Skip to main content
Log in

Spastic Cerebral Palsy

Approaches to Drug Treatment

  • Practical Therapeutics
  • Published:
CNS Drugs Aims and scope Submit manuscript

Abstract

Summary

Spasticity is the most common movement disorder of persons with cerebral palsy, and is attributable to the insufficient release of γ-aminobutyric acid (GABA) in the spinal cord. The goals of treating spasticity vary, depending on its severity and on the extent of the muscles involved, and should be identified before treatment begins.

While surgical/orthopaedic management of spastic cerebral palsy is the most common form of therapy, drug treatment is used to delay or supplement those treatments. The 3 orally administered medications most commonly used to treat spastic cerebral palsy are baclofen, diazepam and dantrolene. These drugs reduce spasticity significantly more than placebo, but their relative ineffectiveness has resulted in an interest in more invasive pharmacological treatments, including intramuscularly administered botulinum toxin and intrathecally administered baclofen. Botulinum toxin acts by preventing the release of acetylcholine from synaptic vesicles at the neuromuscular junction. It significantly reduces hypertonia in the injected muscles for 2 to 4 months and has virtually no systemic adverse effects. Continuously administered intrathecal baclofen significantly reduces spasticity in the upper and lower extremities of approximately 80% of patients with cerebral spasticity and improves their ability to transfer positions. It is appropriate therapy for patients with suboptimal underlying strength, who rely on some spasticity to stand and be mobile Future evaluation of the active enantiomer, L-baclofen, is anticipated.

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.

Similar content being viewed by others

References

  1. Ashworth B. Preliminary trial of carisoprodol in multiple sclerosis. Practitioner 1964; 192: 540–2

    PubMed  CAS  Google Scholar 

  2. Zieglgansberger W, Howe JR, Sutor B. The neuropharmacology ofbaclofen. In: Muller H, Zierski J, Penn RD, editors. Localspinal therapy of spasticity. New York: Springer-Verlag, 1988: 37–49

    Chapter  Google Scholar 

  3. Dolphin AC, Scott RY. Inhibition of calcium currents in cultured rat dorsal root ganglion neurons by baclofen. Br J Pharmacol 1986; 88: 213–20

    Article  PubMed  CAS  Google Scholar 

  4. Van Hemert JCJ. A double-blind comparison of baclofen and placebo in patients with spasticity of cerebral origin. In: Feldman RD, Young RR, Koella WP, editors. Spasticity: disordered motor control. Chicago: Yearbook Medical Publishers, 1980: 41–9

    Google Scholar 

  5. Hattab JR. Review of European clinical trials with baclofen. In: Feldman RG, Young R, Koella WP, editors. Spasticity: disordered motor control. Chicago: Yearbook Medical Publishers, 1980: 71–85

    Google Scholar 

  6. McKinlay I, Hyde E, Gordon N. Baclofen: a team approach to drug evaluation of spasticity in childhood. Scottish Med J 1980; 25 Suppl.: S26–8

    Google Scholar 

  7. Hedley DW, Matoun lA, Espir ML. Evaluation of baclofen (lioresal) for spasticity in mUltiple sclerosis. Postgrad Med J 1975; 51: 615–8

    Article  PubMed  CAS  Google Scholar 

  8. Knutsson E, Lindblom U, Martensson A. Plasma and cerebrospinal fluid levels of baclofen (Lioresal) at optimal therapeutic responses in spastic paresis. J Neurol Sci 1974; 23: 473–84

    Article  PubMed  CAS  Google Scholar 

  9. Burgard EC, Sarvey 1M. Long-lasting potentiation and epileptiform activity produced by GABAB receptor activation in the dentate gyrus of the rat hippocampal slice. J Neuro Sci 1991; 11: 1198–209

    CAS  Google Scholar 

  10. Terrence CF, Fromm GH, Roussan MS. Baclofen: effect on seizure frequency. Arch Neurol 1983; 40: 28–9

    Article  PubMed  CAS  Google Scholar 

  11. Coffey Rl, Cahill D, Steers W, et al. Intrathecal bac10fen for intractable spasticity of spinal origin: results of a long-term multicenter study. J Neurosurg 1993; 78: 226–32

    Article  PubMed  CAS  Google Scholar 

  12. Rivas DA, Chancellor MB, Hill K, et al. Neurological manifestations of baclofen withdrawal. J Urol 1993; 150: 1903–5

    PubMed  CAS  Google Scholar 

  13. Muller-Schwefe G, Penn RD. Physostigmine in the treatment of intrathecal bac10fen overdose: report of three cases. J Neurosurg 1989; 71: 273–5

    Article  PubMed  CAS  Google Scholar 

  14. Dahlin M, Knutsson E, Nergardh A. Treatment of spasticity in children with low dose benzodiazepine. J Neurol Sci 1993; 117: 54–60

    Article  PubMed  CAS  Google Scholar 

  15. Grant SM, Heel RC. Vigabatrin: a review of its pharmacodynamic and pharmacokinetic properties, and therapeutic potential in epilepsy and disorders of motor control. Drugs 1991; 41: 889–926

    Article  PubMed  CAS  Google Scholar 

  16. Jaeken J, Casaer P, DeCock P. Vigabatrin in GABA metabolism disorders [letter]. Lancet 1989; 1: 1074

    Article  PubMed  CAS  Google Scholar 

  17. Kurlemann G, Palm DG. Vigabatrin in metachromatic leukodystrophy; positive influence on spasticity [letter]. Dev Med Child Neurol 1991; 33: 182

    Article  PubMed  CAS  Google Scholar 

  18. Lapierre Y, Bouchard S, Tansey C, et al. Treatment of spasticity with tizanidine in multiple sclerosis. Can J Neurol Sci 1987; 14: 513–7

    PubMed  CAS  Google Scholar 

  19. Medici M, Pebet M, Ciblis D. A double-blind, long-term study of tizanidine (Sirdalud) in spasticity due to cerebrovascular lesions. Curr Med Res Opin 1989 11; 398–407

    Article  PubMed  CAS  Google Scholar 

  20. Rice G. Tizanidine vs baclofen in the treatment of spasticity in patients with multiple sclerosis. Can J Neurol Sci 1988; 15: 15–9

    PubMed  Google Scholar 

  21. Rudick RA, Breton D, Krall RL. The GABA-agonist progabide for spasticity in multiple sclerosis. Arch Neurol 1987; 44: 1033–6

    Article  PubMed  CAS  Google Scholar 

  22. Muller H, Zierski J, Dralle D, et al. Pharmacokinetics of intrathecal baclofen. In: Muller H, Muller H, Zierski J, et al., editors. Local-spinal therapy of spasticity. New York: Springer-Verlag Inc., 1988: 223–6

    Chapter  Google Scholar 

  23. Penn RD. Intrathecal baclofen for spasticity of spinal origin: seven years of experience. J Neurosurg 1992; 77: 236–40

    Article  PubMed  CAS  Google Scholar 

  24. Saltuari L, Kronenberg M, Maros Ml, et al. Long-term intrathecal baclofen treatment in supraspinal spasticity. Acta Neurol 1992; 14: 195–207

    CAS  Google Scholar 

  25. Albright AL, Cervi A, Singeltary J. Intrathecal baclofen for spasticity in cerebral palsy. JAMA 1991; 265: 1418–22

    Article  PubMed  CAS  Google Scholar 

  26. Albright AL, Barron WB, Fasick MP, et al. Continuous intrathecal baclofen infusion for spasticity of cerebral origin. lAMA 1993; 270: 2475–7

    CAS  Google Scholar 

  27. Akman MN, Loubser PG, Donovan WH, et al. Intrathecal baclofen: does tolerance occur? Paraplegia 1993; 31: 516–20

    Article  PubMed  CAS  Google Scholar 

  28. Kroin lS, Bianchi GD, Penn RD. Intrathecal baclofen downregulated GABAB receptors in the rat substantia gelatinosa. J Neurosurg 1993; 79: 544–9

    Article  PubMed  CAS  Google Scholar 

  29. Saltuari L, Baumgartner H, Kofler M, et al. Failure of physostigmine in treatment of acute severe intrathecal baclofen intoxication [Jetter]. N Engl J Med 1990; 332: 1533

    Google Scholar 

  30. Fromm GH, Shibuya T, Nakata M, et al. Effects of D-baclofen and L-baclofen on the trigeminal nucleus. Neuropharmacology 1990; 29: 249–54

    Article  PubMed  CAS  Google Scholar 

  31. Fromm GH, Terrence CF. Comparison of L-baclofen and racemic baclofen in trigeminal neuralgia. Neurology 1987; 37: 1725–8

    Article  PubMed  CAS  Google Scholar 

  32. Albright AL, Barry Ml, Hoffman P. Intrathecal baclofen for cerebral spasticity. Neurology. In press

  33. Ward A, Chaffman MO, Sorkin EM. Dantrolene: review of its pharmacodynamic and pharmacokinetic properties and therapeutic uses in malignant hyperthermia, neuroleptic malignant syndrome and update of its use in muscle spasticity. Drugs 1986; 32: 130–68

    Article  PubMed  CAS  Google Scholar 

  34. Ford F, Bleek EE, Aptekar RG, et al. Efficacy of dantrolene sodium in the treatment of spastic cerebral palsy. Dev Med Child Neurol 1976; 18: 770–83

    Article  Google Scholar 

  35. Haslam RHA, Walcher lR, Lietman Pl, et al. Dantrolene sodium in children with spasticity. Arch Phys Med Rehabil 1974; 55: 384–8

    PubMed  CAS  Google Scholar 

  36. Joynt RL, Leonard jr JA. Dantrolene sodium suspension in treatment of spastic cerebral palsy. Dev Med Child Neurol 1980; 755-67

  37. Inotsume N, Higashi A, Matsukane I, et al. Relationship between serum concentration and daily dose of dantrolene in cerebral palsy patients. Pediatr Pharm 1986; 5: 253–9

    CAS  Google Scholar 

  38. Chan CH. Dantrolene sodium and hepatic injury. Neurology 1990; 40: 1427–32

    Article  PubMed  CAS  Google Scholar 

  39. Greene P, Fahn S, Diamond B. Development of resistance to botulinum toxin type A in patients with torticollis. Mov Disord 1994; 9: 213–7

    Article  PubMed  CAS  Google Scholar 

  40. Koman LA, Mooney III JF, Smith B, et al. Management of cerebral palsy with botulinum-A toxin: preliminary investigation. J Pediatr Orthop 1993; 13: 489–95

    Article  PubMed  CAS  Google Scholar 

  41. Cosgrove AP, Corry IS, Graham HK. Botulinum toxin in the management of the lower limb in cerebral palsy. Dev Med Child Neurol 1994; 36: 3886–96

    Google Scholar 

  42. Sutherland DH, Kaufman KR, Wyatt MP, et al. Effects of botulinum toxin on gait of patients with cerebral palsy: preliminary results [abstract 11]. Dev Med Child Neurol 1994; 36 Suppl. 70: 11

    Google Scholar 

  43. Corry IS, Cosgrove AP, Walsh EG, et al. Botulinum toxin A in the hemiplegic upper limb: a double blind trial [abstract 14]. Dev Med Child Neurol 1994; 36 Suppl. 70: 11–2

    Google Scholar 

  44. Albright AL. Neurosurgical treatment of spasticity: selective posterior rhizotomy and intrathecal baclofen. Stereotact Funct Neurosurg 1992; 58: 3–13

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Albright, A.L. Spastic Cerebral Palsy. CNS Drugs 4, 17–27 (1995). https://doi.org/10.2165/00023210-199504010-00003

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.2165/00023210-199504010-00003

Keywords

Navigation