Abstract
Background: West syndrome is an age dependant syndrome, which includes a peculiar
type of epileptic seizure (infantile spasms), usually hypsarrhythmia and in the majority
psychomotor retardation. Despite huge advances in medicine it still remains a poorly
understood entity and although with newer imaging techniques we are more often able
to elicit the underlying ‘causes’ of these spasms, still little is known about their
pathophysiological basis and treatment remains problematic.
Objectives: To compare the effects of single pharmaceutical therapies used to treat
infantile spasms in terms of long-term psychomotor development, subsequent epilepsy,
control of the spasms and side effects.
Methods: A search of the central trials register of the Cochrane Epilepsy Group, medline
database, embase database and the reference lists of all retrieved articles was undertaken.
Correspondence with colleagues and drug companies and appeals at international conferences
were also undertaken to try and discover unpublished data. All randomised controlled
trials (RCTs) on the medical treatment of infantile spasms were included. Data was
then extracted independently by the three reviewers and analysed using the RevMan
software package.
Main results: We found ten small RCTs on the pharmacological treatment of infantile
spasms. No unpublished trials were discovered. These ten studies looked at just 335
patients treated with a total of eight different pharmaceutical agents. Overall methodology
of the studies was poor, partly because of ethical dilemmas such as giving placebo
injections to children. No study considered the effects of treatment on long-term
psychomotor development or onset of other seizure types. One small study found vigabatrin
to be more efficacious in stopping infantile spasms in a group of patients with tuberous
sclerosis than hydrocortisone. One underpowered study showed a trend for vigabatrin
to be more efficacious than placebo in stopping infantile spasms, another two equally
underpowered studies suggested adrenocorticotrophic hormone (ACTH) to be more efficacious
than low-dose prednisone. It was not possible to compare reduction in the number of
spasms between the different treatments because of differences in methods of analysis.
Overall, only nine patients were reported to have been withdrawn from the trial treatments
due to side effects and two deaths were reported.
Conclusions: There is still little evidence available on the optimum treatment for
infantile spasms. Further trials with larger number of patients, and longer follow-up
are required.
Keywords
To read this article in full you will need to make a payment
Purchase one-time access:
Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online accessOne-time access price info
- For academic or personal research use, select 'Academic and Personal'
- For corporate R&D use, select 'Corporate R&D Professionals'
Subscribe:
Subscribe to Brain and DevelopmentAlready a print subscriber? Claim online access
Already an online subscriber? Sign in
Register: Create an account
Institutional Access: Sign in to ScienceDirect
References
- Proposal for revised classification of epilepsies and epileptic syndromes.Epilepsia. 1989; 30: 389-399
- West syndrome: infantile spasms.in: Roger J. Bureau M. Dravet C. Dreifuss F.E. Perret A. Wolf P. Epileptic syndromes in infancy, childhood and adolescence. 2nd ed. John Libbey, London1992: 53-65
- The epidemiology and natural history of infantile spasms.J Child Neurol. 1991; 6: 335-364
- Epilepsy in children: infantile spasms and related syndromes. 2nd ed. Raven, New York, NY1994
- Long-term outcome of West syndrome: a study of adults with a history of infantile spasms.Epilepsia. 1996; 37: 367-372
- Treatment of infantile spasms.Ann Pharmactherapy. 1994; 28: 779-791
- Randomised, placebo-controlled study of vigabatrin as first-line treatment of infantile spasms.Epilepsia. 1991; 40: 1627-1633
- Vigabatrin versus ACTH as the first line treatment of infantile spasms.Epilepsia. 1997; 38: 1270-1274
- High-dose corticotrophin (ACTH) versus prednisone for infantile spasms: a prospective, randomised, blinded study.Pediatrics. 1996; 97: 375-379
- Randomised trial comparing vigabatrin and hydrocortisone in infantile spasms due to tuberous sclerosis.Epilepsy Res. 1997; 26: 389-395
- Infantile spasms. Comparative trial of nitrazepam and corticotrophin.Arch Neurol. 1986; 43: 1107-1110
- Short term effects of valproate on infantile spasms.Pediatr Neurol. 1985; 1: 34-37
- Double blind study of ACTH vs. prednisone in infantile spasms.J Pediatr. 1983; 103: 641-645
- Treatment of infantile spasms with methysergide and alpha-methylparatyrosine.Epilepsia. 1989; 30: 607-610
- High-dose, long-duration versus low-dose, short-duration corticotropin therapy for infantile spasms.J Pediatr. 1994; 124: 803-806
- A comparative study of high-dose and low-dose ACTH therapy for West syndrome.Brain Dev. 1999; 21: 461-467
Further reading
- The role of vigabatrin in the management of infantile epileptic syndromes.Neurology. 1993; 43: S21-S23
- Use of valproic acid in treatment of infantile spasms.Arch Neurol. 1982; 39: 49-52
- A double-blind study of clonazepam in the treatment of therapy-resistant epilepsy in children.Dev Med Child Neurol. 1977; 19: 335-342
- High dose B6 treatment in infantile spasms.Neuropediatrics. 1986; 17: 7-10
- The treatment of infantile spasms by child neurologists.J Child Neurol. 1994; 9: 432-435
- Lamotrigine – an update.Can J Neurol Sci. 1996; 23: S6-S9
- Clonazepam.N Engl J Med. 1978; 12: 812-815
- Nitrazepam for refractory infantile spasms and the Lennox–Gastaut syndrome.J Child Neurol. 1996; 11: 31-34
- Therapy of infantile spasms.J Pediatr. 1984; 105: 168
- Vigabatrin.Ann Pharmacother. 1993; 27: 197-204
- Intravenous immune globulin in the treatment of intractable childhood epilepsy.Clin Exp Immunol. 1996; 104: 71-76
- Treatment of hypsarrhythmia and infantile spasms with a lithium analogue.Neurology. 1965; 15: 1173-1176
- Infantile spasms.in: Lockhart J.D. 11th ed. Current problems in pediatrics. Year Book Medical Publisher, Chicago, IL1985: 1-39
- Computed tomography in infantile spasms: effects of hormonal therapy.Pediatr Neurol. 1986; 2: 23-27
- Treatment of infantile spasms.Ann Pharmacother. 1994; 28: 779-791
- A controlled study of prednisone therapy in infantile spasms.Epilepsia. 1979; 20: 403-407
- Clinical study of oral administration of DN-1417, a TRH analog, in patients with intractable epilepsy.Epilepsia. 1989; 30: 438-445
- The effects of ACTH and corticosteroids on eplieptiform disorders.Prog Brain Res. 1970; 32: 263-269
- A prospective study of infantile spasms: clinical and therapeutic correlations.Epilepsia. 1983; 24: 135-158
- Optimizing the indication of vigabatrin in children with refractory epilepsy.J Child Neurol. 1997; 12: 253-259
- Vigabatrin in the treatment of childhood epilepsies: a single-blind placebo-controlled study.Epilepsia. 1989; 30: 430-437
- Clinical effects of thyrotropin-releasing hormone for severe epilepsy in childhood: a comparative study with ACTH therapy.Epilepsia. 1987; 28: 49-55
- Clinical pharmacology and therapeutic drug monitoring of zonisamide.Ther Drug Monit. 1998; 20: 593-597
- Meta-analysis of European placebo controlled studies of vigabatrin in drug resistant epilepsy.Br J Clin Pharmacol. 1989; 27: S101-S107
- Vigabatrin.Epilepsia. 1994; 35: S25-S28
- Preliminary report of a multi-center study on the West syndrome.Brain Dev. 1988; 10: 236-242
- A trial of clonazepam in the treatment of severe epilepsy in infancy and childhood.in: Penry J. Epilepsy: the Eighth International Symposium. Raven, New York, NY1977: 159-162
- Treatment of infantile spasms with high-dosage vitamin B6.Epilepsia. 1993; 34: 757-763
- Controlled and comparative trials with valproate: United States.Epilepsia. 1984; 25: S40-S43
- Lamotrigine in treatment of 120 children with epilepsy.Epilepsia. 1994; 35: 359-367
- Outcome of initial treatment with high-dose vitamin B6, valproate sodium or clonazepam in West syndrome.No to Hattatsu (Brain Dev) (Tokyo). 1996; 28 (in Japanese): 398-402
- Clinical effects of allopurinol on intractable epilepsy.Epilepsia. 1991; 32: 279-283
- Ervaringen met valproinezuur (depakine) bij de behandeling van epilepsie.Ned Tijdschr Geneeskd. 1977; 121: 578-590
- Treatment of infantile spasms and Lennox–Gastaut syndrome with clonazepam (Rivotril).Epilepsia. 1973; 14: 165-175
- Lamotrigine in infantile spasms.Lancet. 1994; 344: 1375-1376
- Vigabatrin versus ACTH come terapia di prima scelta nella sindrome di West.Boll Lega It Epil. 1994; 86/87: 115-116
- Management issues in severe childhood epilepsies.Seizure. 1995; 4: 215-220
- Vigabatrin versus ACTH in the treatment of infantile spasms.Epilepsia. 1995; 36: s265
- Mogadon therapy of infantile spasms.Electroencephalogr clin Neurophysiol. 1967; 23: 183
- Therapieversuch mit einem ACTH-Fragment (ACTH 4–10) bei Fruhkindlichen Anfallen.Monatsschr Kinderheilkd. 1980; 128: 100-103
- Vigabatrin as a first -line drug in West syndrome: clinical and electroencephalographic outcome.Neuropediatrics. 1998; 29: 133-136
- Liposteroid (dexamethasone palmitate) therapy for West syndrome: a comparative study with ACTH therapy.Pediatr Neurol. 1998; 18: 415-419
- Adrenocorticotropic hormone and vigabatrin treatment of children with infantile spasms underlying cerebral palsy.Brain Dev. 1996; 18: 450-452
Article info
Publication history
Accepted:
July 7,
2001
Received in revised form:
July 4,
2001
Received:
May 15,
2001
Identification
Copyright
© 2001 Elsevier Science B.V. Published by Elsevier Inc. All rights reserved.