Skip to main content
Log in

Botulinum toxin treatment failures in cervical dystonia: causes, management, and outcomes

  • Original Communication
  • Published:
Journal of Neurology Aims and scope Submit manuscript

Abstract

Botulinum toxin (BoNT) is highly effective in the treatment of cervical dystonia (CD), yet a significant proportion of patients report low levels of satisfaction following treatment and fail to follow up for repeated treatments. The goal of this study was to determine the reasons that some patients have unsatisfactory responses. A total of 35 subjects who came to our center requesting alternative treatments due to unsatisfactory responses following BoNT treatment for CD were evaluated. Included were 26 women and 9 men with an average age of 57.1 years (range 25–82 years), and an average duration of illness of 12.5 years (range 1–55 years). Details of unsatisfactory BoNT treatments were methodically collected by a movement specialist using a standardized intake form, including provider subspecialty, product used, the number of satisfactory or unsatisfactory trials, doses given, specific muscles treated, the use of electromyographic guidance, side effects, and tests of resistance. The specialist then provided repeat treatments if indicated, and followed each case until the reasons for unsatisfactory outcomes could be determined. Multiple reasons for unsatisfactory outcomes were found. They included suboptimal BoNT doses, suboptimal muscle targeting, intolerable side effects, complex movement patterns, discordant perceptions, and incorrect diagnoses. Only one patient was functionally resistant to BoNT. Of 32 subjects who received repeat BoNT treatments, 25 (78 %) achieved satisfactory responses after revision of the original treatment plan. These results indicate that the majority of unsatisfactory responses to BoNT treatment of CD were caused by correctible factors and imply a need for improved education regarding optimal treatment methods.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1

Similar content being viewed by others

Abbreviations

BoNT:

Botulinum neurotoxin

CD:

Cervical dystonia

EMG:

Electromyography

References

  1. Jinnah HA, Factor S (2015) Diagnosis and treatment of dystonia. In: Jankovic J (ed) Neurologic clinics. Elsevier, Amsterdam, pp 77–100

    Google Scholar 

  2. Evatt ML, Freeman A, Factor S (2011) Adult-onset dystonia. Handb Clin Neurol 100:481–511

    Article  PubMed  Google Scholar 

  3. Hallett M, Albanese A, Dressler D et al (2013) Evidence-based review and assessment of botulinum neurotoxin for the treatment of movement disorders. Toxicon 67:94–114

    Article  CAS  PubMed  Google Scholar 

  4. Albanese A, Abbruzzese G, Dressler D et al (2015) Practical guidance for CD management involving treatment of botulinum toxin: a consensus statement. J Neurol 262:2201–2213

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Sethi KD, Rodriguez R, Olayinka B (2012) Satisfaction with botulinum toxin treatment: a cross-sectional survey of patients with cervical dystonia. J Med Econ 15:419–423

    Article  PubMed  Google Scholar 

  6. Skogseid IM, Kerty E (2005) The course of cervical dystonia and patient satisfaction with long-term botulinum toxin A treatment. Eur J Neurol 12:163–170

    Article  CAS  PubMed  Google Scholar 

  7. Comella C, Bhatia K (2015) An international survey of patients with cervical dystonia. J Neurol 262:837–848

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Jankovic J, Adler CH, Charles D et al (2015) Primary results from the cervical dystonia patient registry for observation of OnabotulinumtoxinA efficacy (CD PROBE). J Neurol Sci 349:84–93

    Article  PubMed  Google Scholar 

  9. Evidente VG, Pappert EJ (2014) Botulinum toxin therapy for cervical dystonia: the science of dosing. Tremor Other Hyperkinet Mov 4:273

    Google Scholar 

  10. Hsiung GY, Das SK, Ranawaya R, Lafontaine AL, Suchowersky O (2002) Long-term efficacy of botulinum toxin A in treatment of various movement disorders over a 10-year period. Mov Disord 17:1288–1293

    Article  PubMed  Google Scholar 

  11. Nijmeijer SW, Koelman JH, Standaar TS, Postma M, Tijssen MA (2013) Cervical dystonia: improved treatment response to botulinum toxin after referral to a tertiary centre and the use of polymyography. Parkinsonism Relat Disord 19:533–538

    Article  CAS  PubMed  Google Scholar 

  12. Brashear A, Bergan K, Wojcieszek J, Siemers ER, Ambrosius W (2000) Patients’ perception of stopping or continuing treatment of cervical dystonia with botulinum toxin type A. Mov Disord 15:150–153

    Article  CAS  PubMed  Google Scholar 

  13. Gill CE, Manus ND, Pelster MW et al (2013) Continuation of long-term care for cervical dystonia at an academic movement disorders clinic. Toxins (Basel) 5:776–783

    Article  Google Scholar 

  14. Albanese A, Bhatia K, Bressman SB et al (2013) Phenomenology and classification of dystonia: a consensus update. Mov Disord 28:863–873

    Article  PubMed  PubMed Central  Google Scholar 

  15. Brin MF, Comella CL, Jankovic J, Lai F, Naumann M (2008) Long-term treatment with botulinum toxin type A in cervical dystonia has low immunogenicity by mouse protection assay. Mov Disord 23:1353–1360

    Article  PubMed  Google Scholar 

  16. Lange O, Bigalke H, Dengler R, Wegner F, deGroot M, Wohlfarth K (2009) Neutralizing antibodies and secondary therapy failure after treatment with botulinum toxin type A: much ado about nothing? Clin Neuropharmacol 32:213–218

    Article  CAS  PubMed  Google Scholar 

  17. Ferreira JJ, Colosimo C, Bhidayasiri R, Marti MJ, Maisonobe P, Om S (2015) Factors influencing secondary non-response to botulinum toxin type A injections in cervical dystonia. Parkinsonism Relat Disord 21:111–115

    Article  PubMed  Google Scholar 

  18. Ferreira JJ, Bhidayasiri R, Colosimo C, Marti MJ, Zakine B, Maisonobe P (2012) Survey of practices employed by neurologists for the definition and management of secondary non-response to botulinum toxin in cervical dystonia. Funct Neurol 27:225–230

    PubMed  PubMed Central  Google Scholar 

  19. Naumann M, Boo LM, Ackerman AH, Gallagher CJ (2013) Immunogenicity of botulinum toxins. J Neural Transm 120:275–290

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Coleman C, Hubble J, Schwab J, Beffy JL, Picaut P, Morte C (2012) Immunoresistance in cervical dystonia patients after treatment with abobotulinumtoxinA. Int J Neurosci 122:358–362

    Article  CAS  PubMed  Google Scholar 

  21. Ruiz PJ, Castrillo JC, Burguera JA et al (2011) Evolution of dose and response to botulinum toxin A in cervical dystonia: a multicenter study. J Neurol 258:1055–1057

    Article  PubMed  Google Scholar 

  22. Fabbri M, Leodori G, Fernandes RM et al (2015) Neutralizing antibody and Botulinum toxin therapy: A systematic review and meta-analysis. Neurotox Res (in press)

  23. Svetel M, Pekmezovic T, Tomic A, Kresojevic N, Kostic VS (2015) The spread of primary late-onset focal dystonia in a long-term follow up study. Clin Neurol Neurosurg 132:41–43

    Article  PubMed  Google Scholar 

  24. Jahanshahi M, Marion MH, Marsden CD (1990) Natural history of adult-onset idiopathic torticollis. Arch Neurol 47:548–552

    Article  CAS  PubMed  Google Scholar 

  25. Martino D, Berardelli A, Abbruzzese G et al (2012) Age at onset and symptom spread in primary adult-onset blepharospasm and cervical dystonia. Mov Disord 27:1447–1450

    Article  PubMed  Google Scholar 

  26. Svetel M, Pekmezovic T, Jovic J et al (2007) Spread of primary dystonia in relation to initially affected region. J Neurol 254:879–883

    Article  PubMed  Google Scholar 

  27. Weiss EM, Hershey T, Karimi M et al (2006) Relative risk of spread of symptoms among the focal onset primary dystonias. Mov Disord 21:1175–1181

    Article  PubMed  Google Scholar 

  28. Gelb DJ, Yoshimura DM, Olney RK, Lowenstein DH, Aminoff MJ (1991) Change in pattern of muscle activity following botulinum toxin injections for torticollis. Ann Neurol 29:370–376

    Article  CAS  PubMed  Google Scholar 

  29. Waln O, LeDoux MS (2011) Blepharospasm plus cervical dystonia with predominant anterocollis: a distinctive subphenotype of segmental craniocervical dystonia? Tremor Other Hyperkinet Mov 2011(1). http://www.tremorjournal.org/article/view/33

  30. Papapetropoulos S, Tuchman A, Sengun C, Russell A, Mitsi G, Singer C (2008) Anterocollis: clinical features and treatment options. Med Sci Monit 14:CR427–CR430

    PubMed  Google Scholar 

  31. Jinnah HA, Berardelli A, Comella C et al (2013) The focal dystonias: current views and challenges for future research. Mov Disord 7:926–943

    Article  Google Scholar 

  32. Revuelta GJ, Montilla J, Benatar M et al (2014) An (18)F-FDG PET study of cervical muscle in parkinsonian anterocollis. J Neurol Sci 340:174–177

    Article  PubMed  PubMed Central  Google Scholar 

  33. Revuelta GJ, Benatar M, Freeman A et al (2011) Clinical subtypes of anterocollis in parkinsonian syndromes. J Neurol Sci 315:100–103

    Article  PubMed  PubMed Central  Google Scholar 

  34. Bhidayasiri R (2011) Treatment of complex cervical dystonia with botulinum toxin: involvement of deep-cervical muscles may contribute to suboptimal responses. Parkinsonism Relat Disord 17(Suppl 1):S20–S24

    Article  PubMed  Google Scholar 

  35. Glass GA, Ku S, Ostrem JL, Heath S, Larson PS (2009) Fluoroscopic, EMG-guided injection of botulinum toxin into the longus colli for the treatment of anterocollis. Parkinsonism Relat Disord 15:610–613

    Article  PubMed  Google Scholar 

  36. Misra VP, Ehler E, Zakine B, Maisonobe P, Simonetta-Moreau M, Group IIC (2012) Factors influencing response to Botulinum toxin type A in patients with idiopathic cervical dystonia: results from an international observational study. BMJ Open 2(3):e000881

    Article  PubMed  PubMed Central  Google Scholar 

  37. Flowers JM, Hicklin LA, Marion MH (2011) Anterior and posterior sagittal shift in cervical dystonia: a clinical and electromyographic study, including a new EMG approach of the longus colli muscle. Mov Disord 26:2409–2414

    Article  PubMed  Google Scholar 

  38. Chinnapongse RB, Lew MF, Ferreira JJ, Gullo KL, Nemeth PR, Zhang Y (2012) Immunogenicity and long-term efficacy of botulinum toxin type B in the treatment of cervical dystonia: report of 4 prospective, multicenter trials. Clin Neuropharmacol 35:215–223

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

This work was supported in part by a grant to the Dystonia Coalition (U54 TR001456 and NS065701), a consortium of the Rare Diseases Clinical Research Network (RDCRN) an initiative of the Office of Rare Diseases Research (ORDR) at the National Center for Advancing Clinical and Translational Studies (NCATS) in collaboration with the National Institute for Neurological Diseases and Stroke (NINDS).

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to H. A. Jinnah.

Ethics declarations

Conflicts of interest

The authors declare no conflicts of interest relating to the material presented in this article.

Ethical standards

This work has been performed in accordance with the ethical standards of the 1964 Declaration of Helsinki, and has been approved by the Emory University Institutional Review Board.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Jinnah, H.A., Goodmann, E., Rosen, A.R. et al. Botulinum toxin treatment failures in cervical dystonia: causes, management, and outcomes. J Neurol 263, 1188–1194 (2016). https://doi.org/10.1007/s00415-016-8136-x

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00415-016-8136-x

Keywords

Navigation