Pulsatile Dexamethasone in Patients with Infantile Spasms: A Retrospective Analysis of a Unique Therapy Regime

Abstract

Objective Infantile spasms (IS) are an age-specific epilepsy syndrome associated with poor outcomes. Sustained and early spasm control remains the main goal of therapy. We aimed to evaluate a unique pulsatile dexamethasone therapy regime in children with IS.

Methods Children with IS were treated with oral pulsatile-applied dexamethasone in the Children's Hospital Jena between 2002 and 2021, regardless of duration since IS onset or previous therapy (except ACTH). A prolonged initial pulse was given in case of insufficient response (standard: 5–7 days, prolonged: 10–14 days). We analyzed spasm reduction, electroencephalographic response, adverse reactions, neurodevelopmental status, and epileptic disorders at the last follow-up.

Results Included were 26 patients with a median age of 5.5 months (interquartile range 4–8) at IS onset and a mean follow-up of 6.2 years (standard deviation [SD] 3.99). Fifty percent had an unknown etiology. Patients received on average 10.8 pulses (SD 6.0); 69.2% achieved initial seizure freedom, however, 38.9% relapsed. Seventeen patients had an initial prolonged pulse, of those, 14 got initially seizure-free (82.4%). Sixty-four percent of the cases had a sustained spasm cessation after the third pulse. At the last follow-up, half of the patients had no persisting epileptic disorder; 22.2% had a favorable neurocognitive development. Patients with unknown etiology were more likely to achieve seizure freedom during therapy (p = 0.025), had a more favorable neurocognitive outcome (p = 0.049), and were less likely to suffer from epileptic disorders (p = 0.037). No serious adverse effects were observed.

Conclusion Our results show that our treatment is safe and leads to outcomes comparable to usually applied hormonal therapy regimes. Etiology remains the most influential factor.

Keywords

west syndrome - infantile spasms - pulsatile therapy - dexamethasone - corticosteroids

Publication History

Received: 13 December 2024

Accepted: 21 January 2025

Accepted Manuscript online:
27 January 2025

Article published online:
06 February 2025

• References

• 1 Pavone P, Striano P, Falsaperla R, Pavone L, Ruggieri M. Infantile spasms syndrome, West syndrome and related phenotypes: what we know in 2013. Brain Dev 2014; 36 (09) 739-751
• 2 Lux AL, Osborne JP. A proposal for case definitions and outcome measures in studies of infantile spasms and West syndrome: consensus statement of the West Delphi group. Epilepsia 2004; 45 (11) 1416-1428
• 3 Gibbs EL, Fleming MM, Gibbs FA. Diagnosis and prognosis of hypsarhythmia and infantile spasms. Pediatrics 1954; 13 (01) 66-73
• 4 Berg AT, Berkovic SF, Brodie MJ. et al. Revised terminology and concepts for organization of seizures and epilepsies: report of the ILAE Commission on Classification and Terminology, 2005-2009. Epilepsia 2010; 51 (04) 676-685
• 5 Scheffer IE, Berkovic S, Capovilla G. et al. ILAE classification of the epilepsies: Position paper of the ILAE Commission for Classification and Terminology. Epilepsia 2017; 58 (04) 512-521
• 6 Wirrell EC, Shellhaas RA, Joshi C, Keator C, Kumar S, Mitchell WG. Pediatric Epilepsy Research Consortium. How should children with West syndrome be efficiently and accurately investigated? Results from the National Infantile Spasms Consortium. Epilepsia 2015; 56 (04) 617-625
• 7 Low NL. Infantile spasms with mental retardation. II. Treatment with cortisone and adrenocorticotropin. Pediatrics 1958; 22 (06) 1165-1169
• 8 Tibussek D, Klepper J, Korinthenberg R. et al. Treatment of infantile spasms: report of the interdisciplinary guideline committee coordinated by the German-Speaking Society for Neuropediatrics. Neuropediatrics 2016; 47 (03) 139-150
• 9 Song JM, Hahn J, Kim SH, Chang MJ. Efficacy of treatments for infantile spasms: a systematic review. Clin Neuropharmacol 2017; 40 (02) 63-84
• 10 Riikonen R. Infantile spasms: outcome in clinical studies. Pediatr Neurol 2020; 108: 54-64
• 11 Mytinger JR, Heyer GL. Oral corticosteroids versus adrenocorticotropic hormone for infantile spasms–an unfinished story. Pediatr Neurol 2014; 51 (01) 13-14
• 12 Lux AL, Edwards SW, Hancock E. et al. The United Kingdom Infantile Spasms Study comparing vigabatrin with prednisolone or tetracosactide at 14 days: a multicentre, randomised controlled trial. Lancet 2004; 364 (9447) 1773-1778
• 13 Kossoff EH, Hartman AL, Rubenstein JE, Vining EP. High-dose oral prednisolone for infantile spasms: an effective and less expensive alternative to ACTH. Epilepsy Behav 2009; 14 (04) 674-676
• 14 Yi ZS, Wu HP, Yu XY, Chen Y, Zhong JM. Efficacy and tolerability of high-dose prednisone in Chinese children with infantile spasms. Brain Dev 2015; 37 (01) 23-28
• 15 Wanigasinghe J, Arambepola C, Sri Ranganathan S, Sumanasena S, Muhandiram EC. The efficacy of moderate-to-high dose oral prednisolone versus low-to-moderate dose intramuscular corticotropin for improvement of hypsarrhythmia in West syndrome: a randomized, single-blind, parallel clinical trial. Pediatr Neurol 2014; 51 (01) 24-30
• 16 O'Callaghan FJ, Edwards SW, Alber FD. et al; participating investigators. Safety and effectiveness of hormonal treatment versus hormonal treatment with vigabatrin for infantile spasms (ICISS): a randomised, multicentre, open-label trial. Lancet Neurol 2017; 16 (01) 33-42
• 17 Knupp KG, Coryell J, Nickels KC. et al; Pediatric Epilepsy Research Consortium. Response to treatment in a prospective national infantile spasms cohort. Ann Neurol 2016; 79 (03) 475-484
• 18 Mytinger JR, Albert DVF, Twanow JD. et al. Compliance with standard therapies and remission rates after implementation of an infantile spasms management guideline. Pediatr Neurol 2020; 104: 23-29
• 19 Chellamuthu P, Sharma S, Jain P, Kaushik JS, Seth A, Aneja S. High dose (4 mg/kg/day) versus usual dose (2 mg/kg/day) oral prednisolone for treatment of infantile spasms: an open-label, randomized controlled trial. Epilepsy Res 2014; 108 (08) 1378-1384
• 20 Hussain SA, Shinnar S, Kwong G. et al. Treatment of infantile spasms with very high dose prednisolone before high dose adrenocorticotropic hormone. Epilepsia 2014; 55 (01) 103-107
• 21 Gonzalez-Giraldo E, Stafstrom CE, Stanfield AC, Kossoff EH. Treating infantile spasms with high-dose oral corticosteroids: a retrospective review of 87 children. Pediatr Neurol 2018; 87: 30-35
• 22 Mytinger JR, Quigg M, Taft WC, Buck ML, Rust RS. Outcomes in treatment of infantile spasms with pulse methylprednisolone. J Child Neurol 2010; 25 (08) 948-953
• 23 Hassanzadeh Rad A, Aminzadeh V. Infantile spasms treated with intravenous methypredinsolone pulse. Iran J Child Neurol 2017; 11 (02) 8-12
• 24 Yeh HR, Kim MJ, Ko TS, Yum MS, You SJ. Short-term outcome of intravenous methylprednisolone pulse therapy in patients with infantile spasms. Pediatr Neurol 2017; 71: 50-55
• 25 Rajpurohit M, Gupta A, Madaan P, Sahu JK, Singhi P. Safety, feasibility and effectiveness of pulse methylprednisolone therapy in comparison with intramuscular adrenocorticotropic hormone in children with West Syndrome. Indian J Pediatr 2020; 88: 663-667
• 26 Yamamoto H, Asoh M, Murakami H, Kamiyama N, Ohta C. Liposteroid (dexamethasone palmitate) therapy for West syndrome: a comparative study with ACTH therapy. Pediatr Neurol 1998; 18 (05) 415-419
• 27 Haberlandt E, Weger C, Sigl SB. et al. Adrenocorticotropic hormone versus pulsatile dexamethasone in the treatment of infantile epilepsy syndromes. Pediatr Neurol 2010; 42 (01) 21-27
• 28 Wanigasinghe J, Arambepola C, Ranganathan SS, Sumanasena S. Randomized, single-blind, parallel clinical trial on efficacy of oral prednisolone versus intramuscular corticotropin: a 12-month assessment of spasm control in West Syndrome. Pediatr Neurol 2017; 76: 14-19
• 29 Wanigasinghe J, Arambepola C, Sri Ranganathan S, Sumanasena S, Attanapola G. Randomized, single-blind, parallel clinical trial on efficacy of oral prednisolone versus intramuscular corticotropin on immediate and continued spasm control in West Syndrome. Pediatr Neurol 2015; 53 (03) 193-199
• 30 Lux AL, Edwards SW, Hancock E. et al; United Kingdom Infantile Spasms Study. The United Kingdom Infantile Spasms Study (UKISS) comparing hormone treatment with vigabatrin on developmental and epilepsy outcomes to age 14 months: a multicentre randomised trial. Lancet Neurol 2005; 4 (11) 712-717
• 31 O'Callaghan FJ, Lux AL, Darke K. et al. The effect of lead time to treatment and of age of onset on developmental outcome at 4 years in infantile spasms: evidence from the United Kingdom Infantile Spasms Study. Epilepsia 2011; 52 (07) 1359-1364
• 32 O'Callaghan FJK, Edwards SW, Alber FD. et al; International Collaborative Infantile Spasms Study (ICISS) investigators. Vigabatrin with hormonal treatment versus hormonal treatment alone (ICISS) for infantile spasms: 18-month outcomes of an open-label, randomised controlled trial. Lancet Child Adolesc Health 2018; 2 (10) 715-725
• 33 Riikonen R. Long-term outcome of patients with West syndrome. Brain Dev 2001; 23 (07) 683-687
• 34 Ko A, Youn SE, Chung HJ. et al. Vigabatrin and high-dose prednisolone therapy for patients with West syndrome. Epilepsy Res 2018; 145: 127-133
• 35 Grief SN. Upper respiratory infections. Prim Care 2013; 40 (03) 757-770