Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

Use of botulinum toxin in the neurology clinic

Abstract

Botulinum neurotoxin (BoNT) is an effective treatment for conditions associated with overactivity of glandular, smooth or skeletal muscle, and this toxin can also ameliorate certain painful conditions. Electromyography, endoscopy and imaging techniques such as ultrasonography and fluoroscopy have been used to increase the accuracy of BoNT injections. This Review assesses the mechanisms of action of BoNT, and examines the use of BoNT injections in numerous neurological conditions, including dystonia, spasticity, headaches and other painful disorders, hemifacial spasm, essential tremor, motor tics, hyperhidrosis, and sialorrhea and drooling. Important practical aspects, such as the reconstitution of BoNT, dosing, and methods of administration, are also addressed.

Key Points

  • Seven serotypes of botulinum neurotoxin (BoNT)—BoNT/A–G—have been identified, but only BoNT/A and BoNT/B are used in clinical practice

  • BoNT is used to treat conditions associated with overactivity of glandular, smooth or skeletal muscle, and to ameliorate some painful conditions

  • BoNT is probably an effective treatment for focal and segmental dystonia; spasticity; back, joint, neuropathic and pelvic pain; hemifacial spasm; essential tremor; motor tics; and palmar and axillary hyperhidrosis

  • Electromyography, endoscopy and imaging techniques have been used to increase the accuracy of BoNT injections

  • A lack of controlled or comparative studies prevents assessment of the effectiveness of electromyography, endoscopy and imaging techniques over other localization techniques

This is a preview of subscription content, access via your institution

Relevant articles

Open Access articles citing this article.

Access options

Buy article

Get time limited or full article access on ReadCube.

$32.00

All prices are NET prices.

Figure 1: Decision tree to aid identification of the most appropriate technique for injecting botulinum toxin.
Figure 2: Typical equipment required for the injection of botulinum toxin.

References

  1. Schulte-Mattler, W. J. Use of botulinum toxin A in adult neurological disorders: efficacy, tolerability and safety. CNS Drugs 22, 725–738 (2008).

    CAS  PubMed  Google Scholar 

  2. Erbguth, F. J. & Naumann, M. Historical aspects of botulinum toxin: Justinus Kerner (1786–1862) and the ''sausage poison''. Neurology 53, 1850–1853 (1999).

    CAS  PubMed  Google Scholar 

  3. van Ermengem, E. Classics in infectious diseases. A new anaerobic bacillus and its relation to botulism. E. van Ermengem. Originally published as ''Ueber einen neuen anaeroben Bacillus und seine Beziehungen zum Botulismus'' in Zeitschrift für Hygiene und Infektionskrankheiten. 26, 1–56, 1897. Rev. Infect. Dis. 1, 701–719 (1979).

    Google Scholar 

  4. Scott, A. B., Rosenbaum, A. & Collins, C. C. Pharmacologic weakening of extraocular muscles. Invest. Ophthalmol. 12, 924–927 (1973).

    CAS  PubMed  Google Scholar 

  5. Scott, A. B. Botulinum toxin injection into extraocular muscles as an alternative to strabismus surgery. J. Pediatr. Ophthalmol. Strabismus 17, 21–25 (1980).

    CAS  PubMed  Google Scholar 

  6. Kerner, J. Das Fettgift oder die Fettsaure und ihre Wirkungen auf den thierischen Organismus, ein Beytrag zur untersuchung des in verdorbenen Wursten giftig wirkenden Stoffes (Stuttgart, Tubingen: Cotta; 1822).

    Google Scholar 

  7. Lim, E. C. & Seet, R. C. Botulinum toxin: description of injection techniques and examination of controversies surrounding toxin diffusion. Acta Neurol. Scand. 117, 73–84 (2008).

    CAS  PubMed  Google Scholar 

  8. Esquenazi, A. Botulinum neurotoxin in muscle overactivity. J. Head Trauma Rehabil. 20, 563–567 (2005).

    PubMed  Google Scholar 

  9. Aoki, K., Smith, L. A. & Atassi, M. Mode of action of botulinum neurotoxins: current vaccination strategies and molecular immune recognition. Crit. Rev. Immunol. 30, 167–187 (2010).

    CAS  PubMed  Google Scholar 

  10. Kukreja, R. et al. Immunological characterization of the subunits of type A botulinum neurotoxin and different components of its associated proteins. Toxicon 53, 616–624 (2009).

    CAS  PubMed  Google Scholar 

  11. Oguma, K. et al. Structure and function of clostridium botulinum progenitor toxin. J. Toxicol. Toxin Rev. 18, 17–34 (1999).

    CAS  Google Scholar 

  12. Poulain, B., Popoff, M. & Molgó, J. How do the botulinum neurotoxins block neurotransmitter release: from botulism to the molecular mechanism of action. Botulinum J. 1, 14–87 (2008).

    Google Scholar 

  13. Panjwani, N., O'Keefe, R. & Pickett, A. Biochemical, functional and potency characteristics of type A botulinum toxin in clinical use. Botulinum J. 1, 153–166 (2008).

    Google Scholar 

  14. Dressler, D. Pharmacological aspects of therapeutic botulinum toxin preparations [German]. Nervenarzt. 77, 912–921 (2006).

    CAS  PubMed  Google Scholar 

  15. Pickett, A. Dysport: pharmacological properties and factors that influence toxin action. Toxicon 54, 683–689 (2009).

    CAS  PubMed  Google Scholar 

  16. Arezzo, J. C. NeuroBloc/Myobloc: unique features and findings. Toxicon 54, 690–696 (2009).

    CAS  PubMed  Google Scholar 

  17. Simpson, L. L. Identification of the major steps in botulinum toxin action. Annu. Rev. Pharmacol. Toxicol. 44, 167–193 (2004).

    CAS  PubMed  Google Scholar 

  18. Black, J. D. & Dolly, J. O. Interaction of 125I-labeled botulinum neurotoxins with nerve terminals. I. Ultrastructural autoradiographic localization and quantitation of distinct membrane acceptors for types A and B on motor nerves. J. Cell Biol. 103, 521–534 (1986).

    CAS  PubMed  Google Scholar 

  19. Jankovic, J. Botulinum toxin in clinical practice. J. Neurol. Neurosurg. Psychiatry 75, 951–957 (2004).

    CAS  PubMed Central  PubMed  Google Scholar 

  20. Jabbari, B. Botulinum neurotoxins in the treatment of refractory pain. Nat. Clin. Pract. Neurol. 4, 676–685 (2008).

    CAS  PubMed  Google Scholar 

  21. Pickett, A. Re-engineering clostridial neurotoxins for the treatment of chronic pain: current status and future prospects. BioDrugs 24, 173–182 (2010).

    CAS  PubMed  Google Scholar 

  22. Jankovic, J. & Fahn, S. Dystonic disorders. In Parkinson's Disease And Movement Disorders (eds Jankovic, J. & Tolosa, E.) 321–347 (Williams and Wilkins, Baltimore, 1993).

    Google Scholar 

  23. Albanese, A. et al. A systematic review on the diagnosis and treatment of primary (idiopathic) dystonia and dystonia plus syndromes: report of an EFNS/MDS-ES Task Force. Eur. J. Neurol. 13, 433–444 (2006).

    CAS  PubMed  Google Scholar 

  24. Rosenkranz, K. et al. Sensorimotor reorganization by proprioceptive training in musician's dystonia and writer's cramp. Neurology 70, 304–315 (2008).

    CAS  PubMed  Google Scholar 

  25. Nelson, A. J., Blake, D. T. & Chen, R. Digit-specific aberrations in the primary somatosensory cortex in writer's cramp. Ann. Neurol. 66, 146–154 (2009).

    PubMed  Google Scholar 

  26. Brashear, A. Botulinum toxin type A in the treatment of patients with cervical dystonia. Biologics 3, 1–7 (2009).

    CAS  PubMed Central  PubMed  Google Scholar 

  27. Dashtipour, K. & Pender, R. A. Evidence for the effectiveness of botulinum toxin for writer's cramp. J. Neural Transm. 115, 653–656 (2008).

    CAS  PubMed  Google Scholar 

  28. Kenney, C. & Jankovic, J. Botulinum toxin in the treatment of blepharospasm and hemifacial spasm. J. Neural Transm. 115, 585–591 (2008).

    CAS  PubMed  Google Scholar 

  29. Bhidayasiri, R., Cardoso, F. & Truong, D. D. Botulinum toxin in blepharospasm and oromandibular dystonia: comparing different botulinum toxin preparations. Eur. J. Neurol. 13 (Suppl. 1), 21–29 (2006).

    PubMed  Google Scholar 

  30. Simpson, D. M. et al. Assessment: botulinum neurotoxin for the treatment of movement disorders (an evidence-based review): report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology. Neurology 70, 1699–1706 (2008).

    CAS  PubMed  Google Scholar 

  31. Jankovic, J. Treatment of dystonia. Lancet Neurol. 5, 864–872 (2006).

    CAS  PubMed  Google Scholar 

  32. Turjanski, N. et al. Botulinum toxin in the treatment of writer's cramp. Clin. Neuropharmacol. 19, 314–320 (1996).

    CAS  PubMed  Google Scholar 

  33. Dressler, D. Electromyographic evaluation of cervical dystonia for planning of botulinum toxin therapy. Eur. J. Neurol. 7, 713–718 (2000).

    CAS  PubMed  Google Scholar 

  34. Tey, H. L. & Lim, E. C. Neurology. In The Black Book Of Clinical Examination (eds Tey, H. L. & Lim, E. C.) 54–150 (McGraw-Hill, Singapore, 2009).

    Google Scholar 

  35. Singer, C., Papapetropoulos, S. & Vela, L. Use of mirror dystonia as guidance for injection of botulinum toxin in writing dysfunction. J. Neurol. Neurosurg. Psychiatry 76, 1608–1609 (2005).

    CAS  PubMed Central  PubMed  Google Scholar 

  36. Hallett, M. et al. Treatment of focal dystonias with botulinum neurotoxin. Toxicon 54, 628–633 (2009).

    CAS  PubMed  Google Scholar 

  37. Adam, O. R. & Jankovic, J. Treatment of dystonia. Parkinsonism Relat. Disord. 13 (Suppl. 3), S362–S368 (2007).

    PubMed  Google Scholar 

  38. Ivanhoe, C. B. & Reistetter, T. A. Spasticity: the misunderstood part of the upper motor neuron syndrome. Am. J. Phys. Med. Rehabil. 83 (10 Suppl.), S3–S9 (2004).

    PubMed  Google Scholar 

  39. Esquenazi, A. et al. Botulinum toxin for the management of adult patients with upper motor neuron syndrome. Toxicon 54, 634–638 (2009).

    CAS  PubMed  Google Scholar 

  40. Esquenazi, A. & Mayer, N. Botulinum toxin for the management of muscle overactivity and spasticity after stroke. Curr. Atheroscler. Rep. 3, 295–298 (2001).

    CAS  PubMed  Google Scholar 

  41. Simpson, D. M. et al. 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. Neurology 70, 1691–1698 (2008).

    CAS  PubMed  Google Scholar 

  42. Lim, E. C., Ong, B. K. & Seet, R. C. Botulinum toxin-A injections for spastic toe clawing. Parkinsonism Relat. Disord. 12, 43–47 (2006).

    PubMed  Google Scholar 

  43. Lim, E. C., Quek, A. M. & Seet, R. C. Botulinum toxin-A injections via electrical motor point stimulation to treat writer's cramp: pilot study. Neurol. Neurophysiol. Neurosci. 4, 1–7 (2006).

    Google Scholar 

  44. Keenan, M. A. et al. Management of intrinsic spasticity in the hand with phenol injection or neurectomy of the motor branch of the ulnar nerve. J. Hand Surg. Am. 12, 734–739 (1987).

    CAS  PubMed  Google Scholar 

  45. Shaw, L. & Rodgers, H. Botulinum toxin type A for upper limb spasticity after stroke. Expert Rev. Neurother. 9, 1713–1725 (2009).

    CAS  PubMed  Google Scholar 

  46. Hoare, B. J. et al. Botulinum toxin A as an adjunct to treatment in the management of the upper limb in children with spastic cerebral palsy (UPDATE). Cochrane Database of Systematic Reviews Issue 1, Art. No.: CD003469. doi: 10.1002/14651858.CD003469.pub4 (2010).

  47. Lukban, M. B., Rosales, R. L. & Dressler, D. Effectiveness of botulinum toxin A for upper and lower limb spasticity in children with cerebral palsy: a summary of evidence. J. Neural Transm. 116, 319–331 (2009).

    CAS  PubMed  Google Scholar 

  48. Francisco, G. E. Botulinum toxin for post-stroke spastic hypertonia: a review of its efficacy and application in clinical practice. Ann. Acad. Med. Singapore 36, 22–30 (2007).

    PubMed  Google Scholar 

  49. Turner-Stokes, L. et al. Goal attainment scaling in the evaluation of treatment of upper limb spasticity with botulinum toxin: a secondary analysis from a double-blind placebo-controlled randomized clinical trial. J. Rehabil. Med. 42, 81–89 (2010).

    PubMed  Google Scholar 

  50. Delgado, M. R. et al. Practice parameter: pharmacologic treatment of spasticity in children and adolescents with cerebral palsy (an evidence-based review): report of the Quality Standards Subcommittee of the American Academy of Neurology and the Practice Committee of the Child Neurology Society. Neurology 74, 336–343 (2010).

    CAS  PubMed Central  PubMed  Google Scholar 

  51. Chang, C. L. et al. Effect of baseline spastic hemiparesis on recovery of upper-limb function following botulinum toxin type A injections and postinjection therapy. Arch. Phys. Med. Rehabil. 90, 1462–1468 (2009).

    PubMed Central  PubMed  Google Scholar 

  52. Gracies, J. M., Singer, B. J. & Dunne, J. W. The role of botulinum toxin injections in the management of muscle overactivity of the lower limb. Disabil. Rehabil. 29, 1789–1805 (2007).

    PubMed  Google Scholar 

  53. Brin, M. F. et al. Localized injections of botulinum toxin for the treatment of focal dystonia and hemifacial spasm. Mov. Disord. 2, 237–254 (1987).

    CAS  PubMed  Google Scholar 

  54. Binder, W. J. et al. Botulinum toxin type A (BOTOX) for treatment of migraine headaches: an open-label study. Otolaryngol. Head Neck Surg. 123, 669–676 (2000).

    CAS  PubMed  Google Scholar 

  55. Mahowald, M. L., Singh, J. A. & Dykstra, D. Long term effects of intra-articular botulinum toxin A for refractory joint pain. Neurotox. Res. 9, 179–188 (2006).

    CAS  PubMed  Google Scholar 

  56. Piovesan, E. J. et al. An open study of botulinum-A toxin treatment of trigeminal neuralgia. Neurology 65, 1306–1308 (2005).

    CAS  PubMed  Google Scholar 

  57. Qerama, E. et al. A double-blind, controlled study of botulinum toxin A in chronic myofascial pain. Neurology 67, 241–245 (2006).

    CAS  Article  PubMed  Google Scholar 

  58. Winner, P. Botulinum toxins in the treatment of migraine and tension-type headaches. Phys. Med. Rehabil. Clin. N. Am. 14, 885–899 (2003).

    PubMed  Google Scholar 

  59. Naumann, M. et al. Assessment: botulinum neurotoxin in the treatment of autonomic disorders and pain (an evidence-based review): report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology. Neurology 70, 1707–1714 (2008).

    CAS  PubMed  Google Scholar 

  60. Harden, R. N. et al. Botulinum toxin a in the treatment of chronic tension-type headache with cervical myofascial trigger points: a randomized, double-blind, placebo-controlled pilot study. Headache 49, 732–743 (2009).

    PubMed  Google Scholar 

  61. Burstein, R., Dodick, D. & Silberstein, S. Migraine prophylaxis with botulinum toxin A is associated with perception of headache. Toxicon 54, 624–627 (2009).

    CAS  PubMed Central  PubMed  Google Scholar 

  62. Kim, C. C. et al. Predicting migraine responsiveness to botulinum toxin type A injections. Arch. Dermatol. 146, 159–163 (2010).

    CAS  PubMed  Google Scholar 

  63. Jakubowski, M. et al. Exploding vs. imploding headache in migraine prophylaxis with botulinum toxin A. Pain 125, 286–295 (2006).

    CAS  PubMed Central  PubMed  Google Scholar 

  64. Qerama, E., Fuglsang-Frederiksen, A. & Jensen, T. S. The role of botulinum toxin in management of pain: an evidence-based review. Curr. Opin. Anaesthesiol. 23, 602–610 (2010).

    PubMed  Google Scholar 

  65. Yang, S. S., Seet, R. C. & Lim, E. C. Action-induced hemifacial spasm and its resolution with botulinum toxin. Mov. Disord. 24, 147–148 (2009).

    CAS  PubMed  Google Scholar 

  66. Frei, K., Truong, D. D. & Dressler, D. Botulinum toxin therapy of hemifacial spasm: comparing different therapeutic preparations. Eur. J. Neurol. 13 (Suppl. 1), 30–35 (2006).

    PubMed  Google Scholar 

  67. Bentsianov, B. & Blitzer, A. Facial anatomy. Clin. Dermatol. 22, 3–13 (2004).

    PubMed  Google Scholar 

  68. Borodic, G. E., Cheney, M. & McKenna, M. Contralateral injections of botulinum A toxin for the treatment of hemifacial spasm to achieve increased facial symmetry. Plast. Reconstr. Surg. 90, 972–977 (1992).

    CAS  PubMed  Google Scholar 

  69. Ondo, W. G. Essential tremor: treatment options. Curr. Treat. Options Neurol. 8, 256–267 (2006).

    PubMed  Google Scholar 

  70. Shprecher, D. & Kurlan, R. The management of tics. Mov. Disord. 24, 15–24 (2009).

    PubMed Central  PubMed  Google Scholar 

  71. Blaheta, H. J. et al. Intravenous regional anesthesia (Bier's block) for botulinum toxin therapy of palmar hyperhidrosis is safe and effective. Dermatol. Surg. 28, 666–671 (2002).

    PubMed  Google Scholar 

  72. Haider, A. & Solish, N. Focal hyperhidrosis: diagnosis and management. CMAJ 172, 69–75 (2005).

    PubMed Central  PubMed  Google Scholar 

  73. Stolman, L. P. Treatment of hyperhidrosis. J. Drugs Dermatol. 2, 521–527 (2003).

    PubMed  Google Scholar 

  74. Grunfeld, A., Murray, C. A. & Solish, N. Botulinum toxin for hyperhidrosis: a review. Am. J. Clin. Dermatol. 10, 87–102 (2009).

    PubMed  Google Scholar 

  75. Lowe, N. J. et al. Botulinum toxin type A in the treatment of primary axillary hyperhidrosis: a 52-week multicenter double-blind, randomized, placebo-controlled study of efficacy and safety. J. Am. Acad. Dermatol. 56, 604–611 (2007).

    PubMed  Google Scholar 

  76. Weber, A. et al. Psychosocial aspects of patients with focal hyperhidrosis. Marked reduction of social phobia, anxiety and depression and increased quality of life after treatment with botulinum toxin A. Br. J. Dermatol. 152, 342–345 (2005).

    CAS  PubMed  Google Scholar 

  77. Kontochristopoulos, G., Gregoriou, S., Zakopoulou, N. & Rigopoulos, D. Cryoanalgesia with dichlorotetrafluoroethane spray versus ice packs in patients treated with botulinum toxin-a for palmar hyperhidrosis: self-controlled study. Dermatol. Surg. 32, 873–874 (2006).

    CAS  PubMed  Google Scholar 

  78. Richards, R. N. Ethyl chloride spray for sensory relief for botulinum toxin injections of the hands and feet. J. Cutan. Med. Surg. 13, 253–256 (2009).

    CAS  PubMed  Google Scholar 

  79. Smith, K. C., Comite, S. L. & Storwick, G. S. Ice minimizes discomfort associated with injection of botulinum toxin type A for the treatment of palmar and plantar hyperhidrosis. Dermatol. Surg. 33, S88–S91 (2007).

    CAS  PubMed  Google Scholar 

  80. Lim, E. C. & Seet, R. C. Another injection-free method to effect analgesia when injecting botulinum toxin for palmar hyperhidrosis: cryoanalgesia. Dermatol. Online J. 13, 25 (2007).

    PubMed  Google Scholar 

  81. Merello, M. Sialorrhoea and drooling in patients with Parkinson's disease: epidemiology and management. Drugs Aging 25, 1007–1019 (2008).

    CAS  PubMed  Google Scholar 

  82. Scully, C., Limeres, J., Gleeson, M., Tomás, I. & Diz, P. Drooling. J. Oral Pathol. Med. 38, 321–327 (2009).

    PubMed  Google Scholar 

  83. Brin, M. F. Dosing, administration, and a treatment algorithm for use of botulinum toxin A for adult-onset spasticity. Spasticity Study Group. Muscle Nerve Suppl. 6, S208–S220 (1997).

    CAS  PubMed  Google Scholar 

  84. Moore, P. & Naumann, M. Muscles and recommended dose ranges of botulinum toxins for adults. In Handbook of Botulinum Toxin Treatment (eds Moore, P. & Naumann, M.) 438–453 (Blackwell, Cornwall, 2005).

    Google Scholar 

  85. Brin, M. F., Danisi, F. & Blitzer, A. Blepharospasm, oromandibular dystonia, Meige's syndrome and hemifacial spasm. In Handbook of Botulinum Toxin Treatment (eds Moore, P. & Naumann, M.) 119–141 (Blackwell Science, Oxford, 2003).

    Google Scholar 

  86. Rosales, R. L., Bigalke, H. & Dressler, D. Pharmacology of botulinum toxin: differences between type A preparations. Eur. J. Neurol. 13 (Suppl. 1), 2–10 (2006).

    PubMed  Google Scholar 

  87. Wohlfarth, K., Kampe, K. & Bigalke, H. Pharmacokinetic properties of different formulations of botulinum neurotoxin type A. Mov. Disord. 19 (Suppl. 8), S65–S67 (2004).

    PubMed  Google Scholar 

  88. Dressler, D. Botulinum toxin for treatment of dystonia. Eur. J. Neurol. 17 (Suppl. 1), 88–96 (2010).

    PubMed  Google Scholar 

  89. Coté, T. R., Mohan, A. K., Polder, J. A., Walton, M. K. & Braun, M. M. Botulinum toxin type A injections: adverse events reported to the US Food and Drug Administration in therapeutic and cosmetic cases. J. Am. Acad. Dermatol. 53, 407–415 (2005).

    PubMed  Google Scholar 

  90. O'Flaherty, S. & Waugh, M. C. Pharmacologic management of the spastic and dystonic upper limb in children with cerebral palsy. Hand Clin. 19, 585–589 (2003).

    PubMed  Google Scholar 

  91. Gracies, J. M., Nance, P., Elovic, E., McGuire, J. & Simpson, D. M. Traditional pharmacological treatments for spasticity. Part II: general and regional treatments. Muscle Nerve Suppl. 6, S92–S120 (1997).

    CAS  PubMed  Google Scholar 

  92. Esquenazi, A., Mayer, N. H., Elia, A. E. & Albanese, A. Botulinum toxin for the management of adult patients with upper motor neuron syndrome. Toxicon 54, 634–638 (2009).

    CAS  PubMed  Google Scholar 

  93. Sakzewski, L., Ziviani, J. & Boyd, R. Systematic review and meta-analysis of therapeutic management of upper-limb dysfunction in children with congenital hemiplegia. Pediatrics 123, e1111–e1122 (2009).

    PubMed  Google Scholar 

  94. Hexsel, D., Rutowitsch, M. S., de Castro, L. C., do Prado, D. Z. & Lima, M. M. Blind multicenter study of the efficacy and safety of injections of a commercial preparation of botulinum toxin type A reconstituted up to 15 days before injection. Dermatol. Surg. 35, 933–939 (2009).

    CAS  PubMed  Google Scholar 

  95. Carruthers, A. & Carruthers, J. Botulinum toxin type A: history and current cosmetic use in the upper face. Semin. Cutan. Med. Surg. 20, 71–84 (2001).

    CAS  PubMed  Google Scholar 

  96. Trindade De Almeida, A. R. Kadunc, B. V., Di Chiacchio, N. & Neto, D. R. Foam during reconstitution does not affect the potency of botulinum toxin type A. Dermatol. Surg. 29, 530–531 (2003).

    PubMed  Google Scholar 

  97. Redaelli, A. & Forte, R. Botulinum toxin dilution: our technique. J. Cosmet. Laser Ther. 5, 218–219 (2003).

    CAS  PubMed  Google Scholar 

  98. Vadoud-Seyedi, J. & Simonart, T. Treatment of axillary hyperhidrosis with botulinum toxin type A reconstituted in lidocaine or in normal saline: a randomized, side-by-side, double-blind study. Br. J. Dermatol. 156, 986–989 (2007).

    CAS  PubMed  Google Scholar 

  99. Li, M., Goldberger, B. A. & Hopkins, C. Fatal case of BOTOX-related anaphylaxis? J. Forensic Sci. 50, 169–172 (2005).

    PubMed  Google Scholar 

  100. Perouansky, M. Liaisons dangereuses? General anesthetics and long-term toxicity in the CNS. Eur. J. Anaesthesiol. 24, 107–115 (2007).

    CAS  PubMed  Google Scholar 

  101. Brée, B., Gourdin, M. & De Kock, M. Anesthesia and cerebral apoptosis. Acta Anaesthesiol. Belg. 59, 127–137 (2008).

    PubMed  Google Scholar 

  102. Haller, I. et al. Neurotoxicity of lidocaine involves specific activation of the p38 mitogenactivated protein kinase, but not extracellular signal regulated or c-jun N-terminal kinases, and is mediated by arachidonic acid metabolites. Anesthesiology 105, 1024–1033 (2006).

    CAS  PubMed  Google Scholar 

  103. Callaway, J. E., Arezzo, J. C. & Grethlein, A. J. Botulinum toxin type B: an overview of its biochemistry and preclinical pharmacology. Semin. Cutan. Med. Surg. 20, 127–136 (2001).

    CAS  PubMed  Google Scholar 

  104. Setler, P. The biochemistry of botulinum toxin type B. Neurology 55 (Suppl. 5), S22–S28 (2000).

    CAS  PubMed  Google Scholar 

  105. Perotto, A. O. et al. in Anatomical Guide for the Electromyographer: the Limbs and Trunk (ed. Perotto, A. O.) 6–292 (Charles C. Thomas, Springfield, IL, 2005).

    Google Scholar 

  106. Mejia, N. I., Vuong, K. D. & Jankovic, J. Long-term botulinum toxin efficacy, safety, and immunogenicity. Mov. Disord. 20, 592–597 (2005).

    PubMed  Google Scholar 

  107. Greene, P., Fahn, S. & Diamond, B. Development of resistance to botulinum toxin type A in patients with torticollis. Mov. Disord. 9, 213–217 (1994).

    CAS  PubMed  Google Scholar 

  108. Jankovic, J., Vuong, K. D. & Ahsan, J. Comparison of efficacy and immunogenicity of original versus current botulinum toxin in cervical dystonia. Neurology 60, 1186–1188 (2003).

    CAS  PubMed  Google Scholar 

  109. Hanna, P. A. & Jankovic, J. Mouse bioassay versus Western blot assay for botulinum toxin antibodies: correlation with clinical response. Neurology 50, 1624–1629 (1998).

    CAS  PubMed  Google Scholar 

  110. Jankovic, J. et al. Clinico-immunologic aspects of botulinum toxin type B treatment of cervical dystonia. Neurology 67, 2233–2235 (2006).

    CAS  PubMed  Google Scholar 

  111. de Oliveira Monteiro, E. Botulinum toxin and pregnancy. Skinmed 5, 308 (2006).

    PubMed  Google Scholar 

  112. Morgan, J. C. Iyer, S. S., Moser, E. T., Singer, C. & Sethi, K. D. Botulinum toxin A during pregnancy: a survey of treating physicians. J. Neurol. Neurosurg. Psychiatry 77, 117–119 (2006).

    CAS  PubMed Central  PubMed  Google Scholar 

  113. Fasano, A., Bentivoglio, A. R., Ialongo, T., Soleti, F. & Evoli, A. Treatment with botulinum toxin in a patient with myasthenia gravis and cervical dystonia. Neurology 64, 2155–2156 (2005).

    CAS  PubMed  Google Scholar 

  114. Molgó, J., Lemeignan, M. & Thesleff, S. Aminoglycosides and 3, 4-diaminopyridine on neuromuscular block caused by botulinum type A toxin. Muscle Nerve 10, 464–470 (1987).

    PubMed  Google Scholar 

  115. Santos, J. I., Swensen, P. & Glasgow, L. A. Potentiation of Clostridium botulinum toxin aminoglycoside antibiotics: clinical and laboratory observations. Pediatrics 68, 50–54 (1981).

    CAS  PubMed  Google Scholar 

  116. Smith, A. G. Pearls and pitfalls in the therapeutic use of botulinum toxin. Semin. Neurol. 24, 165–174 (2004).

    PubMed  Google Scholar 

  117. O'Brien, C. F. Injection techniques for botulinum toxin using electromyography and electrical stimulation. Muscle Nerve Suppl. 6, S176–S180 (1997).

    CAS  PubMed  Google Scholar 

  118. Lim, A. Y. et al. Intramuscular innervation of upper-limb skeletal muscles. Muscle Nerve 29, 523–530 (2004).

    PubMed  Google Scholar 

  119. Bickerton, L. E., Agur, A. M. & Ashby, P. Flexor digitorum superficialis: locations of individual muscle bellies for botulinum toxin injections. Muscle Nerve 20, 1041–1043 (1997).

    CAS  PubMed  Google Scholar 

  120. Wang, L., Li, Y. M. & Li, L. Meta-analysis of randomized and controlled treatment trials for achalasia. Dig. Dis. Sci. 54, 2303–2311 (2009).

    CAS  PubMed  Google Scholar 

  121. Doodnath, R. & Puri, P. Internal anal sphincter achalasia. Semin. Pediatr. Surg. 18, 246–248 (2009).

    PubMed  Google Scholar 

  122. Kinney, T. P., Shah, A. G., Rogers, B. H. & Ehrenpreis, E. D. Retrograde endoscopic delivery of botulinum toxin for anal fissures. Endoscopy 38, 654 (2006).

    CAS  PubMed  Google Scholar 

  123. Bistritz, L. & Bain, V. G. Sphincter of Oddi dysfunction: managing the patient with chronic biliary pain. World J. Gastroenterol. 12, 3793–3802 (2006).

    PubMed Central  PubMed  Google Scholar 

  124. DasGupta, R. & Murphy, F. L. Botulinum toxin in paediatric urology: a systematic literature review. Pediatr. Surg. Int. 25, 19–23 (2009).

    PubMed  Google Scholar 

  125. Rhew, K., Fiedler, D. A. & Ludlow, C. L. Technique for injection of botulinum toxin through a flexible nasolaryngoscope. Otolaryngol. Head Neck Surg. 111, 787–794 (1994).

    CAS  PubMed  Google Scholar 

  126. Ford, C. N., Bless, D. M. & Lowery, J. D. Indirect laryngoscopic approach for injection of botulinum toxin in spasmodic dysphonia. Otolaryngol. Head Neck Surg. 103, 752–758 (1990).

    CAS  PubMed  Google Scholar 

  127. Chuang, Y. C. & Chancellor, M. B. The application of botulinum toxin in the prostate. J. Urol. 176, 2375–2382 (2006).

    CAS  PubMed  Google Scholar 

  128. Wilken, B., Aslami, B. & Backes, H. Successful treatment of drooling in children with neurological disorders with botulinum toxin A or B. Neuropediatrics 39, 200–204 (2008).

    CAS  PubMed  Google Scholar 

  129. Berweck, S., Schroeder, A. S., Fietzek, U. M. & Heinen, F. Sonography-guided injection of botulinum toxin in children with cerebral palsy. Lancet 363, 249–250 (2004).

    PubMed  Google Scholar 

  130. Berweck, S. & Heinen, F. in Treatment of Cerebral Palsy with Botulinum Toxin A—Principles, Clinical Practice, Atlas (eds Berweck, S. et al.) 1–142 (Child & Brain, Bonn, Berlin, 2003).

    Google Scholar 

  131. Berweck, S. & Wissel, J. Sonographic imaging for guiding botulinum toxin injections in limb muscles. Adv. Clin. Neurosci. Rehab. 4, 28–31 (2004).

    Google Scholar 

  132. Shaari, C. M., George, E., Wu, B. L., Biller, H. F. & Sanders, I. Quantifying the spread of botulinum toxin through muscle fascia. Laryngoscope 101, 960–964 (1991).

    CAS  PubMed  Google Scholar 

  133. Carli, L., Montecucco, C. & Rossetto, O. Assay of diffusion of different botulinum neurotoxin type a formulations injected in the mouse leg. Muscle Nerve 40, 374–380 (2009).

    CAS  PubMed  Google Scholar 

  134. Goodman, G. Diffusion and short-term efficacy of botulinum toxin A after the addition of hyaluronidase and its possible application for the treatment of axillary hyperhidrosis. Dermatol. Surg. 29, 533–538 (2003).

    PubMed  Google Scholar 

  135. Brisinda, G. et al. Effectiveness of higher doses of botulinum toxin to induce healing in patients with chronic anal fissures. Surgery 131, 179–184 (2002).

    PubMed  Google Scholar 

  136. Francisco, G. E. Botulinum toxin for post-stroke spastic hypertonia: a review of its efficacy and application in clinical practice. Ann. Acad. Med. Singapore 36, 22–30 (2007).

    PubMed  Google Scholar 

  137. Karp, B. I. Botulinum toxin treatment of occupational and focal hand dystonia. Mov. Disord. 19 (Suppl. 8), S116–S119 (2004).

    PubMed  Google Scholar 

  138. Edlund, W. et al. American Academy of Neurology Clinical Practice Guideline Process Manual [online], (2004).

Download references

Acknowledgements

The authors would like to thank Dr. Andy Pickett (Biologicals Science and Technology, Ipsen Biopharm Limited) for invaluable help with the Mechanisms of action section of the article.

Author information

Authors and Affiliations

Authors

Contributions

E. C. H. Lim researched the data and wrote the article, and provided substantial contributions to discussions of the content, reviewing and editing of the manuscript. R. C. S. Seet researched the data for the article and provided substantial contributions to discussions of the content, and contributed to the reviewing and editing of the manuscript.

Corresponding author

Correspondence to Erle C. H. Lim.

Ethics declarations

Competing interests

The authors declare no competing financial interests.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Lim, E., Seet, R. Use of botulinum toxin in the neurology clinic. Nat Rev Neurol 6, 624–636 (2010). https://doi.org/10.1038/nrneurol.2010.149

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/nrneurol.2010.149

This article is cited by

Search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing