Skip to main content
×
×
Home

Adverse Clinical Effects of Botulinum Toxin Intramuscular Injections for Spasticity

  • Chetan P. Phadke (a1) (a2) (a3), Chitra K. Balasubramanian (a4), Alanna Holz (a1), Caitlin Davidson (a1), Farooq Ismail (a1) (a2) and Chris Boulias (a1) (a2)...
Abstract

Objective: The adverse events (AEs) with botulinum toxin type-A (BoNTA), used for indications other than spasticity, are widely reported in the literature. However, the site, dose, and frequency of injections are different for spasticity when compared to the treatment for other conditions and hence the AEs may be different as well. The objective of this study was to summarize the AEs reported in Canada and systematically review the AEs with intramuscular botulinum toxin injections to treat focal spasticity. Methods : Data were gathered from Health Canada (2009-2013) and major electronic databases. Results : In a 4 year period, 285 AEs were reported. OnabotulinumtoxinA (n=272 events): 68% females, 53% serious, 18% hospitalization, and 8% fatalities. The type of AEs reported were – muscle weakness (19%), oropharyngeal (14%), respiratory (14%), eye related (8%), bowel/bladder related (8%), and infection (5%). IncobotulinumtoxinA (n=13): 38% females, 62% serious, and 54% hospitalization. The type of AEs reported were – muscle weakness (15%), oropharyngeal (15%), respiratory (38%), eye related (23%), bowel/bladder related (15%), and infection (15%). Commonly reported AEs in the literature were muscle weakness, pain, oropharyngeal, bowel/bladder, blood circulation, neurological, gait, and respiratory problems. Conclusion: While BoNTA is useful in managing spasticity, future studies need to investigate the factors that can minimize AEs. A better understanding of the underlying mechanisms of the AEs can also improve guidelines for BoNTA administration and enhance outcomes.

Réactions indésirables à des injections intramusculaires de toxine botulique utilisée pour traiter la spasticité. Objectif: Les réactions indésirables (RI) à la toxine botulique de type A (BoNTA) utilisée à des fins autres que le traitement de la spasticité ont été abondamment rapportées dans la littérature. Cependant, le point d’injection, la dose et la fréquence des injections sont différents quand elle est utilisée pour traiter la spasticité par rapport à son utilisation pour traiter d’autres affections et donc les RI peuvent également être différentes. Le but de cette étude était de présenter un sommaire des RI rapportées au Canada et de revoir systématiquement les RI rencontrées lors d’injections intramusculaires de toxine botulique pour traiter la spasticité focale. Méthode: Nous avons recueilli les données de Santé Canada de 2009 à 2013 et ainsi que celles des principales bases de données électroniques. Résultats: Au cours d’une période de 4 ans, 285 RI ont été rapportées, dont 272 RI avec l’onabotulinum toxine A. Soixante-huit pour cent sont survenues chez des femmes, 53% étaient des RI sérieuses, 18% ont nécessité une hospitalisation et 8% ont été fatales. Les RI rapportées étaient de la faiblesse musculaire (19%), des RI oropharyngées (14%), respiratoires (14%), oculaires (8%), en lien à l’intestin / la vessie (8%) et infectieuses (5%). Avec l’incobotulinum toxine A (n=13) les RI rapportées sont survenues chez des femmes dans 38% des cas, 62% étaient sérieuses et 54% ont nécessité une hospitalisation. Ces RI étaient de la faiblesse musculaire (15%), des troubles oropharyngés (15%), respiratoires (38%), en lien avec les yeux (23%), en lien avec l’intestin / la vessie (15%) et infectieuses (15%). Les RI fréquemment rapportées dans la littérature étaient la faiblesse musculaire, la douleur, des troubles oropharyngés, intestinaux / vésicaux, circulatoires, neurologiques, des troubles de la démarche et des troubles respiratoires. Conclusion: Bien que la BoNTA soit utile dans le traitement de la spasticité, des études méritent d’être entreprises pour identifier les facteurs qui pourraient minimiser les RI. Une meilleure compréhension des mécanismes sous-jacents est également susceptible d’améliorer les lignes directrices concernant l’administration de la BoNTA ainsi que les résultats de ce traitement.

  • View HTML
    • Send article to Kindle

      To send this article to your Kindle, first ensure no-reply@cambridge.org is added to your Approved Personal Document E-mail List under your Personal Document Settings on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part of your Kindle email address below. Find out more about sending to your Kindle. Find out more about sending to your Kindle.

      Note you can select to send to either the @free.kindle.com or @kindle.com variations. ‘@free.kindle.com’ emails are free but can only be sent to your device when it is connected to wi-fi. ‘@kindle.com’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.

      Find out more about the Kindle Personal Document Service.

      Adverse Clinical Effects of Botulinum Toxin Intramuscular Injections for Spasticity
      Available formats
      ×
      Send article to Dropbox

      To send this article to your Dropbox account, please select one or more formats and confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your <service> account. Find out more about sending content to Dropbox.

      Adverse Clinical Effects of Botulinum Toxin Intramuscular Injections for Spasticity
      Available formats
      ×
      Send article to Google Drive

      To send this article to your Google Drive account, please select one or more formats and confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your <service> account. Find out more about sending content to Google Drive.

      Adverse Clinical Effects of Botulinum Toxin Intramuscular Injections for Spasticity
      Available formats
      ×
Copyright
Corresponding author
Correspondence to: Chetan P. Phadke, Spasticity Research Program, West Park Healthcare Centre, Toronto, ON, Canada M6M 2J5. Email: chetan.phadke@westpark.org
References
Hide All
1. Shaw, L, Rodgers, H, Price, C, et al. BoTULS: a multicentre randomised controlled trial to evaluate the clinical effectiveness and cost-effectiveness of treating upper limb spasticity due to stroke with botulinum toxin type A. Health Technol Assess. 2010;14:1-113, iii-iv.
2. Ward, AB, Aguilar, M, De Beyl, Z, et al. Use of botulinum toxin type A in management of adult spasticity--a European consensus statement. J Rehabil Med. 2003;35(2):98-99.
3. Turkel, CC, Bowen, B, Liu, J, Brin, MF. Pooled analysis of the safety of botulinum toxin type A in the treatment of poststroke spasticity. Arch Phys Med Rehab. 2006;87:786-792.
4. Truong, DD, Stenner, A, Reichel, G. Current clinical applications of botulinum toxin. Curr Pharm Des. 2009;15:3671-3680.
5. Allergan Inc. C.Botox Product Monograph (Canada). 2013. http://www.allergan.ca/assets/pdf/ca_botox_pm.pdf. Accessed Date of approval: October 10,2013.
6. Merz, C. Xeomin Product Monograph. Merz Canada Ltd.; 2011.
7. Roche, N, Schnitzler, A, Genet, FF, Durand, MC, Bensmail, D. Undesirable distant effects following botulinum toxin type a injection. Clin Neuropharmacol. 2008;31:272-280.
8. Coté, TR, Mohan, AK, Polder, JA, Walton, MK, Braun, MM. Botulinum toxin type A injections: adverse events reported to the US Food and Drug Administration in therapeutic and cosmetic cases. J Am Acad Dermatol. 2005;53:407-415.
9. DGNews. Canada Approves Botox (Botulinum Toxin Type A) For Focal Spasticity. DocGuide.com. 2001. http://www.docguide.com/canada-approves-botox-botulinum-toxin-type-focal-spasticity.
10. Howick, J, Chalmers, I, Library, JL, et al. The Oxford 2011 Levels of Evidence. 2011; http://www.cebm.net/index.aspx?o=5653. Accessed 4th October, 2012.
11. Muller, F, Cugy, E, Ducerf, C, et al. Safety and self-reported efficacy of botulinum toxin for adult spasticity in current clinical practice: a prospective observational study. Clin Rehabil. Feb 2012;26(2):174-179.
12. Thomas, AM, Simpson, DM. Contralateral weakness following botulinum toxin for poststroke spasticity. Muscle Nerve. Sep 2012;46(3):443-448.
13. Varghese-Kroll, E, Elovic, EP. Contralateral weakness and fatigue after high-dose botulinum toxin injection for management of poststroke spasticity. Am J Phys Med Rehabil. 2009;88:495-499.
14. Bakheit, AM, Ward, CD, McLellan, DL. Generalised botulism-like syndrome after intramuscular injections of botulinum toxin type A: a report of two cases. J Neurol Neurosurg Psychiatry. 1997;62:198.
15. Borg-Stein, J, Pine, ZM, Miller, JR, Brin, MF. Botulinum toxin for the treatment of spasticity in multiple sclerosis. New observations. Am J Phys Med Rehabil. 1993;72:364-368.
16. Crowner, BE, Torres-Russotto, D, Carter, AR, Racette, BA. Systemic weakness after therapeutic injections of botulinum toxin a: a case series and review of the literature. Clin Neuropharmacol. 2010;33:243-247.
17. Gusev, Y, Banach, M, Simonow, A, et al. Efficacy and Safety of Botulinum Type A Toxin in Adductor Spasticity Due to Multiple Sclerosis. J Musculoskelet Pain. 2008;16(3):175-188.
18. Simpson, DM, Gracies, JM, Yablon, SA, Barbano, R, Brashear, A, Team, BTS. Botulinum neurotoxin versus tizanidine in upper limb spasticity: a placebo-controlled study. J Neurol Neurosurg Psychiatry. 2009;80:380-385.
19. Barnes, M, Schnitzler, A, Medeiros, L, Aguilar, M, Lehnert-Batar, A, Minnasch, P. Efficacy and safety of NT 201 for upper limb spasticity of various etiologies--a randomized parallel-group study. Acta Neurol Scand. 2010;12:295-302.
20. Joshi, T. Unwanted Muscle Weakness following Botulinum Neurotoxin A Administration in Spinal Cord Injury with Literature Review. Indian J Phys Med Rehab. 2012;23:20-24.
21. Gordon, MF, Brashear, A, Elovic, E, et al. Repeated dosing of botulinum toxin type A for upper limb spasticity following stroke. Neurology. 2004;63:1971-1973.
22. Hecht, MJ, Stolze, H, Auf dem Brinke, M, et al. Botulinum neurotoxin type A injections reduce spasticity in mild to moderate hereditary spastic paraplegia--report of 19 cases. Mov Disord. 2008;23:228-233.
23. Pittock, SJ, Moore, AP, Hardiman, O, et al. A double-blind randomised placebo-controlled evaluation of three doses of botulinum toxin type A (Dysport) in the treatment of spastic equinovarus deformity after stroke. Cerebrovasc Dis. 2003;15:289-300.
24. Coban, A, Matur, Z, Hanagasi, HA, Parman, Y. Iatrogenic botulism after botulinum toxin type A injections. Clin Neuropharmacol. 2010;33:158-160.
25. Hyman, N, Barnes, M, Bhakta, B, et al. Botulinum toxin (Dysport) treatment of hip adductor spasticity in multiple sclerosis: a prospective, randomised, double blind, placebo controlled, dose ranging study. J Neurol Neurosurg Psychiatry. 2000;68:707-712.
26. Suputtitada, A, Suwanwela, NC. The lowest effective dose of botulinum A toxin in adult patients with upper limb spasticity. Disabil Rehabil. 2005;27:176-184.
27. Dunne, JW, Heye, N, Dunne, SL. Treatment of chronic limb spasticity with botulinum toxin A. J Neurol Neurosurg Psychiatry. 1995;58:232-235.
28. Mohammadi, B, Balouch, SA, Dengler, R, Kollewe, K. Long-term treatment of spasticity with botulinum toxin type A: an analysis of 1221 treatments in 137 patients. Neurol Res. 2010;32:309-313.
29. Pullman, S, Greene, P, Fahn, S, Pedersen, S. Approach to the treatment of limb disorders with botulinum toxin A. Experience with 187 patients. Arch Neurol. J996;53:617-624.
30. Bakheit, AM, Fedorova, NV, Skoromets, AA, Timerbaeva, SL, Bhakta, BB, Coxon, L. The beneficial antispasticity effect of botulinum toxin type A is maintained after repeated treatment cycles. J Neurol Neurosurg Psychiatry. 2004;75:1558-1561.
31. Kanovsky, P, Slawek, J, Denes, Z, et al. Efficacy and safety of treatment with incobotulinum toxin A (botulinum neurotoxin type A free from complexing proteins; NT 201) in post-stroke upper limb spasticity. J Rehab Med. 2011;43:486-492.
32. Kaji, R, Osako, Y, Suyama, K, et al. Botulinum toxin type A in post-stroke lower limb spasticity: a multicenter, double-blind, placebo-controlled trial. J Neurol. 2010;257:1330-1337.
33. Kanovský, P, Slawek, J, Denes, Z, et al. Efficacy and safety of botulinum neurotoxin NT 201 in poststroke upper limb spasticity. Clin Neuropharmacol. 2009;32:259-265.
34. Bruggemann, N, Dognitz, L, Harms, L, Moser, A, Hagenah, J. Skin reactions after intramuscular injection of Botulinum toxin A: a rare side effect. BMJ Case Rep. 2009;2009.
35. Papadonikolakis, AS, Vekris, MD, Kostas, JP, Korompilias, AV, Soucacos, PN. Transient erectile dysfunction associated with intramuscular injection of botulinum toxin type A. J South Orthop Assoc. 2002;11:116-118.
36. Opara, J, Hordyńska, E, Swoboda, A. Effectiveness of botulinum toxin A in the treatment of spasticity of the lower extremities in adults - preliminary report. Ortop Traumatol Rehabil. 2007, May-Jun 2007;9(3):277-285.
37. Lange, DJ, Brin, MF, Warner, CL, Fahn, S, Lovelace, RE. Distant effects of local injection of botulinum toxin. Muscle Nerve. 1987;10:552-555.
38. Naidu, K, Smith, K, Sheedy, M, Adair, B, Yu, X, Graham, HK. Systemic adverse events following botulinum toxin A therapy in children with cerebral palsy. Dev Med Child Neurol. 2010;52:139-144.
39. Ghasemi, M, Salari, M, Khorvash, F, Shaygannejad, V. A literature review on the efficacy and safety of botulinum toxin: an injection in post-stroke spasticity. Int J Prev Med. 2013;4(Suppl 2):S147-S158.
40. Yucesoy, CA, Emre Arıkan, Ö, Ateş, F. BTX-A administration to the target muscle affects forces of all muscles within an intact compartment and epimuscular myofascial force transmission. J Biomech Eng. 2012;134:111002.
41. Brin, MF, Lyons, KE, Doucette, J, et al. A randomized, double masked, controlled trial of botulinum toxin type A in essential hand tremor. Neurology. 2001;56:1523-1528.
42. Heinen, F, Molenaers, G, Fairhurst, C, et al. European consensus table 2006 on botulinum toxin for children with cerebral palsy. Eur J Paediatr Neurol. 2006;10:215-225.
43. Wissel, J, Ward, AB, Erztgaard, P, et al. European consensus table on the use of botulinum toxin type A in adult spasticity. J Rehabil Med. 2009;41:13-25.
44. Phadke, CP, Davidson, C, Ismail, F, Boulias, C. The effect of neural lesion type on botulinum toxin dosage: a retrospective chart review. PMR. 2014;6:406-411.
45. Esquenazi, A, Mayer, N, Lee, S, et al. Patient registry of outcomes in spasticity care. Am J Phys Med Rehabil. 2012;91:729-746.
46. Caleo, M, Antonucci, F, Restani, L, Mazzocchio, R. A reappraisal of the central effects of botulinum neurotoxin type A: by what mechanism? J Neurochem. 2009;109:15-24.
47. Calne, S. Local treatment of dystonia and spasticity with injections of botulinum-A toxin. Axone. 1993;14:85-88.
48. Kaji, R, Osako, Y, Suyama, K, et al. Botulinum toxin type A in post-stroke upper limb spasticity. Curr Med Res Opin. 2010;26:1983-1992.
49. Monograph D. Highlights of prescribing information. http://www.dysport.com/hcp/PDFs/Dysport_Patiens_PI_Aug2012.pdf. Accessed 31st March, 2015.
50. Phadke, CP, Balasubramanian, CK, Ismail, F, Boulias, C. Revisiting physiologic and psychologic triggers that increase spasticity. Am J Phys Med Rehabil. 2013;92:357-369.
51. Fung, S, Phadke, CP, Kam, A, Ismail, F, Boulias, C. Effect of topical anesthetics on needle insertion pain during botulinum toxin type A injections for limb spasticity. Arch Phys Med Rehabil. 2012;93:1643-1647.
52. Chin, TY, Nattrass, GR, Selber, P, Graham, HK. Accuracy of intramuscular injection of botulinum toxin A in juvenile cerebral palsy: a comparison between manual needle placement and placement guided by electrical stimulation. J Pediatr Orthop. 2005;25:286-291.
53. Wendel, I, Cole, J. Treatment of extensor digitorum brevis manus myalgia with botulinum toxin. PMR. 2014;6:284-286.
54. Garner, CG, Straube, A, Witt, TN, Gasser, T, Oertel, WH. Time course of distant effects of local injections of botulinum toxin. Mov Disord. 1993;8:33-37.
55. Schnider, P, Brichta, A, Schmied, M, Auff, E. Gallbladder dysfunction induced by botulinum A toxin. Lancet. 1993;342:811-812.
56. Girlanda, P, Vita, G, Nicolosi, C, Milone, S, Messina, C. Botulinum toxin therapy: distant effects on neuromuscular transmission and autonomic nervous system. J Neurol Neurosurg Psychiatry. 1992;55:844-845.
57. MacKenzie, I, Burnstock, G, Dolly, JO. The effects of purified botulinum neurotoxin type A on cholinergic, adrenergic and non-adrenergic, atropine-resistant autonomic neuromuscular transmission. Neuroscience. 1982;7:997-1006.
58. Nigam, PK, Nigam, A. Botulinum toxin. Indian J Dermatol. 2010;55:8-14.
59. Schnider, P, Berger, T, Schmied, M, Fertl, L, Auff, E. Increased residual urine volume after local injection of botulinum A toxin. Nervenarzt. 1995;66:465-467.
60. Shaw, L, Rodgers, H. Botulinum toxin type A for upper limb spasticity after stroke. Expert Rev Neurother. 2009;9:1713-1725.
61. Wiegand, H, Erdmann, G, Wellhöner, HH. 125I-labelled botulinum A neurotoxin: pharmacokinetics in cats after intramuscular injection. Naunyn Schmiedebergs Arch Pharmacol. 1976;292:161-165.
62. Matak, I, Bach-Rojecky, L, Filipović, B, Lacković, Z. Behavioral and immunohistochemical evidence for central antinociceptive activity of botulinum toxin A. Neuroscience. 2011;186:201-207.
63. Matak, I, Riederer, P, Lacković, Z. Botulinum toxin’s axonal transport from periphery to the spinal cord. Neurochem Int. 2012;61:236-239.
64. Restani, L, Giribaldi, F, Manich, M, et al. Botulinum neurotoxins A and E undergo retrograde axonal transport in primary motor neurons. PLoS Pathog. 2012;8:e1003087.
65. Koman, LA, Mooney, JF, Smith, BP, Walker, F, Leon, JM. Botulinum toxin type A neuromuscular blockade in the treatment of lower extremity spasticity in cerebral palsy: a randomized, double-blind, placebo-controlled trial. BOTOX Study Group. J Pediatr Orthop. 2000;20:108-115.
66. Phadke, CP, Ismail, F, Boulias, C. Assessing the neurophysiological effects of botulinum toxin treatment for adults with focal limb spasticity: a systematic review. Disabil Rehab. 2011.
67. Marchand-Pauvert, V, Aymard, C, Giboin, LS, Dominici, F, Rossi, A, Mazzocchio, R. Beyond muscular effects: depression of spinal recurrent inhibition after botulinum neurotoxin A. J Physiol. 2013;591:1017-1029.
68. Phadke, C, On, A, Kirazli, Y, Ismail, F, Boulias, C. Intrafusal effects of botulinum toxin injections for spasticity: revisiting a previous paper. Neurosci Letters. 2013;Accepted manuscript in press.
69. Borodic, GE, Ferrante, R, Pearce, LB, Smith, K. Histologic assessment of dose-related diffusion and muscle fiber response after therapeutic botulinum A toxin injections. Mov Disord. 1994;9:31-39.
70. Brodsky, MA, Swope, DM, Grimes, D. Diffusion of botulinum toxins. Tremor Other Hyperkinet Mov (N Y). 2012;2.
71. Benecke, R. Clinical relevance of botulinum toxin immunogenicity. BioDrugs. 2012;26:e1-e9.
72. Walker, HW, Lee, MY, Bahroo, LB, Hedera, P, Charles, D. Botulinum Toxin Injection Techniques for the Management of Adult Spasticity. PM & R: the journal of injury, function, and rehabilitation. Apr 2015;7(4):417-427.
73. Truong, D, Brodsky, M, Lew, M, et al. Long-term efficacy and safety of botulinum toxin type A (Dysport) in cervical dystonia. Parkinsonism Relat Disord. 2010;16:316-323.
74. Anderson, TJ, Rivest, J, Stell, R, et al. Botulinum toxin treatment of spasmodic torticollis. J R Soc Med. 1992;85:524-529.
75. Zuber, M, Sebald, M, Bathien, N, de Recondo, J, Rondot, P. Botulinum antibodies in dystonic patients treated with type A botulinum toxin: frequency and significance. Neurology. 1993;43:1715-1718.
76. Canada DMRF. Botulinum Toxin Injections. http://www.dystoniacanada.org/about-dystonia/treatments/botulinum-injections. Accessed 30th March, 2015.
77. Canada DMRF. New XEOMIN® – Available in Canada. http://www.dystoniacanada.org/news/research/new-xeomin%C2%AE-%E2%80%93-available-canada. Accessed 30th March, 2015.
Recommend this journal

Email your librarian or administrator to recommend adding this journal to your organisation's collection.

Canadian Journal of Neurological Sciences
  • ISSN: 0317-1671
  • EISSN: 2057-0155
  • URL: /core/journals/canadian-journal-of-neurological-sciences
Please enter your name
Please enter a valid email address
Who would you like to send this to? *
×

Keywords

Metrics

Altmetric attention score

Full text views

Total number of HTML views: 0
Total number of PDF views: 0 *
Loading metrics...

Abstract views

Total abstract views: 0 *
Loading metrics...

* Views captured on Cambridge Core between <date>. This data will be updated every 24 hours.

Usage data cannot currently be displayed