Advertisement

Therapeutic Botulinum Toxin: Histologic Effects and Diffusion Properties

  • Gary E. Borodic
  • L. Bruce Pearce
  • Robert Ferrante

Abstract

Since the introduction of botulism toxin into therapeutic medicine in 1978,1,2 the use of this drug has been expanded to other indications including blepharospasm, adult onset spasmodic torticollis, spasmodic dysphonia, occupational hand disease and jaw dystonia. Application of this therapy to other disorders is on the horizon and is further contributing to the driving force for expansion of clinical and basic research. However, despite the success obtained with botulinum toxin for treatment of blepharospasm and other focal and segmental movement disorders, its application is limited by the following properties of the therapy:
  1. 1.

    Repeated injections are required indefinitely when treating chronic disease.

     
  2. 2.

    Untoward spread of toxin to other muscles not targeted for injection.

     
  3. 3.

    Antibody formation with resistance to the therapeutic action of the toxin subsequent to repeated injections.

     
  4. 4.

    The consistency of biologic activity contained within the labeled vials.

     
  5. 5.

    Lack of standardization of the injections sites for the treatment of each syndrome.

     
  6. 6.

    Placement of the therapeutic toxin preparation into the correct anatomic position when access to the muscles is difficult requiring teflon coated electromyographic assistance (particularly for treatment of occupational hand disorders).

     
  7. 7.

    Adequate understanding of long term effects of repeated treatment with the therapeutic preparation.

     

Keywords

Botulinum Toxin Botulinum Toxin Injection Hemifacial Spasm Motor Point Fiber Atrophy 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Scott AB. Botulinum toxin injections to eye muscles to correct strabismus. J Am Ophthalmol Soc 1981; 79: 734–770.Google Scholar
  2. 2.
    Scott AB, Magoon EH, McNeer KW, Stager DR. Botulinum treatment of strabismus in children. Trans Am Ophthalmol Soc 1990; 87: 174–180 (discussion 180–184).Google Scholar
  3. 3.
    Scott AB, Kennedy, EG, Stubbs HA. Botulinum A toxin injection as a treatment for blepharospasm. Arch Ophthalmol 1985; 103: 347–350.PubMedCrossRefGoogle Scholar
  4. 4.
    Scott AB. Strabismus injection treatment. NIH Consensus Development Conference on Clinical use of botulinum toxin. 1990; Nov 12–14: 117–118.Google Scholar
  5. 5.
    Borodic GE, Cozzolino D. Blepharospasm and its treatment, with emphasis on the use of botulinum toxin. Plast Reconst Surg 1989; 83 (3): 546–554.PubMedCrossRefGoogle Scholar
  6. 6.
    Borodic GE, Mills L, Joseph M. Botulinum A toxin for the treatment of adult-onset spasmodic torticollis. Plast Reconst Surg 1991; 87 (2): 285–289.PubMedCrossRefGoogle Scholar
  7. 7.
    Borodic GE, Cozzolino D, Townsend, DJ. Dose-response relationships in patients treated with botulinum toxin for more than three years (abstract). Sixth International Meeting of the Benign Essential Blepharospasm Research Foundation: 1988 Aug 25–27; Cambridge, MA. Ear Nose Throat J 1988; 67 (12): 914.Google Scholar
  8. 8.
    Jankovic J, Orman J. Botulinum toxin for cranial cervical dystonia: A double blind placebo controlled study. Neurology 1987; 37: 616–623.Google Scholar
  9. 9.
    Blitzer A, Brin MF, Greene PE, Fahn S. Botulinum toxin injection for the treatment of oromandibular dystonia. Ann Oto Rhin Largyngol 1989; 98: 93–97.Google Scholar
  10. 10.
    Fletcher NA, Quinn N. Dystonic syndromes. Cuff Opin Neurol Neurosurg 1989; 2: 330–333.Google Scholar
  11. 11.
    Gelb DJ, Lowenstein DH, Arminoff MJ. Controlled trial of botulinum toxin injections in the treatment of spasmodic torticollis. Neurology 1989; 39: 80–84.PubMedCrossRefGoogle Scholar
  12. 12.
    Scott AB, Kennedy RA, Stubbs HA. Botulinum toxin injection as a treatment for blepharospasm. Arch Ophthalmol 1985; 103: 347–350.PubMedCrossRefGoogle Scholar
  13. 13.
    Jankovic J, Ford J. Blepharospasm and oro-facial dystonia. Pharmacologic findings in 100 patients. Ann Neurol 1979: 36: 635.Google Scholar
  14. 14.
    Frueh BR, Callahan A, Dortzbach RR et al. The effects of differential section of the seventh nerve on patient with blepharospasm. Trans Am Acad Ophthalmol Otolaryngol 1976; 81: 595.Google Scholar
  15. 15.
    Callahan A. Surgical correction of intractable blepharospasm, technical improvement. Am J Ophthalmol 1965; 60: 788.PubMedGoogle Scholar
  16. 16.
    Janetta PJ, Abbasy M, Maroon JC, Ramos FM, Albin MS. Etiology and differential micro-surgical treatment of hemifacial spasm. J Neurosurg 1977; 47: 321.CrossRefGoogle Scholar
  17. 17.
    Borodic GE, Pearce LB, Johnson EJ, Schantz E. Clinical and scientific aspects of botulinum toxin. Ophthalmol Clin N Am 1991; 4 (3): 491–503.Google Scholar
  18. 18.
    Borodic GE, Metson R, Townsend D, McKenna M, Pearce LB. Botulinum toxin for aberrant facial nerve regeneration. Dose response relationships. Plast Reconst Surg, December 1991 (in press).Google Scholar
  19. 19.
    Frueh BR, Nelson CC, Kapustiak JF, Musch DC. The effects of omitting the lower eyelid in blepharospasm treatment. Am J Ophthalmol 1988; 106: 45–47.PubMedCrossRefGoogle Scholar
  20. 20.
    Borodic GE, Weigner A, Ferrante R, Young R. Orbicularis oculi innervation zone and implications for Botulinum A toxin therapy for blepharospasm. Ophthalmol Plast Reconst Surg 1991; 7 (1): 54–59.CrossRefGoogle Scholar
  21. 21.
    Bertrand C, Molina-Negro P, Martinez SN. Technical aspects of selective peripheral denervation for spasmodic torticollis. Appl Neurophysiol 1982; 45: 326–330.PubMedGoogle Scholar
  22. 22.
    Bertrand C, Molina-Negro P, Bouvier G, Gorczyca W. Observations and results in 131 cases of spasmodic torticollis after selective denervation. Appl Neurophysiol 1987; 50: 319–323.PubMedGoogle Scholar
  23. 23.
    Borodic GE, Pearce LB, Smith, K, Joseph M. Botulinum A toxin for spasmodic torticollis: Multiple vs single injection points per muscle. Head Neck 1992; 14: 33–37.PubMedCrossRefGoogle Scholar
  24. 24.
    Borodic GE, Joseph M, Fay L, Cozzolino D, Ferrante R. Botulinum A toxin for the treatment of spasmodic torticollis. Dysphagia and regional toxin spread. Head Neck 1990; 12: 392–398.PubMedCrossRefGoogle Scholar
  25. 25.
    Tsui JK, Eisen A, Mak E, Carruthers J et al. A pilot study on the use of botulinum toxin in spasmodic torticollis. Can J Neurol Sci 1985; 12: 314–316.PubMedGoogle Scholar
  26. 26.
    Borodic, GE. Botulinum A toxin (expressionistic) ptosis overcorrection after frontalis sling. Ophthalmic Plast Reconst Surg 1991; 2: 137–142.Google Scholar
  27. 27.
    Kao I, Drachman D, Price DL. Botulinum toxin: mechanism of presynaptic blockade. Science 1976; 193: 1256.PubMedCrossRefGoogle Scholar
  28. 28.
    Duchen LW. Changes in motor innervation and cholinesterase localization induced by botulinum toxin in skeletal muscle of mouse: Differences between fast and slow muscles. J Neurol Neurosurg Psychiatry 1970; 33: 40–54.PubMedCrossRefGoogle Scholar
  29. 29.
    Duchen LW. Histologic differences between soleus and gastrocnemius muscles in the mouse after local injection of botulinum toxin. J Physiol (Lond) 1969; 204: 17–18.Google Scholar
  30. 30.
    Aldersen K, Holds JB, Andersen RL Botulinum induced alteration of nerve muscle interactions in human orbicularis oculi following treatment for blepharospasm. Neurology 1991; 41: 1800–1805.CrossRefGoogle Scholar
  31. 31.
    Borodic GE, Ferrante R. Effects of repeated botulinum toxin injections on orbicularis oculi muscle. J Clin Neuro-Ophthalmol 1992; 12 (2): 121–127.CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 1993

Authors and Affiliations

  • Gary E. Borodic
    • 1
  • L. Bruce Pearce
    • 2
  • Robert Ferrante
    • 3
  1. 1.Department of OphthalmologyMassachusetts Eye and Ear InfirmaryUSA
  2. 2.Department of PharmacologyBoston University School of MedicineUSA
  3. 3.Department of Neuropathology, Massachusetts General HospitalHarvard Medical SchoolUSA

Personalised recommendations