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Botulinum toxin — how a poison turned to a fascinating ally against an old adversary

Toxina botulínica — de como um veneno transformou-se num fascinante aliado contra um velho adversário

The clinical features of dystonia were first reported in 1911, when Oppehneim1. Oppenheim H. Über eine eigenartige Krampfkrankheit des kindlichen und jugendlichen Alters (Dysbasia lordotica progressiva, Dystonia musculorum deformans). Neurologische Centralblatt 1911;30:1090-1107. and Flatau2. Eldridge R., Flatau E, Sterling W. Torsion spasm in Jewish children, and the early history of human genetics. Adv Neurol 1976;14:105-114. described some Jewish children affected by a syndrome that was retrospectively considered to represent familial cases of DYT1 dystonia. In 1975 it was recognized that the dystonia phenotype also encompasses poorly-progressive focal and segmental cases with onset in adulthood, such as blepharospasm, cervical dystonia (CD) and writer's cramp3. Marsden CD. Dystonia: the spectrum of the disease. Res Publ Assoc Res Nerv Ment Dis 1976;55:351-367.. A modern definition of dystonia was worded some years later, in 19844. Fahn S, Marsden CD, Calne DB. Classification and investigation of dystonia. In: Marsden CD, Fahn S, (Eds). Movement disorders 2. London: Butterworths; 1987:332-358.,5. Bragg DC1, Sharma N. Update on treatments for dystonia. Curr Neurol Neurosci Rep 2014 ;14:454. doi: 10.1007/s11910-014-0454-8.
https://doi.org/10.1007/s11910-014-0454-...
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CD is the most common form of focal dystonia and its prevalence is estimated to be 11.5 cases per 100,000 individuals. CD is characterized by involuntary contractions of cervical region muscles, leading to awkward posture of the head and neck. Most of the cases have idiopathic origin6. Camfield L, Ben-Shlomo Y, Warner TT. Impact of cervical dystonia in quality of life. Mov Disord 2002;17:838-841..

In this volume of Arquivos de Neuropsiquiatria, Werle et al. published the article “The physical, social and emotional aspects are the most affected in the quality of life (QoL) of the patients with cervical dystonia”, showing how painful and distressing this disease can be without the treatment effect. Among those seventy Brazilian patients, 84% had pain, disabling in half of them. The vast majority showed difficulty in keeping up with professional and personal demands, felt uneasy in public and suffered depression. The greater are the disability, pain and severity of dystonia, the worse is the QoL7. Werle WR, Takeda SYM, Zonta MB, Guimarães ATB, Teive HAG. The physical, social and emotional aspects are the most affected in the quality of life of the patients with cervical dystonia. Arq Neuropsiquiatr 2014;72:405-410..

Botulinum toxin (BT) poisoning has afflicted mankind through since a long time ago. The physician and poet Justinus Kerner published the first accurate descriptions of food-borne botulism in 1822, and also postulated that the toxin might be used for treatment purposes. In 1895, in the Belgian village of Ellezelles, an outbreak of botulism led to the discovery by Emile Pierre van Ermengem of the pathogen Clostridium Botulinum, the anaerobic bacterium that produces the neurotoxin. Alan B. Scott and Edward J. Schantz, in the 1970s, were the modern pioneers of botulinum toxin (BT) treatment to correct strabismus8. Erbguth FJ. Historical notes on botulism, Clostridium botulinum, botulinum toxin, and the idea of the therapeutic use of the toxin. Mov Disord 2004;19(Suppl 8):S2-S6..

The molecular biology cleared about the precise Clostridium Botulinum toxin mechanism, showing that BT acts in the cytosol of nerve endings to cleave the SNAP-25 protein that mediates the docking and fusion of neurotransmitter-containing vesicles to the presynaptic membrane. This cleavage prevents exocytosis of acetylcholine from the presynaptic terminal of neuromuscular junctions, resulting in a temporary, reversible block of the motor fibers and weakened muscle contraction. This is the rationale for its use in dystonia treatment. To date, BT has been used to treat a wide variety of diseases associated with muscular hyperactivity, glandular hypersecretions and pain9. Lim EC, Seet RC. Use of botulinum toxin in the neurology clinic. Nat Rev Neurol 2010;6:624-636.,1010 . Esquenazi A, Novak I, Sheean G, Singer BJ, Ward AB. International consensus statement for the use of botulinum toxin treatment in adults and children with neurological impairments--introduction. Eur J Neurol 2010;17(Suppl 2):S1-S8..

In Brazil, this friendly poison has been employed in many neurologic conditions since 1991, improving patient's lives and turned out a precious tool for skilled doctors. Many Brazilian articles has been published and more and more doctors are familiarized its indications, injection technics and results1111 . Quagliato EMAB, Carelli EF, Viana MA. A prospective, randomized, double-blind study comparing the efficacy and safety of type a botulinum toxins botox and prosigne in the treatment of cervical dystonia. Clin Neuropharmacol 2010;33:22-26.,1212 . QueirozMR, ChienHF, Barbosa ER.Quality of life in individuals with cervical dystonia before botulinum toxin injection in a Brazilian tertiary care hospital. Arq Neuropsiquiatr 2011;69:900-904..

BT injections continue, aside oral medication, and, more recently, deep brain stimulation, as the current mainstays of treatment for dystonia. In addition, physical and other supportive therapies may help prevent further complications, as contractures, and improve function. Evidence-based medical treatment of dystonia enhances BT impact on QoL and motor aspects on those patients1313 . Queiroz MA, Chien HF, Sekeff-Sallem FA, Barbosa ER. Physical therapy program for cervical dystonia: a study of 20 cases. Funct Neurol 2012 ;27:187-192..

References

  • 1
    Oppenheim H. Über eine eigenartige Krampfkrankheit des kindlichen und jugendlichen Alters (Dysbasia lordotica progressiva, Dystonia musculorum deformans). Neurologische Centralblatt 1911;30:1090-1107.
  • 2
    Eldridge R., Flatau E, Sterling W. Torsion spasm in Jewish children, and the early history of human genetics. Adv Neurol 1976;14:105-114.
  • 3
    Marsden CD. Dystonia: the spectrum of the disease. Res Publ Assoc Res Nerv Ment Dis 1976;55:351-367.
  • 4
    Fahn S, Marsden CD, Calne DB. Classification and investigation of dystonia. In: Marsden CD, Fahn S, (Eds). Movement disorders 2. London: Butterworths; 1987:332-358.
  • 5
    Bragg DC1, Sharma N. Update on treatments for dystonia. Curr Neurol Neurosci Rep 2014 ;14:454. doi: 10.1007/s11910-014-0454-8.
    » https://doi.org/10.1007/s11910-014-0454-8
  • 6
    Camfield L, Ben-Shlomo Y, Warner TT. Impact of cervical dystonia in quality of life. Mov Disord 2002;17:838-841.
  • 7
    Werle WR, Takeda SYM, Zonta MB, Guimarães ATB, Teive HAG. The physical, social and emotional aspects are the most affected in the quality of life of the patients with cervical dystonia. Arq Neuropsiquiatr 2014;72:405-410.
  • 8
    Erbguth FJ. Historical notes on botulism, Clostridium botulinum, botulinum toxin, and the idea of the therapeutic use of the toxin. Mov Disord 2004;19(Suppl 8):S2-S6.
  • 9
    Lim EC, Seet RC. Use of botulinum toxin in the neurology clinic. Nat Rev Neurol 2010;6:624-636.
  • 10
    Esquenazi A, Novak I, Sheean G, Singer BJ, Ward AB. International consensus statement for the use of botulinum toxin treatment in adults and children with neurological impairments--introduction. Eur J Neurol 2010;17(Suppl 2):S1-S8.
  • 11
    Quagliato EMAB, Carelli EF, Viana MA. A prospective, randomized, double-blind study comparing the efficacy and safety of type a botulinum toxins botox and prosigne in the treatment of cervical dystonia. Clin Neuropharmacol 2010;33:22-26.
  • 12
    QueirozMR, ChienHF, Barbosa ER.Quality of life in individuals with cervical dystonia before botulinum toxin injection in a Brazilian tertiary care hospital. Arq Neuropsiquiatr 2011;69:900-904.
  • 13
    Queiroz MA, Chien HF, Sekeff-Sallem FA, Barbosa ER. Physical therapy program for cervical dystonia: a study of 20 cases. Funct Neurol 2012 ;27:187-192.

Publication Dates

  • Publication in this collection
    June 2014

History

  • Received
    21 Apr 2014
  • Accepted
    09 May 2014
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