Abstract
Objective
To assess the feasibility, effectiveness, and safety of pulse methylprednisolone in comparison with intramuscular adrenocorticotropic hormone (ACTH) therapy in children with West syndrome (WS).
Methods
This open-label, pilot study with a parallel-group assignment included 44 recently diagnosed children with WS. Methylprednisolone therapy was given as intravenous infusion at a dose of 30 mg/kg/d for five days followed by oral steroids 1 mg/kg gradually tapered over 5–6 wk. The efficacy outcomes included a cessation of epileptic spasms (as per caregiver reporting) and resolution of hypsarrhythmia on electroencephalogram; safety outcome was the frequency of various adverse effects.
Results
By day 14 of therapy, 6/18 (33.3%) children in the methylprednisolone group and 10/26 (38.5%) children in the ACTH group achieved cessation of epileptic spasms [group difference − 5.2%; confidence interval (CI) -30.7 to 22.8; p = 0.73]. However, by six weeks of therapy, 4/18 (22.2%) children in the methylprednisolone group and 11/26 (42.3%) children in the ACTH group had cessation of epileptic spasms (group difference − 20.1%; CI -43.0 to 8.4; p = 0.17). Hypertension was more commonly observed in the ACTH group (10 children) than in the methylprednisolone group (2 children; p = 0.046). Pulse methylprednisolone therapy was relatively safe.
Conclusions
The study observed limited effectiveness of both ACTH and pulse methylprednisolone therapy, which may partially be due to preponderance of structural etiology and a long treatment lag. However, pulse methylprednisolone therapy appeared to be safe, tolerable, and feasible for management of WS.
Similar content being viewed by others
References
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;45:1416–28.
Sakakihara Y. Treatment of west syndrome. Brain Dev. 2011;33:202–6.
Frost DJ, Hrachovy RA. Pathogenesis of infantile spasms: a model based on developmental desynchronization. J Clin Neurophysiol. 2005;22:25–36.
Sorel L, Dusaucy BA. Findings in 21 cases of Gibbs’ hypsarrhythmia: spectacular effectiveness of ACTH. Acta Neurol Psychiatr Belg. 1958;58:130–41.
Aicardi J. Clinical approach to the management of intractable epilepsy. Dev Med Child Neurol. 1988;30:429–40.
Gupta R, Appleton R. Corticosteroids in the management of pediatric epilepsies. Arch Dis Child. 2005;90:379–84.
Sahu JK. Infantile spasms--evidence based medical management. Indian J Pediatr. 2014;81:1052–5.
Madaan P, Negi S, Sharma R, Kaur A, Sahu JK. X-linked ALG13 gene variant as a cause of epileptic encephalopathy in girls. Indian J Pediatr. 2019;86:1072–3.
Raga SV, Wilmshurst J. Epileptic spasms: evidence for oral corticosteroids and implications for low and middle income countries. Seizure. 2018;59:90–8.
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;53:193–9.
Mytinger JR, Quigg M, Taft WC, Buck ML, Rust RS. Outcomes in treatment of infantile spasms with pulse methylprednisolone. J Child Neurol. 2010;25:948–53.
Yeh H-R, Kim M-J, Ko T-S, Yum M-S, You S-J. Short-term outcome of intravenous methylprednisolone pulse therapy in patients with infantile spasms. Pediatr Neurol. 2017;71:50–5.
Haberlandt E, Weger C, Sigl SB, et al. Adrenocorticotropic hormone versus pulsatile dexamethasone in the treatment of infantile epilepsy syndromes. Pediatr Neurol. 2010;42:21–7.
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;18:415–9.
Madaan P, Chand P, Linn K, et al. Management practices for West syndrome in South Asia: a survey study and meta-analysis. Epilepsia Open. 2020;5:461–74. https://doi.org/10.1002/epi4.12419.
Bower BD, Jeavons PM. Infantile spasms and hypsarrhythmia. Lancet. 1959;273:605–9.
Singhi P, Ray M. Profile of west syndrome in north Indian children. Brain Dev. 2005;27:135–40.
Gulati S, Jain P, Kannan L, Sehgal R, Chakrabarty B. The clinical characteristics and treatment response in children with west syndrome in a developing country: a retrospective case record analysis. J Child Neurol. 2015;30:1440–7.
Ibrahim S, Gulab S, Ishaque S, Saleem T. Clinical profile and treatment of infantile spasms using vigabatrin and ACTH--a developing country perspective. BMC Pediatr. 2010;10:1.
Angappan D, Sahu JK, Malhi P, Singhi P. Safety, tolerability, and effectiveness of oral zonisamide therapy in comparison with intramuscular adrenocorticotropic hormone therapy in infants with west syndrome. Eur J Paediatr Neurol. 2019;23:136–42.
Gowda VK, Narayanaswamy V, Shivappa SK, Benakappa N, Benakappa A. Corticotrophin-ACTH in comparison to prednisolone in West syndrome - a randomized study. Indian J Pediatr. 2019;86:165–70.
Hussain SA, Lay J, Cheng E, Weng J, Sankar R, Baca CB. Recognition of infantile spasms is often delayed: the ASSIST study. J Pediatr. 2017;190:215–21.e1.
Vaddi VK, Sahu JK, Dhawan SR, Suthar R, Sankhyan N. Knowledge, attitude and practice (KAP) study of pediatricians on infantile spasms. Indian J Pediatr. 2018;85:836–40.
Lux AL, Edwards SW, Hancock E, et al. 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;4:712–7.
Widjaja E, Go C, McCoy B, Snead OC. Neurodevelopmental outcome of infantile spasms: a systematic review and meta-analysis. Epilepsy Res. 2015;109:155–62.
Mytinger JR, Hussain SA, Islam MP, et al. Improving the inter-rater agreement of hypsarrhythmia using a simplified EEG grading scale for children with infantile spasms. Epilepsy Res. 2015;116:93–8.
Author information
Authors and Affiliations
Contributions
MR, PS, AG planned the study design. MR collected data. MR, AG, JKS, PM and PS were involved in data interpretation. MR and PM wrote the draft. All authors approved the final draft. PS would be the guarantor of the study.
Corresponding author
Ethics declarations
Conflict of Interest
None.
Additional information
Publisher’s Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Rights and permissions
About this article
Cite this article
Rajpurohit, M., Gupta, A., Madaan, P. et al. Safety, Feasibility and Effectiveness of Pulse Methylprednisolone Therapy in Comparison with Intramuscular Adrenocorticotropic Hormone in Children with West Syndrome. Indian J Pediatr 88, 663–667 (2021). https://doi.org/10.1007/s12098-020-03521-7
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s12098-020-03521-7