Efficacy Analysis of Oral Dexamethasone in the Treatment of Infantile Spasms and Infantile Spasms Related Lennox-Gastaut Syndrome

Overview

Journal BMC Pediatr

Publisher Biomed Central

Specialty Pediatrics

Date 2023 May 22

PMID 37217894

Authors

Jieling Li

Yujing Gao

Jie Cao

Fangcheng Cai

Xiuquan Zhai

Affiliations

Soon will be listed here.

Abstract

Objective: Treatment with adrenocorticotropic hormone (ACTH) or a corticosteroid is the first choice for infantile spasms (IS), and vigabatrin is the first choice for children with tuberous sclerosis. Although corticosteroids may be also effective against IS and IS-related Lennox-Gastaut syndrome (LGS), the use of dexamethasone (DEX), a kind of corticosteroid, for these diseases has been rarely reported. This retrospective study aimed to evaluate the efficacy and tolerability of DEX for the treatment of IS and IS-related LGS.

Methods: Patients diagnosed as having IS (including patients whose condition evolved to LGS after the failure of early treatment) in our hospital between May 2009 and June 2019 were treated with dexamethasone after failure of prednisone treatment. The oral dose of DEX was 0.15-0.3 mg/kg/d. Thereafter, the clinical efficacy, electroencephalogram (EEG) findings, and adverse effects were observed every 4-12 weeks depending on the individual patient's response. Then, the efficacy and safety of DEX in the treatment of IS and IS-related LGS were retrospectively evaluated.

Results: Among 51 patients (35 cases of IS; 16 cases of IS-related LGS), 35 cases (68.63%) were identified as responders to DEX treatment, comprising 20 cases (39.22%) and 15 cases (29.41%) with complete control and obvious control, respectively. To discuss the syndromes individually, complete control and obvious control were achieved in 14/35 and 9/35 IS cases and in 6/16 and 6/16 IS-related LGS cases, respectively. During DEX withdrawal, 11 of the 20 patients with complete control relapsed (9/14 IS; 2/6 LGS). The duration of dexamethasone treatment (including weaning) in most of the 35 responders was less than 1 year. However, 5 patients were treated with prolonged, low-dose maintenance therapy, which continued for more than 1.5 years. These 5 patients showed complete control, and 3 patients had no recurrence. Except for one child who died of recurrent asthma and epileptic status 3 months after stopping DEX, there were no serious or life-threatening adverse effects during DEX treatment.

Conclusion: Oral DEX is effective and tolerable for IS and IS-related LGS. all LGS patients were evolved from IS in this study. The conclusion may not apply to patients with other etiology and courses of LGS. Even when prednisone or ACTH is failed, DEX may still be considered as a treatment option. For children who respond to DEX but do not show complete control after 6 months of treatment, prolonged treatment with low-dose DEX administered in the morning might be considered.

Citing Articles

Clinical trials for Lennox-Gastaut syndrome: Challenges and priorities.

Knowles J, Warren A, Mohamed I, Stafstrom C, Koh H, Samanta D Ann Clin Transl Neurol. 2024; 11(11):2818-2835.

PMID: 39440617 PMC: 11572735. DOI: 10.1002/acn3.52211.

Ulinastatin modulates NLRP3 inflammasome pathway in PTZ-induced epileptic mice: A potential mechanistic insight.

Wang H, Ma Y, Jin D, Yang X, Xu X Heliyon. 2024; 10(19):e38050.

PMID: 39386862 PMC: 11462202. DOI: 10.1016/j.heliyon.2024.e38050.

References

Marchi N, Granata T, Freri E, Ciusani E, Ragona F, Puvenna V . Efficacy of anti-inflammatory therapy in a model of acute seizures and in a population of pediatric drug resistant epileptics. PLoS One. 2011; 6(3):e18200. PMC: 3065475. DOI: 10.1371/journal.pone.0018200. View

Vigevano F, Cilio M . Vigabatrin versus ACTH as first-line treatment for infantile spasms: a randomized, prospective study. Epilepsia. 1998; 38(12):1270-4. DOI: 10.1111/j.1528-1157.1997.tb00063.x. View

OHTAHARA S, Ohtsuka Y, Kobayashi K . Lennox-Gastaut syndrome: a new vista. Psychiatry Clin Neurosci. 1995; 49(3):S179-83. DOI: 10.1111/j.1440-1819.1995.tb02168.x. View

Wheless J, Clarke D, Arzimanoglou A, Carpenter D . Treatment of pediatric epilepsy: European expert opinion, 2007. Epileptic Disord. 2007; 9(4):353-412. DOI: 10.1684/epd.2007.0144. View

Yamamoto H, Fukuda M, Miyamoto Y, Murakami H, Kamiyama N . A new trial liposteroid (dexamethasone palmitate) therapy for intractable epileptic seizures in infancy. Brain Dev. 2007; 29(7):421-4. DOI: 10.1016/j.braindev.2006.12.002. View

Lagae L, Verhelst H, Ceulemans B, De Meirleir L, Nassogne M, De Borchgrave V . Treatment and long term outcome in West syndrome: the clinical reality. A multicentre follow up study. Seizure. 2010; 19(3):159-64. DOI: 10.1016/j.seizure.2010.01.008. View

Baram T, Mitchell W, Tournay A, Snead O, Hanson R, Horton E . High-dose corticotropin (ACTH) versus prednisone for infantile spasms: a prospective, randomized, blinded study. Pediatrics. 1996; 97(3):375-9. PMC: 3100715. View

Haberlandt E, Weger C, Sigl S, Rauchenzauner M, Scholl-Burgi S, Rostasy K . Adrenocorticotropic hormone versus pulsatile dexamethasone in the treatment of infantile epilepsy syndromes. Pediatr Neurol. 2009; 42(1):21-7. DOI: 10.1016/j.pediatrneurol.2009.07.011. View

Ahmed S, Tucker P, Mushtaq T, Wallace A, Williams D, Hughes I . Short-term effects on linear growth and bone turnover in children randomized to receive prednisolone or dexamethasone. Clin Endocrinol (Oxf). 2002; 57(2):185-91. DOI: 10.1046/j.1365-2265.2002.01580.x. View

10.

Lux A, Edwards S, Hancock E, Johnson A, Kennedy C, Newton R . The United Kingdom Infantile Spasms Study comparing vigabatrin with prednisolone or tetracosactide at 14 days: a multicentre, randomised controlled trial. Lancet. 2004; 364(9447):1773-8. DOI: 10.1016/S0140-6736(04)17400-X. View

11.

Roger J, Remy C, Bureau M, OLLER-DAURELLA L, Beaumanoir A, FAVEL P . [Lennox-Gastaut syndrome in the adult]. Rev Neurol (Paris). 1987; 143(5):401-5. View

12.

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. 2013; 36(9):739-51. DOI: 10.1016/j.braindev.2013.10.008. View

13.

Hrachovy R, Frost Jr J, KELLAWAY P, Zion T . Double-blind study of ACTH vs prednisone therapy in infantile spasms. J Pediatr. 1983; 103(4):641-5. DOI: 10.1016/s0022-3476(83)80606-4. View

14.

Kossoff E, Hartman A, Rubenstein J, Vining E . High-dose oral prednisolone for infantile spasms: an effective and less expensive alternative to ACTH. Epilepsy Behav. 2009; 14(4):674-6. DOI: 10.1016/j.yebeh.2009.01.023. View

15.

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(3):193-9. DOI: 10.1016/j.pediatrneurol.2015.05.004. View

16.

Roger J, Dravet C, Bureau M . The Lennox-Gastaut syndrome. Cleve Clin J Med. 1989; 56 Suppl Pt 2:S172-80. DOI: 10.3949/ccjm.56.s1.172. View

17.

Go C, Mackay M, Weiss S, Stephens D, Adams-Webber T, Ashwal S . Evidence-based guideline update: medical treatment of infantile spasms. Report of the Guideline Development Subcommittee of the American Academy of Neurology and the Practice Committee of the Child Neurology Society. Neurology. 2012; 78(24):1974-80. PMC: 3369510. DOI: 10.1212/WNL.0b013e318259e2cf. View

18.

Chen J, Cai F, Jiang L, Hu Y, Feng C . A prospective study of dexamethasone therapy in refractory epileptic encephalopathy with continuous spike-and-wave during sleep. Epilepsy Behav. 2016; 55:1-5. DOI: 10.1016/j.yebeh.2015.10.003. View

19.

Jones K, Snead 3rd O, Boyd J, Go C . Adrenocorticotropic hormone versus prednisolone in the treatment of infantile spasms post vigabatrin failure. J Child Neurol. 2014; 30(5):595-600. DOI: 10.1177/0883073814533148. View

20.

Paciorkowski A, Thio L, Dobyns W . Genetic and biologic classification of infantile spasms. Pediatr Neurol. 2011; 45(6):355-67. PMC: 3397192. DOI: 10.1016/j.pediatrneurol.2011.08.010. View