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Song T, Marmur ES. RimabotulinumtoxinB: An Update. Dermatol Surg 2024; 50:S52-S57. [PMID: 39196834 DOI: 10.1097/dss.0000000000004253] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 08/30/2024]
Abstract
BACKGROUND Botulinum type-A toxin is a well established aesthetic and medical treatment. While the usage of type-B toxin is less common, there is a growing interest in using type-B toxin, especially in those who are treatment resistant. OBJECTIVE To evaluate the primary FDA-approved clinical applications of rimabotulinumtoxinB, along with established and emerging off-label clinical indications. MATERIAL AND METHODS Articles were reviewed from PubMed database and Food and Drug Adminstration guidelines. RESULTS Facial rhytids tend to use a higher conversion ratio between type A and type B toxin, due to type B toxin's weaker affinity to muscles and higher affinity for sweat glands. Specially, a 1:100 to 1:50 ratio was utilized for glabellar rhytids, a 1:25 to 1:50 ratio for periocular rhytids, a 1:50 to 1:66.6 ratio for cervical dystonia, a 1:20 to 1:50 ratio for hyperhidrosis, and a 1:25 to 30 ratio for sialorrhea. CONCLUSION Type B toxin has demonstrated its safety and efficacy in treating facial rhytids, cervical dystonia, sialorrhea and hyperhidrosis, with potential for novel applications under investigation. Regardless of injection location and clinical applications, dry mouth and dysphagia remained the most common side effects. Across all indications, type B toxin appeared to have a faster onset of action, a dose-dependent clinical duration, and a dose-dependent adverse effect profile.
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Affiliation(s)
- Teresa Song
- Marmur Medical, New York, New York
- Department of Dermatology, The Mount Sinai Hospital, New York, New York
| | - Ellen S Marmur
- Marmur Medical, New York, New York
- Department of Dermatology, The Mount Sinai Hospital, New York, New York
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Knockin mouse models demonstrate differential contributions of synaptotagmin-1 and -2 as receptors for botulinum neurotoxins. PLoS Pathog 2021; 17:e1009994. [PMID: 34662366 PMCID: PMC8553082 DOI: 10.1371/journal.ppat.1009994] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/27/2021] [Revised: 10/28/2021] [Accepted: 09/30/2021] [Indexed: 12/11/2022] Open
Abstract
Botulinum neurotoxins (BoNTs) are the most potent toxins known and are also utilized to treat a wide range of disorders including muscle spasm, overactive bladder, and pain. BoNTs' ability to target neurons determines their specificity, potency, and therapeutic efficacy. Homologous synaptic vesicle membrane proteins synaptotagmin-1 (Syt1) and synaptotagmin-2 (Syt2) have been identified as receptors for BoNT family members including BoNT/B, DC, and G, but their contributions at physiologically relevant toxin concentrations in vivo have yet to be validated and established. Here we generated two knockin mutant mouse models containing three designed point-mutations that specifically disrupt BoNT binding in endogenous Syt1 or Syt2, respectively. Utilizing digit abduction score assay by injecting toxins into the leg muscle, we found that Syt1 mutant mice showed similar sensitivity as the wild type mice, whereas Syt2 mutant mice showed reduced sensitivity to BoNT/B, DC, and G, demonstrating that Syt2 is the dominant receptor at skeletal neuromuscular junctions. We further developed an in vivo bladder injection assay for analyzing BoNT action on bladder tissues and demonstrated that Syt1 is the dominant toxin receptor in autonomic nerves controlling bladder tissues. These findings establish the critical role of protein receptors for the potency and specificity of BoNTs in vivo and demonstrate the differential contributions of Syt1 and Syt2 in two sets of clinically relevant target tissues.
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Vova JA, Green MM, Brandenburg JE, Davidson L, Paulson A, Deshpande S, Oleszek JL, Inanoglu D, McLaughlin MJ. A consensus statement on the use of botulinum toxin in pediatric patients. PM R 2021; 14:1116-1142. [PMID: 34558213 DOI: 10.1002/pmrj.12713] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/05/2020] [Revised: 08/12/2021] [Accepted: 09/10/2021] [Indexed: 11/10/2022]
Abstract
Botulinum toxin has been used in medicine for the past 30 years. However, there continues to be controversy about the appropriate uses and dosing, especially in the pediatric population. A panel of nine pediatric physiatrists from different regions and previous training programs in the United States were nominated based on institutional reputation and botulinum toxin (BoNT) experience. Based on a review of the current literature, the goal was to provide the rationale for recommendations on the administration of BoNT in the pediatric population. The goal was not only to review safety, dosing, and injection techniques but also to develop a consensus on the appropriate uses in the pediatric population. In addition to upper and lower limb spasticity, the consensus also provides recommendations for congenital muscular torticollis, cervical dystonia, sialorrhea, and brachial plexus palsies.
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Affiliation(s)
- Joshua A Vova
- Children's Healthcare of Atlanta, Emory University School of Medicine, Atlanta, Georgia, USA
| | - Michael M Green
- University of Utah/Primary Children's Hospital, Salt Lake City, Utah, USA
| | | | - Loren Davidson
- University of California Davis, Sacramento, California, USA
| | - Andrea Paulson
- Cincinnati Children's Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA.,Gillette Children's Specialty Healthcare, Minneapolis, Minnesota, USA
| | - Supreet Deshpande
- Gillette Children's Specialty Healthcare, Minneapolis, Minnesota, USA
| | | | - Didem Inanoglu
- Children's Health Specialty Center, University of Texas Southwestern Medical Center, Dallas, Texas, USA
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Park MY, Ahn KY. Scientific review of the aesthetic uses of botulinum toxin type A. Arch Craniofac Surg 2021; 22:1-10. [PMID: 33714246 PMCID: PMC7968983 DOI: 10.7181/acfs.2021.00003] [Citation(s) in RCA: 27] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/02/2021] [Revised: 02/02/2021] [Accepted: 02/05/2021] [Indexed: 01/02/2023] Open
Abstract
Botulinum toxin type A (BoNT-A), onabotulinumtoxinA (Botox) was approved by the United States Food and Drug Administration for temporary improvement of glabellar lines in patients 65 years and younger in 2002, and has also been used widely for aesthetic purposes such as hyperhidrosis, body shape contouring, and other noninvasive facial procedures. BoNT-A inhibits presynaptic exocytosis of acetylcholine (ACh)-containing vesicles into the neuromuscular junction at cholinergic nerve endings of the peripheral nervous system, thereby paralyzing skeletal muscles. ACh is the most broadly used neurotransmitter in the somatic nervous system, preganglionic and postganglionic fibers of parasympathetic nerves, and preganglionic fibers or postganglionic sudomotor nerves of sympathetic nerves. The scientific basis for using BoNT-A in various cosmetic procedures is that its function goes beyond the dual role of muscle paralysis and neuromodulation by inhibiting the secretion of ACh. Although the major target organs for aesthetic procedures are facial expression muscles, skeletal body muscles, salivary glands, and sweat glands, which are innervated by the somatic or autonomic nerves of the peripheral cholinergic nerve system, few studies have attempted to directly explain the anatomy of the areas targeted for injection by addressing the neural physiology and rationale for specific aesthetic applications of BoNT-A therapy. In this article, we classify the various cosmetic uses of BoNT-A according to the relevant component of the peripheral nervous system, and describe scientific theories regarding the anatomy and physiology of the cholinergic nervous system. We also review critical physiological factors and conditions influencing the efficacy of BoNT-A for the rational aesthetic use of BoNT-A. We hope that this comprehensive review helps promote management policies to support long-term, safe, successful practice. Furthermore, based on this, we look forward to developing and expanding new advanced indications for the aesthetic use of BoNT-A in the future.
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Affiliation(s)
- Mee Young Park
- Department of Neurology, Yeungnam University Medical Center, Daegu, Korea
| | - Ki Young Ahn
- Dr. Ahn’s Aesthetic and Plastic Surgical Clinic and Botulinum Center, Daegu, Korea
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Hefter H, Samadzadeh S, Moll M. Transient Improvement after Switch to Low Doses of RimabotulinumtoxinB in Patients Resistant to AbobotulinumtoxinA. Toxins (Basel) 2020; 12:toxins12110677. [PMID: 33121133 PMCID: PMC7693617 DOI: 10.3390/toxins12110677] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/01/2020] [Revised: 10/24/2020] [Accepted: 10/25/2020] [Indexed: 11/16/2022] Open
Abstract
Botulinum toxin type B (BoNT/B) has been recommended as an alternative for patients who have become resistant to botulinum toxin type A (BoNT/A). This study aimed to compare the clinical effect, within a patient, of four injections with low doses of rimabotulinumtoxinB with the effect of the preceding abobotulinumtoxinA (aboBoNT/A) injections. In 17 patients with cervical dystonia (CD) who had become resistant to aboBoNT/A, the clinical effect of the first four rimabotulinumtoxinB (rimaBoNT/B) injections was compared to the effect of the first four aboBoNT/A injections using a global assessment scale and the TSUI score. After the first two BoNT/B injections, all 17 patients responded well and to a similar extent as to the first two BoNT/A injections, but with more side effects such as dry mouth and constipation. After the next BoNT/B injection, the improvement started to decline. The response to the fourth BoNT/B injection was significant (p < 0.048) lower than the fourth BoNT/A injection. Only three patients developed a complete secondary treatment failure (CSTF) and five patients a partial secondary treatment failure (PSTF) after four BoNT/B injections. In nine patients, the usual response persisted. With the use of low rimaBoNT/B doses, the induction of CSTF and PSTF to BoNT/B could not be avoided but was delayed in comparison to the use of higher doses. In contrast to aboBoNT/A injections, PSTF and CSTF occurred much earlier, although low doses of rimaBoNT/B had been applied.
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Affiliation(s)
- Harald Hefter
- Correspondence: ; Tel.: +49-211-811-7025; Fax: +49-211-810-4903
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Brodoehl S, Wagner F, Prell T, Klingner C, Witte OW, Günther A. Cause or effect: Altered brain and network activity in cervical dystonia is partially normalized by botulinum toxin treatment. NEUROIMAGE-CLINICAL 2019; 22:101792. [PMID: 30928809 PMCID: PMC6444302 DOI: 10.1016/j.nicl.2019.101792] [Citation(s) in RCA: 25] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 12/12/2018] [Revised: 03/14/2019] [Accepted: 03/24/2019] [Indexed: 01/17/2023]
Abstract
Background Idiopathic cervical dystonia (CD) is a chronic movement disorder characterized by impressive clinical symptoms and the lack of clear pathological findings in clinical diagnostics and imaging. At present, the injection of botulinum toxin (BNT) in dystonic muscles is an effective therapy to control motor symptoms and pain in CD. Objectives We hypothesized that, although it is locally injected to dystonic muscles, BNT application leads to changes in brain and network activity towards normal brain function. Methods Using 3 T functional MR imaging along with advanced analysis techniques (functional connectivity, Granger causality, and regional homogeneity), we aimed to characterize brain activity in CD (17 CD patients vs. 17 controls) and to uncover the effects of BNT treatment (at 6 months). Results In CD, we observed an increased information flow within the basal ganglia, the thalamus, and the sensorimotor cortex. In parallel, some of these structures became less responsive to regulating inputs. Furthermore, our results suggested an altered somatosensory integration. Following BNT administration, we noted a shift towards normal brain function in the CD patients, especially within the motor cortex, the somatosensory cortex, and the basal ganglia. Conclusion The changes in brain function and network activity in CD can be interpreted as related to the underlying cause, the effort to compensate or a mixture of both. Although BNT is applied in the last stage of the cortico-neuromuscular pathway, brain patterns are shifted towards those of healthy controls.
we characterized brain activity in CD and the effects of BNT using 3T fMR imaging and network analysis techniques following treatment with botulinum toxin (BNT), abnormal brain activity patterns in primary dystonia are attenuated critical key regions for both the pathophysiology and BNT-induced improvement in cervical dystonia are the BG
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Affiliation(s)
- Stefan Brodoehl
- Hans Berger Department for Neurology, Friedrich Schiller University of Jena, Germany; Brain Imaging Center, Friedrich Schiller University Jena, Germany.
| | - Franziska Wagner
- Hans Berger Department for Neurology, Friedrich Schiller University of Jena, Germany; Brain Imaging Center, Friedrich Schiller University Jena, Germany
| | - Tino Prell
- Hans Berger Department for Neurology, Friedrich Schiller University of Jena, Germany; Center for Healthy Aging, Jena University Hospital, Jena, Germany
| | - Carsten Klingner
- Hans Berger Department for Neurology, Friedrich Schiller University of Jena, Germany; Brain Imaging Center, Friedrich Schiller University Jena, Germany
| | - O W Witte
- Hans Berger Department for Neurology, Friedrich Schiller University of Jena, Germany; Brain Imaging Center, Friedrich Schiller University Jena, Germany; Center for Healthy Aging, Jena University Hospital, Jena, Germany
| | - Albrecht Günther
- Hans Berger Department for Neurology, Friedrich Schiller University of Jena, Germany
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Dashtipour K, Bhidayasiri R, Chen JJ, Jabbari B, Lew M, Torres-Russotto D. RimabotulinumtoxinB in sialorrhea: systematic review of clinical trials. JOURNAL OF CLINICAL MOVEMENT DISORDERS 2017; 4:9. [PMID: 28593050 PMCID: PMC5460542 DOI: 10.1186/s40734-017-0055-1] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 12/29/2016] [Accepted: 04/04/2017] [Indexed: 11/15/2022]
Abstract
OBJECTIVE The aim of this study was to examine the efficacy, safety and dosing practices of rimabotulinumtoxinB (BoNT-B) for the treatment of patients with sialorrhea based on a systematic review of clinical trials. METHODS A systematic literature review was performed to identify randomized controlled trials and other comparative clinical studies of BoNT-B for the treatment of sialorrhea published in English between January 1999 and December 2015. Medical literature databases (PubMed, Cochrane Library, and EMBASE) were searched and a total of 41 records were identified. Of these, six primary publications that evaluated BoNT-B for the treatment of sialorrhea met criteria and were included in the final data report. SYNTHESIS Total BoNT-B doses ranged from 1500 to 4000 units for sialorrhea. Most of the studies in sialorrhea showed statistically significant benefits of BoNT-B versus placebo (range 4-19.2 weeks). BoNT-B was generally well tolerated across the individual studies; most adverse events reported were considered unrelated to treatment. Adverse events considered potentially associated with BoNT-B included: dry mouth, change in saliva thickness, mild transient dysphagia, mild weakness of chewing and diarrhea. CONCLUSIONS BoNT-B significantly reduces sialorrhea at doses between 1500 and 4000 units. The relatively mild dose-dependent adverse events suggest both direct and remote toxin effects.
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Affiliation(s)
- Khashayar Dashtipour
- Division of Movement Disorders, Department of Neurology/Movement Disorders, Loma Linda University School of Medicine, Faculty of Medical Offices, 11370 Anderson, Suite B-100, Loma Linda, CA USA
| | - Roongroj Bhidayasiri
- Department of Medicine, Chulalongkorn Center of Excellence for Parkinson’s Disease & Related Disorders, Faculty of Medicine, Chulalongkorn University and King Chulalongkorn Memorial Hospital, Thai Red Cross Society, Bangkok, 10330 Thailand
- Department of Rehabilitation Medicine, Juntendo University, Tokyo, Japan
| | - Jack J. Chen
- Department of Neurology, Loma Linda University School of Medicine, Loma Linda, CA USA
- Loma Linda University, School of Pharmacy, Loma Linda, CA USA
| | - Bahman Jabbari
- Department of Neurology, Yale University School of Medicine, New Haven, CT USA
| | - Mark Lew
- Department of Neurology, Keck School of Medicine at the University of Southern California, Los Angeles, CA USA
| | - Diego Torres-Russotto
- Department of Neurological Sciences, University of Nebraska Medical Center, Omaha, USA
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Contarino MF, Van Den Dool J, Balash Y, Bhatia K, Giladi N, Koelman JH, Lokkegaard A, Marti MJ, Postma M, Relja M, Skorvanek M, Speelman JD, Zoons E, Ferreira JJ, Vidailhet M, Albanese A, Tijssen MAJ. Clinical Practice: Evidence-Based Recommendations for the Treatment of Cervical Dystonia with Botulinum Toxin. Front Neurol 2017; 8:35. [PMID: 28286494 PMCID: PMC5323428 DOI: 10.3389/fneur.2017.00035] [Citation(s) in RCA: 60] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/24/2016] [Accepted: 01/25/2017] [Indexed: 12/14/2022] Open
Abstract
Cervical dystonia (CD) is the most frequent form of focal dystonia. Symptoms often result in pain and functional disability. Local injections of botulinum neurotoxin are currently the treatment of choice for CD. Although this treatment has proven effective and is widely applied worldwide, many issues still remain open in the clinical practice. We performed a systematic review of the literature on botulinum toxin treatment for CD based on a question-oriented approach, with the aim to provide practical recommendations for the treating clinicians. Key questions from the clinical practice were explored. Results suggest that while the beneficial effect of botulinum toxin treatment on different aspects of CD is well established, robust evidence is still missing concerning some practical aspects, such as dose equivalence between different formulations, optimal treatment intervals, treatment approaches, and the use of supportive techniques including electromyography or ultrasounds. Established strategies to prevent or manage common side effects (including excessive muscle weakness, pain at injection site, dysphagia) and potential contraindications to this treatment (pregnancy and lactation, use of anticoagulants, neurological comorbidities) should also be further explored.
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Affiliation(s)
- Maria Fiorella Contarino
- Department of Neurology, Haga Teaching Hospital, The Hague, Netherlands; Department of Neurology, Leiden University Medical Centre, Leiden, Netherlands
| | - Joost Van Den Dool
- Department of Neurology AB 51, University Medical Centre Groningen, Groningen, Netherlands; ACHIEVE Centre of Expertise, Faculty of Health, Amsterdam University of Applied Sciences, Amsterdam, Netherlands
| | - Yacov Balash
- Movement Disorders Unit of the Department of Neurology, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel; Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
| | - Kailash Bhatia
- Sobell Department, Institute of Neurology, National Hospital for Neurology, University College London , London , UK
| | - Nir Giladi
- Movement Disorders Unit of the Department of Neurology, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel; Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
| | - Johannes H Koelman
- Department of Neurology/Clinical Neurophysiology, Academic Medical Center , Amsterdam , Netherlands
| | - Annemette Lokkegaard
- Department of Neurology, Copenhagen University Hospital Bispebjerg , Copenhagen , Denmark
| | - Maria J Marti
- Department of Neurology, Hospital Clinic i Universitari, Institut D'Investigacio Biomedica August Pi i Sunyer (IDIBAPS), CIBERNED , Barcelona , Spain
| | - Miranda Postma
- Department of Neurology/Clinical Neurophysiology, Academic Medical Center , Amsterdam , Netherlands
| | - Maja Relja
- Movement Disorders Center, Department of Neurology, Clinical Medical Center School of Medicine, Zagreb University , Zagreb , Croatia
| | - Matej Skorvanek
- Department of Neurology, P. J. Safarik University, Kosice, Slovakia; Department of Neurology, University Hospital of L. Pasteur, Kosice, Slovakia
| | - Johannes D Speelman
- Department of Neurology/Clinical Neurophysiology, Academic Medical Center , Amsterdam , Netherlands
| | - Evelien Zoons
- Department of Neurology/Clinical Neurophysiology, Academic Medical Center , Amsterdam , Netherlands
| | - Joaquim J Ferreira
- Clinical Pharmacology Unit, Faculty of Medicine, Instituto de Medicina Molecular, University of Lisbon , Lisbon , Portugal
| | - Marie Vidailhet
- Sorbonne University, UPMC Paris-6, Paris, France; Brain and Spine Institute - ICM, Centre for Neuroimaging Research - CENIR, UPMC UMR 1127, Paris, France; INSERM U 1127, Paris, France; CNRS UMR 7225, Team Control of Normal and Abnormal Movement, Paris, France; Department of Neurology, Salpêtriere Hospital, AP-HP, Paris, France
| | - Alberto Albanese
- Department of Neurology, Humanitas Research Hospital, Milano, Italy; Department of Neurology, Università Cattolica del Sacro Cuore, Milano, Italy
| | - Marina A J Tijssen
- Department of Neurology AB 51, University Medical Centre Groningen , Groningen , Netherlands
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BoNT/AB hybrid maintains similar duration of paresis as BoNT/A wild-type in murine running wheel assay. Neurotoxicology 2016; 59:1-8. [PMID: 28043867 DOI: 10.1016/j.neuro.2016.12.008] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/16/2016] [Revised: 12/15/2016] [Accepted: 12/27/2016] [Indexed: 11/21/2022]
Abstract
The highly potent Botulinum neurotoxins (BoNT) are successful drugs to treat neuromuscular disorders. Efforts are being made to further reduce the injected BoNT dose and to lengthen the interval between treatments. Detailed knowledge of the BoNT structure-activity relationship (SAR) allows combining the best features of the different BoNT serotypes. Of all seven BoNT serotypes A-G, BoNT/A displays the highest potency despite low neuronal binding affinity, while BoNT/B exhibits much higher affinity. Recently, a new BoNT/AB hybrid (AABB) was constructed comprising the catalytic and translocation domain of BoNT/A and the 50kDa cell binding domain of BoNT/B. Here, we compared BoNT/A wild-type (AAAA) and AABB with regard to ex vivo potency and in vivo potency, efficacy and duration of action using the mouse phrenic nerve hemidiaphragm assay and the murine running wheel assay, respectively. The ex vivo potency of AABB was found to be 8.4-fold higher than that of AAAA. For the latter, two and 5 pg each of AAAA and AABB, respectively, were bilaterally injected into the calf muscles and mouse running wheel performance was automatically monitored during the following weeks to determine potency, efficacy and duration. Mice displayed a dose-dependent impairment of running performance. AABB showed potency, efficacy and duration equal to AAAA demonstrating successful exchange of the cell binding domain. AABB might combine the higher potency and longer duration of BoNT/A with the target specificity for the autonomic nervous system of BoNT/B. AABB might therefore constitute an improved treatment option for acetylcholine-mediated autonomic disorders such as hypersalivation or hyperhidrosis.
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Hentschel F, Dressler D, Abele M, Paus S. Impaired heart rate variability in cervical dystonia is associated to depression. J Neural Transm (Vienna) 2016; 124:245-251. [DOI: 10.1007/s00702-016-1639-x] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/05/2016] [Accepted: 10/28/2016] [Indexed: 12/19/2022]
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Hill F, Miller N, Walsh RA, Mockler D, McDowell R, Walshe M. Botulinum toxin for drooling in Parkinson’s disease. THE COCHRANE DATABASE OF SYSTEMATIC REVIEWS 2016. [DOI: 10.1002/14651858.cd012408] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/08/2022]
Affiliation(s)
- Fiona Hill
- Tallaght Hospital; Department of Speech & Language Therapy; Tallaght Dublin 24 Ireland
| | - Nick Miller
- Newcastle University; Institute of Health and Society; Newcastle upon Tyne UK NE1 4LP
| | - Richard A Walsh
- Tallaght Hospital; Department of Neurology; Tallaght Dublin 24 Ireland
| | - David Mockler
- Trinity Centre for Health Sciences, St. James Hospital; John Stearne Library; St James's Hospital Dublin 8 Dublin Ireland
| | - Ronald McDowell
- Royal College of Surgeons; Department of General Practice; Dublin 2 Ireland
| | - Margaret Walshe
- Trinity College Dublin; Clinical Speech and Language Studies; 7-9 South Leinster Street Dublin Ireland 2
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Duarte GS, Castelão M, Rodrigues FB, Marques RE, Ferreira J, Sampaio C, Moore AP, Costa J, Cochrane Movement Disorders Group. Botulinum toxin type A versus botulinum toxin type B for cervical dystonia. Cochrane Database Syst Rev 2016; 10:CD004314. [PMID: 27782297 PMCID: PMC6461154 DOI: 10.1002/14651858.cd004314.pub3] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
BACKGROUND 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. OBJECTIVES To compare the efficacy, safety and tolerability of botulinum toxin type A (BtA) versus botulinum toxin type B (BtB) in people with cervical dystonia. SEARCH METHODS 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. SELECTION CRITERIA Double-blind, parallel, randomised, placebo-controlled trials (RCTs) comparing BtA versus BtB in adults with cervical dystonia. DATA COLLECTION AND ANALYSIS 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. MAIN RESULTS 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, with a higher probability of benefit from BtA treatment. None of the trials were free of for-profit bias, nor did they provide information regarding registered study protocols. All trials evaluated the effect of a single Bt treatment session, and not repeated treatment sessions, using doses from 100 U to 250 U of BtA (all onabotulinumtoxinA, or Botox, formulations) and 5000 U to 10,000 U of BtB (rimabotulinumtoxinB, or Myobloc/Neurobloc).We found no difference between the two types of botulinum toxin in terms of overall efficacy, with a mean difference of -1.44 (95% CI -3.58 to 0.70) points lower on the Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) for BtB-treated participants, measured at two to four weeks after injection. The proportion of participants with adverse events was also not different between BtA and BtB (BtB versus BtA risk ratio (RR) 1.40; 95% CI 1.00 to 1.96). However, when compared to BtA, treatment with BtB was associated with an increased risk of one adverse events of special interest, namely treatment-related sore throat/dry mouth (BtB versus BtA RR of 4.39; 95% CI 2.43 to 7.91). Treatment-related dysphagia (swallowing difficulties) was not different between BtA and BtB (RR 2.89; 95% CI 0.80 to 10.41). The two types of botulinum toxin were otherwise clinically non-distinguishable in all the remaining outcomes. AUTHORS' CONCLUSIONS The previous version of this review did not include any trials, since these were still ongoing at the time. Therefore, with this update we are able to change the conclusions of this review. There is low quality evidence that a single treatment session of BtA (specifically onabotulinumtoxinA) and a single treatment session of BtB (rimabotulinumtoxinB) are equally effective and safe in the treatment of adults with certain types of cervical dystonia. Treatment with BtB appears to present an increased risk of sore throat/dry mouth, compared to BtA. Overall, there is no clinical evidence from these single-treatment trials to support or contest the preferential use of one form of botulinum toxin over the other.
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Affiliation(s)
- Gonçalo S Duarte
- Faculdade de Medicina de LisboaLaboratório de Farmacologia Clínica e TerapêuticaAvenida Professor Egas MonizLisboaLisboaPortugal1649‐028
- Instituto de Medicina MolecularClinical Pharmacology UnitAv. Prof. Egas MonizLisboaPortugal1649‐028
| | - Mafalda Castelão
- Faculdade de Medicina de LisboaLaboratório de Farmacologia Clínica e TerapêuticaAvenida Professor Egas MonizLisboaLisboaPortugal1649‐028
- Instituto de Medicina MolecularClinical Pharmacology UnitAv. Prof. Egas MonizLisboaPortugal1649‐028
| | - Filipe B Rodrigues
- Faculdade de Medicina de LisboaLaboratório de Farmacologia Clínica e TerapêuticaAvenida Professor Egas MonizLisboaLisboaPortugal1649‐028
- Instituto de Medicina MolecularClinical Pharmacology UnitAv. Prof. Egas MonizLisboaPortugal1649‐028
| | - Raquel E Marques
- Faculdade de Medicina de LisboaLaboratório de Farmacologia Clínica e TerapêuticaAvenida Professor Egas MonizLisboaLisboaPortugal1649‐028
- Instituto de Medicina MolecularClinical Pharmacology UnitAv. Prof. Egas MonizLisboaPortugal1649‐028
| | - Joaquim Ferreira
- Faculdade de Medicina de LisboaLaboratório de Farmacologia Clínica e TerapêuticaAvenida Professor Egas MonizLisboaLisboaPortugal1649‐028
- Instituto de Medicina MolecularClinical Pharmacology UnitAv. Prof. Egas MonizLisboaPortugal1649‐028
| | - Cristina Sampaio
- CHDI Foundation155 Village BoulevardSuite 200PrincetonNJUSA08540
| | - Austen P Moore
- The Walton Centre NHS Foundation TrustLower LaneLiverpoolUKL9 7LJ
| | - João Costa
- Faculdade de Medicina de LisboaLaboratório de Farmacologia Clínica e TerapêuticaAvenida Professor Egas MonizLisboaLisboaPortugal1649‐028
- Instituto de Medicina MolecularClinical Pharmacology UnitAv. Prof. Egas MonizLisboaPortugal1649‐028
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Nassri A, Ramzan Z. Pharmacotherapy for the management of achalasia: Current status, challenges and future directions. World J Gastrointest Pharmacol Ther 2015; 6:145-55. [PMID: 26558149 PMCID: PMC4635155 DOI: 10.4292/wjgpt.v6.i4.145] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/24/2015] [Revised: 09/06/2015] [Accepted: 10/16/2015] [Indexed: 02/06/2023] Open
Abstract
This article reviews currently available pharmacological options available for the treatment of achalasia, with a special focus on the role of botulinum toxin (BT) injection due to its superior therapeutic effect and side effect profile. The discussion on BT includes the role of different BT serotypes, better pharmacological formulations, improved BT injection techniques, the use of sprouting inhibitors, designer recombinant BT formulations and alternative substances used in endoscopic injections. The large body of ongoing research into achalasia and BT may provide a stronger role for BT injection as a form of minimally invasive, cost effective and efficacious form of therapy for patients with achalasia. The article also explores current issues and future research avenues that may prove beneficial in improving the efficacy of pharmacological treatment approaches in patients with achalasia.
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Bentivoglio AR, Del Grande A, Petracca M, Ialongo T, Ricciardi L. Clinical differences between botulinum neurotoxin type A and B. Toxicon 2015; 107:77-84. [PMID: 26260691 DOI: 10.1016/j.toxicon.2015.08.001] [Citation(s) in RCA: 44] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/25/2015] [Accepted: 08/04/2015] [Indexed: 12/23/2022]
Abstract
In humans, the therapeutic use of botulinum neurotoxin A (BoNT/A) is well recognized and continuously expanding. Four BoNTs are widely available for clinical practice: three are serotype A and one is serotype B: onabotulinumtoxinA (A/Ona), abobotulinumtoxinA (A/Abo) and incobotulinumtoxinA (A/Inco), rimabotulinumtoxinB (B/Rima). A/Abo, A/Inco, A/Ona and B/Rima are all licensed worldwide for cervical dystonia. In addition, the three BoNT/A products are approved for blepharospasm and focal dystonias, spasticity, hemifacial spasm, hyperhidrosis and facial lines, with remarkable regional differences. These toxin brands differ for specific activity, packaging, constituents, excipient, and storage. Comparative literature assessing the relative safety and efficacy of different BoNT products is limited, most data come from reports on small samples, and only a few studies meet criteria of evidence-based medicine. One study compared the effects of BoNT/A and BoNT/B on muscle activity of healthy volunteers, showing similar neurophysiological effects with a dose ratio of 1:100. In cervical dystonia, when comparing the effects of BoNT/A and BoNT/B, results are more variable, some studies reporting roughly similar peak effect and overall duration (at a ratio of 1:66, others reporting substantially shorter duration of BoNT/B than BoNT/A (at a ratio 1/24). Although the results of clinical studies are difficult to compare for methodological differences (dose ratio, study design, outcome measures), it is widely accepted that: BoNT/B is clinically effective using appropriate doses as BoNT/A (1:40-50), injections are generally more painful, in most of the studies on muscular conditions, efficacy is shorter, and immunogenicity higher. Since the earliest clinical trials, it has been reported that autonomic side effects are more frequent after BoNT/B injections, and this observation encouraged the use of BoNT/B for sialorrhea, hyperhidrosis and other non-motor symptoms. In these indications the efficacy of toxins A and B are comparable and dose ratio is 1:25-30.
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Affiliation(s)
| | | | - Martina Petracca
- Institute of Neurology, Università Cattolica del Sacro Cuore, Roma, Italy
| | - Tamara Ialongo
- Institute of Neurology, Università Cattolica del Sacro Cuore, Roma, Italy
| | - Lucia Ricciardi
- Sobell Department of Motor Neuroscience and Movement Disorders, UCL Institute of Neurology, University College London, London, UK
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15
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Hellman A, Torres-Russotto D. Botulinum toxin in the management of blepharospasm: current evidence and recent developments. Ther Adv Neurol Disord 2015; 8:82-91. [PMID: 25922620 DOI: 10.1177/1756285614557475] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022] Open
Abstract
Blepharospasm is a focal (although usually bilateral) dystonia of the orbicularis oculi muscles, producing excessive eye closure. This produces significant disability through functional blindness. Botulinum neurotoxins (BoNT) have become the treatment of choice for blepharospasm; the impressive response rate and the tolerable safety profile have been proven through multiple clinical studies. There are currently four BoNT approved in the United States for different indications - we review the data on blepharospasm for each of these drugs. Currently, incobotulinumtoxinA and onabotulinumtoxinA have the most evidence of benefit for patients with blepharospasm. Current evidence, recent development and future directions are discussed.
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Affiliation(s)
- Amy Hellman
- Department of Neurological Sciences, University of Nebraska Medical Center, Omaha, NE, USA
| | - Diego Torres-Russotto
- Department of Neurological Sciences, University of Nebraska Medical Center, 988435 Nebraska Medical Center, Omaha, NE 68198, USA
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16
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Mills R, Bahroo L, Pagan F. An Update on the Use of Botulinum Toxin Therapy in Parkinson’s Disease. Curr Neurol Neurosci Rep 2014; 15:511. [DOI: 10.1007/s11910-014-0511-3] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
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17
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Basciani M, Di Rienzo F, Bizzarrini M, Zanchi M, Copetti M, Intiso D. Efficacy of botulinum toxin type B for the treatment of primary palmar hyperhidrosis: a prospective, open, single-blind, multi-centre study. Arch Dermatol Res 2014; 306:497-503. [PMID: 24522897 DOI: 10.1007/s00403-014-1449-7] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/29/2013] [Revised: 01/20/2014] [Accepted: 01/27/2014] [Indexed: 10/25/2022]
Abstract
Primary palmar hyperhidrosis is a distressing and disabling condition that can produce social, psychological and occupational problems. Although the use of botulinum toxin type A (BoNT-A) has been reported as an efficacious and safe intervention to improve palmar hyperhidrosis, only one study concerned botulinum toxin type B (BoNT-B) in this disorder. The aim of study was to evaluate the efficacy and safety of BoNT-B in treating primary palmar hyperhidrosis. Participants were injected with 5,000 IU of BoNT-B in each palm. Visual analogue test (VAS) to evaluate the intensity of decrease in sweat production, Minor's iodine starch test and measurement of paper towels' weight were used to ascertain palmar sweating at baseline, 4, 12 and 24 weeks after BoNT-B injections by a blind examiner. Thirty-two subjects (12 males, 20 females, mean age 31 ± 11) were enrolled. Significant reduction of palmar sweating was detected after BoNT-B injection: 2.9 ± 1.4, 0.3 ± 0.4, 0.9 ± 0.8, and 2.1 ± 1.5 g (p < 0.001) of paper towels' weight for the right palm at baseline, 4, 12 and 24 weeks; and 2.8 ± 1.7, 0.5 ± 0.6, 0.8 ± 0.7, and 1.8 ± 1.25 g (p < 0.001) at same time, respectively for the left palm. Significant reduction of mean VAS values were also detected after BoNT-B injections: 8.6 ± 1.1, 0.6 ± 0.8, 3.5 ± 2.5, and 7.1 ± 2.4 (p < 0.0001) at baseline, 4, 12 and 24 weeks, respectively. Mild side effects consisting in local pain and hand weakness were observed in 4 (12.5%) subjects. The findings indicated that the use of 5,000 IU BoNT-B injection in each palm was safe and significantly improved the severity of palmar hyperhidrosis.
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Affiliation(s)
- Mario Basciani
- Unit of Neuro-rehabilitation, Hospital Scientific Institute "Casa Sollievo Della Sofferenza", Viale dei Cappuccini, 71013, San Giovanni Rotondo (FG), Italy
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18
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Abstract
Selecting the appropriate treatment for dystonia begins with proper classification of disease based on age, distribution, and underlying etiology. The therapies available for dystonia include oral medications, botulinum toxin, and surgical procedures. Oral medications are generally reserved for generalized and segmental dystonia. Botulinum toxin revolutionized the treatment of focal dystonia when it was introduced for therapeutic purposes in the 1980s. Surgical procedures are available for medication-refractory dystonia, markedly affecting an individual's quality of life.
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Affiliation(s)
- Mary Ann Thenganatt
- Parkinson’s Disease Center & Movement Disorders Clinic, Department of Neurology, Baylor College of Medicine, 6550 Fannin, Suite 1801, Houston, TX 77030 USA
| | - Joseph Jankovic
- Parkinson’s Disease Center & Movement Disorders Clinic, Department of Neurology, Baylor College of Medicine, 6550 Fannin, Suite 1801, Houston, TX 77030 USA
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19
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Jankovic J. Medical treatment of dystonia. Mov Disord 2013; 28:1001-12. [DOI: 10.1002/mds.25552] [Citation(s) in RCA: 119] [Impact Index Per Article: 9.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/01/2013] [Revised: 05/03/2013] [Accepted: 05/10/2013] [Indexed: 01/21/2023] Open
Affiliation(s)
- Joseph Jankovic
- Parkinson's Disease Center and Movement Disorders Clinic, Department of Neurology, Baylor College of Medicine; Houston Texas USA
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20
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Ramirez-Castaneda J, Jankovic J, Comella C, Dashtipour K, Fernandez HH, Mari Z. Diffusion, spread, and migration of botulinum toxin. Mov Disord 2013; 28:1775-83. [PMID: 23868503 DOI: 10.1002/mds.25582] [Citation(s) in RCA: 137] [Impact Index Per Article: 11.4] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/08/2013] [Revised: 04/17/2013] [Accepted: 05/23/2013] [Indexed: 01/17/2023] Open
Abstract
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.
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Affiliation(s)
- Juan Ramirez-Castaneda
- Parkinson's Disease Center and Movement Disorders Clinic, Department of Neurology, Baylor College of Medicine, Houston, Texas, USA
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21
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Lee HJ, Lee SH, Jeong JH. Temporary Accommodation Difficulties after Botulinum Toxin Type B Injection for the Treatment of Hyperhidrosis. JOURNAL OF THE KOREAN OPHTHALMOLOGICAL SOCIETY 2013. [DOI: 10.3341/jkos.2013.54.2.387] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/23/2022]
Affiliation(s)
- Hye Jin Lee
- Department of Ophthalmology, Jeju National University School of Medicine, Jeju, Korea
| | - Sun Ho Lee
- Department of Ophthalmology, Jeju National University School of Medicine, Jeju, Korea
| | - Jin Ho Jeong
- Department of Ophthalmology, Jeju National University School of Medicine, Jeju, Korea
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22
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Abstract
Botulinum neurotoxins are used clinically for conditions characterized by hyperexcitability of peripheral nerve terminals and hypersecretory syndromes. These neurotoxins are synthesized as precursor proteins with low activity, but their effects are mediated by the active form of the neurotoxin through a multistep mechanism. Following a high-affinity interaction with a protein receptor and polysialogangliosides on the synaptic membrane, botulinum neurotoxins enter the neuron and causes a sustained inhibition of synaptic transmission. The active neurotoxin is part of a high-molecular-weight complex that protects the neurotoxin from proteolytic degradation. Although complexing proteins do not affect diffusion of therapeutic neurotoxin, they may lead to the development of neutralizing antibodies that block responsiveness to it. Nerve terminal intoxication is reversible and its duration varies for different BoNT serotypes. Although it was previously assumed that botulinum neurotoxins exert effects only on the peripheral synapses, such as the neuromuscular junction, there is now substantial evidence that these neurotoxins affect neurotransmission at distal central nervous system sites as well.
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Affiliation(s)
- Ann P Tighe
- 74 Schindler Sq, Hackettstown, NJ 07840, USA
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23
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Abstract
BACKGROUND Drooling is a common problem for children with cerebral palsy (CP). This can be distressing for these children as well as for their parents and caregivers. The consequences of drooling include risk of social rejection, damp and soiled clothing, unpleasant odour, irritated chapped skin, mouth infections, dehydration, interference with speech, damage to books, communication aids, computers, and the risk of social isolation (Blasco 1992; Van der Burg 2006). A range of interventions exist that aim to reduce or eliminate drooling. There is a lack of consensus regarding which interventions are most effective for children with CP. OBJECTIVES (1) To evaluate the effectiveness and safety of interventions aimed at reducing or eliminating drooling in children with cerebral palsy. (2) To provide the best available evidence to inform clinical practice. (3) To assist with future research planning. SEARCH METHODS We searched the following databases from inception to December 2010 : Cochrane Central Register of Controlled Trials (CENTRAL); Medline via Ovid; EMBASE; CINAHL; ERIC; Psych INFO; Web of Science; Web of Knowledge; AMED; SCOPUS; Dissertation Abstracts.We searched for ongoing clinical trials in the Clinical Trials web site (http://clinicaltrials.gov.) and in the Current Controlled Trials web site (http://www.controlled-trials.com/). We hand searched a range of relevant journals and conference proceeding abstracts. SELECTION CRITERIA Only randomised controlled trials (RCTs) and controlled clinical trials (CCTs) were included. DATA COLLECTION AND ANALYSIS Data were extracted independently by MW, MS and LP and differences resolved through discussion. MAIN RESULTS Six studies were eligible for inclusion in the review. Four of these studies were trials using botulinum toxin-A (BoNT-A) and two were trials on the pharmacological interventions, benztropine and glycopyrrolate. No RCTs or CCTs were retrieved on surgery, physical, oro-motor and oro-sensory therapies, behavioural interventions, intra-oral appliances or acupuncture. In the studies eligible for review, there was considerable heterogeneity within and across interventions and a meta-analysis was not possible. A descriptive summary of each study is provided. All studies showed some statistically significant change for treatment groups up to 1 month post intervention. However, there were methodological flaws associated with all six studies. AUTHORS' CONCLUSIONS It was not possible to reach a conclusion on the effectiveness and safety of either BoNT-A or the pharmaceutical interventions, benztropine and glycopyrrolate. There is insufficient evidence to inform clinical practice on interventions for drooling in children with CP. Directions for future research are provided.
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Affiliation(s)
- Margaret Walshe
- Clinical Speech and Language Studies,Trinity College Dublin, Dublin 2, Ireland.
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24
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Thenganatt MA, Fahn S. Botulinum toxin for the treatment of movement disorders. Curr Neurol Neurosci Rep 2012; 12:399-409. [PMID: 22661378 DOI: 10.1007/s11910-012-0286-3] [Citation(s) in RCA: 30] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
After botulinum toxin was initially used to treat strabismus in the 1970s, others started using it to treat movement disorders including blepharospasm, hemifacial spasm, cervical dystonia, spasmodic dysphonia, and oromandibular dystonia. It was discovered that botulinum toxin can be an effective treatment for focal movement disorders with limited side effects. Over the past three decades, various formulations of botulinum toxin have been developed and the therapeutic use of these toxins has expanded in movement disorders and beyond. We review the history and mechanism of action of botulinum toxin, as well as describe different formulations available and their potential therapeutic uses in movement disorders.
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Affiliation(s)
- Mary Ann Thenganatt
- Department of Neurology, College of Physicians and Surgeons, Columbia University, 710 West 168th Street, New York, NY 10032, USA.
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25
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Abstract
BACKGROUND Drooling is a common problem for children with cerebral palsy (CP). This can be distressing for these children as well as for their parents and caregivers. The consequences of drooling include risk of social rejection, damp and soiled clothing, unpleasant odour, irritated chapped skin, mouth infections, dehydration, interference with speech, damage to books, communication aids, computers, and the risk of social isolation (Blasco 1992; Van der Burg 2006). A range of interventions exist that aim to reduce or eliminate drooling. There is a lack of consensus regarding which interventions are most effective for children with CP. OBJECTIVES (1) To evaluate the effectiveness and safety of interventions aimed at reducing or eliminating drooling in children with cerebral palsy. (2) To provide the best available evidence to inform clinical practice. (3) To assist with future research planning. SEARCH METHODS We searched the following databases from inception to December 2010 : Cochrane Central Register of Controlled Trials (CENTRAL); Medline via Ovid; EMBASE; CINAHL; ERIC; Psych INFO; Web of Science; Web of Knowledge; AMED; SCOPUS; Dissertation Abstracts.We searched for ongoing clinical trials in the Clinical Trials web site (http://clinicaltrials.gov.) and in the Current Controlled Trials web site (http://www.controlled-trials.com/). We hand searched a range of relevant journals and conference proceeding abstracts. SELECTION CRITERIA Only randomised controlled trials (RCTs) and controlled clinical trials (CCTs) were included. DATA COLLECTION AND ANALYSIS Data were extracted independently by MW, MS and LP and differences resolved through discussion. MAIN RESULTS Six studies were eligible for inclusion in the review. Four of these studies were trials using botulinum toxin-A (BoNT-A) and two were trials on the pharmacological interventions, benztropine and glycopyrrolate. No RCTs or CCTs were retrieved on surgery, physical, oro-motor and oro-sensory therapies, behavioural interventions, intra-oral appliances or acupuncture. In the studies eligible for review, there was considerable heterogeneity within and across interventions and a meta-analysis was not possible. A descriptive summary of each study is provided. All studies showed some statistically significant change for treatment groups up to 1 month post intervention. However, there were methodological flaws associated with all six studies. AUTHORS' CONCLUSIONS It was not possible to reach a conclusion on the effectiveness and safety of either BoNT-A or the pharmaceutical interventions, benztropine and glycopyrrolate. There is insufficient evidence to inform clinical practice on interventions for drooling in children with CP. Directions for future research are provided.
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Affiliation(s)
- Margaret Walshe
- Clinical Speech and Language Studies,TrinityCollegeDublin,Dublin 2, Ireland.
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26
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Truong D. Botulinum toxins in the treatment of primary focal dystonias. J Neurol Sci 2012; 316:9-14. [PMID: 22336699 DOI: 10.1016/j.jns.2012.01.019] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/06/2011] [Revised: 01/05/2012] [Accepted: 01/19/2012] [Indexed: 11/18/2022]
Abstract
Focal dystonia, such as cervical dystonia, blepharospasm, oromandibular dystonia, laryngeal dystonia, and limb dystonia, is often observed in adult-onset primary dystonia syndromes that affect a specific area of the body and tend to have little or no spread. This review will examine the past, present, and future approaches to the treatment of focal dystonia. Botulinum toxin (BoNT) has emerged as the treatment of choice for the majority of focal dystonias. Currently four products are widely available commercially, three of BoNT/A type and one of BoNT/B type. Each has important pharmacological differences that give rise to markedly different dosing recommendations. The four approved BoNTs are safe and effective for treating focal dystonias, including long-term treatment. Adverse events are limited and transient and, for the most part, mild in severity. Potential problems with the use of BoNT agents are diffusion and neutralizing antibody formation; the latter can lead to treatment resistance. Because each BoNT product is developed from distinct purification and manufacturing procedures and has varying toxin complex size and structures, physicians need to be aware of these differences when choosing an agent.
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Affiliation(s)
- Daniel Truong
- Parkinson's and Movement Disorder Institute, 9940 Talbert Avenue, Suite 204, Fountain Valley, CA 92708, USA.
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27
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Therapeutic use of botulinum toxin in neurorehabilitation. J Toxicol 2011; 2012:802893. [PMID: 21941544 PMCID: PMC3172973 DOI: 10.1155/2012/802893] [Citation(s) in RCA: 27] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/05/2011] [Revised: 06/28/2011] [Accepted: 07/13/2011] [Indexed: 12/14/2022] Open
Abstract
The botulinum toxins (BTX), type A and type B by blocking vesicle acetylcholine release at neuro-muscular and neuro-secretory junctions can result efficacious therapeutic agents for the treatment of numerous disorders in patients requiring neuro-rehabilitative intervention. Its use for the reduction of focal spasticity following stroke, brain injury, and cerebral palsy is provided. Although the reduction of spasticity is widely demonstrated with BTX type A injection, its impact on the improvement of dexterity and functional outcome remains controversial. The use of BTX for the rehabilitation of children with obstetrical brachial plexus palsy and in treating sialorrhea which can complicate the course of some severe neurological diseases such as amyotrophic lateral sclerosis and Parkinson's disease is also addressed. Adverse events and neutralizing antibodies formation after repeated BTX injections can occur. Since impaired neurological persons can have complex disabling feature, BTX treatment should be viewed as adjunct measure to other rehabilitative strategies that are based on the individual's residual ability and competence and targeted to achieve the best functional recovery. BTX therapy has high cost and transient effect, but its benefits outweigh these disadvantages. Future studies must clarify if this agent alone or adjunctive to other rehabilitative procedures works best on functional outcome.
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28
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Chinnapongse R, Gullo K, Nemeth P, Zhang Y, Griggs L. Safety and efficacy of botulinum toxin type B for treatment of sialorrhea in Parkinson's disease: A prospective double-blind trial. Mov Disord 2011; 27:219-26. [DOI: 10.1002/mds.23929] [Citation(s) in RCA: 60] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/18/2011] [Revised: 07/12/2011] [Accepted: 08/01/2011] [Indexed: 01/18/2023] Open
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29
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Pantel M, Volk GF, Guntinas-Lichius O, Wittekindt C. Botulinum toxin type b for the treatment of a sialocele after parotidectomy. Head Neck 2011; 35:E11-2. [PMID: 21688341 DOI: 10.1002/hed.21778] [Citation(s) in RCA: 13] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 02/15/2011] [Indexed: 11/09/2022] Open
Abstract
BACKGROUND A 41-year-old male patient developed a sialocele after partial parotidectomy for a parotid pleomorphic adenoma. The sialocele was effectively treated by a single injection with botulinum toxin type B combined with multiple needle aspirations. METHODS Ultrasound-guided infiltration of 2500 mouse-units of botulinum toxin type B in the residual parotid gland tissue under local anesthesia. Repeated needle aspirations were performed before and after the infiltration. RESULTS Ten days after the injection, the patient was free of any discomfort. CONCLUSION Botulinum toxin type B is effective in the management of postoperative sialocele after parotid gland surgery.
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Affiliation(s)
- Mira Pantel
- Department of Otorhinolaryngology, University Hospital, Friedrich-Schiller University Jena, Jena, Germany.
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30
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Basciani M, Di Rienzo F, Fontana A, Copetti M, Pellegrini F, Intiso D. Botulinum toxin type B for sialorrhoea in children with cerebral palsy: a randomized trial comparing three doses. Dev Med Child Neurol 2011; 53:559-64. [PMID: 21413974 DOI: 10.1111/j.1469-8749.2011.03952.x] [Citation(s) in RCA: 28] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
AIM The aim of the present study was to evaluate the efficacy and safety of three doses of botulinum toxin type B (BoNT-B) in reducing persistent sialorrhoea in children with cerebral palsy (CP). METHOD Children with CP and refractory sialorrhoea were randomized to one of four groups: a control group and three experimental groups receiving a low (1500 mouse units [MU]), medium (3000 MU), or high (5000 MU) dose of BoNT-B respectively, into bilateral salivary glands. Drooling was measured using the Thomas-Stonell rating scale, and the weight and the number of bibs used per day were counted in all children at baseline, 4, and 12 weeks after BoNT-B injection. RESULTS Twenty-seven children (15 males, 12 females; mean age 7 y 10 mo, SD 1 y 6 mo; range 5-15 y) were randomized into a control (seven children: four males, three females) and experimental groups receiving low (six children: four males, two females), medium (seven children: four males, three females), and high (seven children: three males, four females) doses of BoNT-B respectively. All children had mixed neurological disorders consisting of spastic paraparesis, tetraparesis, dystonic movements, and ataxia. Gross Motor Function Classification System levels ranged from III to V, and all children had moderate or severe intellectual disability. Estimated means with their standard errors (SEM) of drooling were at baseline, 4, and 12 weeks respectively, as follows: control group, 12.1 (2.1), 11.9 (2.1), 11.8 (2.2), p for trend 0.992; low dose group, 13.8 (2.3), 11.4 (2.3), 13.9 (2.3), p for trend 0.952; medium dose group, 13.9 (2.1), 6.7 (2.1), 7.1 (2.1) p for trend 0.008; and for the high dose group 14.4 (2.1), 5.0 (2.1), 5.6 (2.1), p for trend 0.002. Side effects included dense saliva, xerostomia, and difficulty in swallowing, and were more frequent in the high-dose group. INTERPRETATION A 3000 MU injection of BoNT-B into the salivary glands significantly improved the frequency and severity of sialorrhoea in children with CP. The lower dose was ineffective, and the higher dose produced no greater benefit and more side effects.
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Affiliation(s)
- Mario Basciani
- Unit of Neuro-Rehabilitation, Scientific Institute Hospital, IRCSS Casa Sollievo della Sofferenza, San Giovanni Rotondo, Foggia, Italy
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Albanese A, Asmus F, Bhatia KP, Elia AE, Elibol B, Filippini G, Gasser T, Krauss JK, Nardocci N, Newton A, Valls-Solé J. EFNS guidelines on diagnosis and treatment of primary dystonias. Eur J Neurol 2011; 18:5-18. [PMID: 20482602 DOI: 10.1111/j.1468-1331.2010.03042.x] [Citation(s) in RCA: 273] [Impact Index Per Article: 19.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/05/2023]
Abstract
OBJECTIVES to provide a revised version of earlier guidelines published in 2006. BACKGROUND primary dystonias are chronic and often disabling conditions with a widespread spectrum mainly in young people. DIAGNOSIS primary dystonias are classified as pure dystonia, dystonia plus or paroxysmal dystonia syndromes. Assessment should be performed using a validated rating scale for dystonia. Genetic testing may be performed after establishing the clinical diagnosis. DYT1 testing is recommended for patients with primary dystonia with limb onset before age 30, and in those with an affected relative with early-onset dystonia. DYT6 testing is recommended in early-onset or familial cases with cranio-cervical dystonia or after exclusion of DYT1. Individuals with early-onset myoclonus should be tested for mutations in the DYT11 gene. If direct sequencing of the DYT11 gene is negative, additional gene dosage is required to improve the proportion of mutations detected. A levodopa trial is warranted in every patient with early-onset primary dystonia without an alternative diagnosis. In patients with idiopathic dystonia, neurophysiological tests can help with describing the pathophysiological mechanisms underlying the disorder. TREATMENT botulinum toxin (BoNT) type A is the first-line treatment for primary cranial (excluding oromandibular) or cervical dystonia; it is also effective on writing dystonia. BoNT/B is not inferior to BoNT/A in cervical dystonia. Pallidal deep brain stimulation (DBS) is considered a good option, particularly for primary generalized or cervical dystonia, after medication or BoNT have failed. DBS is less effective in secondary dystonia. This treatment requires a specialized expertise and a multidisciplinary team.
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Affiliation(s)
- A Albanese
- Istituto Neurologico Carlo Besta, Milan, Italy Università Cattolica del Sacro Cuore, Milan, Italy.
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Botulinum Toxin Type B in the Treatment of Residual Limb Hyperhidrosis for Lower Limb Amputees. Am J Phys Med Rehabil 2011; 90:321-9. [DOI: 10.1097/phm.0b013e31820636fd] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
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Guidubaldi A, Fasano A, Ialongo T, Piano C, Pompili M, Mascianà R, Siciliani L, Sabatelli M, Bentivoglio AR. 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. Mov Disord 2011; 26:313-9. [PMID: 21259343 DOI: 10.1002/mds.23473] [Citation(s) in RCA: 80] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/29/2010] [Revised: 03/11/2010] [Accepted: 09/13/2010] [Indexed: 06/01/2025] Open
Abstract
BACKGROUND Either botulinum toxins (BoNTs) A and B have been used for improving drooling in different neurological conditions. METHODS 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. RESULTS 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. CONCLUSIONS 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.
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Affiliation(s)
- Arianna Guidubaldi
- Istituto di Neurologia, Università Cattolica del Sacro Cuore, Roma, Italia
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Cantarella G, Berlusconi A, Mele V, Cogiamanian F, Barbieri S. Treatment of Frey's syndrome with botulinum toxin type B. Otolaryngol Head Neck Surg 2010; 143:214-8. [PMID: 20647122 DOI: 10.1016/j.otohns.2010.04.009] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/07/2010] [Revised: 03/24/2010] [Accepted: 04/08/2010] [Indexed: 10/19/2022]
Abstract
OBJECTIVE Frey's syndrome is a frequent sequela of parotidectomy, causing facial sweating and flushing because of gustatory stimuli. Although botulinum toxin type A has become first-line therapy for Frey's syndrome, some patients become resistant. In this study, we investigated whether another serotype, botulinum toxin type B, might be an effective alternative. STUDY DESIGN Case series with planned data collection. SETTING Otolaryngology department in a university hospital. SUBJECTS AND METHODS Seven patients aged 30 to 68 years, with severe Frey's syndrome, underwent the Minor test and had 80 U of botulinum toxin type B per cm(2) (mean total dose, 2354 U) injected intracutaneously in the mapped area of gustatory sweating. All patients were followed up for 12 months. RESULTS One month after treatment, six of the seven patients reported that gustatory sweating and flushing had resolved, and, in the remaining patient, these symptoms had decreased. The Minor test confirmed a significant improvement. The subjective benefits remained stable for six months in four patients and for nine months in the remaining three patients; 12 months after treatment, all patients still reported some improvement. CONCLUSION Botulinum toxin type B afforded symptomatic relief in a small sample of patients with Frey's syndrome and might be considered a potential alternative to botulinum toxin type A.
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Affiliation(s)
- Giovanna Cantarella
- Department of Otolaryngology, Fondazione IRCCS Ca Granda Ospedale Maggiore Policlinico, Milan, Italy.
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Walshe M, Smith M, Pennington L. Interventions for drooling in children with cerebral palsy. THE COCHRANE DATABASE OF SYSTEMATIC REVIEWS 2010. [DOI: 10.1002/14651858.cd008624] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/08/2022]
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Hornik A, Gruener G, Jay WM. Adverse Reactions from Botulinum Toxin Administration. Neuroophthalmology 2010. [DOI: 10.3109/01658100903576334] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022] Open
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Mauskop A. Botulinum neurotoxin in the treatment of headache disorders. HANDBOOK OF CLINICAL NEUROLOGY 2010; 97:217-232. [PMID: 20816423 DOI: 10.1016/s0072-9752(10)97017-6] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/29/2023]
Abstract
Botulinum neurotoxin (BoNT) has been in clinical use for the treatment of headaches for over 15 years. Recent double-blind placebo-controlled trials have confirmed the efficacy of BoNT type A (onabtoulinumtoxinA, Botox) in the treatment of chronic migraine. The efficacy of BoNT in the treatment of episodic migraine headaches, cluster headaches, and chronic tension-type headache (TTH) has not been examined in large controlled trials. Presumed mechanisms of action of BoNT in headache disorders are the reduction of afferent input induced by muscle relaxation and inhibition of the release of neurotransmitters, such as glutamate and calcitonin gene-related peptide, from peripheral sensory nerve terminals. Over 20 years of extensive clinical experience has established a remarkable safety for BoNT, particularly type A and specifically Botox or onabotulinumtoxinA, which has been used much longer and more widely than any other form or serotype of BoNT. Because BoNT is a biological product, the safety and efficacy of one BoNT formulation cannot be extrapolated to a different one, even of the same serotype.
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Affiliation(s)
- Alexander Mauskop
- New York Headache Center and Downstate Medical Center, State University of New York, New York, NY 10021, USA.
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Mostile G, Jankovic J. Treatment of dysautonomia associated with Parkinson's disease. Parkinsonism Relat Disord 2009; 15 Suppl 3:S224-32. [DOI: 10.1016/s1353-8020(09)70820-x] [Citation(s) in RCA: 31] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/30/2023]
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Jankovic J. Clinical efficacy and tolerability of Xeomin® in the treatment of blepharospasm. Eur J Neurol 2009; 16 Suppl 2:14-8. [DOI: 10.1111/j.1468-1331.2009.02880.x] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
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Jankovic J. Disease-oriented approach to botulinum toxin use. Toxicon 2009; 54:614-23. [DOI: 10.1016/j.toxicon.2008.11.013] [Citation(s) in RCA: 74] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/30/2008] [Accepted: 11/28/2008] [Indexed: 11/26/2022]
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Abstract
Dystonia varies in severity from simple focal dystonia, such as writer's cramp to life-threatening status dystonicus. Even though the pathophysiology is still elusive, symptomatic treatments may provide marked relief. Botulinum toxin is considered the treatment of choice for most focal and segmental dystonias. Deep brain stimulation of the basal ganglia, particularly the globus pallidus internum, is emerging as an important treatment for refractory, generalized, and segmental forms of dystonia. Gene therapy is also being explored as a possible treatment of inherited dystonias. This article reviews the therapeutic options available for the various types of dystonia.
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Affiliation(s)
- Octavian R Adam
- Parkinson's Disease Center and Movement Disorders Clinic, Department of Neurology, Baylor College of Medicine, Houston, TX 77030, USA
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Abstract
Botulinum neurotoxin (BoNT) has been used clinically since 1980, with an ever-increasing range of clinical applications. This has coincided with a period of massively expanded interest in the underlying biology of the neurotoxin. Tremendous advances have taken place in the scientific understanding of neurotoxin structure and function since the description of their endopeptidase activity in 1992. These developments have led to an increased understanding of the mechanisms underpinning the clinical use of the neurotoxins and also in the technologies available to support their clinical use. The expanding range of clinical applications, and use in increasing doses, has also generated challenges for the clinicians and manufacturers of BoNT preparations to ensure continuing efficacy and safety margins for these new clinical settings. To date the increased clinical use of BoNTs has occurred largely empirically, and not by application of the recent insights into neurotoxin structure and function. With the increased knowledge regarding the biology of the neurotoxins, however, there is the opportunity to select preferred forms of the toxin for particular clinical applications and even to consider engineering the neurotoxins to produce modified products more suited to specific clinical applications. These developments and opportunities that have arisen, particularly over the last decade, emphasise the increasing need to maintain an active two way dialogue between clinicians and basic scientists to ensure that the advances in the laboratory are translated into clinical benefit and that the clinical developments in use of neurotoxin are supported by the scientific research activity. This article is based upon presentations given in a workshop at the 5th International Conference on Basic and Therapeutic Aspects of Botulinum and Tetanus Toxin in Denver in June, 2005 seeking to address issues relating to the laboratory/clinic interface.
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Affiliation(s)
- K A Foster
- Health Protection Agency, Centre for Emergency Preparedness and Response, Porton Down, Salisbury, UK.
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Kwon JS, Kim ST, Jeon YM, Choi JH. Effect of botulinum toxin type A injection into human masseter muscle on stimulated parotid saliva flow rate. Int J Oral Maxillofac Surg 2009; 38:316-20. [PMID: 19231136 DOI: 10.1016/j.ijom.2009.01.008] [Citation(s) in RCA: 15] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/26/2007] [Revised: 11/02/2008] [Accepted: 01/16/2009] [Indexed: 11/28/2022]
Abstract
Botulinum toxin type A (BTX-A) injection into the masseter muscles is used to treat masseteric hypertrophy. No serious side effects of BTX-A have been reported, but patients sometimes complain of xerostomia. The aim of this study was to evaluate the effect of injecting BTX-A into the masseter for the treatment of masseteric hypertrophy on the flow of saliva from the parotid gland. 34 volunteers enrolled in this study. A total of 25 units of BTX-A was injected into each side bilaterally at two points at the center of the lower third of the masseter muscle. Saliva was collected from the parotid gland over a period of 10 min to determine the flow rate for 18 weeks after injection. The flow rate was calculated by dividing the amount in milliliters by the collection time in minutes. There were no significant changes in the stimulated parotid saliva flow at 4, 8, 12 or 18 weeks compared with the baseline. Within this limited study, it can be concluded that BTX-A injection into the masseter does not cause any significant decrease in the production of saliva from the parotid gland.
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Affiliation(s)
- J S Kwon
- TMJ and Orofacial Pain Clinic, Department of Oral Diagnosis & Oral Medicine, College of Dentistry, Yonsei University, Seoul, Korea
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Pappert EJ, Germanson T. Botulinum toxin type B vs. type A in toxin-naïve patients with cervical dystonia: Randomized, double-blind, noninferiority trial. Mov Disord 2008; 23:510-7. [PMID: 18098274 DOI: 10.1002/mds.21724] [Citation(s) in RCA: 82] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/09/2022] Open
Abstract
The objective of this study was to compare efficacy, safety, and duration of botulinum toxin type A (BoNT-A) and type B (BoNT-B) in toxin-naïve cervical dystonia (CD) subjects. BoNT-naïve CD subjects were randomized to BoNT-A or BoNT-B and evaluated in a double-blind trial at baseline and every 4-weeks following one treatment. The primary measure was the change in Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) from baseline to week 4 post-injection. Secondary measures included change in TWSTRS-subscale scores, pain, global impressions, and duration of response and safety assessments. The study was designed as a noninferiority trial of BoNT-B to BoNT-A. 111 subjects were randomized (55 BoNT-A; 56 BoNT-B). Improvement in TWSTRS-total scores 4 weeks after BoNT-B was noninferior to BoNT-A (adjusted means 11.0 (SE 1.2) and 8.8 (SE 1.2), respectively; per-protocol-population (PPP)). The median duration of effect of BoNT-A and BoNT-B was not different (13.1 vs. 13.7 weeks, respectively; P-value = 0.833; PPP). There were no significant differences in the occurrence of injection site pain and dysphagia. Mild dry mouth was more frequent with BoNT-B but there were no differences for moderate/severe dry mouth. In this study, both BoNT-A and B were shown to be effective and safe for the treatment of toxin-naive CD subjects.
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Affiliation(s)
- Eric J Pappert
- Solstice Neurosciences, Inc, Malvern, Pennsylvania, USA.
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Tiple D, Strano S, Colosimo C, Fabbrini G, Calcagnini G, Prencipe M, Berardelli A. Autonomic cardiovascular function and baroreflex sensitivity in patients with cervical dystonia receiving treatment with botulinum toxin type A. J Neurol 2008; 255:843-7. [PMID: 18458860 DOI: 10.1007/s00415-008-0753-6] [Citation(s) in RCA: 16] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/22/2007] [Revised: 07/19/2007] [Accepted: 09/19/2007] [Indexed: 11/30/2022]
Abstract
OBJECTIVE To investigate possible changes in autonomic cardiovascular regulation and cardiopulmonary baroreflex sensitivity in patients with primary cervical dystonia receiving chronic treatment with botulinum toxin type A. METHODS Short-term power spectral analysis of heart rate and systolic blood pressure variability, high-frequency and low-frequency oscillations of heart rate variability, low frequency/high frequency ratio and baroreflex sensitivity (alpha index) were measured in 12 patients with cervical dystonia before and 2-4 weeks after botulinum toxin type A injection and compared with normative data. RESULTS Before treatment, at rest, patients had significantly lower high frequency power than healthy subjects (p < 0.01), whereas no differences were found in low frequency power. Botulinum toxin injection in patients induced no changes in either power frequency. In patients before treatment and healthy subjects the low frequency oscillatory components increased similarly from rest to tilt (p < 0.01), but tilt induced lower low frequency values in patients than in healthy subjects (p < 0.01). In patients before treatment, the high frequency variations from rest to tilt remained unchanged, whereas in healthy subjects they decreased significantly (p < 0.01). Botulinum toxin type A injection in patients induced no changes in low frequency or high frequency powers. In patients before treatment the low frequency/high frequency ratio increased slightly from rest to tilt, but in healthy subjects increased significantly (p < 0.01). Botulinum toxin type A left the pretreatment low frequency/high frequency ratio unchanged. The alpha-index measured at rest in patients before treatment was lower than in healthy subjects (p<0.05), whereas during tilt was similar in both groups. The alpha-index measured after botulinum toxin injection in patients remained unchanged at rest and during tilt. CONCLUSIONS Patients with cervical dystonia receiving treatment with botulinum toxin type A have mild, subclinical abnormalities in autonomic cardiovascular regulation and cardiopulmonary baroreflex sensitivity. These changes do not worsen after acute botulinum toxin type A injection.
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Affiliation(s)
- D Tiple
- Department of Neurological Sciences and Neuromed Institute (IRCCS), University of Rome "La Sapienza", Viale dell'Università, 30, 00185 Roma, Italy
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Molho E, Jankovic J, Lew M. Role of botulinum toxin in the treatment of cervical dystonia. Neurol Clin 2008; 26 Suppl 1:43-53. [DOI: 10.1016/s0733-8619(08)80004-7] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
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Botulinum toxin type-B improves sialorrhea and quality of life in bulbaronset amyotrophic lateral sclerosis. J Neurol 2008; 255:545-50. [DOI: 10.1007/s00415-008-0738-5] [Citation(s) in RCA: 41] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/03/2007] [Revised: 07/26/2007] [Accepted: 09/05/2007] [Indexed: 11/26/2022]
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Affiliation(s)
- Eric A Johnson
- Department of Bacteriology, Food Research Institute, University of Wisconsin, Madison, WI, USA.
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Chapman MA, Barron R, Tanis DC, Gill CE, Charles PD. Comparison of botulinum neurotoxin preparations for the treatment of cervical dystonia. Clin Ther 2007; 29:1325-37. [PMID: 17825685 DOI: 10.1016/j.clinthera.2007.07.020] [Citation(s) in RCA: 48] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 04/24/2007] [Indexed: 11/28/2022]
Abstract
BACKGROUND Comparative studies of botulinum neurotoxin preparations to date have generally examined 2 preparations at prespecified dose ratios in relatively homogeneous groups of patients under controlled study conditions. It is unclear whether the differences in adverse-event rates that have been noted under these controlled conditions can be generalized to the broader population of cervical dystonia patients, who are treated with a wider range of doses in a variety of settings. OBJECTIVE We conducted a systematic review and analysis of the published literature to compare rates of dysphagia and dry mouth in studies of botulinum neurotoxin products. METHODS We searched the MEDLINE, EMBASE, Biosis, SciSearch, JICST (Japan Science and Technology Center), and Pascal databases from 1985 through 2006 using the terms cervical dystonia, spasmodic torticollis, and botulinum toxin for original English-language studies of Botox, Dysport, or Myobloc in the treatment of cervical dystonia (or spasmodic torticollis) that documented adverse events by treatment or patient. Studies that involved patients with various types of dystonias or movement disorders were included as long as adverse events were reported separately for those with cervical dystonia. Rates of dysphagia with the original preparation of Botox were considered separately from those with the current preparation of Botox. RESULTS Seventy published articles were included in the analysis (30 Botox, 24 Dysport, 3 Botox + Dysport, 11 Myobloc, 2 Botox + Myobloc). Mean total doses per treatment ranged from 60 to 374 U for Botox, 125 to 1200 U for Dysport, and 579 to 19,853 U for Myobloc. Botox was associated with a significantly lower rate of dysphagia than Dysport, with mean dysphagia rates of 10.5% for original Botox, 8.9% for current Botox, and 26.8% for Dysport (both, P < 0.05). Myobloc was associated with dry mouth (3.2%-90.0%) in 9 of 13 studies, but this adverse event was not reported in a sufficient number of studies of botulinum toxin type A preparations (Botox, n = 2; Dysport, n = 6) to permit statistical comparison. In the weighted analysis, the duration of effect differed between botulinum neurotoxin products (current Botox > Myobloc > original Botox > Dysport; all, P < 0.001), but only 43 (61.4%) of the 70 studies reported duration, and the definitions varied. CONCLUSION The results of this analysis indicate differences in adverse-event rates between botulinum neurotoxin preparations, suggesting that use of these products should be based on their individual dosing, efficacy, and safety profiles.
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