Preliminary Observations on the Diffusion of Botulinum Toxin from the Site of Injection in Laryngeal Muscles

  • K. Linnea Peterson
  • Erich S. Luschei
  • Mark T. Madsen

Abstract

Botulinum neurotoxin A is a very potent neurotoxin which causes a flaccid paralysis upon ingestion or injection. Although it has been a feared food poisoning for years, clinical uses in medicine have been developed and refined so that localized injection is now an accepted form of treatment of various neuromuscular disorders. The clinical use of botulinum toxin was pioneered by Scott1, who developed it as a treatment modality for strabismus and blepharospasm. It has been used in ophthalmology since about 1980. The implications for otolaryngology and neurology have also been noted and it has since been used for such disorders as hemifacial spasm, torticollis, and spasmodic dysphonia2,3,4,5,6,7. Despite the known systemic effects from ingestion of the toxin, very few systemic effects from local injection have been reported. Ingestion is known to cause symptoms which suggest CNS involvement (e.g. dizziness, lethargy, general locomotor dysfunction), however the toxin has not been shown unequivocally to cross the blood brain barrier8. Antibody production has been noted in patients who received the larger doses (200–300 Units) used in the treatment of torticollis3. In addition, a patient with parkinsonism was noted in one study3 to develop fatigue after two series of injections (81.7 total units). Those studies that have explored the systemic effects physiologically have involved single fiber EMG studies at sites distant from the injection9,10. These studies have shown increased “jitter” in distant muscles, but no clinically apparent effects. A recent study looking at spread of the toxin after intramuscular injection looked at whether or not the toxin crossed fascial planes11. The results showed that botulinum toxin passed through muscle fascia even at subclinical doses, with fascia reducing the spread of toxin by only 23%.

Keywords

Botulinum Toxin Botulinum Toxin Injection Botulinum Neurotoxin Hemifacial Spasm Focal Dystonia 
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.
    A.B. Scott, Botulinum toxin injection of eye muscles to correct strabismus, Trans. Am. Opluhalmol. Soc. 79: 734–770 (1981).Google Scholar
  2. 2.
    C.L. Ludlow, R.F. Naunton, S.E. Sedory, G.M. Schultz, and M. Hallett, Effects of botulinum toxin injections on speech in adductor spasmodic dysphonia, Neurology 38: 1220–1225 (1988).PubMedCrossRefGoogle Scholar
  3. 3.
    M.F. Brin, S. Fahn, C. Moskowitz, A. Friedman, H.M. Shale, P.E. Greene, A. Blitzer, T. List, D. Lange, R.E. Lovelace, and D. McMahon, Localized Injections of botulinum toxin for the treatment of focal dystonia and hemifacial spasm, Movement Disorders 2: 237–254 (1987).PubMedCrossRefGoogle Scholar
  4. 4.
    A. Blitzer, M.F. Brin, P.E. Greene, and S. Fahn, Botulinum toxin injection for the treatment of oromandibular dystonia, Ann. of Otol., Rhin. and Laryngol 98: 93–97 (1989).Google Scholar
  5. 5.
    J. Jankovic and J. Orman, Botulinum A toxin for cranial-cervical dystonia: A double-blind, placebo-controlled study, Neurology 37: 616–623 (1987).PubMedCrossRefGoogle Scholar
  6. 6.
    C.L. Ludlow, R.F. Naunton, S. Terada, and B.J. Anderson, Successful treatment of selected cases of abductor spasmodic dysphonia using botulinum toxin injection, Otolaryngol. Head Neck Surg. 104: 849–855 (1991).PubMedGoogle Scholar
  7. 7.
    C.L. Ludlow, M. Hallett, S.E. Sedory, M. Fujita, and R.F. Naunton, The pathophysiology of spasmodic dysphonia and its modification by botulinum toxin, in: “Motor Disturbances II,” A. Berardelli, R. Benecke, M. Manfredi, and C.D. Marsden, eds., Academic Press Limited, London (1989).Google Scholar
  8. 8.
    D.A. Boroff, and G.S. Chen, On the question of permeability of the blood-brain barrier to botulinum toxin, Int. Archs. Allergy Appl. Immun. 48: 495–504 (1975).CrossRefGoogle Scholar
  9. 9.
    H. Lundh, H.H. Schiller, and D. Elmqvist, Correlation between single fibre jitter and endplate potentials studied in mild experimental botulinum poisoning, Acta Neurol. Scandinay. 56: 141–152 (1977).CrossRefGoogle Scholar
  10. 10.
    D.B. Sanders, E.W. Massey, aand E.G. Buckley, Botulinum toxin for blepharospasm: Single-fiber EMG studies, Neurology 36: 545–547 (1986).PubMedCrossRefGoogle Scholar
  11. 11.
    C.M. Shaari, E. George, B-L Wu, H.F. Biller, and I. Sanders, Quantifying the spread of botulinum toxin through muscle fascia, Laryngoscope 101: 960–964 (1991).PubMedCrossRefGoogle Scholar
  12. 12.
    R.S. Williams, C-K Tse, J.O. Dolly, P. Hambleton, and J. Melling, Radioiodination of botulinum neurotoxin type A with retention of biological activity and its binding to brain synaptosomes, Eur. J. Biochem. 131: 437–445 (1983).PubMedCrossRefGoogle Scholar
  13. 13.
    F.C. Greenwood, W.M. Hunter, and J.S. Glover, The preparation of 131I-labeled human growth hormone of high specific radioactivity, Biochem J. 89: 114–123 (1963).PubMedGoogle Scholar
  14. 14.
    C-K Tse, J.O. Dolly, P. Hambleton D. Wray, and J. Melling, Preparation and characterisation of homogenous neurotoxin type A from Clostridium botulinum, Eur. J. Biochem. 122: 493–500 (1982).Google Scholar
  15. 15.
    L.J. Reed and H. Muench, A simple method of estimating fifty percent endpoints, Amer. J. Hygiene. 27: 493–497 (1938).Google Scholar
  16. 16.
    L.C. Sellin, The action of botulinum toxin at the neuromuscular junction, Med. Biol. 59: 11–20 (1981).PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media New York 1993

Authors and Affiliations

  • K. Linnea Peterson
    • 1
    • 2
  • Erich S. Luschei
    • 2
    • 3
  • Mark T. Madsen
    • 4
  1. 1.Department of Otolaryngology-Head and Neck SurgeryThe University of IowaIowa CityUSA
  2. 2.The National Center for Voice and SpeechThe University of IowaIowa CityUSA
  3. 3.Department of Speech Pathology and AudiologyThe University of IowaIowa CityUSA
  4. 4.Department of Radiology, Division of Nuclear MedicineThe University of IowaIowa CityUSA

Personalised recommendations