Skip to main content Accessibility help

We use cookies to distinguish you from other users and to provide you with a better experience on our websites. Close this message to accept cookies or find out how to manage your cookie settings.

Close cookie message
×
Hostname: page-component-669899f699-tzmfd Total loading time: 0 Render date: 2025-04-28T22:41:38.879Z Has data issue: false hasContentIssue false

4 - Botulinum toxin: primary and secondary resistance

Published online by Cambridge University Press:  02 December 2009

By
Benjamin Anyanwu ,
Philip A. Hanna  and
Joseph Jankovic
Edited by
Anthony B. Ward  and
Michael P. Barnes
Benjamin Anyanwu
Affiliation:
New Jersey Neuroscience Institute, JFK Medical Center, Edison, NJ, USA; Seton Hall University School of Graduate Medical Education, South Orange, NJ, USA
Philip A. Hanna
Affiliation:
New Jersey Neuroscience Institute, JFK Medical Center, Edison, NJ, USA; Seton Hall University School of Graduate Medical Education, South Orange, NJ, USA
Joseph Jankovic
Affiliation:
Parkinson's Disease Center and Movement Disorders Clinic, Baylor College of Medicine, Houston, Texas, USA
Anthony B. Ward
Affiliation:
University Hospital of North Staffordshire
Michael P. Barnes
Affiliation:
Hunters Moor Regional Neurological Rehabilitation Centre
Get access

Summary

Introduction

Botulinum toxin (BoNT), the most potent biologic toxin, is a highly effective therapeutic tool in a variety of neurologic and other disorders. In minute doses it has the ability to block Ach release and, therefore, has been exploited to relieve disease symptoms associated with muscle hyperactivity. Intramuscular injection of BoNT produces a chemodenervertion at the neuromuscular junction that results in reversible partial paralysis. While used primarily for conditions characterized by abnormal, excessive, or inappropriate muscle contractions, BoNT is also increasingly used in the management of a variety of ophthalmologic, urologic, gastrointestinal, orthopedic, cosmetic and dermatologic disorders.

As the use of BoNT continues to increase, the antigenicity of BoNT and development of immunoresistance secondary to blocking antibodies has continued to be a pressing concern. A certain percentage of patients receiving repeated injections develop blocking antibodies (immunoresistance) against BoNT (BoNT-Abs) causing them to be completely resistant to the effects of subsequent BoNT injections. This is termed secondary resistance. Primary resistance refers to lack of response to initial BoNT treatment, which is extremely rare, and may be due to pre-existing BoNT-Abs, possibly as a result of prior immunization against botulism. The frequency of neutralizing or blocking antibodies (immunoresistance) against BoNT is not known. This lack of information is partly due to a paucity of well-designed epidemiological studies utilizing appropriate assays to determine the frequency of blocking antibodies in a prospectively followed population of BoNT-treated patients.

Type
Chapter
Information
Clinical Uses of Botulinum Toxins , pp. 45 - 57
Publisher: Cambridge University Press
Print publication year: 2007

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

Book purchase

Temporarily unavailable

References

Comella, C. L., Jankovic, J. and Brin, M. F. (2000). Use of botulinum toxin type A in the treatment of cervical dystonia. Neurology, 55(Suppl. 5), S15–S21.Google ScholarPubMed
Jankovic, J. (2004). Botulinum toxin in clinical practice. J. Neurol. Neurosurg. Psychiatry, 75, 951–7.CrossRefGoogle ScholarPubMed
Gracies, J.-M. and Simpson, D. M. (2000). Botulinum toxin therapy. Neurologist, 6, 98–115.CrossRefGoogle Scholar
Brin, M. F., Hallett, M. and Jankovic, J. (2002). Scientific and Therapeutic Aspects of Botulinum Toxin. Philadelphia, PA: Lippincott Williams & Wilkins.Google Scholar
Zuber, M., Sebald, M., Bathien, N.et al. (1993). Botulinum antibodies in dystonic patients treated with type A botulinum toxin: frequency and significance. Neurology, 43, 1715–18.CrossRefGoogle ScholarPubMed
Greene, P., Fahn, S. and Diamond, B. (1994). Development of resistance to botulinum toxin type A in patients with torticollis. Mov. Disord., 9, 213–17.CrossRefGoogle ScholarPubMed
Jankovic, J. and Schwartz, K. (1995). Response and immunoresistance to botulinum toxin injections. Neurology, 45, 1743–6.CrossRefGoogle ScholarPubMed
Borodic, G., Johnson, E., Goodenough, M. and Schantz, E. (1996). Botulinum toxin therapy, immunologic resistance, and problems with available materials. Neurology, 46, 26–9.CrossRefGoogle ScholarPubMed
Göschel, H., Wolhfart, K., Frevert, J.et al. (1997). Botulinum A toxin therapy: neutralizing and non-neutralizing antibodies – therapeutic consequences. Experimental Neurology, 147, 96–102.CrossRefGoogle Scholar
Hanna, P. A. and Jankovic, J. (1998). Mouse bioassay versus Western blot assay for botulinum toxin antibodies: correlation with clinical response. Neurology, 50, 1624–9.CrossRefGoogle ScholarPubMed
Hanna, P. A., Jankovic, J. and Vincent, A. (1999). Comparison of mouse bioassay and immunoprecipitation assay for botulinum toxin antibodies. J. Neurol. Neurosurg. Psychiatry, 66, 612–16.CrossRefGoogle ScholarPubMed
Jankovic, J., Vuong, K. D. and Ahsan, J. (2003). Comparison of efficacy and immunogenicity of original versus current botulinum toxin in cervical dystonia. Neurology, 60, 1186–8.CrossRefGoogle ScholarPubMed
Kessler, K. R., Skutta, M. and Benecke, R. (1999). Long-term treatment of cervical dystonia with botulinum toxin A: efficacy, safety, and antibody frequency. German Dystonia Study Group. J. Neurol., 246(4), 265–74.CrossRefGoogle ScholarPubMed
BOTOX® (Botulinum Toxin Type A) (2000). Purified Neurotoxin Complex, Product Information, http://www.botox.com/prescribing_info.html.
MYOBLOCTMhttp://www.myobloc.com/product_information/full_prescribing_info.pdf
Truong, D. D., Dubinsky, R., Hermanowicz, N.et al. (1991). Posttraumatic torticollis. Arch. Neurol., 48, 221–3.CrossRefGoogle ScholarPubMed
Dolimbek, B. Z., Jankovic, J. and Atassi, M. Z. (2002). Cross reaction of tetanus and botulinum neurotoxins A and B and the boosting effect of botulinum neurotoxins A and B on a primary anti-tetanus antibody response. Immunol. Invest., 31, 247–62.CrossRefGoogle Scholar
Dressler, D. (2004). Clinical presentation and management of antibody-induced failure of botulinum toxin therapy. Mov. Disord., 19(Suppl. 8), S92–S100.CrossRefGoogle ScholarPubMed
Dressler, D. and Bigalke, H. (2004). Antibody-induced failure of botulinum toxin type B therapy in de novo patients. Eur. Neurol., 52, 132–5.CrossRefGoogle ScholarPubMed
DasGupta, B. R. (1994). Structures of botulinum neurotoxin, its functional domains and perspectives on crystalline type A toxin. In Jankovic, J. and Hallett, M., eds., Therapy with Botulinum Toxin. New York: Marcel Dekker, pp. 15–40.Google ScholarPubMed
Aoki, K. R., Merlino, G., Spanoyannis, A. F. and Wheeler, L. A. (1999). BOTOX® (Botulinum Toxin Type A) Purified Neurotoxin Complex prepared from the new bulk toxin retains the same preclinical efficacy as the original but with reduced antigenicity. Neurology, 52(Suppl. 2), A521–2.Google Scholar
Benabou, R., Brin, M. F. and Doucette, J. T. (1999). Cervical dystonia: a retrospective study on safety and efficacy of BOTOX lots 79–11 and 2024. Neurology, 52(Suppl. 2), A117–18.Google Scholar
Racette, B. A., McGee-Minnich, L. and Perlmutter, J. S. (1999). Efficacy and safety of a new bulk toxin of botulinum toxin in cervical dystonia: a blinded evaluation. Clin. Neuropharmacol., 22, 337–9.Google ScholarPubMed
Jankovic, J., Davis, T., Wooten-Watts, M. and the BOTOX Cervical Dystonia Retrospective Study Group. (2005). The safety of BOTOX® (Botulinum Toxin Type A) prepared from new US bulk toxin is comparable to the original in cervical dystonia treatment: a retrospective analysis. Mov. Disord., 15(Suppl. 2), 31.Google Scholar
Atassi, M. Z. (2004). Basic immunological aspects of botulinum toxin therapy. Mov. Disord. 19(Suppl. 8), S68–84.CrossRefGoogle ScholarPubMed
Atassi, M. Z. and Oshima, M. (1999). Structure, activity, and immune (T and B cell) recognition of botulinum neurotoxins. Critical Reviews Immunol., 19, 219–60.Google Scholar
Kazim, A. L. and Atassi, M. Z. (1980). A novel and comprehensive synthetic approach for the elucidation of protein antigenic structures. Determination of the full antigenic profile of the alpha-chain of human haemoglobin. Biochem. J., 191(1), 261–4.CrossRefGoogle ScholarPubMed
Halpern, J. L., Smith, L. A., Seamon, K. B.et al. (1989). Sequence homology between tetanus and botulinum toxins detected by an antipeptide antibody. Infect. Immun., 57, 13–22.Google ScholarPubMed
Doellgast, G. J., Brown, J. E., Koufman, J. A.et al. (1997). Sensitive assay for measurement of antibodies to Clostridium botulinum toxins A, B, and E: use of hapten-labeled-antibody elution to isolate specific complexes. J. Clin. Microbiol., 35, 578–83.Google Scholar
Aoki, K. R. (1999). Preclinical update on BOTOX (botulinum toxin-A)-purified neurotoxin complex relative to other botulinum toxin preparations. Eur. J. Neurol., 6(Suppl. 4), S3–S10.CrossRefGoogle Scholar
Dertzbaugh, M. T. and West, M. W. (1996). Mapping of protective and cross-reactive domains of the type A neurotoxin of Clostridium botulinum. Vaccine, 14, 1538–44.CrossRefGoogle ScholarPubMed
Hatheway, C. L. and Dang, C. (1994). Immunogenicity of the neurotoxins of Clostridium botulinum. In Jankovic, J. and Hallett, M., eds., Therapy with Botulinum Toxin. New York, NY: Marcel Dekker, Inc., 93–108.Google ScholarPubMed
Dressler, D., Lange, M., Bigalke, H. (2005). Mouse diaphragm assay for detection of antibodies against botulinum toxin type B. Mov. Disord., 12, 1617–9.Google Scholar
Palace, J., Nairne, A., Hyman, N.et al. (1998). A radioimmunoprecipitation asssay for antibodies to botulinum A. Neurology, 50, 1463–6.CrossRefGoogle Scholar
Dressler, D., Bigalke, H. and Rothwell, J. C. (2000). The sternocleidomastoid test: an in vivo assay to investigate botulinum toxin antibody formation in humans. J. Neurol., 247, 630–2.CrossRefGoogle Scholar
Kessler, K. R. and Benecke, R. (1997). The EBD test – a clinical test for the detection of antibodies to botulinum toxin type A. Mov. Disord., 12(1), 95–9.CrossRefGoogle Scholar
Birklein, F. and Erbguth, F. (2000). Sudomotor testing discriminates between subjects with and without antibodies against botulinum toxin A – A preliminary observation. Mov. Disord., 15, 146–9.3.0.CO;2-X>CrossRefGoogle ScholarPubMed
Siatkowski, R. M., Tyutyunikov, A., Biglan, A. W.et al. (1993). Serum antibody production to botulinum A toxin. Ophthalmology, 100, 1861–6.CrossRefGoogle ScholarPubMed
Notermans, S. and Nagel, J. (1989). Assays for botulinum and tetanus toxins. In Simpson, L. L., eds., Botulinum Neurotoxin and Tetanus Toxin. San Diego: Academic Press, pp. 319–31.Google Scholar
Shone, C., Wilton-Smith, P., Appleton, N.et al. (1985). Monoclonal antibody-based immunoassay for type A Clostridium botulinum toxin is comparable to the mouse bioassay. Appl. Environ. Microbiol., 50, 63–7.Google ScholarPubMed
Hall, Y. H., Chaddock, J. A., Moulsdale, H. J.et al. (2004). Novel application of an in vitro technique to the detection and quantification of botulinum neurotoxin antibodies. J. Immunol. Methods, 288, 55–60.CrossRefGoogle Scholar
Sankhla, C., Jankovic, J. and Duane, D. (1998). Variability of the immunologic and clinical response in dystonic patients immunoresistant to botulinum toxin injections. Mov. Disord., 13, 150–4.CrossRefGoogle ScholarPubMed
Siegel, L. S. (1988). Human immune response to botulinum pentavalent (ABCDE) toxoid determined by a neutralizing test and by an enzyme-linked immunoabsorbent assay. J. Clin. Microbiol., 26, 2351–6.Google Scholar
Eleopra, R., Tugnoli, V., Quatrale, R.et al. (2006). Clinical use of non-A botulinum toxins: botulinum toxin type C and botulinum toxin type F. Neurotox Res., 9, 127–31.Google Scholar
Greene, P. E. and Fahn, S. (1996). Response to botulinum toxin F in seronegative botulinum toxin A-resistant patients. Mov. Disord., 11, 181–4.CrossRefGoogle ScholarPubMed
Jankovic, J., Hunter, C., Dolimbek, B. Z.et al. Clinico-Immunologic Aspects of botulinum toxin type B treatment of cervical dystonia. Neurology (in press).
Eleopra, R., Tugnoli, V., Rossetto, O.et al. (1997). Botulinum neurotoxin serotype C: a novel effective botulinum toxin therapy in human. Neurosci. Lett., 224, 91–4.CrossRefGoogle ScholarPubMed
Lew, M. F., Adomato, B. T., Duane, D. D.et al. (1997). Botulinum toxin type B (BotB): A double-blind, placebo-controlled, safety and efficacy study in cervical dystonia. Neurology, 49, 701–7.CrossRefGoogle ScholarPubMed
Houser, M. K., Sheean, G. L. and Lees, A. J. (1998). Further studies using higher doses of botulinum toxin type F for torticollis resistant to botulinum toxin type A. J. Neurol. Neurosurg. Psychiatry, 64, 577–80.CrossRefGoogle ScholarPubMed
Chen, R., Karp, B. I. and Hallett, M. (1998). Botulinum toxin type F for treatment of dystonia: long-term experience. Neurology, 51, 1494–6.CrossRefGoogle ScholarPubMed
Brashear, A., Lew, M. F., Dykstra, D. D.et al. (1999). Safety and efficacy of Neurobloc (botulinum toxin type B) in type A-responsive cervical dystonia. Neurology, 53, 1439–46.CrossRefGoogle ScholarPubMed
Brin, M. F., Lew, M. F., Adler, C. H.et al. (1999). Safety and efficacy of NeuroBloc (botulinum toxin type B) in type A-resistant cervical dystonia. Neurology, 53, 1431–8.CrossRefGoogle Scholar
Mezaki, T., Kaji, R., Brin, M. F.et al. (1999). Combined use of type A and F botulinum toxins for blepharospasm: a double-blind controlled trial. Mov. Disord., 14, 1017–20.3.0.CO;2-3>CrossRefGoogle Scholar
Naumann, M., Toyka, K. V., Taleghani, M.et al. (1998). Depletion of neutralizing antibodies resensitizes a secondary nonresponder to botulinum A neurotoxin. J. Neurol. Neurosurg. Psychiatry, 65, 924–7.CrossRefGoogle Scholar
Dressler, D., Zettl, U., Bigalke, H. and Benecke, R. (2000). Can intravenous immunoglobulin improve antibody mediated botulinum toxin therapy failure?Mov. Disord., 15, 1279–81.3.0.CO;2-4>CrossRefGoogle ScholarPubMed
Duane, D., Monroe, J. and Morris, R. E. (2000). Mycophenolate in the prevention of recurrent neutralizing botulinum toxin A antibodies in cervical dystonia. Mov. Disord., 15, 365–6.3.0.CO;2-0>CrossRefGoogle ScholarPubMed

Save book to Kindle

To save this book to your Kindle, first ensure [email protected] 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 saving to your Kindle.

Note you can select to save to either the @free.kindle.com or @kindle.com variations. ‘@free.kindle.com’ emails are free but can only be saved 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.

  • Botulinum toxin: primary and secondary resistance
    • By Benjamin Anyanwu, New Jersey Neuroscience Institute, JFK Medical Center, Edison, NJ, USA; Seton Hall University School of Graduate Medical Education, South Orange, NJ, USA, Philip A. Hanna, New Jersey Neuroscience Institute, JFK Medical Center, Edison, NJ, USA; Seton Hall University School of Graduate Medical Education, South Orange, NJ, USA, Joseph Jankovic, Parkinson's Disease Center and Movement Disorders Clinic, Baylor College of Medicine, Houston, Texas, USA
  • Edited by Anthony B. Ward, Michael P. Barnes
  • Book: Clinical Uses of Botulinum Toxins
  • Online publication: 02 December 2009
  • Chapter DOI: https://doi.org/10.1017/CBO9780511544842.004
Available formats
×

Save book to Dropbox

To save content items to your account, please 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 account. Find out more about saving content to Dropbox.

  • Botulinum toxin: primary and secondary resistance
    • By Benjamin Anyanwu, New Jersey Neuroscience Institute, JFK Medical Center, Edison, NJ, USA; Seton Hall University School of Graduate Medical Education, South Orange, NJ, USA, Philip A. Hanna, New Jersey Neuroscience Institute, JFK Medical Center, Edison, NJ, USA; Seton Hall University School of Graduate Medical Education, South Orange, NJ, USA, Joseph Jankovic, Parkinson's Disease Center and Movement Disorders Clinic, Baylor College of Medicine, Houston, Texas, USA
  • Edited by Anthony B. Ward, Michael P. Barnes
  • Book: Clinical Uses of Botulinum Toxins
  • Online publication: 02 December 2009
  • Chapter DOI: https://doi.org/10.1017/CBO9780511544842.004
Available formats
×

Save book to Google Drive

To save content items to your account, please 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 account. Find out more about saving content to Google Drive.

  • Botulinum toxin: primary and secondary resistance
    • By Benjamin Anyanwu, New Jersey Neuroscience Institute, JFK Medical Center, Edison, NJ, USA; Seton Hall University School of Graduate Medical Education, South Orange, NJ, USA, Philip A. Hanna, New Jersey Neuroscience Institute, JFK Medical Center, Edison, NJ, USA; Seton Hall University School of Graduate Medical Education, South Orange, NJ, USA, Joseph Jankovic, Parkinson's Disease Center and Movement Disorders Clinic, Baylor College of Medicine, Houston, Texas, USA
  • Edited by Anthony B. Ward, Michael P. Barnes
  • Book: Clinical Uses of Botulinum Toxins
  • Online publication: 02 December 2009
  • Chapter DOI: https://doi.org/10.1017/CBO9780511544842.004
Available formats
×