectively, after the injection, whereas only 15% and 10% of the responders in the placebo group reported a similar level of pain relief. Improvements in the score for the physical health domain of the WHOQOL-BREF in the BTX-A group showed a marginal trend toward significance (p = 0.0521) at 4 weeks after the injection. These results indicate that BTX-A may reduce intractable chronic neuropathic pain in patients with spinal cord injury. © 2016 The Authors. Annals of Neurology published by Wiley Periodicals, Inc. on behalf of American Neurological Association.

  17. Studies on growth and toxin production of C. botulinum type E on cod homogenate treated with a combination of spices, sodium chloride and gamma-radiation

    International Nuclear Information System (INIS)

    Siddiqui, A.K.; Ando, Y.; Karashimada, T.; Kameyama, K.

    1979-01-01

    Cod homogenates inoculated with spores of C. botulinum type E strain Erimo at 10 2 and 10 4 /g were treated with 1% and 2% sodium chloride, 0.25% each of mustard, garlic and turmeric and 0.3 Mrad ν-radiation either in single or combination treatments. The growth and toxin production of type E spores in the inoculated homogenates were followed at incubation temperatures of 30 0 , 10 0 and 5 0 C for 7, 28 and 56 days respectively. Growth and gas formation were noted in all the samples but type E toxin could not be detected. The reason for the absence of toxin in both the untreated and treated homogenates could not be ascertained. Inadequate detection method, unfavourable growth conditions in the homogenate and weak toxigenicity of the strain employed have been advanced as probable factors that contributed to the negative results on the toxin assay. (author)

  18. Botulinum toxin for the treatment of motor imbalance in obstetrical brachial plexus palsy.

    Science.gov (United States)

    Arad, Ehud; Stephens, Derek; Curtis, Christine G; Clarke, Howard M

    2013-06-01

    Residual muscle imbalance is a common problem affecting obstetrical brachial plexus palsy patients. The goal of this study was to examine the efficacy of botulinum toxin type A (Botox) in improving this muscle imbalance. The authors retrospectively reviewed obstetrical brachial plexus palsy patients treated with Botox for muscle imbalance as an isolated procedure. Outcomes were the change in Active Movement Scale scores from pre-Botox scores to scores at 1 month after Botox and 1 year after Botox. Twenty-seven patients were included, 19 treated for shoulder imbalance and eight treated for elbow imbalance. Active Movement Scale scores (mean±SD) for shoulder external rotation improved from 0.6±1.0 before Botox to 2.6±2.14 (pimbalance produces improvement in external rotation that is not sufficiently sustained over time to be of clinical benefit. However, Botox for elbow movement imbalance produces a sustained and clinically useful improvement. Therapeutic, IV.

  19. Assessing the immediate impact of botulinum toxin injection on impedance of spastic muscle.

    Science.gov (United States)

    Li, Xiaoyan; Shin, Henry; Li, Le; Magat, Elaine; Li, Sheng; Zhou, Ping

    2017-05-01

    This study aimed to investigate the immediate impacts of Botulinum Toxin A (BoNT-A) injections on the inherent electrical properties of spastic muscles using a newly developed electrical impedance myography (EIM) technique. Impedance measures were performed before and after a BoNT-A injection in biceps brachii muscles of 14 subjects with spasticity. Three major impedance variables, resistance (R), reactance (X) and phase angle (θ) were obtained from three different configurations, and were evaluated using the conventional EIM frequency at 50kHz as well as multiple frequency analysis. Statistical analysis demonstrated a significant decrease of resistance in the injected muscles (Multiple-frequency: R pre =25.17±1.94Ohm, R post =23.65±1.63Ohm, ptoxin effects on the muscle. This study demonstrated high sensitivity of the EIM technique in the detection of alterations to muscle composition. Copyright © 2017 IPEM. Published by Elsevier Ltd. All rights reserved.

  20. Using translational medicine to understand clinical differences between botulinum toxin formulations.

    Science.gov (United States)

    Aoki, K R; Ranoux, D; Wissel, J

    2006-12-01

    When using botulinum toxin-based products, the physician must decide the optimal location and dose required to alleviate symptoms and improve the patient's quality of life. To deliver effective treatment, the physician needs to understand the importance of accurate target muscle selection and localization and the implications of each product's migration properties when diluted in different volumes. Pre-clinical mouse models of efficacy and safety have been utilized to compare local and distal muscle relaxation effects following defined intramuscular administration. Data from the model allow the products to be ranked based on their propensity for local efficacy versus their distal migration properties. Using standardized dilutions, the non-parallel dose-response curves for the various formulations demonstrate that they have different efficacy profiles. Distal effects were also noted at different treatment doses, which are reflected in the different safety and/or therapeutic margins. Based on these pre-clinical data, the safety and therapeutic margin rankings are ordered, largest to smallest, as BOTOX, Dysport and Myobloc. The results of subsequent clinical trials are variable and dose comparisons are inconclusive, thus supporting the regulatory position that the dose units of the individual preparations are unique and cannot be simply converted between products.

  1. Embryonic Stem Cell-Derived Neurons are a Novel, Highly Sensitive Tissue Culture Platform for Botulinum Research

    Science.gov (United States)

    2011-01-01

    and acceleration of toxin degradation may be more amenable to therapeutic intervention, the neuronal response to intoxication and the molecular ...References [1] L.L. Simpson, Identification of the major steps in botulinum toxin action, Annu. Rev. Pharmacol. Toxicol. 44 (2004) 167–193. [2] J.C...BoNT) therapeutics: time to think outside the BoNT?, Botulinum J 1 (2009) 261–269. [6] L.L. Simpson, The origin, structure , and pharmacological

  2. Mechano- and metabosensitive alterations after injection of botulinum toxin into gastrocnemius muscle.

    Science.gov (United States)

    Caron, Guillaume; Rouzi, Talifujiang; Grelot, Laurent; Magalon, Guy; Marqueste, Tanguy; Decherchi, Patrick

    2014-07-01

    This study was designed to investigate effects of motor denervation by Clostridium botulinum toxin serotype A (BoNT/A) on the afferent activity of fibers originating from the gastrocnemius muscle of rats. Animals were randomized in two groups, 1) untreated animals acting as control and 2) treated animals in which the toxin was injected in the left muscle. Locomotor activity was evaluated once per day during 12 days with a test based on footprint measurements of walking rats (sciatic functional index). At the end of the functional assessment period, electrophysiological tests were used to measure muscle properties, metabosensitive afferent fiber responses to chemical (KCl and lactic acid) injections, electrically induced fatigue (EIF), and mechanosensitive responses to tendon vibrations. Additionally, ventilatory response was recorded during repetitive muscle contractions. Then, rats were sacrificed, and the BoNT/A-injected muscles were weighed. Twelve days postinjection we observed a complete motor denervation associated with a significant muscle atrophy and loss of force to direct muscle stimulation. In the BoNT/A group, the metabosensitive responses to KCl injections were unaltered. However, we observed alterations in responses to EIF and to 1 mM of lactic acid (which induces the greatest activation). The ventilatory adjustments during repetitive muscle activation were abolished, and the mechanosensitive fiber responses to tendon vibrations were reduced. These results indicate that BoNT/A alters the sensorimotor loop and may induce insufficient motor and physiological adjustments in patients in whom a motor denervation with BoNT/A was performed. Copyright © 2014 Wiley Periodicals, Inc.

  3. Effects of Botulinum Toxin on Jaw Motor Events during Sleep in Sleep Bruxism Patients: A Polysomnographic Evaluation

    Science.gov (United States)

    Shim, Young Joo; Lee, Moon Kyu; Kato, Takafumi; Park, Hyung Uk; Heo, Kyoung; Kim, Seong Taek

    2014-01-01

    Study Objectives: To investigate the effects of botulinum toxin type A (BoNT-A) injection on jaw motor episodes during sleep in patients with or without orofacial pain who did not respond to oral splint treatment. Methods: Twenty subjects with a clinical diagnosis of SB completed this study. Ten subjects received bilateral BoNT-A injections (25 U per muscle) into the masseter muscles only (group A), and the other 10 received the injections into both the masseter and temporalis muscles (group B). Video-polysomnographic (vPSG) recordings were made before and at 4 weeks after injection. Rhythmic masticatory muscle activity (RMMA) and orofacial activity (OFA) were scored and analyzed for several parameters (e.g., frequency of episodes, bursts per episode, episode duration). The peak amplitude of electromyographic (EMG) activity in the two muscles was also measured. Results: BoNT-A injection did not reduce the frequency, number of bursts, or duration for RMMA episodes in the two groups. The injection decreased the peak amplitude of EMG burst of RMMA episodes in the injected muscles (p < 0.001, repeated measure ANOVA) in both groups. At 4 weeks after injection, 9 subjects self-reported reduction of tooth grinding and 18 subjects self-reported reduction of morning jaw stiffness. Conclusions: A single BoNT-A injection is an effective strategy for controlling SB for at least a month. It reduces the intensity rather than the generation of the contraction in jaw-closing muscles. Future investigations on the efficacy and safety in larger samples over a longer follow-up period are needed before establishing management strategies for SB with BoNT-A. Citation: Shim YJ; Lee MK; Kato T; Park HU; Heo K; Kim ST. Effects of botulinum toxin on jaw motor events during sleep in sleep bruxism patients: a polysomnographic evaluation. J Clin Sleep Med 2014;10(3):291-298. PMID:24634627

  4. Botulinum toxin-induced facial muscle paralysis affects amygdala responses to the perception of emotional expressions: preliminary findings from an A-B-A design

    OpenAIRE

    Kim, M Justin; Neta, Maital; Davis, F Caroline; Ruberry, Erika J; Dinescu, Diana; Heatherton, Todd F; Stotland, Mitchell A; Whalen, Paul J

    2014-01-01

    Background It has long been suggested that feedback signals from facial muscles influence emotional experience. The recent surge in use of botulinum toxin (BTX) to induce temporary muscle paralysis offers a unique opportunity to directly test this ?facial feedback hypothesis.? Previous research shows that the lack of facial muscle feedback due to BTX-induced paralysis influences subjective reports of emotional experience, as well as brain activity associated with the imitation of emotional fa...

  5. Hemimasticatory spasm treated with botulinum toxin: case report Espasmo hemimastigatório tratado com toxina botulínica: relato de caso

    Directory of Open Access Journals (Sweden)

    Hélio A.G. Teive

    2002-06-01

    Full Text Available We describe a female patient with hemimasticatory spasm, a rare movement disorder due to dysfunction of the motor trigeminal nerve of unknown origin. This patient had an excellent response to botulinum toxin therapy.Relatamos o caso de paciente feminina com espasmo hemimastigatório, distúrbio do movimento raro decorrente de disfunção da porção motora do nervo trigeminal, de etiologia desconhecida. A paciente teve excelente resposta clínica ao tratamento com toxina botulínica.

  6. In Vivo Toxicity and Immunological Characterization of Detoxified Recombinant Botulinum Neurotoxin Type A.

    Science.gov (United States)

    Ravichandran, Easwaran; Janardhanan, Pavithra; Patel, Kruti; Riding, Stephen; Cai, Shuowei; Singh, Bal Ram

    2016-03-01

    A double-mutant E224A/E262A full-length botulinum neurotoxin (BoNT) Type A with structural similarity to native BoNT/A but lacking the endopeptidase activity provides an ideal surrogate for testing pharmacokinetics and immunochemical characteristics of BoNT. We determined lethality (LD50) of deactivated recombinant botulinum neurotoxin (drBoNT/A) to be 24.0 μg by intraperitoneal route (i.p). The polypeptide drBoNT/A labeled with near infra-red dye 800 (NIR 800) was used to examine its distribution to different organs using whole body imaging when administered to mice via intravenous (i.v) or i.p route. Also, drBoNT/A was used to evaluate its immunogenicity in Balb/C mice model. drBoNT/A was found to be highly immunogenic when tested under various in vivo conditions in Balb/C mice model. For the first time we have demonstrated that a full length 150 kDa drBoNT/A, by administering via inhalation route in mice model, has evoked both circulating immunoglobulin levels of IgG and secretory IgA at the mucosal surface. The immunoglobulin levels were sufficient enough to protect against the challenge dose of native BoNT toxin in mice model. Tissue distribution of drBoNT/A seems to be similar to that of native toxin. Based on the characteristics described in this report this nontoxic holotoxin protein will assist us to explore the window of opportunity available for therapeutic treatment in case of unnatural poisoning, and also it can be an effective vaccine candidate.

  7. SiMa Cells for a Serotype Specific and Sensitive Cell-Based Neutralization Test for Botulinum Toxin A and E.

    Science.gov (United States)

    Bak, Nicola; Rajagopal, Shalini; Stickings, Paul; Sesardic, Dorothea

    2017-07-20

    Botulinum toxins (BoNTs), of which there are seven serotypes, are among the most potent neurotoxins, with serotypes A, B and E causing human botulism. Antitoxins form the first line of treatment for botulism, and functional, highly sensitive in vitro methods for toxin neutralization are needed to replace the current in vivo methods used for determination of antitoxin potency. In this preliminary proof of concept study, we report the development of a neutralization test using the neuroblastoma SiMa cell line. The assay is serotype specific for either BoNT/A or BoNT/E, which both cleave unique sequences on SNAP-25 within SiMa cells. The end point is simple immunodetection of cleaved SNAP-25 from cell lysates with antibodies detecting only the newly exposed sequence on SNAP-25. Neutralizing antibodies prevent the toxin-induced cleavage of SNAP-25. The toxin neutralization assay, with an EC50 of ~2 mIU/mL determined with a standardized reference antiserum, is more sensitive than the mouse bioassays. Relevance was demonstrated with commercial and experimental antitoxins targeting different functional domains, and of known in vivo neutralizing activities. This is the first report describing a simple, specific, in vitro cell-based assay for the detection of neutralizing antibodies against BoNT/A and BoNT/E with a sensitivity exceeding that of the mouse bioassay.

  8. Botulinum toxin injections for low-back pain and sciatica.

    Science.gov (United States)

    Waseem, Zeeshan; Boulias, Chris; Gordon, Allan; Ismail, Farooq; Sheean, Geoffrey; Furlan, Andrea D

    2011-01-19

    Adequate relief from low-back pain (LBP) is not always possible. Emerging evidence suggests a role for botulinum neurotoxin (BoNT) injections in treating pain disorders. Proponents of BoNT suggest its properties can decrease muscle spasms, ischemia and inflammatory markers, thereby reducing pain. To determine the effects of botulinum toxin injections in adults with LBP. We searched CENTRAL (The Cochrane Library 2009, issue 3) and MEDLINE, EMBASE, and CINAHL to August 2009; screened references from included studies; consulted with content experts and Allergan. We included published and unpublished randomised controlled trials without language restrictions We included randomised trials that evaluated BoNT serotypes versus other treatments in patients with non-specific LBP of any duration. Two review authors selected the studies, assessed the risk of bias using the Cochrane Back Review Group criteria, and extracted the data using standardized forms. We performed a qualitative analysis due to lack of data. We excluded evidence from nineteen studies due to non-randomisation, incomplete or unpublished data. We included three randomised trials (N =123 patients). Only one study included patients with chronic non-specific LBP; the other two examined unique subpopulations. Only one of the three trials had a low risk of bias and demonstrated that BoNT injections reduced pain at three and eight weeks and improved function at eight weeks better than saline injections. The second trial showed that BoNT injections were better than injections of corticosteroid plus lidocaine or placebo in patients with sciatica attributed to piriformis syndrome. The third trial concluded that BoNT injections were better than traditional acupuncture in patients with third lumbar transverse process syndrome. Both studies with high risk of bias had several key limitations. Heterogeneity of the studies prevented meta-analysis. There is low quality evidence that BoNT injections improved pain, function

  9. Studies on growth and toxin production of C. botulinum type E on cod homogenate treated with a combination of spices, sodium chloride and gamma-radiation

    Energy Technology Data Exchange (ETDEWEB)

    Siddiqui, A K [Atomic Energy Centre, Dacca (Bangladesh); Ando, Y; Karashimada, T; Kameyama, K

    1979-09-01

    Cod homogenates inoculated with spores of C. botulinum type E strain Erimo at 10/sup 2/ and 10/sup 4//g were treated with 1% and 2% sodium chloride, 0.25% each of mustard, garlic and turmeric and 0.3 Mrad ..gamma..-radiation either in single or combination treatments. The growth and toxin production of type E spores in the inoculated homogenates were followed at incubation temperatures of 30/sup 0/, 10/sup 0/ and 5/sup 0/C for 7, 28 and 56 days respectively. Growth and gas formation were noted in all the samples but type E toxin could not be detected. The reason for the absence of toxin in both the untreated and treated homogenates could not be ascertained. Inadequate detection method, unfavourable growth conditions in the homogenate and weak toxigenicity of the strain employed have been advanced as probable factors that contributed to the negative results on the toxin assay.

  10. Botulinum neurotoxin type A versus punctal plug insertion in the management of dry eye disease

    Directory of Open Access Journals (Sweden)

    Amal A Bukhari

    2014-01-01

    Full Text Available Purpose: To compare the efficacies of punctal plug insertion and Botulinum toxin injection in dry eye disease not responding to topical medications. Materials and Methods: A non-controlled randomized clinical trial of two parallel groups of 60 dry eye patients seen in the clinic not responding to topical medications were divided into two groups. One group received punctal plugs and the other group received Botulinum toxin injections to prevent lacrimal tear drainage. Results: Of a total of 36 patients with a mean age of 44.5 years who received punctal plugs, 50% of them experienced improvements in the clinical manifestations of their disease. 12/36 (33.3% developed plug extrusion, and 6/36 (16.7% patients developed conjunctival erosions with irritation that necessitated plug removal within one week of insertion. A total of 24 patients with a mean age of 47.5 years received injections of Botulinum toxin. Of these, 83.3% had improvement in all of the clinical manifestations of dry eye. 4/24 (16.7% had no improvement in the degrees to which they experienced foreign body sensations, 33.3% reported shampoo entering the eye while showering. All of the patients who received Botulinum toxin injections were satisfied with the results of their treatment, whereas only 72.3% of the patients who received punctal plugs were satisfied with their results. Conclusion: Botulinum neurotoxin A injections can be a very good alternative to punctal plugs in improving the clinical manifestations of dry eye disease They are associated with the development of fewer and milder complications and with higher levels of patient satisfaction.

  11. The convergence of medicine and neurotoxins: a focus on botulinum toxin type A and its application in aesthetic medicine--a global, evidence-based botulinum toxin consensus education initiative: part II: incorporating botulinum toxin into aesthetic clinical practice.

    Science.gov (United States)

    Carruthers, Jean; Fournier, Nathalie; Kerscher, Martina; Ruiz-Avila, Javier; Trindade de Almeida, Ada R; Kaeuper, Gina

    2013-03-01

    The new world of safe aesthetic injectables has become increasingly popular with patients. Not only is there less risk than with surgery, but there is also significantly less downtime to interfere with patients' normal work and social schedules. Botulinum toxin (BoNT) type A (BoNTA) is an indispensable tool used in aesthetic medicine, and its broad appeal has made it a hallmark of modern culture. The key to using BoNTA to its best effect is to understand patient-specific factors that will determine the treatment plan and the physician's ability to personalize injection strategies. To present international expert viewpoints and consensus on some of the contemporary best practices in aesthetic BoNTA, so that beginner and advanced injectors may find pearls that provide practical benefits. Expert aesthetic physicians convened to discuss their approaches to treatment with BoNT. The discussions and consensus from this meeting were used to provide an up-to-date review of treatment strategies to improve patient results. Information is presented on patient management and assessment, documentation and consent, aesthetic scales, injection strategies, dilution, dosing, and adverse events. A range of product- and patient-specific factors influence the treatment plan. Truly optimized outcomes are possible only when the treating physician has the requisite knowledge, experience, and vision to use BoNTA as part of a unique solution for each patient's specific needs. © 2013 by the American Society for Dermatologic Surgery, Inc. Published by Wiley Periodicals, Inc.

  12. Repetitive transcranial magnetic stimulation versus botulinum toxin injection in chronic migraine prophylaxis: a pilot randomized trial

    Directory of Open Access Journals (Sweden)

    Shehata HS

    2016-10-01

    Full Text Available Hatem S Shehata, Eman H Esmail, Ahmad Abdelalim, Shaimaa El-Jaafary, Alaa Elmazny, Asmaa Sabbah, Nevin M Shalaby Neurology Department, Faculty of Medicine, Cairo University, Cairo, Egypt Background: Chronic migraine is a prevalent disabling disease, with major health-related burden and poor quality of life. Long-term use of preventive medications carries risk of side effects. Objectives: The aim of this study was to compare repetitive transcranial magnetic stimulation (rTMS to botulinum toxin-A (BTX-A injection as preventive therapies for chronic migraine. Methods: A pilot, randomized study was conducted on a small-scale sample of 29 Egyptian patients with chronic migraine, recruited from Kasr Al-Aini teaching hospital outpatient clinic and diagnosed according to ICHD-III (beta version. Patients were randomly assigned into two groups; 15 patients received BTX-A injection following the Phase III Research Evaluating Migraine Prophylaxis Therapy injection paradigm and 14 patients were subjected to 12 rTMS sessions delivered at high frequency (10 Hz over the left motor cortex (MC, M1. All the patients were requested to have their 1-month headache calendar, and they were subjected to a baseline 25-item (beta version Henry Ford Hospital Headache Disability Inventory (HDI, Headache Impact Test (HIT-6, and visual analogue scale assessment of headache intensity. The primary efficacy measures were headache frequency and severity; secondary measures were 25-item HDI, HIT-6, and number of acute medications. Follow-up visits were scheduled at weeks 4, 6, 8, 10, and 12 after baseline visit. Results: A reduction in all outcome measures was achieved in both the groups. However, this improvement was more sustained in the BTX-A group, and both the therapies were well tolerated. Conclusion: BTX-A injection and rTMS have favorable efficacy and safety profiles in chronic migraineurs. rTMS is of comparable efficacy to BTX-A injection in chronic migraine

  13. Alteration of Skin Mechanical Properties in Patients Undergoing Botulinum Toxin Type A Injections of Forehead Rhytides.

    Science.gov (United States)

    Min, Peiru; Zhang, Zheng; Grassetti, Luca; Perdanasari, Aurelia Trisliana; Torresetti, Matteo; Pu, Zheming; Zhang, Yan; Han, Sheng; Marsili, Riccardo; Zhang, Yi Xin; di Benedetto, Giovanni; Lazzeri, Davide

    2016-06-01

    Although application of botulinum toxin type A (BTX-A) for the treatment of forehead rhytides has become very popular, the effects of its intramuscular injections on the skin mechanical properties remain unclear. We prospectively investigated the alterations in the mechanical properties of the skin of patients who received intramuscular injections of botulinum toxin A (BTX-A) for forehead rhytides and compared two injection doses. Of the 42 enrolled patients, one randomly assigned half received intramuscular injections of two units (group I), and the other half received four units (group II) of BTX-A in each injection point. The baseline and post-treatment skin mechanical parameters, including gross elasticity (R2), net elasticity (R5), viscoelastic ratio (R6) and biological elasticity (R7), were measured using the Cutometer(®) and compared. Treatment with BTX-A resulted in significant overall alterations in the mechanical properties of skin at the injection sites of both treatment groups during the 16-week period, and no significant differences were observed between groups. Significant decreases in biological elasticity, net elasticity and viscoelasticity properties were observed at 2 weeks follow-up and began to recover at that time. All of the skin mechanical properties recovered to baseline levels by 16 weeks of follow-up in both dosage groups, which indicates that the higher dosage (4 units) did not delay relapse compared to the two-unit dosage. We concluded that intramuscular injections of BTX-A significantly regulated the gross elasticity, net elasticity, functional elasticity and viscoelastic elasticity at the injection point over a radius of 1.5 cm at 2, 4 and 8 weeks follow-up. The alteration in the skin measurements had completely diminished by the 16-week follow-up. This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or

  14. On the translocation of botulinum and tetanus neurotoxins across the membrane of acidic intracellular compartments.

    Science.gov (United States)

    Pirazzini, Marco; Azarnia Tehran, Domenico; Leka, Oneda; Zanetti, Giulia; Rossetto, Ornella; Montecucco, Cesare

    2016-03-01

    Tetanus and botulinum neurotoxins are produced by anaerobic bacteria of the genus Clostridium and are the most poisonous toxins known, with 50% mouse lethal dose comprised within the range of 0.1-few nanograms per Kg, depending on the individual toxin. Botulinum neurotoxins are similarly toxic to humans and can therefore be considered for potential use in bioterrorism. At the same time, their neurospecificity and reversibility of action make them excellent therapeutics for a growing and heterogeneous number of human diseases that are characterized by a hyperactivity of peripheral nerve terminals. The complete crystallographic structure is available for some botulinum toxins, and reveals that they consist of four domains functionally related to the four steps of their mechanism of neuron intoxication: 1) binding to specific receptors of the presynaptic membrane; 2) internalization via endocytic vesicles; 3) translocation across the membrane of endocytic vesicles into the neuronal cytosol; 4) catalytic activity of the enzymatic moiety directed towards the SNARE proteins. Despite the many advances in understanding the structure-mechanism relationship of tetanus and botulinum neurotoxins, the molecular events involved in the translocation step have been only partially elucidated. Here we will review recent advances that have provided relevant insights on the process and discuss possible models that can be experimentally tested. This article is part of a Special Issue entitled: Pore-Forming Toxins edited by Mauro Dalla Serra and Franco Gambale. Copyright © 2015. Published by Elsevier B.V.

  15. Nonallergic Eyelid Edema After Botulinum Toxin Type A Injection: Case Report and Review of Literature.

    Science.gov (United States)

    Chang, Yin-Shuo; Chang, Chang-Cheng; Shen, Jen-Hsiang; Chen, Yu-Tsung; Chan, Karen Kar-Wun

    2015-09-01

    Periocular botulinum toxin type A (BoNTA) injections are generally safe. Ptosis is the most common adverse effect, whereas eyelid edema is rarely reported. There is no consensus on the latter's incidence, clinical course, or treatment strategy. Here we managed a 59-year-old woman who received BoNTA injections to her forehead, glabella, and eye corner. At 3-day follow-up, she presented with painless, nonpruritic, bilateral periorbital edema, and erythema. Preliminary diagnosis was a local allergic reaction, and topical corticosteroid was administered, but upon lack of improvement, edema secondary to venous and lymphatic congestion was hypothesized, and she was advised to apply hot pads over her eyes, blink frequently, and massage the area. Her eyelid edema resolved 2 weeks later. At 4-month follow-up, the patient requested and received another course of BoNTA at half the dose. Frequent blinking was instructed, and the patient reported a satisfactory outcome with no adverse effects. In our literature review, incidence of BoNTA-induced eyelid edema was 1.4% and showed Asian tendency. Although rare, BoNTA-induced periorbital edema is self-limiting, and normally resolves in 2 to 4 weeks without medical treatment. Patients at risk for edema, including Asian ethnicity, dermatochalasis, and poor periocular muscle tone, are advised to receive injections at half the dosage. Examination of the function and tone of the orbicularis oculi and levator palpebrae superioris muscles before treatment is recommended, and application of hot pads over the eyes, frequent blinking in the morning, and self-massage of the affected area to increase venous return have demonstrated to improve outcome.

  16. A literature review on the efficacy and safety of botulinum toxin: An injection in post-stroke spasticity

    Directory of Open Access Journals (Sweden)

    Majid Ghasemi

    2013-01-01

    Full Text Available Background: A variety of techniques for the management of spasticity have been suggested, including positioning, cryotherapy, splinting and casting, biofeedback, electrical stimulation, and medical management by pharmacological agents, Botulinum toxin A (BTA is now the pharmacological treatment of choice in focal spasticity. BTA by blocking acetylcholine release at neuromuscular junctions accounts for its therapeutic action to relieve spasticity. Methods: A computerized search of Pub Med was carried out to find the latest result about efficacy of BTA in management of post stroke spasticity. Result: Among 84 articles were found, frothy of them included in this review and divided to lower and upper extremity. Conclusions: BTA is a treatment choice in reducing tone and managing post stroke spasticity .

  17. Muscle changes can account for bone loss after botulinum toxin injection.

    Science.gov (United States)

    Manske, Sarah L; Boyd, Steven K; Zernicke, Ronald F

    2010-12-01

    Studies to date have assumed that botulinum toxin type A (BTX) affects bone indirectly, through its action on muscle. We hypothesized that BTX has no discernable effect on bone morphometry, independent of its effect on muscle. Therefore, we investigated whether BTX had an additional effect on bone when combined with tenotomy compared to tenotomy in isolation. Female BALB/c mice (n = 73) underwent one of the following procedures in the left leg: BTX injection and Achilles tenotomy (BTX-TEN), BTX injection and sham surgery (BTX-sham), Achilles tenotomy (TEN), or sham surgery (sham). BTX groups were injected with 20 μL of BTX (1 U/100 g) in the posterior lower hindlimb. At 4 weeks, muscle cross-sectional area (MCSA) and tibial bone morphometry were assessed using micro-CT. Each treatment, other than sham, resulted in significant muscle and bone loss (P properties. We found that BTX injection resulted in more adverse muscle and bone effects than tenotomy and that effects were amplified when the procedures were combined. However, between-group differences in bone could be accounted for by MCSA. We conclude that any independent effect of BTX on bone morphometry is likely small or negligible compared with the effect on muscle.

  18. Botulinum toxin type A chemodenervation treatment in spastic forms of cerebral palsy

    Directory of Open Access Journals (Sweden)

    A. L. Kurenkov

    2013-01-01

    Full Text Available Cerebral palsy (CP is one of the most serious outcomes of the perinatal lesion of central nervous system and the most common reason for neurological disability in children. Being the key cause of pathological dynamic stereotypes that frequently result in pathological posture and contractures, spasticity is critically important for CP. The use of botulinum toxin type A (BTA in complex treatment 2-6 years old CP patients allows significantly to improve motor abilities, help to change the surgical procedure, delay or even avoid some types of surgery. For elder children the use of BTA allows to improve local motor impairment. The treatment of spasticity in CP with BTA is safe (evidence level A and highly effective (evidence level A. It leads to the positive change of pathological dynamic stereotype, significantly improves gait, decreases muscle tone with Ashworth and Tardeu scales and rises the gross motor function score. Our own experience of onabotulinumtoxinA treatment as a part of complex therapy in 68 patients with spastic forms of CP demonstrates the significant improvement of motor function, most noticeable in younger patients(early pre-school age with GMFS I-III.

  19. An Open Study of Botulinum-A Toxin Treatment of Idiopathic Trigeminal Neuralgia

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    Karim Nikkhah

    2015-07-01

    Full Text Available Introduction: Trigeminal Neuralgia (TN is a unilateral, recurrent, sharp facial pain disorder that is limited to the distribution of divisions of the trigeminal nerve. The aim of this study was to evaluate the efficacy of Botulinum neurotoxin type A (BTX-A for alleviating the frequency and severity of TN pain. Materials and Methods: This trial was performed as a before and after study. We treated 31 patients (15 male and 16 female with mean age of 52 year old that their diagnosis was made at least 4.5 years before. We injected BTX-A in various parts of face and particularly in the origin of mandibular and maxillary branches of trigeminal nerve. Injection volume was determined by the necessity and pain intensity measured with visual analog scale up to 100U. Patients were evaluated before and after the injection and were followed after week, and each month, for a three months period. Other related variables were recorded such as: toxin complications, pain status variations by brushing, chewing, cold weather and patient’s satisfaction with their therapy. Results: showed that after injection, pain intensity and frequency decreased after tooth brushing, chewing and cold weather (P

  20. Differences in botulinum toxin dosing between patients with adductor spasmodic dysphonia and essential voice tremor.

    Science.gov (United States)

    Orbelo, Diana M; Duffy, Joseph R; Hughes Borst, Becky J; Ekbom, Dale; Maragos, Nicolas E

    2014-01-01

    To explore possible dose differences in average botulinum toxin (BTX) given to patients with adductor spasmodic dysphonia (ADSD) compared with patients with essential voice tremor (EVT). A retrospective study compared the average BTX dose injected in equal doses to the thyroarytenoid (TA) muscles of 51 patients with ADSD with 52 patients with EVT. Those with ADSD received significantly higher total doses (6.80 ± 2.79 units) compared with those with EVT (5.02 ± 1.65 units). Dose at time of first injection, age at time of first injection, gender, year of first injection, and average time between injections were included in multivariate analysis but did not interact with total average dose findings. Patients with ADSD may need relatively higher doses of BTX injections to bilateral TA muscles compared with patients with EVT. Copyright © 2014 The Voice Foundation. Published by Mosby, Inc. All rights reserved.

  1. Toxin production in food as influenced by pH, thermal treatment and ...

    African Journals Online (AJOL)

    STORAGESEVER

    2008-06-03

    Jun 3, 2008 ... toxigenic properties and thirteen of the sixteen were positive for toxin production ... treatment and chemical preservatives on the growth rate and toxin ..... Clostridium botulinum in cooked pureed vegetables at Refrigerated.

  2. Flagellar glycosylation in Clostridium botulinum.

    Science.gov (United States)

    Twine, Susan M; Paul, Catherine J; Vinogradov, Evgeny; McNally, David J; Brisson, Jean-Robert; Mullen, James A; McMullin, David R; Jarrell, Harold C; Austin, John W; Kelly, John F; Logan, Susan M

    2008-09-01

    Flagellins from Clostridium botulinum were shown to be post-translationally modified with novel glycan moieties by top-down MS analysis of purified flagellin protein from strains of various toxin serotypes. Detailed analyses of flagellin from two strains of C. botulinum demonstrated that the protein is modified by a novel glycan moiety of mass 417 Da in O-linkage. Bioinformatic analysis of available C. botulinum genomes identified a flagellar glycosylation island containing homologs of genes recently identified in Campylobacter coli that have been shown to be responsible for the biosynthesis of legionaminic acid derivatives. Structural characterization of the carbohydrate moiety was completed utilizing both MS and NMR spectroscopy, and it was shown to be a novel legionaminic acid derivative, 7-acetamido-5-(N-methyl-glutam-4-yl)-amino-3,5,7,9-tetradeoxy-D-glycero-alpha-D-galacto-nonulosonic acid, (alphaLeg5GluNMe7Ac). Electron transfer dissociation MS with and without collision-activated dissociation was utilized to map seven sites of O-linked glycosylation, eliminating the need for chemical derivatization of tryptic peptides prior to analysis. Marker ions for novel glycans, as well as a unique C-terminal flagellin peptide marker ion, were identified in a top-down analysis of the intact protein. These ions have the potential for use in for rapid detection and discrimination of C. botulinum cells, indicating botulinum neurotoxin contamination. This is the first report of glycosylation of Gram-positive flagellar proteins by the 'sialic acid-like' nonulosonate sugar, legionaminic acid.

  3. Botulinum toxin type A-a novel treatment for provoked vestibulodynia? Results from a randomized, placebo controlled, double blinded study

    DEFF Research Database (Denmark)

    Petersen, Christina Damsted; Giraldi, Annamaria; Lundvall, Lene

    2009-01-01

    to receive Botox (N = 32) or saline placebo (N = 32). Botulinum toxin A (20 I.E.) diluted in 0.5 mL saline or 0.5 mL saline was injected in the musculus bulbospongiosus at baseline. MAIN OUTCOME MEASURES: Pain was measured monthly on a visual analog scale (VAS) Likert scale. Sexual function was measured...... pain reduction (P placebo group...... in the vestibule of women diagnosed with vestibulodynia does not reduce pain, improve sexual functioning, or impact the quality of life compared to placebo and evaluated at 3 and 6 moths follow up. Both the Botox group and the placebo groups experienced a reduction in pain on the VAS Likert scale at 6 months...

  4. An in vivo analysis of facial muscle change treated with botulinum toxin type A using digital image speckle correlation

    Science.gov (United States)

    Xu, Yan; Palmaccio, Samantha Palmaccio; Bui, Duc; Dagum, Alexander; Rafailovich, Miriam

    Been famous for clinical use from early 1980s, the neuromuscular blocking agent Botulinum toxin type A (BTX-A), has been used to reduce wrinkles for a long time. Only little research has been done to quantify the change of muscle contraction before and after injection and most research paper depend on subjective evaluation from both patients and surgeons. In our research, Digital Image Speckle Correlation (DISC) was employed to study the mechanical properties of skin, contraction mode of muscles (injected) and reaction of neighbor muscle group (un-injected).At the same time, displacement patterns (vector maps)generated by DISC can predict injection locus for surgeons who normally handle it depending only on visual observation.

  5. Electromyography in cervical dystonia: changes after botulinum and trihexyphenidyl

    NARCIS (Netherlands)

    Brans, J. W.; Aramideh, M.; Koelman, J. H.; Lindeboom, R.; Speelman, J. D.; Ongerboer de Visser, B. W.

    1998-01-01

    BACKGROUND: The value of physical examination in detecting involved neck muscles in cervical dystonia (CD) is uncertain and little is known about changes in electromyographic (EMG) features after botulinum toxin type A (BTA) treatment. METHODS: In a double-blind, randomized study we recorded the EMG

  6. Systems analysis of transcriptional data provides insights into muscle's biological response to botulinum toxin.

    Science.gov (United States)

    Mukund, Kavitha; Mathewson, Margie; Minamoto, Viviane; Ward, Samuel R; Subramaniam, Shankar; Lieber, Richard L

    2014-11-01

    This study provides global transcriptomic profiling and analysis of botulinum toxin A (BoNT-A)-treated muscle over a 1-year period. Microarray analysis was performed on rat tibialis anterior muscles from 4 groups (n = 4/group) at 1, 4, 12, and 52 weeks after BoNT-A injection compared with saline-injected rats at 12 weeks. Dramatic transcriptional adaptation occurred at 1 week with a paradoxical increase in expression of slow and immature isoforms, activation of genes in competing pathways of repair and atrophy, impaired mitochondrial biogenesis, and increased metal ion imbalance. Adaptations of the basal lamina and fibrillar extracellular matrix (ECM) occurred by 4 weeks. The muscle transcriptome returned to its unperturbed state 12 weeks after injection. Acute transcriptional adaptations resemble denervated muscle with some subtle differences, but resolved more quickly compared with denervation. Overall, gene expression across time correlates with the generally accepted BoNT-A time course and suggests that the direct action of BoNT-A in skeletal muscle is relatively rapid. © 2014 Wiley Periodicals, Inc.

  7. Multilevel Botulinum Toxin A (Abobotulinum Toxin A Injections in Spastic Forms of Cerebral Palsy: Retrospective Analysis of 8 Russian Centers Experience

    Directory of Open Access Journals (Sweden)

    O. A. Klochkova

    2016-01-01

    Full Text Available Background: The contemporary application of Botulinum toxin A (BTA in cerebral palsy (CP implies multilevel injections both in on-label and off-label muscles. However, there is no single international opinion on the effective and safe dosages, target muscles, and intervals between the injections.Objective: Our aim was to analyze the Russian multicenter independent experience of single and repeated multilevel injections of Abobotulinum toxin А in patients with spastic forms of CP.Methods: 8 independent referral CP-centers (10 hospitals in different regions of Russia. Authors evaluated intervals between the injections, dosages of the BTA for the whole procedure, for the body mass, for the each muscle, and functional segment of the extremities.Results: 1872 protocols of effective BTA injections (1–14 repeated injections for 724 patients with spastic CP were included. The age of the patients was between 8 months to 17 years 4 months at the beginning of the treatment (with a mean of 3 years 10 months. Multilevel BTA injections were indicated for the majority (n = 634, 87.6% of the patients in all the centers. The medians of the dosages for the first BTA injection were between 30–31 U/kg (500 U, the repeated injections doses up to 45 U/kg (1000 U (in most centers. The median intervals between the repeated injections were 180–200 days in 484 (66.9% patients and 140–180 days in 157 (24.7% patients. In 2 centers, children with GMFCS IV–V were injected more often than others.Conclusion: Multilevel BTA injections were indicated for the most patients. The initial dose of Abobotulinum toxin A was 30–31 U/kg. The repeated injections dose could increase up to 40 U/kg. The repeated injections were done in 140–200 days after the previous injection.

  8. [Myths and evidence on the use of botulinum toxin: neuropharmacology and dystonia].

    Science.gov (United States)

    Garcia-Ruiz, P J; Sanz-Cartagena, P; Martinez-Castrillo, J C; Ares-Pensado, B; Aviles-Olmos, I; Blazquez-Estrada, M; Fanjul-Arbos, S; Garcia-Caldentey, J; Gazulla, J; Gutierrez-Garcia, J; Huete-Anton, B; Lucas-Rodenas, C; Luquin, M R; Martinez-Torres, I; Medialdea-Natera, P; Mendoza-Rodriguez, A; Mir-Rivera, P; Posada, I J; Ruiz-Martinez, J; Sanchez-Alonso, P; Trejo-Gabriel Y Galan, J M; Vela, L; Pena-Segura, J L

    2018-03-01

    Botulinum toxin type A (BTA) is a bacterial endotoxin, whose therapeutic use has had a dramatic impact on different neurological disorders, such as dystonia and spasticity. To analyze and summarize different questions about the use of BTA in our clinical practice. A group of experts in neurology developed a list of topics related with the use of BTA. Two groups were considered: neuropharmacology and dystonia. A literature search at PubMed, mainly for English language articles published up to June 2016 was performed. The manuscript was structured as a questionnaire that includes those questions that, according to the panel opinion, could generate more controversy or doubt. The initial draft was reviewed by the expert panel members to allow modifications, and after subsequent revisions for achieving the highest degree of consensus, the final text was then validated. Different questions about diverse aspects of neuropharmacology, such as mechanism of action, bioequivalence of the different preparations, immunogenicity, etc. were included. Regarding dystonia, the document included questions about methods of evaluation, cervical dystonia, blepharospasm, etc. This review does not pretend to be a guide, but rather a tool for continuous training of residents and specialists in neurology, about different specific areas of the management of BTA.

  9. Comparison of oral toxicological properties of botulinum neurotoxin

    Science.gov (United States)

    Botulinum neurotoxins (BoNTs) are among the most potent biological toxins for humans. Of the seven known serotypes (A-G) of BoNT, serotypes A, B and E cause most of the foodborne intoxications in humans. BoNTs in nature are associated with non-toxic accessory proteins known as neurotoxin-associated ...

  10. Safety of Botulinum Toxin A in Children and Adolescents with Cerebral Palsy in a Pragmatic Setting

    Directory of Open Access Journals (Sweden)

    George Mitsou

    2013-03-01

    Full Text Available This retrospective study aimed to examine the safety of botulinum toxin A (BoNT-A treatment in a paediatric multidisciplinary cerebral palsy clinic. In a sample of 454 patients who had 1515 BoNT-A sessions, data on adverse events were available in 356 patients and 1382 sessions; 51 non-fatal adverse events were reported (3.3% of the total injections number, 8.7% of the patients. On five occasions, the adverse reactions observed in GMFCS V children were attributed to the sedation used (rectal midazolam plus pethidine; buccal midazolam and resulted in prolongation of hospitalization. Of the reactions attributed to the toxin, 23 involved an excessive reduction of the muscle tone either of the injected limb(s or generalized; others included local pain, restlessness, lethargy with pallor, disturbance in swallowing and speech production, seizures, strabismus, excessive sweating, constipation, vomiting, a flu-like syndrome and emerging hypertonus in adjacent muscles. Their incidence was associated with GMFCS level and with the presence of epilepsy (Odds ratio (OR = 2.74 − p = 0.016 and OR = 2.35 − p = 0.046, respectively but not with BoNT-A dose (either total or per kilogram. In conclusion, treatment with BoNT-A was safe; adverse reactions were mostly mild even for severely affected patients. Their appearance did not necessitate major changes in our practice.

  11. Treatment of achalasia: the short-term response to botulinum toxin injection seems to be independent of any kind of pretreatment

    Directory of Open Access Journals (Sweden)

    Meining A

    2002-08-01

    Full Text Available Abstract Background It has been suggested that intrasphincteric injection of botulinum toxin (BTX may represent an alternative therapy to balloon dilatation in achalasia. The aim of the present study was to test the effectiveness of botulinum toxin injections in achalasia patients, as assessed using lower oesophageal sphincter pressure (LOSP and symptom scores, and to compare the response in patients with different types of pretreatment (no previous treatment, balloon dilatation, myotomy, BTX injection. Methods Forty patients who presented with symptomatic achalasia were treated with BTX injection (48 injections in 40 patients. Some of the patients had received prior treatment (seven with myotomy, seven with dilatation and eight with BTX. The symptoms were assessed using a global symptom score (0–10, which was evaluated before treatment, 1 week afterwards, and 1 month afterwards. Manometry was also carried out before and after treatment. Three different selections of patients were studied: all patients; untreated patients; and patients with prior BTX, dilatation, or myotomy. Results After BTX injection, there was a significant reduction in LOSP (before, 38.2 ± 11.3 mmHg; 1 week after, 20.5 ± 6.9 mmHg; 1 month after, 17.8 ± 6.8 mmHg; P Conclusions BTX injection offers an alternative treatment for achalasia which is safe and can be performed in an outpatient setting. The initial response to BTX, in terms of symptom scores and LOSP, appears to be independent of any prior treatment. A number of patients do not adequately respond to balloon dilatation or myotomy, which are the first-line treatment modalities in achalasia patients. BTX injection can be performed in these patients, and symptomatic benefit can be expected in the same percentages as with BTX injection in untreated patients.

  12. An evidence-based review of botulinum toxin (Botox) applications in non-cosmetic head and neck conditions

    Science.gov (United States)

    Persaud, Ricardo; Garas, George; Silva, Sanjeev; Stamatoglou, Constantine; Chatrath, Paul; Patel, Kalpesh

    2013-01-01

    Botulinum toxin (Botox) is an exotoxin produced from Clostridium botulinum. It works by blocking the release of acetylcholine from the cholinergic nerve end plates leading to inactivity of the muscles or glands innervated. Botox is best known for its beneficial role in facial aesthetics but recent literature has highlighted its usage in multiple non-cosmetic medical and surgical conditions. This article reviews the current evidence pertaining to Botox use in the head and neck. A literature review was conducted using The Cochrane Controlled Trials Register, Medline and EMBASE databases limited to English Language articles published from 1980 to 2012. The findings suggest that there is level 1 evidence supporting the efficacy of Botox in the treatment of spasmodic dysphonia, essential voice tremor, headache, cervical dystonia, masticatory myalgia, sialorrhoea, temporomandibular joint disorders, bruxism, blepharospasm, hemifacial spasm and rhinitis. For chronic neck pain there is level 1 evidence to show that Botox is ineffective. Level 2 evidence exists for vocal tics, trigeminal neuralgia, dysphagia and post-laryngectomy oesophageal speech. For stuttering, ‘first bite syndrome’, facial nerve paresis, Frey's syndrome, oromandibular dystonia and palatal/stapedial myoclonus the evidence is level 4. Thus, the literature highlights a therapeutic role for Botox in a wide range of non-cosmetic conditions pertaining to the head and neck (mainly level 1 evidence). With ongoing research, the spectrum of clinical applications and number of people receiving Botox will no doubt increase. Botox appears to justify its title as ‘the poison that heals’. PMID:23476731

  13. O uso da toxina botulínica no tratamento da distonia laríngea (disfonia espasmódica: estudo preliminar com doze pacientes Use of botulinum toxin in the treatment of laryngeal dystonia (spasmodic dysphonia: preliminary study of twelve patients

    Directory of Open Access Journals (Sweden)

    Hélio A. G. Teive

    2001-03-01

    Full Text Available A distonia laríngea (disfonia espasmódica é distúrbio do movimento caracterizado por contrações involuntárias da musculatura laríngea envolvida no processo de vocalização. A utilização da toxina botulínica no tratamento da distonia laríngea trouxe consideráveis benefícios clínicos. Descrevemos os resultados preliminares do uso terapêutico da toxina botulínica no tratamento da distonia laríngea em 12 pacientes. Após investigação clínica, os pacientes foram submetidos a videolaringoestroboscopia para confirmação diagnóstica e as injeções de toxina botulínica foram realizadas através de punção da membrana cricotireóidea em direção ao músculo tireoaritenóideo, com uso de eletromiografia. A maioria dos pacientes submetidos ao tratamento com toxina botulínica apresentou melhora significativa da distonia laríngea (83% dos casos, com duração média do efeito de quatro meses, sem efeitos colaterais significativos.Laryngeal dystonia (spasmodic dysphonia is a movement disorder characterized by involuntary contractions of laryngeal muscles involved with vocalization. The introduction of botulinum toxin in the treatment of laryngeal dystonia had a major clinical impact due to the striking improvement of symptoms. We report the preliminary results of therapeutical use of botulinum toxin in the treatment of twelve patients with laryngeal dystonia. After an extensive clinical evaluation, the patients underwent a videostroboscopic exam for diagnostic confirmation. Botulinum toxin was injected in the cricothyreoid membrane, directed towards the thyreoaritenoid muscle, with the aid of eletromyography needles. Most of patients who underwent botulinum toxin injection had a significant improvement of their symptoms (83%, with effects lasting for four months in average and without important side effects.

  14. A Label Free Colorimetric Assay for the Detection of Active Botulinum Neurotoxin Type A by SNAP-25 Conjugated Colloidal Gold

    Directory of Open Access Journals (Sweden)

    Christopher Gwenin

    2013-08-01

    Full Text Available Botulinum neurotoxins are one of the most potent toxins known to man. Current methods of detection involve the quantification of the toxin but do not take into account the percentage of the toxin that is active. At present the assay used for monitoring the activity of the toxin is the mouse bioassay, which is lengthy and has ethical issues due to the use of live animals. This report demonstrates a novel assay that utilises the endopeptidase activity of the toxin to detect Botulinum neurotoxin in a pharmaceutical sample. The cleaving of SNAP-25 is monitored via UV-Visible spectroscopy with a limit of detection of 373 fg/mL and has been further developed into a high throughput method using a microplate reader detecting down to 600 fg/mL of active toxin. The results show clear differences between the toxin product and the placebo, which contains the pharmaceutical excipients human serum albumin and lactose, showing that the assay detects the active form of the toxin.

  15. Botulinum Toxin Confers Radioprotection in Murine Salivary Glands

    Energy Technology Data Exchange (ETDEWEB)

    Zeidan, Youssef H., E-mail: zeidan@miami.edu [Department of Radiation Oncology, University of Miami Miller School of Medicine, Miami, Florida (United States); Xiao, Nan; Cao, Hongbin [Department of Radiation Oncology, Stanford University School of Medicine, Stanford, California (United States); Kong, Christina [Department of Otolaryngology-Head and Neck Surgery, Stanford University School of Medicine, Stanford, California (United States); Department of Pathology, Stanford University School of Medicine, Stanford, California (United States); Le, Quynh-Thu; Sirjani, Davud [Department of Radiation Oncology, Stanford University School of Medicine, Stanford, California (United States)

    2016-04-01

    Purpose: Xerostomia is a common radiation sequela, which has a negative impact on the quality of life of patients with head and neck cancer. Current treatment strategies offer only partial relief. Botulinum toxins (BTX) have been successfully used in treating a variety of radiation sequelae such as cystitis, proctitis, fibrosis, and facial pain. The purpose of this study was to evaluate the effect of BTX on radiation-induced salivary gland damage. Methods and Materials: We used a previously established model for murine salivary gland irradiation (IR). The submandibular glands (SMGs) of C5BL/6 mice (n=6/group) were injected with saline or BTX 72 hours before receiving 15 Gy of focal irradiation. Saliva flow was measured 3, 7, and 28 days after treatment. The SMGs were collected for immunohistochemistry, confocal microscopy, and Western blotting. A cytokine array consisting of 40 different mouse cytokines was used to evaluate cytokine profiles after radiation treatment. Results: Irradiated mice showed a 50% reduction in saliva flow after 3 days, whereas mice preinjected with BTX had 25% reduction in saliva flow (P<.05). Cell death detected by TUNEL staining was similar in SMG sections of both groups. However, neutrophil infiltrate, detected by myeloperoxidase staining, was 3-fold lower for the BTX treated mice. A cytokine array showed a 2-fold upregulation of LPS-induced chemokine (LIX/CXCL5) 3 days after IR. BTX pretreatment reduced LIX levels by 40%. At 4 weeks after IR, the saline (control) group showed a 40% reduction in basal SMG weight, compared with 20% in the BTX group. Histologically, BTX-pretreated glands showed relative preservation of acinar structures after radiation. Conclusions: These data suggest that BTX pretreatment ameliorates radiation-induced saliva dysfunction. Moreover, we demonstrate a novel role for CXCL5 in the acute phase of salivary gland damage after radiation. These results carry important clinical implications for the treatment of

  16. Occurrence of human pathogenic Clostridium botulinum among healthy dairy animals: an emerging public health hazard.

    Science.gov (United States)

    Abdel-Moein, Khaled A; Hamza, Dalia A

    2016-01-01

    The current study was conducted to investigate the occurrence of human pathogenic Clostridium botulinum in the feces of dairy animals. Fecal samples were collected from 203 apparently healthy dairy animals (50 cattle, 50 buffaloes, 52 sheep, 51 goats). Samples were cultured to recover C. botulinum while human pathogenic C. botulinum strains were identified after screening of all C. botulinum isolates for the presence of genes that encode toxins type A, B, E, F. The overall prevalence of C. botulinum was 18.7% whereas human pathogenic C. botulinum strains (only type A) were isolated from six animals at the rates of 2, 2, 5.8, and 2% for cattle, buffaloes, sheep, and goats, respectively. High fecal carriage rates of C. botulinum among apparently healthy dairy animals especially type A alarm both veterinary and public health communities for a potential role which may be played by dairy animals in the epidemiology of such pathogen.

  17. Production and characterisation of a neutralising chimeric antibody against botulinum neurotoxin A.

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    Julie Prigent

    Full Text Available Botulinum neurotoxins, produced by Clostridium botulinum bacteria, are the causative agent of botulism. This disease only affects a few hundred people each year, thus ranking it among the orphan diseases. However, botulinum toxin type A (BoNT/A is the most potent toxin known to man. Due to their potency and ease of production, these toxins were classified by the Centers for Disease Control and Prevention (CDC as Category A biothreat agents. For several biothreat agents, like BoNT/A, passive immunotherapy remains the only possible effective treatment allowing in vivo neutralization, despite possible major side effects. Recently, several mouse monoclonal antibodies directed against a recombinant fragment of BoNT/A were produced in our laboratory and most efficiently neutralised the neurotoxin. In the present work, the most powerful one, TA12, was selected for chimerisation. The variable regions of this antibody were thus cloned and fused with the constant counterparts of human IgG1 (kappa light and gamma 1 heavy chains. Chimeric antibody production was evaluated in mammalian myeloma cells (SP2/0-Ag14 and insect cells (Sf9. After purifying the recombinant antibody by affinity chromatography, the biochemical properties of chimeric and mouse antibody were compared. Both have the same very low affinity constant (close to 10 pM and the chimeric antibody exhibited a similar capacity to its parent counterpart in neutralising the toxin in vivo. Its strong affinity and high neutralising potency make this chimeric antibody interesting for immunotherapy treatment in humans in cases of poisoning, particularly as there is a probable limitation of the immunological side effects observed with classical polyclonal antisera from heterologous species.

  18. Toxina botulínica no tratamento da dor Toxina botulínica en el tratamiento del dolor Botulinum toxin in pain treatment

    Directory of Open Access Journals (Sweden)

    Orlando Carlos Gomes Colhado

    2009-06-01

    indicaciones, todavía están en fase de comprobación con relación a su eficacia. El objetivo de este estudio fue revisar el historial, las propiedades farmacológicas y las aplicaciones clinicas de la TxB, cuando se usa en el tratamiento de dolores de diferentes etiologías. CONTENIDO: La TxB es el producto de la fermentación del Clostridium Botulinum, una bacteria anaerobia Gram-positiva. Comercialmente, las TxB existen bajo las formas A y B, agentes biológicos obtenidos laboratorialmente. La TxB, una neurotoxina que posee una alta afinidad por las sinapsis colinérgicas, ocasiona un bloqueo en la liberación de acetilcolina por el terminal nervioso, sin alterar la conducción neural de las señales eléctricas o la síntesis y el almacenaje de acetilcolina. Se ha comprobado que la TxB puede debilitar selectivamente la musculatura dolorosa, interrumpiendo el ciclo espasmo-dolor. Con relación a él, varias publicaciones han demostrado la eficacia y la seguridad de la TxB-A en el tratamiento de la cefalea tipo tensión, migraña, dolor lumbar crónico y dolor miofacial. CONCLUSIONES: La TxB-A es segura y se tolera muy bien en los desórdenes dolorosos crónicos, donde los regímenes de farmacoterapia pueden de hecho provocar efectos colaterales. Otra ventaja es la reducción del uso de analgésicos y el tiempo de acción de 3 a 4 meses por dosis. Sin embargo, investigaciones futuras serán necesarias para establecer la eficacia de la TxB-A en los desórdenes dolorosos crónicos y su exacto mecanismo en el alivio del dolor, como también su potencial en tratamientos multifactoriales.BACKGROOUND AND OBJECTIVES: Botulinum toxin (BTX is one of the most potent bacterial toxins known and its effectiveness in the treatment of some pain syndromes is well known. However, the efficacy of some of its indications is still in the process of being confirmed. The objective of this study was to review the history, pharmacological properties, and clinical applications of BTX in the

  19. Effects of intraplantar botulinum toxin-B on carrageenan-induced changes in nociception and spinal phosphorylation of GluA1 and Akt.

    Science.gov (United States)

    Sikandar, Shafaq; Gustavsson, Ynette; Marino, Marc J; Dickenson, Anthony H; Yaksh, Tony L; Sorkin, Linda S; Ramachandran, Roshni

    2016-07-01

    Increasing evidence suggests that botulinum neurotoxins (BoNTs) delivered into the skin and muscle in certain human and animal pain states may exert antinociceptive efficacy though their uptake and transport to central afferent terminals. Cleavage of soluble N-methylaleimide-sensitive attachment protein receptor by BoNTs can impede vesicular mediated neurotransmitter release as well as transport/insertion of channel/receptor subunits into plasma membranes, an effect that can reduce activity-evoked facilitation. Here, we explored the effects of intraplantar botulinum toxin- B (BoNT-B) on peripheral inflammation and spinal nociceptive processing in an inflammatory model of pain. C57BL/6 mice (male) received unilateral intraplantar BoNT (1 U, 30 μL) or saline prior to intraplantar carrageenan (20 μL, 2%) or intrathecal N-methyl-D-aspartate (NMDA), substance P or saline (5 μL). Intraplantar carrageenan resulted in edema and mechanical allodynia in the injected paw and increased phosphorylation of a glutamate subunit (pGluA1ser845) and a serine/threonine-specific protein kinase (pAktser473) in spinal dorsal horn along with an increased incidence of spinal c-Fos positive cells. Pre-treatment with intraplantar BoNT-B reduced carrageenan evoked: (i) allodynia, but not edema; (ii) pGluA1 and pAkt and (iii) c-Fos expression. Further, intrathecal NMDA and substance P each increased dorsal horn levels of pGluA1 and pAkt. Intraplantar BoNT-B inhibited NMDA, but not substance P evoked phosphorylation of GluA1 and Akt. These results suggest that intraplantar toxin is transported centrally to block spinal activation and prevent phosphorylation of a glutamate receptor subunit and a kinase, which otherwise contribute to facilitated states. © 2016 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

  20. Influence of injection of Chinese botulinum toxin type A on the histomorphology and myosin heavy chain composition of rat gastrocnemius muscles.

    Science.gov (United States)

    Hong, Bin; Chen, Min; Hu, Xing-yue

    2013-11-01

    Botulinum toxin type A (BoNT/A) is a metalloprotease that blocks synaptic transmission via the cleavage of a synaptosomal-associated protein of 25 kDa (SNAP-25). It has gained widespread use as a treatment for cerebral palsy and skeletal muscle hypertrophy. In China, Chinese botulinum toxin type A (CBTX-A), a type of BoNT/A, is in widespread clinical use. However, the changes in the morphological and biochemical properties of treated muscles and in remote muscles from the CBTX-A injection site are relatively unknown. Therefore, we investigated the changes in histomorphology and myosin heavy chain (MyHC) isoform composition and distribution in rat gastrocnemius muscles after intramuscular injection of CBTX-A. The weakness of the injected muscles was assessed periodically to identify their functional deficiency. Muscle slices were stained with hematoxylin-eosin (HE) and adenosine triphosphatase (ATPase). MyHC isoform composition was analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) to uncover changes in morphological and biochemical properties. Our findings demonstrate that following injection of CBTX-A 5 U into rat gastrocnemius muscles, shifts in MyHC isoform composition emerged on the third day after injection and peaked in the fourth week. The composition remained distinctly different from that of the control group after the twelfth week. More specifically, there was a decrease in the proportion of the type IIb isoform and an increase in the proportions of type IIx, type IIa, and type I isoforms. Data revealed that CBTX-A led to a shift in MyHC composition towards slower isoforms and that the MyHC composition remained far from normal six months after a single injection. However, no noticeable remote muscle weakness was induced.

  1. Comparative study between botulinum toxin injection and partial division of puborectalis for treating anismus.

    Science.gov (United States)

    Farid, Mohamed; Youssef, Tamer; Mahdy, Tarek; Omar, Waleed; Moneim, Hesham Abdul; El Nakeeb, Ayman; Youssef, Mohamed

    2009-03-01

    The objective of this study was to compare the results of partial division of puborectalis (PDPR) versus local botulinum toxin type A (BTX-A) injection in treating patients with anismus. This prospective randomized study included 30 male patients suffering from anismus. Diagnosis was made by clinical examination, barium enema, colonoscopy, colonic transit time, anorectal manometry, balloon expulsion test, defecography, and electromyography. Patients were randomized into: group I which included 15 patients who were injected with BTX-A and group II which included 15 patients who underwent bilateral PDPR. Follow-up was conducted for about 1 year. Improvement was considered when patients returned to their normal habits. BTX-A injection achieved initial success in 13 patients (86.7%). However, long-term success persisted only in six patients (40%). This was in contrast to PDPR which achieved initial success in all patients (100%) with a long-term success in ten patients (66.6%). Recurrence was observed in seven patients (53.8%) and five patients (33.4%) following BTX-A injection and PDPR, respectively. Minor degrees of incontinence were confronted in two patients (13.3%) following PDPR. BTX-A injection seems to be successful for temporary treatment of anismus.

  2. Spasmodic dysphonia follow-up with videolaryngoscopy and voice spectrography during treatment with botulinum toxin.

    Science.gov (United States)

    Esposito, Marcello; Dubbioso, R; Apisa, P; Allocca, R; Santoro, L; Cesari, U

    2015-09-01

    Spasmodic dysphonia (SD) is a focal dystonia of laryngeal muscles seriously impairing quality of voice. Adductor SD (ADSD) is the most common presentation of this disorder that can be identified by specialized phoniatricians and neurologists firstly on a clinical evaluation and then confirmed by videolaryngoscopy (VL). Botulinum toxin (BTX) injection with electromyographic guidance in muscles around vocal cords is the most effective treatment. Voice Handicap Index (VHI) questionnaire is the main tool to assess dysphonia and response to treatment. Objective of this study is to perform VL and voice spectrography (VS) to confirm the efficacy of BTX injections over time. 13 patients with ADSD were studied with VHI, VL and VS before and after 4 consecutive treatment with onobotulinumtoxin-A. For each treatment vocal improvement was proved by a significant reduction of VHI score and increase of maximum time phonation and harmonic-to-noise ratio while VL showed the absence of spasm in most of patients. No change of the response to BTX was found between injections. This study supports the efficacy of the treatment of SD with BTX with objective measurements and suggests that the efficacy of recurring treatments is stable over time.

  3. Combinatorial Strategies and High Throughput Screening in Drug Discovery Targeted to Channel of Botulinum

    National Research Council Canada - National Science Library

    Montel, Mauricio

    2004-01-01

    This program examines innovative approaches and powerful new technologies to identify selective and potent agents directed to prevent or relieve the neuroparalytic toxic actions of botulinum toxin A (BoNTA)1...

  4. CLINICAL APPLICATION OF BOTULINUM TOXIN TYPE B IN MOVEMENT DISORDERS AND AUTONOMIC SYMPTOMS

    Institute of Scientific and Technical Information of China (English)

    Xin-hua Wan; Kevin Dat Vuong; Joseph Jankovic

    2005-01-01

    Objective To evaluate efficacy and safety of botulinum toxin type B (BTX-B) in treatment of movement disorders including blepharospasm, oromandibular dystonia, hemifacial spasm, tremor, tics, and hypersecretory disorders such as sialorrhea and hyperhidrosis.Methods A retrospective study of BTX-B injections in treatment of 58 patients with various neurological disorders was performed. The mean follow-up time was 0.9 ± 0.8 years. Results of the first and last treatment of patients with at least 3injection sessions were compared.Results The response of 58 patients to a total of 157 BTX-B treatment sessions was analyzed. Of the 157 treatment sessions, 120 sessions (76.4%) resulted in moderate or marked improvement while 17 sessions (10.8%) had no response.The clinical benefits after BTX-B treatment lasted an average of 14 weeks. Of the 41 patients with at least 3 injection sessions (mean 10 ± 8.6), most patients needed increased dosage upon the last session compared to the first session. Nineteen patients (32.8%) with 27 sessions (17.2%) reported adverse effects with BTX-B treatment.Conclusios Though most patients require increased dosage to maintain effective response after repeated injections,BTX-B is an effective and safe treatment drug for a variety of movement disorders, as well as drooling and hyperhidrosis.

  5. The first non Clostridial botulinum-like toxin cleaves VAMP within the juxtamembrane domain.

    Science.gov (United States)

    Zornetta, Irene; Azarnia Tehran, Domenico; Arrigoni, Giorgio; Anniballi, Fabrizio; Bano, Luca; Leka, Oneda; Zanotti, Giuseppe; Binz, Thomas; Montecucco, Cesare

    2016-07-22

    The genome of Weissella oryzae SG25T was recently sequenced and a botulinum neurotoxin (BoNT) like gene was identified by bioinformatics methods. The typical three-domains organization of BoNTs with a N-terminal metalloprotease domain, a translocation and a cell binding domains could be identified. The BoNT family of neurotoxins is rapidly growing, but this was the first indication of the possible expression of a BoNT toxin outside the Clostridium genus. We performed molecular modeling and dynamics simulations showing that the 50 kDa N-terminal domain folds very similarly to the metalloprotease domain of BoNT/B, whilst the binding part is different. However, neither the recombinant metalloprotease nor the binding domains showed cross-reactivity with the standard antisera that define the seven serotypes of BoNTs. We found that the purified Weissella metalloprotease cleaves VAMP at a single site untouched by the other VAMP-specific BoNTs. This site is a unique Trp-Trp peptide bond located within the juxtamembrane segment of VAMP which is essential for neurotransmitter release. Therefore, the present study identifies the first non-Clostridial BoNT-like metalloprotease that cleaves VAMP at a novel and relevant site and we propose to label it BoNT/Wo.

  6. Detection of Botulinum Toxin Muscle Effect in Humans Using Magnetic Resonance Imaging: A Qualitative Case Series.

    Science.gov (United States)

    O'Dell, Michael W; Villanueva, Mark; Creelman, Carly; Telhan, Gaurav; Nestor, Jaclyn; Hentel, Keith D; Ballon, Douglas; Dyke, Jonathan P

    2017-12-01

    Although important for dosing and dilution, there are few data describing botulinum toxin (BT) movement in human muscle. To better understand BT movement within human muscle. Proof-of-concept study with descriptive case series. Outpatient academic practice. Five subjects with stroke who were BT naive with a mean age of 60.4 ± 14 years and time poststroke of 4.6 ± 3.7 years. Three standardized injections were given to the lateral gastrocnemius muscle (LGM): 2 contained 25 units (U) of onabotulinumtoxinA (Botox) in 0.25 mL of saline solution and the third 0.25 mL of saline solution only. The tibialis anterior muscle (TAM) was not injected in any subject. A leg magnetic resonance image was obtained at baseline, 2 months, and 3 months later with a 3.0 Tesla Siemens scanner. Three muscles, the LGM, lateral soleus muscle (LSM), and TAM, were manually outlined on the T2 mapping sequence at each time point. A histogram of T2 relaxation times (T2-RT) for all voxels at baseline was used to calculate a mean and standard deviation (SD) T2-RT for each muscle. Botulinum toxin muscle effect (BTME) at 2 months and 3 months was defined as a subject- and muscle-specific T2-RT voxel threshold ≥3 SD above the baseline mean at or near BT injection sites. BTME volume for each leg magnetic resonance imaging slice at 3 time points and 3 muscles for all subjects. One subject missed the 3-month scan, leaving 18 potential observations of BTME. Little to no BTME effect was seen in the noninjected TAM. A BTME was detected in the LGM in 13 of 18 possible observations, and no effect was detected in 5 observations. Possible BTME effect was seen in the LSM in 3 subjects due to either diffusion through fascia or needle misplacement. Volume of BTME, as defined here, appeared to be substantially greater than the 0.25-mL injection volume. This descriptive case series is among the first attempts to quantify BTME within human muscle. Our findings are preliminary and are limited by a few

  7. Botulinum Toxin A for Oral Cavity Cancer Patients: In Microsurgical Patients BTX Injections in Major Salivary Glands Temporarily Reduce Salivary Production and the Risk of Local Complications Related to Saliva Stagnation

    Directory of Open Access Journals (Sweden)

    Bartolo Corradino

    2012-10-01

    Full Text Available In patients suffering from oral cavity cancer surgical treatment is complex because it is necessary to remove carcinoma and lymph node metastasis (through a radical unilateral or bilateral neck dissection and to reconstruct the affected area by means of free flaps. The saliva stagnation in the post-operative period is a risk factor with regard to local complications. Minor complications related to saliva stagnation (such as tissue maceration and wound dehiscence could become major complications compromising the surgery or the reconstructive outcome. In fact the formation of oro-cutaneous fistula may cause infection, failure of the free flap, or the patient’s death with carotid blow-out syndrome. Botulinum injections in the major salivary glands, four days before surgery, temporarily reduces salivation during the healing stage and thus could reduce the incidence of saliva-related complications. Forty three patients with oral cancer were treated with botulinum toxin A. The saliva quantitative measurement and the sialoscintigraphy were performed before and after infiltrations of botulinum toxin in the major salivary glands. In all cases there was a considerable, but temporary, reduction of salivary secretion. A lower rate of local complications was observed in the post-operative period. The salivary production returned to normal within two months, with minimal side effects and discomfort for the patients. The temporary inhibition of salivary secretion in the post-operative period could enable a reduction in saliva-related local complications, in the incidence of oro-cutaneous fistulas, and improve the outcome of the surgery as well as the quality of residual life in these patients.

  8. Botulinum toxin A for oral cavity cancer patients: in microsurgical patients BTX injections in major salivary glands temporarily reduce salivary production and the risk of local complications related to saliva stagnation.

    Science.gov (United States)

    Corradino, Bartolo; Di Lorenzo, Sara; Moschella, Francesco

    2012-10-24

    In patients suffering from oral cavity cancer surgical treatment is complex because it is necessary to remove carcinoma and lymph node metastasis (through a radical unilateral or bilateral neck dissection) and to reconstruct the affected area by means of free flaps. The saliva stagnation in the post-operative period is a risk factor with regard to local complications. Minor complications related to saliva stagnation (such as tissue maceration and wound dehiscence) could become major complications compromising the surgery or the reconstructive outcome. In fact the formation of oro-cutaneous fistula may cause infection, failure of the free flap, or the patient’s death with carotid blow-out syndrome. Botulinum injections in the major salivary glands, four days before surgery, temporarily reduces salivation during the healing stage and thus could reduce the incidence of saliva-related complications. Forty three patients with oral cancer were treated with botulinum toxin A. The saliva quantitative measurement and the sialoscintigraphy were performed before and after infiltrations of botulinum toxin in the major salivary glands. In all cases there was a considerable, but temporary, reduction of salivary secretion. A lower rate of local complications was observed in the post-operative period. The salivary production returned to normal within two months, with minimal side effects and discomfort for the patients. The temporary inhibition of salivary secretion in the post-operative period could enable a reduction in saliva-related local complications, in the incidence of oro-cutaneous fistulas, and improve the outcome of the surgery as well as the quality of residual life in these patients.

  9. Factors influencing botulinum toxin dose instability in spasmodic dysphonia patients.

    Science.gov (United States)

    Rosow, David E; Pechman, Amanda; Saint-Victor, Sandra; Lo, Kaming; Lundy, Donna S; Casiano, Roy R

    2015-05-01

    Many patients with spasmodic dysphonia (SD) see consistent effects from botulinum toxin (BTX) injections of the same dose, whereas others require dosage changes over time. We sought to determine whether demographics (age and gender) or environmental factors (smoking) affect the long-term stability of BTX dosing in these patients. Retrospective review. Charts of all patients undergoing BTX injection for adductor SD were reviewed. Dosage change, defined as whether there was any difference in total dosage used between two beneficial injections, was used as a measure of dosing stability. Beneficial injections were indicated by a voice rating score of at least three of four and any non-zero duration of improved voice. Logistic regression analysis was performed to determine whether age, gender, smoking status, or duration of treatment correlated with odds of having a dosage change. A total of 211 patients were ultimately included. Age, gender, and smoking status were all found to have no correlative effect on dosing stability. The only factor that was predictive of dose stability was the number of previous beneficial injections, as every additional injection led to decreased odds of a change in dosage for the next injection (odds ratio=0.964; 95% confidence interval=0.947-0.981). Dosage of BTX injections for long-term treatment of SD has a significant propensity to remain stable over time. Factors such as age, gender, and smoking status do not appear to influence the dosage stability. These findings should allow for better patient counseling regarding expectations for their long-term treatment. Copyright © 2015 The Voice Foundation. Published by Elsevier Inc. All rights reserved.

  10. Three enzymatically active neurotoxins of Clostridium botulinum strain Af84: BoNT/A2, /F4, and /F5.

    Science.gov (United States)

    Kalb, Suzanne R; Baudys, Jakub; Smith, Theresa J; Smith, Leonard A; Barr, John R

    2014-04-01

    Botulinum neurotoxins (BoNTs) are produced by various species of clostridia and are potent neurotoxins which cause the disease botulism, by cleaving proteins needed for successful nerve transmission. There are currently seven confirmed serotypes of BoNTs, labeled A-G, and toxin-producing clostridia typically only produce one serotype of BoNT. There are a few strains (bivalent strains) which are known to produce more than one serotype of BoNT, producing either both BoNT/A and /B, BoNT/A and /F, or BoNT/B and /F, designated as Ab, Ba, Af, or Bf. Recently, it was reported that Clostridium botulinum strain Af84 has three neurotoxin gene clusters: bont/A2, bont/F4, and bont/F5. This was the first report of a clostridial organism containing more than two neurotoxin gene clusters. Using a mass spectrometry based proteomics approach, we report here that all three neurotoxins, BoNT/A2, /F4, and /F5, are produced by C. botulinum Af84. Label free MS(E) quantification of the three toxins indicated that toxin composition is 88% BoNT/A2, 1% BoNT/F4, and 11% BoNT/F5. The enzymatic activity of all three neurotoxins was assessed by examining the enzymatic activity of the neurotoxins upon peptide substrates, which mimic the toxins' natural targets, and monitoring cleavage of the substrates by mass spectrometry. We determined that all three neurotoxins are enzymatically active. This is the first report of three enzymatically active neurotoxins produced in a single strain of Clostridium botulinum.

  11. Botulinum toxin type B micromechanosensor.

    Science.gov (United States)

    Liu, W; Montana, Vedrana; Chapman, Edwin R; Mohideen, U; Parpura, Vladimir

    2003-11-11

    Botulinum neurotoxin (BoNT) types A, B, E, and F are toxic to humans; early and rapid detection is essential for adequate medical treatment. Presently available tests for detection of BoNTs, although sensitive, require hours to days. We report a BoNT-B sensor whose properties allow detection of BoNT-B within minutes. The technique relies on the detection of an agarose bead detachment from the tip of a micromachined cantilever resulting from BoNT-B action on its substratum, the synaptic protein synaptobrevin 2, attached to the beads. The mechanical resonance frequency of the cantilever is monitored for the detection. To suspend the bead off the cantilever we use synaptobrevin's molecular interaction with another synaptic protein, syntaxin 1A, that was deposited onto the cantilever tip. Additionally, this bead detachment technique is general and can be used in any displacement reaction, such as in receptor-ligand pairs, where the introduction of one chemical leads to the displacement of another. The technique is of broad interest and will find uses outside toxicology.

  12. Clostridium botulinum neurotoxin type B is heat-stable in milk and not inactivated by pasteurization.

    Science.gov (United States)

    Rasooly, Reuven; Do, Paula M

    2010-12-08

    Foodborne botulism is caused by the ingestion of foods containing botulinum neurotoxins (BoNTs). To study the heat stability of Clostridium botulinum neurotoxins, we needed to measure and compare the activity of botulinum neurotoxins, serotypes A and B, under various pasteurization conditions. Currently, the only accepted assay to detect active C. botulinum neurotoxin is an in vivo mouse bioassay, which raises ethical concerns with regard to the use of experimental animals. In this study, noninvasive methods were used to simultaneously detect and distinguish between active BoNT serotypes A and B in one reaction and sample. We developed an enzymatic activity assay employing internally quenched fluorogenic peptides corresponding to SNAP-25, for BoNT-A, and VAMP2, for BoNT-B, as an alternative method to the mouse bioassay. Because each peptide is labeled with different fluorophores, we were able to distinguish between these two toxins. We used this method to analyze the heat stability of BoNT-A and BoNT-B. This study reports that conventional milk pasteurization (63 °C, 30 min) inactivated BoNT serotype A; however, serotype B is heat-stable in milk and not inactivated by pasteurization. Using this activity assay, we also showed that the commonly used food processes such as acidity and pasteurization, which are known to inhibit C. botulinum growth and toxin production, are more effective in inactivating BoNT serotype A than serotype B when conventional pasteurization (63 °C, 30 min) is used.

  13. Monoclonal antibodies and toxins--a perspective on function and isotype.

    Science.gov (United States)

    Chow, Siu-Kei; Casadevall, Arturo

    2012-06-01

    Antibody therapy remains the only effective treatment for toxin-mediated diseases. The development of hybridoma technology has allowed the isolation of monoclonal antibodies (mAbs) with high specificity and defined properties, and numerous mAbs have been purified and characterized for their protective efficacy against different toxins. This review summarizes the mAb studies for 6 toxins--Shiga toxin, pertussis toxin, anthrax toxin, ricin toxin, botulinum toxin, and Staphylococcal enterotoxin B (SEB)--and analyzes the prevalence of mAb functions and their isotypes. Here we show that most toxin-binding mAbs resulted from immunization are non-protective and that mAbs with potential therapeutic use are preferably characterized. Various common practices and caveats of protection studies are discussed, with the goal of providing insights for the design of future research on antibody-toxin interactions.

  14. Botulinum toxin for treatment of cocontractions related to obstetrical brachial plexopathy Toxina botulínica para tratamento das co-contrações relacionadas à plexopatia braquial obstétrica

    Directory of Open Access Journals (Sweden)

    Carlos O. Heise

    2005-09-01

    Full Text Available Botulinum toxin type A was recently introduced for treatment of biceps - triceps muscle cocontraction, which compromises elbow function in children with obstetrical brachial plexopathy. This is our preliminary experience with this new approach. Eight children were treated with 2 - 3 U/kg of botulinum toxin injected in the triceps (4 patients and biceps (4 patients muscle, divided in 2 or 3 sites. All patients submitted to triceps injections showed a long-lasting improvement of active elbow flexion and none required new injections, after a follow-up of 3 to 18 months. Three of the patients submitted to biceps injections showed some improvement of elbow extension, but none developed anti-gravitational strength for elbow extension and the effect lasted only three to five months. One patient showed no response to triceps injections. Our data suggest that botulinum toxin can be useful in some children that have persistent disability secondary to obstetrical brachial plexopathy.A toxina botulínica do tipo A foi introduzida recentemente para o tratamento das co-contrações entre os músculos biceps e triceps, que comprometem a função do cotovelo nas crianças com plexopatia braquial obstétrica. Apresentamos nossa experiência preliminar com esta abordagem. Oito crianças foram tratadas com 2 - 3 U/kg de toxina botulínica injetada nos músculos triceps (4 pacientes e biceps (4 pacientes, divididas em 2 ou 3 sítios. Todos os pacientes submetidos a injeções no triceps apresentaram melhora persistente da flexão do cotovelo e nenhum precisou de novas aplicações após seguimento de 3 a 18 meses. Três pacientes submetidos a aplicações no biceps apresentaram melhora na extensão do cotovelo, mas nenhum adquiriu força antigravitacional e o efeito durou apenas 3 a 5 meses. Um paciente não respondeu às injeções. Nossos dados sugerem que a toxina botulínica pode ser útil no tratamento de algumas crianças com seqüelas de plexopatia braquial

  15. Food irradiation and bacterial toxins

    International Nuclear Information System (INIS)

    Tranter, H.S.; Modi, N.K.; Hambleton, P.; Melling, J.; Rose, S.; Stringer, M.F.

    1987-01-01

    The authors' findings indicate that irradiation confers no advantage over heat processing in respect of bacterial toxins (clostridium botulinum, neurotoxin A and staphylococcal enterotoxin A). It follows that irradiation at doses less than the ACINF recommended upper limit of 10 kGy could not be used to improve the ambient temperature shelf life on non-acid foods. (author)

  16. Molecular diversity of neurotoxins from Clostridium botulinum type D strains.

    OpenAIRE

    Moriishi, K; Syuto, B; Kubo, S; Oguma, K

    1989-01-01

    The molecular properties of Clostridium botulinum type D South African (D-SA) were compared with those of neurotoxins from type D strain 1873 (D-1873) and type C strains Stockholm and 6813. D-SA toxin, purified 610-fold from the culture supernatant in an overall yield of 30%, consisted of an intact peptide chain with a molecular weight of 140,000. Limited proteolysis of the toxin by trypsin formed a dichain structure consisting of a light chain (Mr, 50,000) and a heavy chain (Mr, 90,000) link...

  17. Crystallization and preliminary X-ray analysis of a novel haemagglutinin component of the toxin complex of serotype C Clostridium botulinum.

    Science.gov (United States)

    Hayashi, Shintaro; Akiyama, Tomonori; Sagane, Yoshimasa; Miyashita, Shin-Ichiro; Watanabe, Toshihiro; Yajima, Shunsuke; Niwa, Koichi

    2014-03-01

    The botulinum toxin complex, the causative agent of botulism, passes through the intestinal wall via sugar-chain-dependent cell binding of a haemagglutinin of 33 kDa molecular weight (HA-33). The amino-acid sequence of the C-terminal half of HA-33 of the serotype C strain Yoichi (C-Yoichi) shares only 46% identity with those of the major serotype C strains. Additionally, C-Yoichi HA-33 exhibits a unique sugar-binding specificity. In the present work, C-Yoichi HA-33 was expressed in Escherichia coli and crystallized. Diffraction data were collected at a resolution of 2.2 Å. The crystals belonged to space group R3. The complete detailed protein structure will yield insight into how the unique HA-33 protein recognizes sugar moieties.

  18. Early Botulinum Toxin Injections in Infants With Musculoskeletal Disorders: A Systematic Review of Safety and Effectiveness.

    Science.gov (United States)

    Bourseul, Jean-Sébastien; Molina, Anais; Lintanf, Mael; Houx, Laetitia; Chaléat-Valayer, Emmanuelle; Pons, Christelle; Brochard, Sylvain

    2018-06-01

    To report current evidence regarding the safety of intramuscular botulinum toxin injection (BTI) in children with orthopedic- and neurologic-related musculoskeletal disorders >2 years of age. PubMed, Cochrane Library, and ScienceDirect, Google Scholar, and Web of Science. Two reviewers independently selected studies based on predetermined inclusion criteria. Data relating to the aim were extracted. Methodologic quality was graded independently by 2 reviewers using the Physiotherapy Evidence Database scale for randomized controlled trials (RCTs) and the Downs and Black evaluation tool for non-RCTs. Level of evidence was determined using the modified Sackett scale. Data of 473 infants were analyzed. Fifty-five infants had cerebral palsy, 112 had obstetric brachial plexus palsy, 257 had clubfoot, and 44 had congenital torticollis. No studies reported any severe adverse event that could be attributed to the BTI. The rate of mild to moderate adverse events reported varied from 5% to 25%. Results regarding efficacy were preliminary, dependent on the pathology, and limited by the small number of studies and their low levels of evidence. BTI is already widely used as an early treatment for this age group. The safety profile of BTI in infants appears similar to that of older children and risks appear more related to the severity of the pathology and the location of the injections than to the toxin itself. Regarding effectiveness, other studies with higher levels of evidence should be carried out for each specific pathology. Copyright © 2017 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.

  19. The Effect of Total Cumulative Dose, Number of Treatment Cycles, Interval between Injections, and Length of Treatment on the Frequency of Occurrence of Antibodies to Botulinum Toxin Type A in the Treatment of Muscle Spasticity

    Science.gov (United States)

    Bakheit, Abdel Magid O.; Liptrot, Anthea; Newton, Rachel; Pickett, Andrew M.

    2012-01-01

    A large cumulative dose of botulinum toxin type A (BoNT-A), frequent injections, a short interval between treatment cycles, and a long duration of treatment have all been suggested, but not confirmed, to be associated with a high incidence of neutralizing antibodies to the neurotoxin. The aim of this study was to investigate whether these…

  20. The therapeutic usage of botulinum toxin (Botox in non-cosmetic head and neck conditions – An evidence based review

    Directory of Open Access Journals (Sweden)

    Kamran Habib Awan

    2017-01-01

    Full Text Available Botulinum toxin (Botox is an exotoxin produced from Clostridium botulinum. It blocks the release of acetylcholine from the cholinergic nerve end plates resulting in inactivity of the muscles or glands innervated. The efficacy of Botox in facial aesthetics is well established; however, recent literature has highlighted its utilization in multiple non-cosmetic medical and surgical conditions. The present article reviews the current evidence pertaining to Botox use in the non-cosmetic head and neck conditions. A literature search was conducted using MEDLINE, EMBASE, ISI Web of Science and the Cochrane databases limited to English Language articles published from January 1980 to December 2014. The findings showed that there is level 1 evidence supporting the efficacy of Botox in the treatment of laryngeal dystonia, headache, cervical dystonia, masticatory myalgia, sialorrhoea, temporomandibular joint disorders, bruxism, blepharospasm, hemifacial spasm and rhinitis. For chronic neck pain there is level 1 evidence to show that Botox is ineffective. Level 2 evidence exists for vocal tics and trigeminal. For stuttering, facial nerve paresis, Frey’s syndrome and oromandibular dystonia the evidence is level 4. Thus, there is compelling evidence in the published literature to demonstrate the beneficial role of Botox in a wide range of non-cosmetic conditions pertaining to the head and neck (mainly level 1 evidence. With more and more research, the range of clinical applications and number of individuals getting Botox will doubtlessly increase. Botox appears to justify its title as ‘the poison that heals’.

  1. Botulinum therapy for poststroke spasticity of the lower extremity (clinical cases

    Directory of Open Access Journals (Sweden)

    L. V. Krylova

    2014-01-01

    Full Text Available The paper deals with the topical problem – the medical rehabilitation of patients with poststroke spasticity. It describes clinical cases of patients with poststroke spasticity of the upper and lower extremities who have received combined therapy using botulinum toxin type A (Botox injections.

  2. Inhibiting oral intoxication of botulinum neurotoxin A by carbohydrate receptor mimics

    Science.gov (United States)

    Botulinum neurotoxins (BoNTs) cause the disease botulism manifested by flaccid paralysis that could be fatal to humans and animals. Oral ingestion of the toxin with contaminated food is one of the most common routes of BoNT intoxication, where BoNT assembles with several auxiliary proteins to surviv...

  3. Probiotic microorganisms inhibit epithelial cell internalization of botulinum neurotoxin serotype A

    Science.gov (United States)

    Botulinum neurotoxins (BoNTs) are some of the most poisonous natural toxins known to man and are threats to public health and safety. Previous work from our laboratory showed that BoNT serotype A (BoNT/A) complex (holotoxin with neurotoxin-associated proteins) bind and transit through the intestinal...

  4. Prevalence of C. botulinum and C. perfringens spores in food products available on Polish market

    Directory of Open Access Journals (Sweden)

    Grenda Tomasz

    2017-09-01

    Full Text Available Introduction: The aim of this study was to evaluate the prevalence of Clostridium botulinum and Clostridium perfringens in food samples purchased from Polish producers. Material and Methods: The analyses were performed on 260 food samples collected in Lublin and Subcarpathian regions: 56 of smoked meat, 21 of pork meat, 20 of dairy products, 26 of vegetable and fruit preserves, 40 of ready-to-eat meals, 27 of fish preserves, and 70 of honey collected directly from apiaries. Results: C. botulinum strains were isolated from 2.3% (6/260 of samples and the isolates were classified as toxin types A (4/260 and B (2/260. C. perfringens strains were isolated from 14% (37/260 of samples. All the isolates were classified as toxin type A, 28 of them were able also to produce α toxin and 9 - β2 toxin. Conclusion: On the basis of the obtained results it could be suggested that risk assessment, especially regarding the entire honey harvesting process, should be provided in order to ensure the microbiological safety of the products to be consumed by infants and people with a weakened immune system.

  5. Egg yolk antibodies for detection and neutralization of Clostridium botulinum type A neurotoxin.

    Science.gov (United States)

    Trott, D L; Yang, M; Gonzalez, J; Larson, A E; Tepp, W H; Johnson, E A; Cook, M E

    2009-05-01

    The objective of this research project was to determine the usefulness of an egg antibody platform for producing materials for the detection and neutralization of botulinum type A neurotoxin. Yield estimates for detection and neutralizing antibodies produced using methods described were calculated. Antibody specific to botulinum toxoid A (aToxoid) and toxin A (aBoNT/A) was produced by immunizing hens with botulinum toxoid A (toxoid) followed by increasing amounts of botulinum neurotoxin A (BoNT/A) in Freund incomplete adjuvant. Egg yolks were extracted with polyethylene glycol (PEG) for antibody detection and neutralization experiments. A model aToxoid/toxoid immunoassay using only egg yolk antibody was developed and had a detection limit of 1 pg/ml of toxoid. In an indirect enzyme-linked immunosorbent assay of BoNT/A-specific antibody, the aBoNT/A contained more BoNT/A-specific antibody than did the aToxoid, and aBoNT/A was as effective as commercial rabbit antibody. The aToxoid provided no protection against BoNT/A in a standard mouse neutralization assay; however, 1 mg of PEG-extracted aBoNT/A neutralized 4,000 lethal doses of BoNT/A injected intraperitoneally. Based on these results, we calculated that in 1 month one hen could produce more than 100 liters of antibody detection reagents or enough antibody to neutralize approximately 11.6 million mouse lethal doses of botulinum toxin. Utilization of an egg antibody platform is potentially rapid (28 to 70 days) and scalable to kilogram quantities using current egg production facilities with as few as 1,000 hens.

  6. Rotavirus 2/6 Viruslike Particles Administered Intranasally with Cholera Toxin, Escherichia coli Heat-Labile Toxin (LT), and LT-R192G Induce Protection from Rotavirus Challenge

    OpenAIRE

    O’Neal, Christine M.; Clements, John D.; Estes, Mary K.; Conner, Margaret E.

    1998-01-01

    We have shown that rotavirus 2/6 viruslike particles composed of proteins VP2 and VP6 (2/6-VLPs) administered to mice intranasally with cholera toxin (CT) induced protection from rotavirus challenge, as measured by virus shedding. Since it is unclear if CT will be approved for human use, we evaluated the adjuvanticity of Escherichia coli heat-labile toxin (LT) and LT-R192G. Mice were inoculated intranasally with 10 μg of 2/6-VLPs combined with CT, LT, or LT-R192G. All three adjuvants induced ...

  7. Botulinum toxin A versus B in sialorrhea: a prospective, randomized, double-blind, crossover pilot study in patients with amyotrophic lateral sclerosis or Parkinson's disease.

    Science.gov (United States)

    Guidubaldi, Arianna; Fasano, Alfonso; Ialongo, Tamara; Piano, Carla; Pompili, Maurizio; Mascianà, Roberta; Siciliani, Luisa; Sabatelli, Mario; Bentivoglio, Anna Rita

    2011-02-01

    Either botulinum toxins (BoNTs) A and B have been used for improving drooling in different neurological conditions. Consecutive patients affected by Amyotrophic Lateral Sclerosis (ALS) or Parkinson's Disease (PD) accompanied by severe drooling were randomized to receive botulinum neurotoxin type A (BoNT-A) or B (BoNT-B) injections into the salivary glands. Following the first treatment, when sialorrhea returned to baseline (at least three months after the first injection), subjects were re-treated with the other serotype. Ultrasound-guided injections into parotid and submandibular glands were bilaterally performed: total doses were 250 U BoNT-A (Dysport) and 2500 U BoNT-B (Neurobloc). Objective (cotton roll weight) and subjective (ad hoc clinical scales) evaluations were performed at baseline, after 1 and 4 weeks, and every 4 weeks until drooling returned to baseline. Twenty-seven patients (15 ALS and 12 PD) were enrolled, fourteen completed the study. BoNT-A and BoNT-B treatments gave both subjective and objective improvements in all patients. The latency was significantly shorter after BoNT-B treatments (3.2 ± 3.7 days) compared to BoNT-A (6.6 ± 4.1 days; P = 0.002). The mean benefit duration was similar at 75 and 90 days for BoNT-A and BoNT-B, respectively (P = NS). The only toxin-related side effect was a change to saliva thickness. Either 250 U Dysport or 2500 U Neurobloc have similar effectiveness and safety in controlling sialorrhea. BoNT-B has a shorter latency and comparable duration. Cost analysis, considering the doses used in this study protocol favored BoNT-B treatment. Copyright © 2010 Movement Disorder Society.

  8. Structural Studies on Intact Clostridium Botulinum Neurotoxins Complexed with Inhibitors Leading to Drug Design

    National Research Council Canada - National Science Library

    Swaminathan, Subramanyam

    2005-01-01

    .... While one is common to botulinum toxins, the other is unique for tetanus. The second unique site also binds a tri-peptide which suggests that this peptide could be used as an inhibitor for tetanus, at least...

  9. Expression of Ras-related C3 botulinum toxin substrate 1 (RAC1) in human cholesteatoma.

    Science.gov (United States)

    Lee, No Hee; Chang, Ji-Won; Choi, June; Jung, Hak Hyun; Im, Gi Jung

    2013-02-01

    Ras-related C3 botulinum toxin substrate 1 (RAC1) is a 21-kDa signaling G protein that functions as a pleiotropic regulator of many cellular processes including epithelial differentiation. RAC1 activates the nicotinamide adenine dinucleotide phosphate oxidase complex which promotes formation of reactive oxygen species and degradation enzymes. RAC1 has been associated with rapid epithelial differentiation and invasive properties in human cholesteatoma. This study aimed to identify the presence of RAC1 in human cholesteatoma and analyze its functional role as a regulator of proteolysis and overgrowth. Tissue samples from human cholesteatoma and normal postaural skin were obtained from patients during otologic surgery for cholesteatoma. The expression of RAC1 mRNA was quantified by real-time RT-PCR, and localization of RAC1 expression was confirmed using immunohistochemical staining. Expression of RAC1 mRNA in the epithelium of cholesteatoma was significantly elevated 2.94 fold on average, compared with normal control skin. RAC1 expression in the suprabasal and basal layer of cholesteatoma epithelium was stronger than normal control skin. Our results suggest that RAC1 can be associated with rapid epithelial differentiation and invasive properties of human cholesteatoma.

  10. Tridimensional assessment of adductor spasmodic dysphonia pre- and post-treatment with Botulinum toxin.

    Science.gov (United States)

    Dejonckere, P H; Neumann, K J; Moerman, M B J; Martens, J P; Giordano, A; Manfredi, C

    2012-04-01

    Spasmodic dysphonia voices form, in the same way as substitution voices, a particular category of dysphonia that seems not suited for a standardized basic multidimensional assessment protocol, like the one proposed by the European Laryngological Society. Thirty-three exhaustive analyses were performed on voices of 19 patients diagnosed with adductor spasmodic dysphonia (SD), before and after treatment with Botulinum toxin. The speech material consisted of 40 short sentences phonetically selected for constant voicing. Seven perceptual parameters (traditional and dedicated) were blindly rated by a panel of experienced clinicians. Nine acoustic measures (mainly based on voicing evidence and periodicity) were achieved by a special analysis program suited for strongly irregular signals and validated with synthesized deviant voices. Patients also filled in a VHI-questionnaire. Significant improvement is shown by all three approaches. The traditional GRB perceptual parameters appear to be adequate for these patients. Conversely, the special acoustic analysis program is successful in objectivating the improved regularity of vocal fold vibration: the basic jitter remains the most valuable parameter, when reliably quantified. The VHI is well suited for the voice-related quality of life. Nevertheless, when considering pre-therapy and post-therapy changes, the current study illustrates a complete lack of correlation between the perceptual, acoustic, and self-assessment dimensions. Assessment of SD-voices needs to be tridimensional.

  11. Unilateral versus bilateral thyroarytenoid Botulinum toxin injections in adductor spasmodic dysphonia: a prospective study

    Science.gov (United States)

    Upile, Tahwinder; Elmiyeh, Behrad; Jerjes, Waseem; Prasad, Vyas; Kafas, Panagiotis; Abiola, Jesuloba; Youl, Bryan; Epstein, Ruth; Hopper, Colin; Sudhoff, Holger; Rubin, John

    2009-01-01

    Objectives In this preliminary prospective study, we compared unilateral and bilateral thyroarytenoid muscle injections of Botulinum toxin (Dysport) in 31 patients with adductor spasmodic dysphonia, who had undergone more than 5 consecutive Dysport injections (either unilateral or bilateral) and had completed 5 concomitant self-rated efficacy and complication scores questionnaires related to the previous injections. We also developed a Neurophysiological Scoring (NPS) system which has utility in the treatment administration. Method and materials Data were gathered prospectively on voice improvement (self-rated 6 point scale), length of response and duration of complications (breathiness, cough, dysphagia and total voice loss). Injections were performed under electromyography (EMG) guidance. NPS scale was used to describe the EMG response. Dose and unilateral/bilateral injections were determined by clinical judgment based on previous response. Time intervals between injections were patient driven. Results Low dose unilateral Dysport injection was associated with no significant difference in the patient's outcome in terms of duration of action, voice score (VS) and complication rate when compared to bilateral injections. Unilateral injections were not associated with any post treatment total voice loss unlike the bilateral injections. Conclusion Unilateral low dose Dysport injections are recommended in the treatment of adductor spasmodic dysphonia. PMID:19852852

  12. Unilateral versus bilateral thyroarytenoid Botulinum toxin injections in adductor spasmodic dysphonia: a prospective study

    Directory of Open Access Journals (Sweden)

    Abiola Jesuloba

    2009-10-01

    Full Text Available Abstract Objectives In this preliminary prospective study, we compared unilateral and bilateral thyroarytenoid muscle injections of Botulinum toxin (Dysport in 31 patients with adductor spasmodic dysphonia, who had undergone more than 5 consecutive Dysport injections (either unilateral or bilateral and had completed 5 concomitant self-rated efficacy and complication scores questionnaires related to the previous injections. We also developed a Neurophysiological Scoring (NPS system which has utility in the treatment administration. Method and materials Data were gathered prospectively on voice improvement (self-rated 6 point scale, length of response and duration of complications (breathiness, cough, dysphagia and total voice loss. Injections were performed under electromyography (EMG guidance. NPS scale was used to describe the EMG response. Dose and unilateral/bilateral injections were determined by clinical judgment based on previous response. Time intervals between injections were patient driven. Results Low dose unilateral Dysport injection was associated with no significant difference in the patient's outcome in terms of duration of action, voice score (VS and complication rate when compared to bilateral injections. Unilateral injections were not associated with any post treatment total voice loss unlike the bilateral injections. Conclusion Unilateral low dose Dysport injections are recommended in the treatment of adductor spasmodic dysphonia.

  13. Short-term muscle atrophy caused by botulinum toxin-A local injection impairs fracture healing in the rat femur.

    Science.gov (United States)

    Hao, Yongqiang; Ma, Yongcheng; Wang, Xuepeng; Jin, Fangchun; Ge, Shengfang

    2012-04-01

    Damaged bone is sensitive to mechanical stimulation throughout the remodeling phase of bone healing. Muscle damage and muscular atrophy associated with open fractures and subsequent fixation are not beneficial to maintaining optimum conditions for mechanical stability. The aim of this study was to investigate whether local muscle atrophy and dysfunction affect fracture healing in a rat femur fracture model. We combined the rat model of a short period atrophy of the quadriceps with femur fracture. Forty-four-month-old male Wistar rats were adopted for this study. Two units of botulinum toxin-A (BXTA) were administered locally into the right side of the quadriceps of each rat, while the same dose of saline was injected into the contralateral quadriceps. After BXTA had been fully absorbed by the quadriceps, osteotomy was performed in both femurs with intramedullary fixation. Gross observation and weighing of muscle tissue, X-ray analysis, callus histology, and bone biomechanical testing were performed at different time points up to 8 weeks post-surgery. Local injection of BXTA led to a significant decrease in the volume and weight of the quadriceps compared to the control side. At the eighth week, the left side femurs of the saline-injected quadriceps almost reached bony union, and fibrous calluses were completely calcified into woven bone. However, a gap was still visible in the BXTA-treated side on X-ray images. As showed by bone histology, there were no mature osseous calluses or woven bone on the BXTA-treated side, but a resorption pattern was evident. Biomechanical testing indicated that the femurs of the BXTA-treated side exhibited inferior mechanical properties compared with the control side. The inferior outcome following BXTA injection, compared with saline injection, in terms of callus resistance may be the consequence of unexpected load and mechanical unsteadiness caused by muscle atrophy and dysfunction. Copyright © 2011 Orthopaedic Research Society.

  14. Recovery of rat muscle size but not function more than 1 year after a single botulinum toxin injection.

    Science.gov (United States)

    Ward, Samuel R; Minamoto, Viviane B; Suzuki, Kentaro P; Hulst, Jonah B; Bremner, Shannon N; Lieber, Richard L

    2018-03-01

    Neurotoxin injection is used to treat a wide variety of neuromuscular disorders. The purpose of this study was to measure the functional and structural properties of botulinum toxin-injected adult rat skeletal muscle over nearly the entire lifespan. Ten groups of animals were subjected to either neurotoxin injection [Botox, Type A (BT-A); Allergan, Irvine, California] or saline solution injection. Neurotoxin-injected animals (n = 90) were analyzed at different time-points: 1 week; 1 month; 3 months; 6 months; 12 months; or 18 months. In spite of the recovery of structural features, such as muscle mass and fiber area, dorsiflexion torque production remained significantly depressed by 25%, even at 12 months after neurotoxin injection. The data demonstrate that, after a single BT-A injection, although gross muscle morphology recovered over a 12-month time period, loss of contractile function did not recover. Muscle Nerve 57: 435-441, 2018. © 2017 Wiley Periodicals, Inc.

  15. TREATMENT OF THE SPASTICITY IN CHILDREN WITH CEREBRAL PALSY

    Science.gov (United States)

    Meholjić-Fetahović, Ajša

    2007-01-01

    Botulinum toxin is a natural purified protein and one of the strongest biological poisons - neurotoxin. It is produced by the bacterium Clostridium botulinum. Its medical usage started in USA in 1981 and in Europe in 1992. There are seven different immune types of the toxin: A, B, C1, D, E, F and G. Toxin types A and B are used to decrease muscular spasticity. Botulinum toxin prevents the formation of acetylcholine from cholinergic nerve tissues in muscles, which in the end irreversibly destroys neuromuscular synapses. It is called temporary local chemodenervation. It does not affect the synthesis of acetylcholine. As it affects neuromuscular bond it also affects one of the symptoms of cerebral palsy - spasticity Decreasing the spasticity of children with cerebral palsy leads to the improvement of conscious movements, muscles are less toned, passive mobility is improved, orthosis tolerance is also improved, and the child is enabled to perform easier and better motor functions such as crawling, standing and walking. Since the action of Botulinum toxin is limited to 2-6 months, new neural collaterals are formed and neuromuscular conductivity is reestablished which in the end once again develops a muscular spasm. This leads to a conclusion that botulinum toxin should again be applied into spastic muscles. It is very important for good effect of Botulinum toxin to set the goals of the therapy in advance. The goals include improvement of a function, prevention of contractions and deformities, ease of care and decrease of pain for children with cerebral palsy. After application of botulinum toxin, it is necessary to perform adequate and intensive physical treatment with regular monitoring of effects. This work shows a case of a boy with spastic form of cerebral palsy. After being habilitated using Vojta therapy and Bobath concept and the conduct of certain physical procedures, botulinum toxin is administered into his lower limbs’ muscles and kinezitherapy intensified

  16. Treatment of the Spasticity in Children with Cerebral Palsy

    Directory of Open Access Journals (Sweden)

    Ajša Meholjić-Fetahović

    2008-11-01

    Full Text Available Botulinum toxin is a natural purified protein and one of the strongest biological poisons - neurotoxin. It is produced by the bacterium Clostridium botulinum. Its medical usage started in USA in 1981 and in Europe in 1992. There are seven different immune types of the toxin: A, B, C1, D, E, F and G. Toxin types A and B are used to decrease muscular spasticity. Botulinum toxin prevents the formation of acetylcholine from cholinergic nerve tissues in muscles, which in the end irreversibly destroys neuromuscular synapses. It is called temporary local chemodenervation. It does not affect the synthesis of acetylcholine.As it affects neuromuscular bond it also affects one of the symptoms of cerebral palsy - spasticity Decreasing the spasticity of children with cerebral palsy leads to the improvement of conscious movements, muscles are less toned, passive mobility is improved, orthosis tolerance is also improved, and the child is enabled to perform easier and better motor functions such as crawling, standing and walking. Since the action of Botulinum toxin is limited to 2-6 months, new neural collaterals are formed and neuromuscular conductivity is reestablished which in the end once again develops a muscular spasm. This leads to a conclusion that botulinum toxin should again be applied into spastic muscles.It is very important for good effect of Botulinum toxin to set the goals of the therapy in advance. The goals include improvement of a function, prevention of contractions and deformities, ease of care and decrease of pain for children with cerebral palsy. After application of botulinum toxin, it is necessary to perform adequate and intensive physical treatment with regular monitoring of effects.This work shows a case of a boy with spastic form of cerebral palsy. After being habilitated using Vojta therapy and Bobath concept and the conduct of certain physical procedures, botulinum toxin is administered into his lower limbs’ muscles and

  17. Development of an inventory of goals using the International Classification of Functioning, Disability and Health in a population of non-ambulatory children and adolescents with cerebral palsy treated with botulinum toxin A

    OpenAIRE

    Nguyen, Linda; Mesterman, Ronit; Gorter, Jan Willem

    2018-01-01

    Background In the management of hypertonicity in children with cerebral palsy (CP), goals should be clearly identified in order to evaluate the effectiveness of botulinum toxin A (BoNT-A) treatment, specifically in non-ambulatory children and adolescents, Gross Motor Function Classification System (GMFCS), level IV or V. A retrospective chart review (Mesterman et al., 2013) identified the need for the development of a set of specific and meaningful goals linked to the International Classifica...

  18. Comparison between neurectomy and botulinum toxin A injection for denervated skeletal muscle.

    Science.gov (United States)

    Tsai, Feng-Chou; Hsieh, Ming-Shium; Chou, Chih-Ming

    2010-08-01

    Neurectomy and botulinum toxin A (BoNT-A) injection cause denervated muscle atrophy, but questions remain about their clinical utility. We investigated time-series alterations of rat muscle weight, functional deficits, signaling pathways, and microscopic structures, to gain an understanding of the clinical implications. Between 2008 and 2009, the maximal calf circumference of patients for calf reduction either by neurectomy or BoNT-A injections were recorded for study. A rat skeletal muscle model was established through repeated or dose-adjusted BoNT-A injections and neurectomy. The survival, apoptosis pathways, functional deficits, and microscopic structures were investigated using Western blot, sciatic functional index (SFI), and transmission electron microscopy (TEM), respectively. The rat muscle weight ratio of the BoNT-A group had recovered to 89.3 +/- 3.8% by week 58, but it never recovered in the neurectomy group. Muscle weight reduction by BoNT-A not only depended on the dose, but additive effects were also obtained through repeated injections. Rat SFI demonstrated rapid recovery in both groups. Molecular expressions showed a coherent and biphasic pattern. p-Akt and apoptosis-inducing factor (AIF) were upregulated significantly, with a peak at 8 weeks in the neurectomy group (p structure disruption and sarcomere discontinuity in the neurectomy and BoNT-A groups, respectively. We demonstrated that denervation induced lasting muscle weight and structural changes of different degrees. Muscle weight reduction by BoNT-A was related to frequency and dose. AIF-mediated caspase-independent apoptosis was significantly different for neurectomy and BoNT-A injection.

  19. Best Clinical Practice in Botulinum Toxin Treatment for Children with Cerebral Palsy

    Directory of Open Access Journals (Sweden)

    Walter Strobl

    2015-05-01

    Full Text Available Botulinum toxin A (BoNT-A is considered a safe and effective therapy for children with cerebral palsy (CP, especially in the hands of experienced injectors and for the majority of children. Recently, some risks have been noted for children with Gross Motor Classification Scale (GMFCS of IV and the risks are substantial for level V. Recommendations for treatment with BoNT-A have been published since 1993, with continuous optimisation and development of new treatment concepts. This leads to modifications in the clinical decision making process, indications, injection techniques, assessments, and evaluations. This article summarises the state of the art of BoNT-A treatment in children with CP, based mainly on the literature and expert opinions by an international paediatric orthopaedic user group. BoNT-A is an important part of multimodal management, to support motor development and improve function when the targeted management of spasticity in specific muscle groups is clinically indicated. Individualised assessment and treatment are essential, and should be part of an integrated approach chosen to support the achievement of motor milestones. To this end, goals should be set for both the long term and for each injection cycle. The correct choice of target muscles is also important; not all spastic muscles need to be injected. A more focused approach needs to be established to improve function and motor development, and to prevent adverse compensations and contractures. Furthermore, the timeline of BoNT-A treatment extends from infancy to adulthood, and treatment should take into account the change in indications with age.

  20. Influence of botulinum toxin on rabbit jaw muscle activity and anatomy

    NARCIS (Netherlands)

    Korfage, J.A.M.; Wang, J.; Lie, S.H.J.T.J.; Langenbach, G.E.J.

    2012-01-01

    Introduction: Muscles can adapt their fiber properties to accommodate to new conditions. We investigated the extent to which a decrease in muscle activation can cause an adaptation of fiber properties in synergistic and antagonistic jaw muscles. Methods: Three months after the injection of botulinum