Tuesday, August 11, 2015

High dose prednisolone for infantile spasms

Hussain SA, Shinnar S, Kwong G, Lerner JT, Matsumoto JH, Wu JY, Shields WD,
Sankar R. Treatment of infantile spasms with very high dose prednisolone before
high dose adrenocorticotropic hormone. Epilepsia. 2014 Jan;55(1):103-7.



This study investigated the short-term response to a standardized hormonal therapy protocol for treatment of infantile spasms.


Twenty-seven children with video electroencephalography (EEG)-confirmed infantile spasms received very high dose (8 mg/kg/day, max 60 mg/day) oral prednisolone for 2 weeks. Response (absence of both hypsarrhythmia and spasms) to prednisolone was ascertained by repeat overnight video-EEG. Responders were tapered over 2 weeks and nonresponders were immediately transitioned to high dose (150 IU/m(2)/day) intramuscular adrenocorticotropic hormone (ACTH) for two additional weeks. Response was again determined by overnight video-EEG after ACTH therapy.


Sixty-three percent (17/27) of patients responded completely to prednisolone. Subsequently, 40% (4/10) of prednisolone nonresponders exhibited a complete response after an additional 2-week course with ACTH. Among 27 subjects with median follow-up of 13.5 months (interquartile range [IQR] 4.8-25.9), 12% (2/17) of prednisolone responders and 50% (2/4) of ACTH responders experienced a relapse between 2 and 9 months after initial response.


Very high dose prednisolone demonstrated significantly higher efficacy than previously reported for lower doses in prior studies. High dose ACTH may be superior to very high dose prednisolone, and in lieu of a definitive clinical trial, the choice between prednisolone and ACTH for initial treatment of infantile spasms remains controversial.


  1. Jithangi Wanigasinghe, Carukshi Arambepola, Shalini Sri Ranganathan, Samanmalie Sumanasena, Gangani Attanapola. Randomized, Single-Blind, Parallel Clinical Trial on Efficacy of Oral Prednisolone Versus Intramuscular Corticotropin on Immediate and Continued Spasm Control in West Syndrome
    Pediatric Neurology article in press



    A single-center, single-blind, parallel-group, randomized clinical trial was performed to test the null hypothesis that adrenocorticotropic hormone is not superior to high-dose prednisolone for treatment of newly diagnosed West syndrome.


    Newly diagnosed infants with West syndrome were randomized to receive 14 days of oral prednisolone (40-60 mg/day) or a synthetically prepared intramuscular long-acting adrenocorticotropic hormone (40-60 IU/every other day [0.5-0.75 mg]) according to the United Kingdom Infantile Spasm Study protocol. They were blindly evaluated for infantile spasm remission by day 14, electroclinical remission (spasm cessation + resolution of hypsarrhythmia on a 30-minute electroencephalograph) by day 14 and continued spasm freedom for 28 days.


    Ninety-seven patients were enrolled in the study, with 48 of them receiving prednisolone and 49 receiving ACTH. There was no significant difference in the baseline characteristics or risk factors for the two treatment groups. By day 14, cessation of infantile spasms occurred in 28/48 (58.3%) infants on prednisolone compared with only 18/49 (36.7%) infants given adrenocorticotropic hormone ( P = 0.03) and electroclinical remission in 21 on prednisolone compared with nine on adrenocorticotropic hormone ( P = 0.007). Sustained spasm control for 28 consecutive days following electroclinical remission occurred in 15 children on prednisolone compared with six on adrenocorticotropic hormone ( P = 0.008). The total number of days required for spasm cessation was significantly less in those treated with prednisolone (3.85 days ± 2.4) compared with adrenocorticotropic hormone (8.65 days ± 3.7) ( P = 0.001). Among patients who did not achieve remission, there was a non-significant trend toward greater quantitative reduction of spasms with prednisolone than with adrenocorticotropic hormone ( P = 0.079).


    Synthetic adrenocorticotropic hormone of 40-60 IU/every other day did not yield superior rates of electroencephalographic or clinical remission when compared with prednisolone of 40-60 mg/day. Significantly, more patients achieved electroclinical remission when treated with prednisolone than with adrenocorticotropic hormone.

  2. Serves Questcor right.

    Mytinger JR, Camfield PR. Synthetic ACTH Is Not Superior to Prednisolone for
    Infantile Spasms: Randomized Clinical Trials and Tribulations. Pediatr Neurol.
    2015 Sep;53(3):181-2.

    However, for decades, oral corticosteroids have been used “off label” for the treatment of infantile spasms. In contrast to the price of ACTH and vigabatrin, oral corticosteroids are far less expensive (less than $40 for a 1-month course), easy to administer, and readily available in most parts of the world. In the United States, the price of ACTH can exceed $100,000 for a typical one-month course and the price of vigabatrin can approximate $50,000 for a typical six-month course. So, despite the lack of Food and Drug Administration approval, oral corticosteroids are a desirable treatment option for patients with infantile spasms...

    In this issue of Pediatric Neurology, Wanigasinghe and colleagues provide the first appropriately powered randomized controlled trial comparing synthetic ACTH to high-dose oral prednisolone (see 9/7/15 entry above). The study comes from a single center in Sri Lanka, one of the largest children's hospitals in the world.

    However, no study is perfect and the study by Wanigasinghe and colleagues has some study limitations. For example, given the absence of prior studies on which to base a power analysis, this study was not designed to show a “sustained” cessation of infantile spasms that was suggested by the West Delphi consensus as an optimal outcome measure...

    In addition, some of the patients analyzed at 2 weeks were lost to follow-up, prompting the authors to recruit additional patients to bolster the secondary outcome analysis (it is for this reason that the number of patients enrolled in this study differs from the number of patients enrolled in authors' prior publication). In addition, some experts will argue that the brief duration of the post-treatment EEG (30 minutes) is a major study limitation in determining electrographic remission...

    Despite these shortcomings, this study represents an enormous undertaking at a single center. This translates into a study that was built upon profound dedication and patience. The authors' work and their contribution to the literature are greatly appreciated. The study's role in the evolution of treatment of infantile spasms may be debated, but it does provide the best evidence to date supporting the use of oral prednisolone for the treatment of infantile spasms.