Treatment of infantile spasms in resource limited settings: A randomized controlled trial

Commentary

Voloshyn Taras, MD PhD
Assistant Professor
Kozyavkin International Rehabilitation Clinic, Truskavets, Ukraine

Karen Skjei, MD
Associate Professor
University of Texas-Austin, Dell Medical School, Austin, Texas

Infantile spasms (IS) or as they are currently termed epileptic spasms (ES), are characterized by a brief contraction followed by flexor, extensor, or mixed movements. The  incidence  of  IS  ranges  from  2  to  3.5  in  10,000  live births,  with  onset  during  the  first  year  of  life  in  90%. When associated with hypsarrhythmia on electroencephalogram (EEG) and developmental delay or regression it is termed West syndrome.  The management of ES continues to pose many challenges. Even with optimal treatment, prognosis is poor, with a high risk of severe neurological deficits and subsequent epilepsy. Prompt  treatment  may  improve  developmental  and  cognitive  outcomes.

Standard first line treatments for ES include intramuscular adrenocorticotropic hormone (ACTH) and oral prednisolone. The cost of ACTH is often orders of magnitude higher than prednisolone, and its limited availability and intramuscular route of administration make it a challenge for many families. The current study compared the efficacy of ACTH vs prednisolone for resolution of clinical spasms (as reported by caretakers) and hypsarrythmia in ES. 

Inclusion criteria included the presence of characteristic spasms with hypsarrhythmia on EEG in patients less than 1 year of age with no previous treatment with steroids of ACTH. Seventy patients who met the selection criteria were randomized into two equal groups using a lottery method. Patients  in  group  A  received oral prednisolone (2 mg/kg/day) for four weeks then tapered gradually over four weeks.  Patients in group B received IM ACTH (150 IU/m/day) for two weeks and then slowly tapered over the next six weeks. No significant differences were noted between the two groups.

In the group receiving prednisolone, 29 (83%) patients were spasm-free, while in the ACTH group 31 (88%) patients were spasm-free ( = 0.022)

There are several limitations of this trial. It was a single center study, and due to the differences in administration of the two treatments it was not a blinded study. While the patients were steroid naive, no information was presented on etiology or time delay between first spasm and initiation of treatment. The treatment courses were asymmetrical (4 weeks at full dose followed by 4 weeks taper in the prednisone group and 2 weeks at full dose followed by 6 weeks taper in the ACTH group), and the long duration of treatment raise concern for increased side effects, which were not mentioned in the paper. And they did not present any data on relapse, although there outcomes were assessed at 4 weeks after completion of treatment, which would have allowed time for many patients to have already relapsed. 

But the main limitation is the atypical patient characteristics. While there were no significant difference between the two groups in terms of age or gender, 80% of the patients included in the study were 3 months of age or less and 77% of the patients in the study were males. These demographics are markedly different than the average age of presentation of spasms of 3-6 months and the slight male predominance in other studies. It makes one wonder whether these results are generalizable to other populations of patients with epileptic spasms. 

Furthermore, there were some areas of disconnect in the paper. They commented that 13% of their patients were greater than 1 year of age (one of their stated inclusion criteria) however, it is unclear how these patients fit into the data analysis, since in tables 1-3 they only list 35 patients per group and ages they cite were all 0-12 months. Further, in Table 1  the mean age in the two groups is listed as 2.11 and 1.69 months, respectively, while in the text the authors cite the same numbers but as age in years.  The treatment groups were small and the difference in efficacy between the two groups was also small (83% response in the prednisone group vs 88% in the ACTH group), ACTH was significantly more effective than prednisone, with a quoted p value of 0.022. 

This study is useful in that it adds to the literature on the efficacy of oral steroids vs ACTH. Despite using a relatively low dose prednisolone the authors attained  a  higher response rate than  Baram et al(1),. This study supports prednisolone as a viable alternative to ACTH in resource-limited settings.

Article abstract

Objective: To compare the outcome of ACTH with oral prednisolone for treatment of infantile spasms.

Methodology: This is a randomized controlled trial conducted at department of paediatric neurology, The Children Hospital, Lahore, Pakistan after ethical approval from January 1st 2014 to December 31st 2017. (Four years). Seventy patients with infantile spasms were randomized in two equal groups of 35 patients in each group. Patients in group A received prednisolone and in group B received ACTH. The two groups were compared for the spasms free period.  Statistical significant determined by chi-square test (p< 0.05 was taken as significant). Non-probability purposive sampling was used and an inclusion criterion was children up to age of one year with infantile spasms. Exclusion criteria include children who had been previously treated with steroids or ACTH. Seventy patients fulfilling inclusion criteria were enrolled through neurology department of Children Hospital, Lahore. History, informed consent was taken by parents and was divided in two groups by lottery method. All the information was collected on a specially designed proforma.

Results: In group A, 29 (83%) patients were spasms free, while in group B, 31 (88%) patients were spasms free.

Conclusion: Significant number of patients with IS were spasms free with prednisolone which is very cost effective drug as compared to ACTH. Developing counties should considered this treatment option as a first line therapy.

Reference

(1) Baram TZ, Mitchell WG, Tournay A, Snead OC, Hanson RA, Horton EJ. High-dose corticotropin (ACTH) versus prednisone for infantile spasms: a prospective, randomized, blinded study. Pediatrics. 1996 mar;97(3):375–9.