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ACTH therapy of West syndrome: Finnish views

      Abstract

      To provide up-to-date information on adrenocorticotropic hormone (ACTH) therapy in the treatment of West syndrome, a review of the Finnish studies was made in answer to the questions: what are (1) its efficacy: doses and comparison with vigabatrin (VGB), (2) its tolerability, (3) its mechanism of action? Why do some patients respond, but others do not? No other drugs have been shown to be more effective than ACTH. High doses were not more effective than low doses. Synthetic derivatives were associated with more frequent side effects. Individualized therapy was developed on the basis of etiology and response. With therapy consisting of ACTH 3–6 IU/kg/day, all the cryptogenic and half of the symptomatic spasms could be controlled within over 2–3 weeks therapy and with minimal risk of side effects. In a Finnish study, 26% of the patients responded to VGB as the first-line drug. Some of the non-responders responded to ACTH. In tuberous sclerosis, the initial response rate to ACTH was high (73%) and did not differ from the response rate to VGB in other series. Both drugs have severe side effects. The visual field defects caused by VGB occur even in children (in 18/91 Finnish children). The patients with cryptogenic spasms, who responded well to ACTH, differed in their biochemical parameters from the patients with symptomatic spasms. The therapeutic action of ACTH may be mediated by potentiation of nerve growth promoting activity. Neurodegeneration may be due to imbalance between nerve growth factors and nitrate/nitrite in the brain. ACTH should be used as the first choice for treatment of West syndrome (at the minimal effective dose and for shortest effective time). The side effects of steroids, unlike VGB, are well known, treatable, and reversible.

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      References

        • Riikonen R
        • Perheentupa J
        Serum steroids and success of corticotropin treatment in infantile spasms.
        Acta Pediatr Scand. 1986; 75: 598-600
        • Riikonen R
        • Donner M
        ACTH therapy in infantile spasms: side effects.
        Arch Dis Child. 1980; 55: 664-672
        • Riikonen R
        A long-term follow-up study of 214 children with the syndrome of infantile spasms.
        Neuropediatrics. 1982; 13: 14-23
        • Perheentupa J
        • Riikonen R
        • Dunkel L
        Adrenocortical hyporesponsiveness after ACTH therapy of infantile spasms.
        Arch Dis Child. 1986; 61: 750-753
        • Riikonen R
        • Simell O
        • Dunkel L
        • Santavuori P
        • Perheentupa J
        Hormonal background of hypertension and fluid derangements associated with adrenocorticotrophic hormone treatment of infants.
        Eur J Pediatr. 1989; 148: 737-741
        • Riikonen R
        Steroids or vigabatrin in the treatment of infantile spasms?.
        Pediatr Neurol. 2000; 23: 403-408
        • Hrachovy R
        • Frost J
        • Glaze D
        High-dose, long-duration versus low-dose, short-duration corticotrophin therapy for infantile spasms.
        J Pediatr. 1994; 124: 803-806
        • Baram T
        • Michell W
        • Tournay A
        • Snead III, O
        • Hanson R
        • Horton E
        High-dose corticotrophin (ACTH) versus prednisone for infantile spasms.
        Pediatrics. 1996; 97: 375-379
        • Heiskala H
        • Riikonen R
        • Santavuori P
        • Simell O
        • Airaksinen E
        • Nuutila A
        • et al.
        West syndrome: individualized ACTH therapy.
        Brain Dev. 1996; 18: 456-460
        • Ross D
        Suppressed pituitary ACTH response after ACTH treatment of infantile spasms.
        J Child Neurol. 1986; 1: 34-37
        • Rao J
        • Willis J
        Hypothalamo–pituitary–adrenal function in infantile spasms: effects of ACTH therapy.
        J Child Neurol. 1987; 2: 220-223
        • Glaze D.G
        • Hrachovy R.A
        • Frost Jr, J.D
        • Kellaway P
        • Zion T.E
        Prospective study of outcome of infants with infantile spasms treated during controlled studies of ACTH and prednisone.
        J Pediatr. 1988; 112: 389-396
        • Lombroso C
        A prospective study of infantile spasms: clinical and therapeutic correlations.
        Epilepsia. 1983; 24: 135-158
        • Koo B
        • Hwang P
        • Logan W
        Infantile spasms: outcome and prognostic factors of cryptogenic and symptomatic groups.
        Neurology. 1993; 43: 2322-2327
        • Vigevano P
        • Cilio R
        Vigabatrin versus ACTH as first-line treatment for infantile spasms: a randomized, prospective study.
        Epilepsia. 1997; 38: 1270-1274
        • Granström M-L
        • Gaily E
        • Liukkonen E
        Treatment of infantile spasms: results of a population-based study with vigabatrin as the first drug for spasms.
        Epilepsia. 1999; 40: 950-957
        • Aicardi J
        • Sabril I.S
        • Mumford J.P
        • Dumas C
        • Wood S
        • Investigator and peer review groups
        Vigabatrin as initial therapy for infantile spasms: a European retrospective survey.
        Epilepsia. 1996; 37: 637-642
        • Chiron C
        • Dumas C
        • Jambaque I
        • Mumford J
        • Dulac O
        Randomized trial comparing vigabatrin and hydrocortisone in infantile spasms due to tuberous sclerosis.
        Epilepsy Res. 1997; 26: 389-395
        • Riikonen R
        • Simell O
        Tuberous sclerosis and infantile spasms.
        Dev Med Child Neurol. 1990; 32: 203-209
        • Matsumoto A
        • Watanabe K
        • Negoro T
        • Sugiura M
        • Iwase K
        • Hara K
        • et al.
        Long-term prognosis after infantile spasms: a statistical study of prognosic factors in 200 cases.
        Dev Med Child Neurol. 1981; 23: 51-65
        • Wohlrab G
        • Boltshauser E
        • Schmitt B
        Vigabatrin as a first-line drug in West syndrome: clinical and electroencephalographic outcome.
        Neuropediatrics. 1998; 29: 133-136
        • Appleton R
        • Peters A
        • Mumford J
        • Shaw D
        Randomised, placebo-controlled study of vigabatrin as first-line treatment of infantile spasms.
        Epilepsia. 1999; 40: 1627-1633
        • Enno A
        • Catovsky D
        • Darrell J
        • Goldman J
        • Hows J
        • Galton D
        Co-trimazole for prevention of infections in acute leukemia.
        Lancet. 1978; 11: 395-397
        • Lang D
        • Muehler E
        • Kupferschmid Ch
        • Tacke E
        • von Bernuth G
        Cardiac hypertrophy secondary to ACTH treatment in children.
        Eur J Pediatr. 1984; 142: 121-125
        • Young R
        • Stern D
        • Darowish C
        Cardiac hypertrophy associated with ACTH therapy for childhood seizure disorder.
        J Child Neurol. 1987; 2: 311-312
        • Boeble G
        • Ward K
        • Bodensteiner J
        Hypertrophic cardiomyopathy during corticotropin therapy for infantile spasms.
        Am J Dis Child. 1993; 147: 223-225
        • Kälviäinen R
        • Nousiainen I
        • Mäntyjärvi M
        • Nikoskelainen E
        • Partanen J
        • Partanen K
        • et al.
        Vigabatrin, a gabaergic antiepileptic drug, causes concentric visual field defects.
        Neurology. 1999; 53: 922-926
        • Vanhatalo S
        • Pääkkönen L
        • Nousiainen I
        Visual field constriction in children treated with vigabatrin.
        Neurology. 1999; 52: 1713-1714
        • Dulac O
        Vigabatrin – optimal use in children. Vigabatrin. Current status and future prospects. 23rd International Epilepsy Congress, Prague, Czech Republik. Workbook. TMG Healthcare Communications Ltd, Prague1999
        • Airaksinen E
        • Tuomisto L
        • Riikonen R
        The concentration of GABA, 5-HIAA and HVA in the cerebrospinal fluid of children with infantile spasms and effects of ACTH treatment.
        Brain Dev. 1992; 14: 386-390
        • Riikonen R
        How do cryptogenic and symptomatic infantile spasms differ? Review of biochemical studies in Finnish patients.
        J Child Neurol. 1996; 11: 383-388
        • Riikonen R
        • Söderström S
        • Vanhala R
        • Ebendal T
        • Lindholm D
        West syndrome: cerebrospinal fluid nerve growth factor and effect of ACTH.
        Pediatr Neurol. 1997; 17: 224-229
        • Vanhatalo S
        • Riikonen R
        Nitric oxide metabolites, nitrates and nitrites in the cerebrospinal fluid in children with West syndrome.
        Epilepsy Res. 2001; 46: 3-13
        • Dunn A
        • Gispen W
        How ACTH acts on the brain.
        Behav Rev. 1977; 1: 15-23
        • Dunn A
        • Schotman P
        Effects of ACTH and related peptides on cerebral RNA and protein synthesis.
        Pharmacol Ther. 1981; 12: 353-372
        • Huttenlocher P
        Dendritic development in neocortex of children with mental defect and infantile spasms.
        Neurology (Minneapol). 1974; 24: 203-210
        • Mochetti I
        • Spiga G
        • Hayes V
        • Isacksson P
        • Coangelo A
        Glucocorticoids differentially increase nerve growth factor and basic fibroblast growth factor in the rat brain.
        J Neurosci. 1996; 16: 214-218