Which medications in the drug class Botulinum Toxins are used in the treatment of Spasticity?

Answer

Botulinum Toxins

Treatment with botulinum toxins are used to reduce muscle tone and improve passive and/or active function in adults with spasticity. Botulinum toxins are a neurotoxin derived from Clostridium botulinum. Botulinum toxin prevents acetylcholine from the presynaptic membrane, causing temporary calming of muscle contractions by blocking the transmission of nerve impulses.

OnabotulinumtoxinA (Botox)

Binds to the motor nerve terminal. The binding domain of the type A molecule appears to be the heavy chain, which is selective for cholinergic nerve terminals. It is then internalized via receptor-mediated endocytosis, a process in which the plasma membrane of the nerve cell invaginates around the toxin-receptor complex, forming a toxin-containing vesicle inside the nerve terminal. After internalization, the light chain of the toxin molecule, which has been demonstrated to contain the transmission-blocking domain, is released into the cytoplasm of the nerve terminal. Subsequently blocks acetylcholine release by cleaving SNAP-25, a cytoplasmic protein that is located on the cell membrane and that is required for the release of this transmitter. The affected terminals are inhibited from stimulating muscle contraction. The toxin does not affect the synthesis or storage of acetylcholine or the conduction of electrical signals along the nerve fiber.

Indications include cervical dystonia, severe primary axillary hyperhidrosis, strabismus, blepharospasm, upper and lower limb spasticity, overactive bladder, urinary incontinence, and migraine headache.

AbobotulinumtoxinA (Dysport)

Binds to receptor sites on the motor nerve terminals and, after uptake, inhibits release of acetylcholine, blocking transmission of impulses in neuromuscular tissue. At 7-14 days after administration of the initial dose, assess the patient for a satisfactory response. Increase the dose 2-fold over the previously administered dose in patients who experience incomplete paralysis of the target muscle.

Approved indications in the U.S. include upper and lower limb spasticity, cervical dystonia, and moderate-to-severe glabellar lines in adults. It is also indicated for lower limb spasticity in children aged 2 years or older.

IncobotulinumtoxinA (Xeomin)

IncobotulinumtoxinA is botulinum toxin type A that is free of complexing proteins found in the natural toxin from Clostridium botulinum. This drug is an acetylcholine release inhibitor and neuromuscular blocking agent. IncobotulinumtoxinA is indicated in adults for cervical dystonia in botulinum toxin–naive patients, and it is also indicated for blepharospasm in adults previously treated with onabotulinumtoxinA (Botox).

RimabotulinumtoxinB (Myobloc)

Inhibits acetylcholine release at the neuromuscular junction via a three stage process: 1) Heavy Chain mediated neurospecific binding of the toxin, 2) internalization of the toxin by receptor-mediated endocytosis, and 3) ATP and pH dependent translocation of the Light Chain to the neuronal cytosol where it acts as a zinc-dependent endoprotease cleaving polypeptides essential for neurotransmitter release. MYOBLOC specifically has been demonstrated to cleave synaptic Vesicle Associated Membrane Protein (VAMP, also known as synaptobrevin) which is a component of the protein complex responsible for docking and fusion of the synaptic vesicle to the presynaptic membrane, a necessary step to neurotransmitter release.

Indicated for cervical dystonia.

Did this answer your question?

Yes No

Additional feedback? (Optional)

Thank you for your feedback!

Gillard PJ, Sucharew H, Kleindorfer D, Belagaje S, Varon S, Alwell K, et al. The negative impact of spasticity on the health-related quality of life of stroke survivors: a longitudinal cohort study. Health Qual Life Outcomes. 2015 Sep 29. 13:159. [Medline].
Wei XJ, Tong KY, Hu XL. The responsiveness and correlation between Fugl-Meyer Assessment, Motor Status Scale, and the Action Research Arm Test in chronic stroke with upper-extremity rehabilitation robotic training. Int J Rehabil Res. 2011 Dec. 34(4):349-56. [Medline].
Burridge JH, Wood DE, Hermens HJ, Voerman GE, Johnson GR, van Wijck F, et al. Theoretical and methodological considerations in the measurement of spasticity. Disabil Rehabil. 2005 Jan 7-21. 27(1-2):69-80. [Medline].
Beaulieu LD, Schneider C. Effects of repetitive peripheral magnetic stimulation on normal or impaired motor control. A review. Neurophysiol Clin. 2013 Oct. 43(4):251-60. [Medline].
Sahin N, Ugurlu H, Karahan AY. Efficacy of therapeutic ultrasound in the treatment of spasticity: a randomized controlled study. NeuroRehabilitation. 2011. 29(1):61-6. [Medline].
Lubsch L, Habersang R, Haase M, Luedtke S. Oral baclofen and clonidine for treatment of spasticity in children. J Child Neurol. 2006 Dec. 21(12):1090-2. [Medline].
Kheder A, Nair KP. Spasticity: pathophysiology, evaluation and management. Pract Neurol. 2012 Oct. 12(5):289-98. [Medline].
Angel RW, Hoffman WW. The H reflex in rigid, spastic and normal subjects. Arch Neurol. 1983. 8:591-596.
Eisen A, Odusote K. Amplitude of the F wave: a potential means of documenting spasticity. Neurology. 1979 Sep. 29(9 Pt 1):1306-9. [Medline].
Rizzo MA, Hadjimichael OC, Preiningerova J, Vollmer TL. Prevalence and treatment of spasticity reported by multiple sclerosis patients. Mult Scler. 2004 Oct. 10(5):589-95. [Medline].
Urban PP, Wolf T, Uebele M, Marx JJ, Vogt T, Stoeter P, et al. Occurence and clinical predictors of spasticity after ischemic stroke. Stroke. 2010 Sep. 41 (9):2016-20. [Medline].
Sommerfeld DK, Gripenstedt U, Welmer AK. Spasticity after stroke: an overview of prevalence, test instruments, and treatments. Am J Phys Med Rehabil. 2012 Sep. 91 (9):814-20. [Medline].
Opheim A, Danielsson A, Alt Murphy M, Persson HC, Sunnerhagen KS. Upper-limb spasticity during the first year after stroke: stroke arm longitudinal study at the University of Gothenburg. Am J Phys Med Rehabil. 2014 Oct. 93 (10):884-96. [Medline].
Chrysagis N, Skordilis EK, Tsiganos G, Koutsouki D. Validity evidence of the Lateral Step Up (LSU) test for adolescents with spastic cerebral palsy. Disabil Rehabil. 2013 Jun. 35(11):875-80. [Medline].
Ansari NN, Naghdi S, Mashayekhi M, Hasson S, Fakhari Z, Jalaie S. Intra-rater reliability of the Modified Modified Ashworth Scale (MMAS) in the assessment of upper-limb muscle spasticity. NeuroRehabilitation. 2012. 31(2):215-22. [Medline].
Tizard JP. Cerebral palsies: treatment and prevention. The Croonian lecture 1978. J R Coll Physicians Lond. 1980 Apr. 14(2):72-7, 80. [Medline].
Coffey RJ, Edgar TS, Francisco GE, Graziani V, Meythaler JM, Ridgely PM, et al. Abrupt withdrawal from intrathecal baclofen: recognition and management of a potentially life-threatening syndrome. Arch Phys Med Rehabil. 2002 Jun. 83 (6):735-41. [Medline].
Alden TD, Lytle RA, Park TS, Noetzel MJ, Ojemann JG. Intrathecal baclofen withdrawal: a case report and review of the literature. Childs Nerv Syst. 2002 Oct. 18 (9-10):522-5. [Medline].
Ammar A, Ughratdar I, Sivakumar G, Vloeberghs MH. Intrathecal baclofen therapy--how we do it. J Neurosurg Pediatr. 2012 Nov. 10(5):439-44. [Medline].
Katrak PH, Cole AM, Poulos CJ, McCauley JC. Objective assessment of spasticity, strength, and function with early exhibition of dantrolene sodium after cerebrovascular accident: a randomized double-blind study. Arch Phys Med Rehabil. 1992 Jan. 73(1):4-9. [Medline].
Collin C, Davies P, Mutiboko IK, Ratcliffe S. Randomized controlled trial of cannabis-based medicine in spasticity caused by multiple sclerosis. Eur J Neurol. 2007 Mar. 14(3):290-6. [Medline].
Lakhan SE, Rowland M. Whole plant cannabis extracts in the treatment of spasticity in multiple sclerosis: a systematic review. BMC Neurol. 2009 Dec 4. 9:59. [Medline]. [Full Text].
Jarrett L, Nandi P, Thompson AJ. Managing severe lower limb spasticity in multiple sclerosis: does intrathecal phenol have a role?. J Neurol Neurosurg Psychiatry. 2002 Dec. 73(6):705-9. [Medline]. [Full Text].
[Guideline] American Academy of Neurology. Assessment: botulinum neurotoxin for the treatment of spasticity (an evidence-based review). Report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology. National Guideline Clearinghouse. Available at http://guideline.gov/content.aspx?id=12942. Accessed: February 4, 2014.
U.S. Food and Drug Administration. Available at . Accessed December 31, 2009. FDA Requires Boxed Warning for All Botulinum Toxin Products. Available at http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm149574.htm. Accessed: February 4, 2014.
Kakuda W, Abo M, Momosaki R, Yokoi A, Fukuda A, Ito H, et al. Combined therapeutic application of botulinum toxin type A, low-frequency rTMS, and intensive occupational therapy for post-stroke spastic upper limb hemiparesis. Eur J Phys Rehabil Med. 2012 Mar. 48(1):47-55. [Medline].
Demetrios M, Khan F, Turner-Stokes L, Brand C, McSweeney S. Multidisciplinary rehabilitation following botulinum toxin and other focal intramuscular treatment for post-stroke spasticity. Cochrane Database Syst Rev. 2013 Jun 5. 6:CD009689. [Medline].
Gooch JL, Patton CP. Combining botulinum toxin and phenol to manage spasticity in children. Arch Phys Med Rehabil. 2004 Jul. 85(7):1121-4. [Medline].
Intiso D, Simone V, Di Rienzo F, Iarossi A, Pazienza L, Santamato A, et al. High doses of a new botulinum toxin type A (NT-201) in adult patients with severe spasticity following brain injury and cerebral palsy. NeuroRehabilitation. 2014 Jan 28. [Medline].
Wang YJ, Gao BQ. Efficacy and safety of serial injections of botulinum toxin A in children with spastic cerebral palsy. World J Pediatr. 2013 Nov. 9(4):342-5. [Medline].
Simpson DM. Clinical trials of botulinum toxin in the treatment of spasticity. Muscle Nerve Suppl. 1997. 6:S169-75. [Medline].
Rosales RL, Chua-Yap AS. Evidence-based systematic review on the efficacy and safety of botulinum toxin-A therapy in post-stroke spasticity. J Neural Transm. 2008. 115(4):617-23. [Medline].
Fehlings D, Rang M, Glazier J, Steele C. An evaluation of botulinum-A toxin injections to improve upper extremity function in children with hemiplegic cerebral palsy. J Pediatr. 2000 Sep. 137(3):331-7. [Medline].
Jost WH, Hefter H, Reissig A, Kollewe K, Wissel J. Efficacy and safety of botulinum toxin type A (Dysport) for the treatment of post-stroke arm spasticity: Results of the German-Austrian open-label post-marketing surveillance prospective study. J Neurol Sci. 2013 Nov 22. [Medline].
Snow BJ, Tsui JK, Bhatt MH, Varelas M, Hashimoto SA, Calne DB. Treatment of spasticity with botulinum toxin: a double-blind study. Ann Neurol. 1990 Oct. 28(4):512-5. [Medline].
Dykstra DD, Sidi AA. Treatment of detrusor-sphincter dyssynergia with botulinum A toxin: a double-blind study. Arch Phys Med Rehabil. 1990 Jan. 71(1):24-6. [Medline].
Koman LA, Mooney JF, Smith BP. Botulinum toxin: potential role in the management of cerebral palsy during childhood. Jankovic J, Hallett M, eds. Therapy with Botulinum Toxin. NY: Marcel Dekker; 1994. 511-522.
Simpson DM, Alexander DN, O'Brien CF, Tagliati M, Aswad AS, Leon JM, et al. Botulinum toxin type A in the treatment of upper extremity spasticity: a randomized, double-blind, placebo-controlled trial. Neurology. 1996 May. 46(5):1306-10. [Medline].
Molenaers G, Fagard K, Van Campenhout A, Desloovere K. Botulinum toxin A treatment of the lower extremities in children with cerebral palsy. J Child Orthop. 2013 Nov. 7(5):383-387. [Medline]. [Full Text].
Schwerin A, Berweck S, Fietzek UM, Heinen F. Botulinum toxin B treatment in children with spastic movement disorders: a pilot study. Pediatr Neurol. 2004 Aug. 31(2):109-13. [Medline].
Francisco GE, Yablon SA, Schiess MC, Wiggs L, Cavalier S, Grissom S. Consensus panel guidelines for the use of intrathecal baclofen therapy in poststroke spastic hypertonia. Top Stroke Rehabil. 2006 Fall. 13(4):74-85. [Medline].
Krach LE, Nettleton A, Klempka B. Satisfaction of individuals treated long-term with continuous infusion of intrathecal baclofen by implanted programmable pump. Pediatr Rehabil. 2006 Jul-Sep. 9(3):210-8. [Medline].
Zahavi A, Geertzen JH, Middel B, Staal M, Rietman JS. Long term effect (more than five years) of intrathecal baclofen on impairment, disability, and quality of life in patients with severe spasticity of spinal origin. J Neurol Neurosurg Psychiatry. 2004 Nov. 75(11):1553-7. [Medline]. [Full Text].
Borowski A, Littleton AG, Borkhuu B, Presedo A, Shah S, Dabney KW, et al. Complications of intrathecal baclofen pump therapy in pediatric patients. J Pediatr Orthop. 2010 Jan-Feb. 30(1):76-81. [Medline].
Centonze D, Koch G, Versace V, Mori F, Rossi S, Brusa L, et al. Repetitive transcranial magnetic stimulation of the motor cortex ameliorates spasticity in multiple sclerosis. Neurology. 2007 Mar 27. 68(13):1045-50. [Medline].
Buckon CE, Thomas S, Pierce R, Piatt JH Jr, Aiona MD. Developmental skills of children with spastic diplegia: functional and qualitative changes after selective dorsal rhizotomy. Arch Phys Med Rehabil. 1997 Sep. 78(9):946-51. [Medline].
Cole GF, Farmer SE, Roberts A, Stewart C, Patrick JH. Selective dorsal rhizotomy for children with cerebral palsy: the Oswestry experience. Arch Dis Child. 2007 Sep. 92(9):781-5. [Medline]. [Full Text].
Kagawa S, Koyama T, Hosomi M, Takebayashi T, Hanada K, Hashimoto F, et al. Effects of constraint-induced movement therapy on spasticity in patients with hemiparesis after stroke. J Stroke Cerebrovasc Dis. 2013 May. 22(4):364-70. [Medline].
Hoseini N, Koceja DM, Riley ZA. The effect of operant-conditioning balance training on the down-regulation of spinal H-reflexes in a spastic patient. Neurosci Lett. 2011 Oct 24. 504(2):112-4. [Medline].
Rayegani SM, Shojaee H, Sedighipour L, Soroush MR, Baghbani M, Amirani OB. The effect of electrical passive cycling on spasticity in war veterans with spinal cord injury. Front Neurol. 2011. 2:39. [Medline]. [Full Text].
Johnston TE, Watson KE, Ross SA, Gates PE, Gaughan JP, Lauer RT, et al. Effects of a supported speed treadmill training exercise program on impairment and function for children with cerebral palsy. Dev Med Child Neurol. 2011 Aug. 53(8):742-50. [Medline].
Negahban H, Rezaie S, Goharpey S. Massage therapy and exercise therapy in patients with multiple sclerosis: a randomized controlled pilot study. Clin Rehabil. 2013 Dec. 27(12):1126-36. [Medline].
Warnink-Kavelaars J, Vermeulen RJ, Becher JG. Study protocol: precision of a protocol for manual intramuscular needle placement checked by passive stretching and relaxing of the target muscle in the lower extremity during BTX-A treatment in children with spastic cerebral palsy, as verified by means of electrical stimulation. BMC Pediatr. 2013 Aug 22. 13:129. [Medline]. [Full Text].
Kubota S, Tanabe S, Sugawara K, Muraoka Y, Itoh N, Kanada Y. Stimulus point distribution in deep or superficial peroneal nerve for treatment of ankle spasticity. Neuromodulation. 2013 May-Jun. 16(3):251-5; discussion 255. [Medline].
Pierson SH. Outcome measures in spasticity management. Muscle Nerve Suppl. 1997. 6:S36-60. [Medline].
Peng Q, Park HS, Shah P, Wilson N, Ren Y, Wu YN, et al. Quantitative evaluations of ankle spasticity and stiffness in neurological disorders using manual spasticity evaluator. J Rehabil Res Dev. 2011. 48(4):473-81. [Medline]. [Full Text].
Nielsen S, Germanos R, Weier M, Pollard J, Degenhardt L, Hall W, et al. The Use of Cannabis and Cannabinoids in Treating Symptoms of Multiple Sclerosis: a Systematic Review of Reviews. Curr Neurol Neurosci Rep. 2018 Feb 13. 18 (2):8. [Medline].
Allan GM, Finley CR, Ton J, Perry D, Ramji J, Crawford K, et al. Systematic review of systematic reviews for medical cannabinoids: Pain, nausea and vomiting, spasticity, and harms. Can Fam Physician. 2018 Feb. 64 (2):e78-e94. [Medline].

Media Gallery

of 0

Author

Krupa Pandey, MD Assistant Professor of Neurology, Department of Neurology, Hackensack Meridian School of Medicine at Seton Hall University; Neurologist in Multiple Sclerosis, Neuroscience Institute at Hackensack University Medical Center; Adjunct Professor of Neurology, Multiple Sclerosis Comprehensive Care Center, NYU Langone School of Medicine

Krupa Pandey, MD is a member of the following medical societies: American Academy of Neurology

Disclosure: Serve(d) as a director, officer, partner, employee, advisor, consultant or trustee for: Biogen; Sanofi-Genzyme; Teva; Serono; Genentech<br/>Serve(d) as a speaker or a member of a speakers bureau for: Biogen; Sanofi-Genzyme; Teva; Genentech.

Specialty Editor Board

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Received salary from Medscape for employment. for: Medscape.

Chief Editor

Stephen A Berman, MD, PhD, MBA Professor of Neurology, University of Central Florida College of Medicine

Stephen A Berman, MD, PhD, MBA is a member of the following medical societies: Alpha Omega Alpha, American Academy of Neurology, Phi Beta Kappa

Disclosure: Nothing to disclose.

Additional Contributors

Zeba F Vanek, MD, MBBS, DCN Associate Professor of Neurology, University of California, Los Angeles, David Geffen School of Medicine

Zeba F Vanek, MD, MBBS, DCN is a member of the following medical societies: American Academy of Neurology

Disclosure: Nothing to disclose.

Acknowledgements

Joseph Carcione Jr, DO, MBA Consultant in Neurology and Medical Acupuncture, Medical Management and Organizational Consulting, Central Westchester Neuromuscular Care, PC; Medical Director, Oxford Health Plans

Joseph Carcione Jr, DO, MBA is a member of the following medical societies: American Academy of Neurology

Disclosure: Nothing to disclose.

Martin K Childers, DO, PhD Professor, Department of Neurology, Wake Forest University School of Medicine; Professor, Rehabilitation Program, Institute for Regenerative Medicine, Wake Forest Baptist Medical Center

Martin K Childers, DO, PhD is a member of the following medical societies: American Academy of Physical Medicine and Rehabilitation, American Congress of Rehabilitation Medicine, American Osteopathic Association, Christian Medical & Dental Society, and Federation of American Societies for Experimental Biology

Disclosure: Allergan pharma Consulting fee Consulting

Glenn Lopate, MD Associate Professor, Department of Neurology, Division of Neuromuscular Diseases, Washington University School of Medicine; Director of Neurology Clinic, St Louis ConnectCare; Consulting Staff, Department of Neurology, Barnes-Jewish Hospital

Glenn Lopate, MD is a member of the following medical societies: American Academy of Neurology, American Association of Neuromuscular and Electrodiagnostic Medicine, and Phi Beta Kappa

Disclosure: Baxter Grant/research funds Other; Amgen Grant/research funds None

Consuelo T Lorenzo, MD Executive Health Resources

Consuelo T Lorenzo, MD is a member of the following medical societies: American Academy of Physical Medicine and Rehabilitation

Disclosure: Nothing to disclose.

Elizabeth A Moberg-Wolff, MD Medical Director, Pediatric Rehabilitation Medicine Associates

Elizabeth A Moberg-Wolff, MD is a member of the following medical societies: American Academy for Cerebral Palsy and Developmental Medicine and American Academy of Physical Medicine and Rehabilitation

Disclosure: Merz None Speaking and teaching

Richard Salcido, MD Chairman, Erdman Professor of Rehabilitation, Department of Physical Medicine and Rehabilitation, University of Pennsylvania School of Medicine

Richard Salcido, MD is a member of the following medical societies: American Academy of Pain Medicine, American Academy of Physical Medicine and Rehabilitation, American College of Physician Executives, American Medical Association, and American Paraplegia Society

Disclosure: Nothing to disclose.

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Medscape Salary Employment

Which medications in the drug class Botulinum Toxins are used in the treatment of Spasticity?

Botulinum Toxins

OnabotulinumtoxinA (Botox)

AbobotulinumtoxinA (Dysport)

IncobotulinumtoxinA (Xeomin)

RimabotulinumtoxinB (Myobloc)

Related Questions:

About

Membership

Apps

WebMD Network

Editions

What to Read Next on Medscape

Which medications in the drug class Botulinum Toxins are used in the treatment of Spasticity?

Botulinum Toxins

OnabotulinumtoxinA (Botox)

AbobotulinumtoxinA (Dysport)

IncobotulinumtoxinA (Xeomin)

RimabotulinumtoxinB (Myobloc)

Related Questions:

References

Tables

Contributor Information and Disclosures

Find Us On

About

Membership

Apps

WebMD Network

Editions

What to Read Next on Medscape

Related Conditions and Diseases

Medscape Consult

News & Perspective

Tools

Most Popular Articles

Recommended