Download PDF
Semin Neurol 2004; 24(2): 165-174
DOI: 10.1055/s-2004-830902
Copyright © 2004 by Thieme Medical Publishers, Inc., 333 Seventh Avenue, New York, NY 10001, USA.

Pearls and Pitfalls in the Therapeutic Use of Botulinum Toxin

A. Gordon Smith1
  • 1Associate Professor of Neurology and Pathology, Director, Therapeutic Botulinum Toxin Clinic, University of Utah, Salt Lake City, Utah
Further Information

Publication History

Publication Date:
15 July 2004 (online)

    Permissions and Reprints

Botulinum toxin is a potent toxin and powerful therapeutic tool. Botulinum toxin has therapeutic application in the treatment of a host of neurological, ophthalmologic, gastroenterological, urologic, and dermatologic conditions. Although there are issues specific to each disorder for which botulinum toxin therapy is employed, there are several common principles. This article reviews several of these general principles by addressing common questions that arise in the therapeutic use of botulinum toxin. Areas of focus include patient selection, drug preparation and delivery, use of electromyography to guide injections, drug resistance, and organization of a therapeutic botulinum toxin clinic.

KEYWORDS

Botulinum toxin - dystonia - therapy

REFERENCES

  • 1 Greenfield R A, Brown B R, Hutchins J B et al.. Microbiological, biological, and chemical weapons of warfare and terrorism.  Am J Med Sci. 2002;  323 326-340
    PubMedGoogle Scholar
  • 2 Aoki K. Pharmacology and immunology of botulinum toxin serotypes.  J Neurol. 2001;  248(suppl 1) 3-10
    PubMedGoogle Scholar
  • 3 Hallett M. How does botulinum toxin work?.  Ann Neurol. 2000;  48 7-8
    CrossrefPubMedGoogle Scholar
  • 4 Byrnes M L, Thickbroom G W, Wilson S A et al.. The corticomotor representation of upper limb muscles in writer's cramp and changes following botulinum toxin injection.  Brain. 1998;  121 977-988
    CrossrefPubMedGoogle Scholar
  • 5 Gilio F, Curra A, Lorenzano C et al.. Effects of botulinum toxin type A on intracortical inhibition in patients with dystonia.  Ann Neurol. 2000;  48 20-26
    CrossrefPubMedGoogle Scholar
  • 6 Saadia D, Voustianiouk A, Wang A K, Kaufmann H. Botulinum toxin type A in primary palmar hyperhidrosis: randomized, single-blind, two-dose study.  Neurology. 2001;  57 2095-2099
    CrossrefPubMedGoogle Scholar
  • 7 Heckmann M, Ceballos-Baumann A O, Plewig G. Botulinum toxin A for axillary hyperhidrosis (excessive sweating).  N Engl J Med. 2001;  344 488-493
    CrossrefPubMedGoogle Scholar
  • 8 Pal P K, Calne D B, Calne S, Tsui J K. Botulinum toxin A as treatment for drooling saliva in PD.  Neurology. 2000;  54 244-247
    PubMedGoogle Scholar
  • 9 Mancini F, Zangaglia R, Cristina S et al.. Double-blind, placebo-controlled study to evaluate the efficacy and safety of botulinum toxin type A in the treatment of drooling in parkinsonism.  Mov Disord. 2003;  18 685-688
    CrossrefPubMedGoogle Scholar
  • 10 Voller B, Sycha T, Gustorff B et al.. A randomized double-blind placebo controlled study on analgesic effects of botulinum toxin A.  Neurology. 2003;  61 940-944
    PubMedGoogle Scholar
  • 11 Kramer H H, Angerer C, Erbguth F, Schmelz M, Birklein F. Botulinum toxin A reduces neurogenic flare but has almost no effect on pain and hyperalgesia in human skin.  J Neurol. 2003;  250 188-193
    PubMedGoogle Scholar
  • 12 Aoki K. Evidence for antinociceptive activity of botulinum toxin type A in pain management.  Headache. 2003;  43 S9-S15
    CrossrefPubMedGoogle Scholar
  • 13 Welch M, Purkiss J, Foster K. Sensitivity of embryonic rat dorsal root ganglia neurons to Clostridium botulinum neurotoxins.  Toxicon. 2000;  38 245-258
    CrossrefPubMedGoogle Scholar
  • 14 Scott A. Botulinum toxin injection into extraocular muscles as an alternative to strabismus surgery.  Ophthalmology. 1980;  87 1044-1049
    CrossrefPubMedGoogle Scholar
  • 15 Tsui J K, Eisen A, Stoessl A J, Calne S, Calne D B. Double-blind study of botulinum toxin in spasmodic torticollis.  Lancet. 1986;  2 245-247
    PubMedGoogle Scholar
  • 16 Jankovic J, Schwartz K. Botulinum toxin injections for cervical dystonia.  Neurology. 1990;  40 277-280
    CrossrefPubMedGoogle Scholar
  • 17 Brin M F, Fahn S, Moskowitz C et al.. Localized injections of botulinum toxin for the treatment of focal dystonia and hemifacial spasm.  Mov Disord. 1987;  2 237-254
    CrossrefPubMedGoogle Scholar
  • 18 Binder W J, Brin M F, Blitzer A, Schoenrock L D, Pogoda J M. Botulinum toxin type A (BOTOX) for treatment of migraine headaches: an open-label study.  Otolaryngol Head Neck Surg. 2000;  123 669-676
    CrossrefPubMedGoogle Scholar
  • 19 Mathew N T, Kaup A O. The use of botulinum toxin type A in headache treatment.  Curr Treat Options Neurol. 2002;  4 365-373
    PubMedGoogle Scholar
  • 20 Porta M. A comparative trial of botulinum toxin type A and methylprednisolone for the treatment of tension-type headache.  Curr Rev Pain. 2000;  4 31-35
    PubMedGoogle Scholar
  • 21 Silberstein S, Mathew N, Saper J, Jenkins S. Botulinum toxin type A as a migraine preventive treatment. For the BOTOX Migraine Clinical Research Group.  Headache. 2000;  40 445-450
    CrossrefPubMedGoogle Scholar
  • 22 Brin M, Swope D, O'Brian C, Abbasi S, Pogoda J. Botox for migraine: double-blind, placebo controlled region specific evaluation.  Cephalgia. 2000;  20 421-422
    CrossrefPubMedGoogle Scholar
  • 23 Troost B. Botulinum toxin type A (Botox) therapy for intractable headache.  Headache. 2002;  42 449-450
    PubMedGoogle Scholar
  • 24 Blumenfeld A. Decrease in headache medication use and cost after botulinum toxin type A (Botox) treatment in a high triptan use population.  Headache. 2002;  42 409
    PubMedGoogle Scholar
  • 25 Gobel H, Heinze A, Heinze-Kuhn K, Jost W. Evidence-based medicine: botulinum toxin A in migraine and tension-type headache.  J Neurol. 2001;  248(suppl 1) 34-38
    PubMedGoogle Scholar
  • 26 Brin M F, Lyons K E, Doucette J et al.. A randomized, double masked, controlled trial of botulinum toxin type A in essential hand tremor.  Neurology. 2001;  56(11) 1523-1528
    CrossrefPubMedGoogle Scholar
  • 27 Guyer B. Some unresolved issues with botulinum toxin.  J Neurol. 2001;  248(suppl 1) 11-13
    PubMedGoogle Scholar
  • 28 Greene P. Potency of frozen/thawed botulinum toxin type A in the treatment of torsion dystonia.  Otolaryngol Head Neck Surg. 1993;  109 968-969
    PubMedGoogle Scholar
  • 29 Setler P. The biochemistry of botulinum toxin type B.  Neurology. 2000;  55 S22-S28
    CrossrefPubMedGoogle Scholar
  • 30 Barbano R L. Needle EMG guidance for injection of botulinum toxin. Needle EMG guidance is useful.  Muscle Nerve. 2001;  24(11) 1567-1568
    CrossrefPubMedGoogle Scholar
  • 31 Jankovic J. Needle EMG guidance for injection of botulinum toxin. Needle EMG guidance is rarely required.  Muscle Nerve. 2001;  24(11) 1568-1570
    CrossrefPubMedGoogle Scholar
  • 32 Van Gerpen J A, Matsumoto J Y, Ahlskog J E, Maraganore D M, McManis P G. Utility of an EMG mapping study in treating cervical dystonia.  Muscle Nerve. 2000;  23(11) 1752-1756
    CrossrefPubMedGoogle Scholar
  • 33 Brans J W, de Boer I P, Aramideh M, Ongerboer de Visser B W, Speelman J D. Botulinum toxin in cervical dystonia: low dosage with electromyographic guidance.  J Neurol. 1995;  242(8) 529-534
    CrossrefPubMedGoogle Scholar
  • 34 Dubinsky R M, Gray C S, Vetere-Overfield B, Koller W C. Electromyographic guidance of botulinum toxin treatment in cervical dystonia.  Clin Neuropharmacol. 1991;  14(3) 262-267
    PubMedGoogle Scholar
  • 35 Comella C L, Buchman A S, Tanner C M, Brown-Toms N C, Goetz C G. Botulinum toxin injection for spasmodic torticollis: increased magnitude of benefit with electromyographic assistance.  Neurology. 1992;  42(4) 878-882
    CrossrefPubMedGoogle Scholar
  • 36 Molloy F M, Shill H A, Kaelin-Lang A, Karp B I. Accuracy of muscle localization without EMG: implications for treatment of limb dystonia.  Neurology. 2002;  58(5) 805-807
    CrossrefPubMedGoogle Scholar
  • 37 Hughes R, Whaler B C. Influence of nerve-ending activity and of drugs on the rate of paralysis of rat diaphragm preparations by Cl. botulinum type A toxin.  J Physiol. 1962;  160 221-233
    PubMedGoogle Scholar
  • 38 Eleopra R, Tugnoli V, De Grandis D. The variability in the clinical effect induced by botulinum toxin type A: the role of muscle activity in humans.  Mov Disord. 1997;  12(1) 89-94
    CrossrefPubMedGoogle Scholar
  • 39 Chen R, Karp B I, Goldstein S R et al.. Effect of muscle activity immediately after botulinum toxin injection for writer's cramp.  Mov Disord. 1999;  14 307-312
    CrossrefPubMedGoogle Scholar
  • 40 Hesse S, Reiter F, Konrad M, Jahnke M T. Botulinum toxin type A and short-term electrical stimulation in the treatment of upper limb flexor spasticity after stroke: a randomized, double-blind, placebo-controlled trial.  Clin Rehabil. 1998;  12(5) 381-388
    CrossrefPubMedGoogle Scholar
  • 41 Ross M H, Charness M E, Sudarsky L, Logigian E L. Treatment of occupational cramp with botulinum toxin: diffusion of toxin to adjacent noninjected muscles.  Muscle Nerve. 1997;  20(5) 593-598
    PubMedGoogle Scholar
  • 42 Borodic G E, Ferrante R, Pearce L B, Smith K. Histologic assessment of dose-related diffusion and muscle fiber response after therapeutic botulinum A toxin injections.  Mov Disord. 1994;  9(1) 31-39
    CrossrefPubMedGoogle Scholar
  • 43 Tarsy D. Comparison of acute- and delayed-onset posttraumatic cervical dystonia.  Mov Disord. 1998;  13(3) 481-485
    CrossrefPubMedGoogle Scholar
  • 44 Truong D D, Dubinsky R, Hermanowicz N et al.. Posttraumatic torticollis.  Arch Neurol. 1991;  48(2) 221-223
    CrossrefPubMedGoogle Scholar
  • 45 Hsiung G Y, Das S K, Ranawaya R, Lafontaine A L, Suchowersky O. Long-term efficacy of botulinum toxin A in treatment of various movement disorders over a 10-year period.  Mov Disord. 2002;  17(6) 1288-1293
    CrossrefPubMedGoogle Scholar
  • 46 Kessler K R, Skutta M, Benecke R. Long-term treatment of cervical dystonia with botulinum toxin A: efficacy, safety, and antibody frequency. German Dystonia Study Group.  J Neurol. 1999;  246(4) 265-274
    CrossrefPubMedGoogle Scholar
  • 47 Greene P, Fahn S, Diamond B. Development of resistance to botulinum toxin type A in patients with torticollis.  Mov Disord. 1994;  9(2) 213-217
    CrossrefPubMedGoogle Scholar
  • 48 Jankovic J, Vuong K D, Ahsan J. Comparison of efficacy and immunogenicity of original versus current botulinum toxin in cervical dystonia.  Neurology. 2003;  60(7) 1186-1188
    CrossrefPubMedGoogle Scholar
  • 49 Turkel C, Dru R, Daggett S, Brin M. Neutralizing antibody formation is rare following repeated injections of a low-protein formulation of botulinum toxin type A (BTX-A) in patients with post-stroke spasticity.  Neurology. 2002;  58(suppl 7) A316
    PubMedGoogle Scholar
  • 50 Hanna P A, Jankovic J, Vincent A. Comparison of mouse bioassay and immunoprecipitation assay for botulinum toxin antibodies.  J Neurol Neurosurg Psychiatry. 1999;  66 612-616
    CrossrefPubMedGoogle Scholar
  • 51 Hanna P A, Jankovic J. Mouse bioassay versus Western blot assay for botulinum toxin antibodies: correlation with clinical response.  Neurology. 1998;  50(6) 1624-1629
    PubMedGoogle Scholar
  • 52 Gordon P H, Gooch C L, Greene P E. Extensor digitorum brevis test and resistance to botulinum toxin type A.  Muscle Nerve. 2002;  26(6) 828-831
    PubMedGoogle Scholar
  • 53 Birklein F, Walther D, Bigalke H, Winterholler M, Erbguth F. Sudomotor testing predicts the presence of neutralizing botulinum A toxin antibodies.  Ann Neurol. 2002;  52(1) 68-73
    CrossrefPubMedGoogle Scholar
  • 54 Birklein F, Erbguth F. Sudomotor testing discriminates between subjects with and without antibodies against botulinum toxin A: a preliminary observation.  Mov Disord. 2000;  15(1) 146-149
    CrossrefPubMedGoogle Scholar
  • 55 Gelb D J, Yoshimura D M, Olney R K, Lowenstein D H, Aminoff M J. Change in pattern of muscle activity following botulinum toxin injections for torticollis.  Ann Neurol. 1991;  29(4) 370-376
    CrossrefPubMedGoogle Scholar
  • 56 Brin M F, Lew M F, Adler C H et al.. Safety and efficacy of NeuroBloc (botulinum toxin type B) in type A-resistant cervical dystonia.  Neurology. 1999;  53(7) 1431-1438
    CrossrefPubMedGoogle Scholar
  • 57 Dressler D, Bigalke H, Benecke R. Botulinum toxin type B in antibody-induced botulinum toxin type A therapy failure.  J Neurol. 2003;  250(8) 967-969
    CrossrefPubMedGoogle Scholar
  • 58 Naumann M, Toyka K V, Mansouri Taleghani B et al.. Depletion of neutralising antibodies resensitises a secondary non-responder to botulinum A neurotoxin.  J Neurol Neurosurg Psychiatry. 1998;  65(6) 924-927
    PubMedGoogle Scholar
  • 59 Munchau A, Palmer J D, Dressler D et al.. Prospective study of selective peripheral denervation for botulinum-toxin resistant patients with cervical dystonia.  Brain. 2001;  124 769-783
    CrossrefPubMedGoogle Scholar
  • 60 Kupsch A, Kuehn A, Klaffke S et al.. Deep brain stimulation in dystonia.  J Neurol. 2003;  250(suppl 1) I47-I52
    PubMedGoogle Scholar

A. Gordon SmithM.D. 

Department of Neurology, University of Utah, 30 North 1900 East

SOM Room 3R152, Salt Lake City, UT 84132-2305

      >