Downloaded 14 times
More Related Content
Similar to Methyl prednisolone in infantile spasm journal presentation
Methyl prednisolone in infantile spasm journal presentation
- 1. Welcome Md. Shukur Ullah DCH(student) Bangladesh Institute of Child Health
- 2. Article Title Short-term outcomeof intravenous methylprednisolone pulse therapy in patients with infantile spasms
- 3. Source Authors Hye-Ryun Yeha, Min-JeeKima, Tae-Sung Koa, Mi-Sun Yuma, Su-Jeong You Journal Pediatric Neurology DOI 10.1016/j.pediatrneurol.2017.03.017
- 4. Introduction • An infantilespasm is an age-specific epileptic disorder of early infancy that typically presents with epileptic spasms occurring in clusters, a disorganized high-amplitude interictal electroencephalographic (EEG) pattern known as hypsarrhythmia, and neurodevelopmental arrest or regression. • Several studies have reported that the duration of hypsarrhythmia affects mental developmental outcomes in infantile spasms.†
- 5. Introduction (contd.) †Primec ZR,Stare J, Neubauer D. The risk of lower mental outcome in infantile spasms increases after three weeks of hypsarrhythmia duration. Epilepsia. 2006;47(12):2202-2205. Goh S, Kwiatkowski DJ, Dorer DJ, Thiele EA. Infantile spasms and intellectual outcomes in children with tuberous sclerosis complex. Neurology. 2005;65(2):235-238. *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(7):1359-1364. • The United Kingdom Infantile Spasms Study (UKISS) has suggested that both early cessation of spasms and a short lead time to treatment reduce the total duration of the epileptic encephalopathy and improve developmental outcome.*
- 6. Introduction (contd.) * LuxAL, 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(11):712-717. † 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):193-199. • Although ACTH is considered the 1st line treatment in several countries, there are practical difficulties in terms of price and availability specially in developing countries.* • In addition, a previous study showed no difference in control of spasms between the ACTH and steroid groups, which means ACTH treatment is not alone a persuasive choice for infantile spasms.†
- 7. Introduction (contd.) ¹ MytingerJR, Quigg M, Taft WC, Buck ML, Rust RS. Outcomes in treatment of infantile spasms with pulse methylprednisolone. J Child Neurol. 2010;25(8):948-953. • Although a small MPD trial was done previously to determine the rate of remission, this is the first study to investigate the safety and short-term efficacy of pulse MPD therapy as the first-line treatment of newly diagnosed infantile spasms.¹
- 8. Objective • To investigatethe short-term response to intravenous MPD pulse therapy for the treatment of infantile spasms.
- 9. Methodology (contd.) Type ofstudy Prospective, open-label, uncontrolled study Place of study 1. Asan Medical Center Children’s Hospital Seoul, Korea 2. Sanggye Paik Hospital, Seoul, Korea Duration of study From February 2014 to January 2016
- 10. Methodology (contd.) Study population 14 InclusionCriteria Infants between the age of 2 to 11 months presenting with infantile spasms and hypsarrhythmia identified on EEG
- 11. Methodology (contd.) Exclusion Criteria 1.Tuberous sclerosis 2. Patients previously treated with infantile spasms 3. Patients with contraindications of steroid therapy
- 12. Study Procedure • Participantswith newly diagnosed infantile spasms intravenously received 30 mg/kg methylprednisolone once daily for 3 days. • Responders were then given a low dosage (1 mg/kg two doses) of oral prednisolone, which was rapidly reduced each week for 2 to 4 weeks. • Non-responders were immediately transitioned to other treatments including antiepileptic drugs or a ketogenic diet.
- 13. Study Procedure (contd.) •Sleep EEG recordings were performed before and 2-22 days after the completion of MPD pulse therapy. All patients treated with MPD pulse therapy had laboratory monitoring of electrolytes and blood sugar, blood pressure, kidney function as well as electrocardiography.
- 14. Study Procedure (contd.) •The outcome measurements were achievement of freedom from spasms and tolerability as per parental reports, improvement of hypsarrhythmia after the completion of therapy. • Freedom from spasms was defined as the cessation of spasms for at least 7 successive days after therapy initiation within 14 days after the MPD initiation.
- 15. Study Procedure (contd.) •An electroclinical responder was defined as patients who had clinical cessations of spasms and resolution of hypsarrhythmia on EEG within 3 weeks after completion of treatment. • Spasm recurrence was referred to as reappearance of spasms during first three months after cessation of steroid. • Time from therapy commencement to the cessation of spasms and time from cessation of spasms to recurrence were also measured.
- 16. Statistical Analysis Software SPSSversion 23 Statistical Analysis Statistical significance was defined as P < 0.05 The mean and standard error for quantitative data and proportions for categorical data were calculated.
- 17. Statistical Analysis(contd.) Theyused Fisher’s Exact tests for comparisons of categorical baseline characteristics and independent t-test in relation to quantitative baseline characteristics between complete responders and non-complete responders.
- 18. Result Table 1. Baselinecharacteristics of enrolled patients Demographics Number of cases (Total N=14) Sex, male N (%) 10 (71.4) Age of onset, months 7.0 ± 2.5 Etiologies of spasms Structural, N (%) Periventricular leukomalacia N (%) HIE N (%) Hydrocephalus N (%) Polymicrogyria N (%) Lissencephaly N (%) Genetic N (%) Unknown N (%) 14 (100) 11 (78.6) 2 (14.3) 2 (14.3) 4 (28.6) 2 (14.3) 1 (7.1) 1 (7.1) 2(14.3)
- 19. Result (contd.) Table 1.Baseline characteristics of enrolled patients (contd.) Demographics Number of cases (Total N=14) Median treatment delay from initial spasms, days 1.0 Spasm loads, clusters per day 3.6 ± 1.2 Gestational age at birth, weeks 34.4 ± 5.6 Prematurity, N (%) 6 (42.6) Birth weight, kg 2.3 (1.2) Developmental delay prior to onset of infantile spasms, N ()% 13 (92.8)
- 20. Result (contd.) Table 2.Comparison of electroclinical responders and non-responders at 3 weeks after MPD therapy Responders (N=9) Non-responders (N=5) P-value Mean age of onset, months 6.1 ± 2.2 8.7 ± 2.6 0.11 Prematurity 3 3 0.58 Mean gestational age, weeks 35.1 ± 6.2 27.7 ± 5.3 0.26 Etiolology Structural Genetic/Unknown 7 2 5 1 1.00 Spasms load, clusters per day 3.1 ± 1.3 4.4 ± 0.9 0.04 Delay from diagnosis to protocol entry, median (only in patients with spasms) 1.0 (0-14) 2.0 (0-8) 0.68
- 21. Result (contd.) In thisstudy • Nine of 14 patients (64.3 %) with spasms achieved cessation of spasms and the mean time to cessation of spasms was 3.0 days (range, 1 to 14 days). • All of 9 clinical responders exhibited resolution of hypsarrhythmia on EEG.
- 22. Result (contd.) • Allfive patients who failed to respond to initial pulse MPD therapy received vigabatrin as a second-line treatment; three out of these patients (60.0 %) showed response to vigabatrin. Of the remainders, none achieved freedom from spasms during the 3 months of follow-up.
- 23. Result (contd.) • Spasmsrelapse was observed in 4 out of 9 patients (45.5%) who showed initial electroclinical responses. In 4 children, the recurrence occurred during the weaning period with oral prednisolone (mean, 15.0 days; range, 14-18 days). Among patients with recurrence, the ketogenic diet yielded freedom from spasms in 2 patients, topiramate was effective in 1 patient, and the other AED treatments failed to control spasms among the others.
- 24. Result (contd.) • Ofthe infants who responded or failed on MPD pulse therapy, the overall rate of freedom from spasms or complete EEG resolution at 3-month follow-up was 11/14 (78.6 %). Five out of 9 (55.6 %) MPD pulse therapy-electroclinical responders remained free of spasms. Three of 5 non-responders who received vigabatrin as second-line therapy were free of spasms at the 3-month follow-up.
- 25. Result (contd.) • Threeof 4 patients who relapsed after MPD pulse therapy received second or third-line therapy and became free of spasms (2 with ketogenic diet; 1 with topiramate) by the first three months.
- 26. Result (contd.) Adverse events •Adverse effects were evaluated during MPD pulse therapy and monthly by the first three months. • No deaths occurred after MPD pulse therapy and no major side effects were noted. Irritabilities were seen in 3 patients (21.4 %) and a lower respiratory tract infection was observed in one out of 14 patients (7.1 %).
- 27. Discussion • This isthe first study to investigate the safety and short-term efficacy of pulse MPD therapy as the first-line treatment of newly diagnosed infantile spasms. • A recent multi-center prospective study by Coryell J et al. showed 55% spasm free rate in participants receiving ACTH (150 IU/m² per day) as an initial treatment and 39% spasms-free rate for oral corticosteroids (40mg per day for 2 weeks) at 3 months.
- 28. Discussion • Although ACTHis generally accepted as the first-line treatment for infantile spasms, its high cost and unavailability are the major obstacles of the ACTH treatment. • The short-term responses of oral prednisolone at 2 weeks was 58.3% (Arambepola C et al.) and 70% (Lux AL et al.) to UKISS protocol prednisolone (40-60mg/day for 2 weeks) and 63% (Hussain SA et al.) to weight-based very
- 29. Discussion high-dose prednisolone (8mg/kg/day for 2 weeks then tapering off for 2 weeks), which is comparable with 64.3% of responder rate found in this study.
- 30. Discussion • Mytinger JRet al. showed a 10 case series using a course of intravenous MPD at a dosage of 20mg/kg for 3 days followed by a 2-month oral prednisolone taper yielded spasms cessation and hypsarrhythmia resolution in 50% of patients within 14 days. In comparison to this study, median treatment delay from initial infantile spasms onset was 18.5 days and 70% of patients had been started on an antiepileptic drug prior to intravenous MPD.
- 31. Discussion • To reducethe deleterious side effects of long term corticosteroid therapy in young infants, this study adopted the short term high dose MPD pulse therapy as protocol for newly diagnosed infantile spasms and the acute adverse events were minor. • A larger, long-term randomized prospective study of intravenous MPD or a direct comparison study to oral corticosteroids is needed to determine the long term effects of spasm control.
- 32. Limitation • Only 2center study. • Small number of patients were included. • Lack of a control group. • Long term follow up was not done.
- 33. Conclusion • MPD pulsetherapy may be a safe and efficient therapeutic choice for patients newly diagnosed with infantile spasms.