Pediatric Neurology 53 (2015) 193e199

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Pediatric Neurology
journal homepage: www.elsevier.com/locate/pnu

Original Article

Randomized, Single-Blind, Parallel Clinical Trial on Efficacy

of Oral Prednisolone Versus Intramuscular Corticotropin on
Immediate and Continued Spasm Control in West Syndrome
Jithangi Wanigasinghe MBBS, DCH, MD (Paed), MPhil a, *,
Carukshi Arambepola MBBS, MSc, MD (Community Medicine) b,
Shalini Sri Ranganathan MBBS, DCH, MD (Paed), PhD c,
Samanmalie Sumanasena MBBS, DCH, MD (Paed) d, Gangani Attanapola MBBS a
a
Department of Paediatrics, Faculty of Medicine, University of Colombo, Colombo, Sri Lanka
b
Department of Community Medicine, Faculty of Medicine, University of Colombo, Colombo, Sri Lanka
c
Department of Pharmacology, Faculty of Medicine, University of Colombo, Colombo, Sri Lanka
d
Department of Disability Studies, Faculty of Medicine, University of Kelaniya, Colombo, Sri Lanka

abstract
OBJECTIVE: 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. METHODS: 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 Infan-
tile Spasm Study protocol. They were blindly evaluated for infantile spasm remission by day 14, electroclinical
remission (spasm cessation þ resolution of hypsarrhythmia on a 30-minute electroencephalograph) by day 14 and
continued spasm freedom for 28 days. RESULTS: 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 ¼ 0.03) and
electroclinical remission in 21 on prednisolone compared with nine on adrenocorticotropic hormone (P ¼ 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 ¼ 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 ¼ 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 ¼ 0.079). CONCLUSION: 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.
Keywords: infantile spasms, West syndrome, hypsarrhythmia, ACTH, prednisolone, treatment
Pediatr Neurol 2015; 53: 193-199
Ó 2015 Elsevier Inc. All rights reserved.

Introduction
Article History:
Received April 1, 2015; Accepted in final form May 6, 2015
West syndrome is a devastating epileptic encephalopa-
* Communications should be addressed to: Dr. Wanigasinghe;
Department of Paediatrics; Faculty of Medicine; University of Colombo;
thy characterized by the triad of epileptic spasms, hypsar-
Colombo, Sri Lanka. rhythmia, and developmental regression. It is associated
E-mail address: jithangi@gmail.com with significant long-term neurological disability. Early

0887-8994/$ e see front matter Ó 2015 Elsevier Inc. All rights reserved.
http://dx.doi.org/10.1016/j.pediatrneurol.2015.05.004
194 J. Wanigasinghe et al. / Pediatric Neurology 53 (2015) 193e199
spasm cessation and improvement of electroencephalog-
raphy may correlate with developmental prognosis.1,2
Since its first description in 1841,3 treatment of West
syndrome has remained a challenge. Neither the mecha-
nism of spasm generation nor how drugs stop spasm gen-
esis is yet clearly understood. Thus, currently available
therapies are all “empirical.” Efficacy of these options has
been demonstrated with different levels of evidence. The
quality of some of this evidence is questionable as it is based
on a small number of clinical trials, mostly underpowered,
with variable outcomes.4,5 Based on “available evidence,”
the favored first line treatment options are vigabatrin for
spasms in tuberous sclerosis and intramuscular adreno-
corticotropin (ACTH) for all other forms of West syndrome.5
ACTH is enormously expensive and availability is limited
to some countries. Need for hospital admission adds to the
cost. Intramuscular administration is also painful. Vigaba-
trin is expensive and may be associated with permanent
visual impairment and transient white matter changes.6
Oral corticosteroids, specifically prednisone and pred-
nisolone, have also been used for treatment of spasms for
more than 40 years. Direct comparison between oral cor-
ticosteroids and ACTH is reported only in three clinical
trials.7-9 This is despite the better affordability, ease of
administration, and universal availability of these agents.
Despite high-dose prednisolone showing some pre-
liminary beneficial response as early as 1998,10 it has been
tested against ACTH in only a single trial. While there are
theoretical pharmacological advantages to prednisolone
over prednisone,5,10,11 its widespread availability and ease
of administration make prednisolone a more practical
choice. This definitely supports a direct comparison of ACTH
and prednisolone because the only earlier study9 that
reported equal efficacy of prednisolone and ACTH for spasm
control and electroencephalograph improvement was
underpowered to provide the required evidence to consider
prednisolone as a first-line medication.
The debate about the most effective and safest first-line
therapy for West syndrome continues.12 The need for an
adequately powered randomized clinical trial to affirm the
role of oral corticosteroids has been reiterated.4,5,12 This
randomized clinical trial was undertaken to fulfill this need.
The null hypothesis tested was that newly diagnosed in-
fantile spasms treated with intramuscular corticotropin
(ACTH) (Action Prolangatum, Himachal Pradesh, India) does
not result in a better spasm control or electroclinical
remission than if treated with high-dose oral prednisolone
(prednisolone, Rathmalana, Sri Lanka).
Methods
Trial design
A single-center, single-blind, parallel-group, equally randomized
(1:1) clinical trial was conducted at the Lady Ridgeway Children’s Hos-
pital, Colombo, Sri Lanka, from 2010 to 2014. Ethical approval was
granted by the Ethics Review Committees of Faculty of Medicine,
Colombo and Lady Ridgeway Hospital (EC-10-181) and was registered in
the Sri Lanka clinical trials registry before commencement (SLCTR/2010/
010). There were two main components to this trial. The first part, which
was published previously, was on the assessment of severity of
hypsarrhythmia and the degree of improvement of the electroenceph-
alograph with hormonal treatment.13 This article describes the second
component, the immediate and sustained control of epileptic spasms
when treated with two hormonal treatment regimens. The earlier EEG
paper contained a slightly smaller number of subjects because enroll-
ment continued briefly following the earlier publication.
Study population
The study setting, study population with their eligibility criteria,
and method of randomization including the treatment allocation and
concealment are all described in detail in the previous publication.13 In
summary, the eligible participants were newly diagnosed patients with
infantile spasms between 2 and 30 months of age admitted to the
hospital. Their diagnosis was confirmed by direct observations, videos
provided by caregivers, or video monitoring of spasms. The initial
estimated minimal sample size was 90 (45 in each treatment arm with a
projected 1:1 ratio) calculated for the primary outcome of clinical
and electroencephalographic improvement on day 14 of the treat-
ment.8 Because sample size calculation for the other outcomes such as
response rate at 42 days and sustained spasm control for 28 consecu-
tive days was not possible, they were considered as secondary
outcomes. However, with the decline or subsequent ineligibility of
approximately 10% of the initially eligible subjects (because of longer
follow-up up to day 42), we expanded the target enrolment sample size
to 98 infants (49 in each arm).
Before treatment allocation, the baseline characteristics of all par-
ticipants were assessed by a detailed clinical history and examination
(supplemented by neuroimaging) and baseline development by the
Bayley III infant and toddler developmental scales. Infants were equally
randomized to receive either oral prednisolone (10 mg four times daily
for 14 days) or intramuscular long acting synthetic ACTH 40 IU (0.5 mg)
administered every other day for 14 days as per the United Kingdom
Infantile Spasm Study.9 If the spasms persisted on day seven, the ACTH
dose was increased to 60 IU every other day and, similarly, the pred-
nisolone dose was increased to 15 mg four times per day. Computer-
generated random numbers that were concealed in sealed envelopes
were sequentially allocated. Details regarding the administration
method, doses, frequency and duration, follow-up during the treatment
schedule, and dose increments in the event of incomplete response,
method of taper off using oral prednisolone are also described
previously.13
Outcome evaluation
The primary outcome measures to prove the null hypothesis were
remission of infantile spasms by end of day 14 and electroclinical
remission by the end of day 14. There were several secondary outcome
measures which were described to support the null hypothesis.
These include: (1) number of days taken to achieve spasm remission;
(2) continued remission of infantile spasms for 28 consecutive days
(sustained spasm cessation) in those with electroclinical remission;
(3) spasm cessation at day 42 review; and (4) quantitative reduction of
spasms in those without spasm control. “Spasm cessation” was defined
as absence of any spasms (single or cluster) for a minimum period of
48 hours at the time of review on day 14. Electroclinical remission was
defined as cessation of spasms with absence of hypsarrhythmia on day
14 on a 30-minute digital sleep electroencephalograph. “Continued
spasm cessation” was defined as achievement of electro-clinical
remission within first 14 days followed by continued spasm freedom for
next consecutive 28 days (West Delphi group).14 Spasm cessation at
42 days was defined as no spasms for 48 hours when reviewed on day
42. Quantitative reduction was calculated in those who did not achieve
spasm cessation, but reduction to less than 50% of pretreatment
infantile spasm load by end of day 14. Adverse events following treat-
ment evaluated at the 14th day review was considered as another
(5) secondary outcome.
Infantile spasm load was evaluated by counting the number of clus-
ters of spasms and the number of spasms in each cluster. This was
documented in a spasm diary from day 0 to 14 by the parent. At the start
and during the hospital stay, this was done under the supervision of a
research assistant to improve the reliability of this “parent report” diary.
 J. Wanigasinghe et al. / Pediatric Neurology 53 (2015) 193e199
All patients were evaluated on day 14 by an independent investigator
who was not affiliated to the hospital staff (SSR) who collected the diary
for days 0-14. Thereafter, the second spasm diary was completed from
day 15 to 42 by the parents with minimal supervision. Before discharge,
parents were adequately educated to facilitate the accurate documen-
tation of spasm load at home. This second diary was used to ascertain
sustained spasm control over next 28 days after initial spasm cessation.
All digital electroencephalographs with concurrent video moni-
toring were obtained when the infants were in nonerapid eye move-
ment sleep. The 30-minute sleep records, performed after sedation,
were evaluated for the classical features of hypsarrhythmia based on
the description given by Gibbs and Gibbs, including (1) abnormal high-
amplitude polymorphic delta slowing and (2) frequent multifocal
epileptic discharges of (3) variable high amplitude with (4) disorgani-
zation of background activity with absence of normal sleep transients.
These electroencephalographs were evaluated pretreatment (day 0)
and posttreatment (day 14) by a single investigator (JW) well versed in
reviewing pediatric electroencephalographs. She remained blind to the
treatment arm and clinical outcome. Resolution of hypsarrhythmia was
defined as disappearance of the previously described four electroen-
cephalographic features from the entire electroencephalograph. How-
ever, persistence of a unifocal, monomorphic epileptic discharges and
or a monomorphic localized slower background rhythm, which is more
likely to be related to the underlying etiology, was not considered as
persistence of hypsarrhythmia.
Tolerance of adverse effects was evaluated using a checklist that
covered likely adverse effects of prednisolone and ACTH. This was
evaluated by SSR, who was not involved in the treatment allocation or
clinical assessment, after interviewing the patients at the time of day 14
review.
Data analysis
Categorical data were summarized in proportions and quantitative
data in mean and standard deviation. Significance of the differences
between the two treatment arms at baseline was assessed by t test for
quantitative data and chi-square test for categorical data. Using the same
tests, significance of the differences in primary and secondary outcomes
of the two treatment arms was assessed. The significance level was set at
0.05. All tests were two-tailed.
The primary analysis was intention-to-treat and involved all patients
who were randomly assigned. The effect size was calculated using risk ratio
(proportion with outcome in the prednisolone group/proportion with
outcome in the ACTH group) and absolute risk reduction (difference of the
proportion with outcome between the two treatment arms) with 95%
confidence interval. Number needed to treat was calculated on the basis of
the number of patients who needed prednisolone to achieve spasm
remission, compared with a patient who did not receive prednisolone.
An interim analysis was performed by an investigator not involved in
outcome assessments (CA) during the trial when 50% of the expected
number of primary events was accrued. This did not reveal any statis-
tically significant relationships: hence adjustment of sample size was not
required.
Results
There were 118 infants with clinically confirmed
epileptic spasms evaluated for participation. Eventually,
only 97 were randomized to receive oral prednisolone or
ACTH, giving a retention rate of 83.6%. Details of recruit-
ment, treatment allocation, and analysis are outlined in the
Figure. The underlying etiology of the spasms was known in
68% and unknown in 24%. However, 7.2% were unable to
complete all relevant investigations. The treatment arms
showed no significant difference for any of the baseline
characteristics or risk factors and are summarized in Table 1.
There was no departure from the initial study protocol
after the trial commenced.
195
The primary clinical outcomes are summarized in
Table 2. By day 14, the cessation of spasms had occurred in
28 infants treated with prednisolone (28/48; 58.3%)
compared with only 18 infants given ACTH (18/49; 36.7%)
(P ¼ 0.03). Both spasm cessation and resolution of hypsar-
rhythmia (electroclinical remission) by day 14 was seen in
21 on prednisolone (43.75%) compared with nine on ACTH
(18.4%) (P ¼ 0.007). The proportion of infants with elec-
troclinical response being spasm free for consecutive
28 days, (more preferred outcome indicator in West syn-
drome), was significantly higher in the prednisolone arm
(15/48) than ACTH (6/49) (31.2% versus 12.22%; P ¼ 0.008).
Spasm cessation by end of day 42 was higher among those
on prednisolone (66.7%) compared with ACTH (40.8%)
(P ¼ 0.01). In those who did not achieve remission, the
quantitative reduction of spasms to less than 50% of the
pretreatment level by day 14, was seen in 66.7% (12/18) in
the prednisolone group compared with 38.7% (12/31) in the
ACTH group (P ¼ 0.079). The total number of days required
for spasm cessation was quicker in those treated with
prednisolone (3.85 days  2.4) compared with ACTH
(8.65 days  3.7) (P ¼ 0.001). Regarding tolerability of
adverse events at the end of 14 days, shown in Table 3, only
one child treated with prednisolone was withdrawn from
the protocol. This was due to hypertension that resolved
after treatment withdrawal. No deaths were reported dur-
ing the 14 days of therapy or 3 weeks of step-down with
oral prednisolone. Some of the adverse events, particularly
increased appetite, abdominal distention, frequent crying
spells, and irritability, were more common with predniso-
lone. However, following statistical correction due to mul-
tiple comparisons, only abdominal distention was found to
be statistically significant.
Discussion
Our findings demonstrate that the null hypothesis is
true: synthetic ACTH at doses of IU/day 40-60 IU every other
day does not yield superior rates of electroclinical remission
when compared with prednisolone at doses of 40-60 mg/
day. We found that significantly more patients achieved
electroclinical remission when treated with prednisolone
than when treated with ACTH. The greater spasm cessation,
better electroclinical response, shorter time to achieve
spasm freedom, and sustained spasm control with pred-
nisolone indicates that control of spasms is significantly
better if newly diagnosed patients are treated with oral
prednisolone than ACTH at the doses that were employed.
This finding is further supported by reduced rate of relapse
during first 28 days with prednisolone than ACTH. This is
the first clinical trial to document therapeutic supremacy
for prednisolone over ACTH for treatment of spasms. Having
a relatively low number needed to treat of five also indicates
the more effectiveness of prednisolone.
The outcome of this trial establishes a definitive role for
oral prednisolone in the management of West syndrome as
first-line therapy. Oral prednisolone, though used success-
fully by many all over the world,15-19 was never considered
as a first-line therapy because of the absence of class I or II
evidence. Several meta-analyses have emphasized the need
for robust clinical evidence to establish its therapeutic role
in West syndrome.4,5 The findings of this study as well
196 J. Wanigasinghe et al. / Pediatric Neurology 53 (2015) 193e199
FIGURE.
Outline of enrollment, treatment allocation, follow-up, and analysis of outcomes. (The color version of this figure is available in the online edition.)
as the component on resolution of hypsarrhythmia (pub-
lished previously13) have now generated the long-awaited
evidence to support this inexpensive, universally available,
culturally accepted oral medication for treatment of West
syndrome. We hope that these findings will benefit many
children, especially those in resource-limited settings
where other forms of therapy are unavailable. Interest in
prednisolone has recently grown because of an ACTH price
increase,15,19 so our results may be valuable even in more
affluent countries.
In this study, outcome assessments (spasm control and
improvement of hypsarrhythmia) were assessed blindly.
The parents were adequately trained to record spasm fre-
quency. Being a single-center study helped to reduce vari-
ability in outcome assessment. The large number of recruits
has facilitated a final outcome parameter with adequate
power to support level I evidence for use of prednisolone.
Limitations in this trial include an inability to establish
the response in the etiology unknown category because
of the small number of subjects in this category. Though
ideal is a longer video electroencephalograph monitoring
to assess the resolution of hypsarrhythmia, we limited it
to a 30-minute electroencephalograph in nonerapid eye
movement sleep because of the limitation of resources.
Estimation of adverse effects was done only at day 14.
Continued evaluation may have helped to exclude risk of
adrenal suppression better.
When comparing the outcome for spasm control with
prednisolone (58.3%), the findings in our trial are compa-
rable to those of Lux et al. (70%), the only other trial pitting
prednisolone against ACTH.9 Our findings are also similar to
those of a recent clinical trial on high- versus low-dose
prednisolone (51.6% response with high dose)20 and two
prospective studies that used high-dose prednisolone
(67%19 and 63%15). However, the spasm control with ACTH
in our study (37%) is below the response rates (42%-86%)
reported previously.7,8 This disparity can be explained by
careful scrutiny of the methodology and results of these
respective trials. Disparity in the doses used is one expla-
nation. A favorable outcome of 86% was reported with a
 J. Wanigasinghe et al. / Pediatric Neurology 53 (2015) 193e199 197

TABLE 1.
Baseline Characteristics of the Children Treated With Prednisolone and ACTH

n Prednisolone ACTH Level of Significance*

n ¼ 48 n ¼ 49
Age in months 8.31 (SD ¼ 6.19) 9.93 (SD ¼ 8.67) 0.29
Sex
Male 25 52.1% 31 63.3% 0.26
Female 23 47.9% 18 36.7%
Ethnicity
Sinhala 42 87.5% 42 87.5% 0.85
Tamil 01 2.1% 02 4.1%
Muslim 05 10.4% 05 10.4%
Gestation
Preterm 07 14.6% 05 10.2% 0.51
Term 41 85.4% 44 89.8%
Age of onset of spasms
<12 months 46 95.8% 44 89.8% 0.25
>12 months 02 4.2% 05 10.2%
Preceding/concurrent seizures
Present 17 35.4% 15 30.6% 0.61
Absent 31 64.6% 34 69.4%
Previous treatment with AED
Yes 12 25.0% 13 26.5% 0.86
No 36 75.0% 36 73.5%
Lead time to treatment
<28 days 21 43.8% 21 42.9% 0.93
>28 days 27 56.2% 28 57.1%
Mean SD Mean SD
Birth weight (kg) 2.57 0.53 2.60 0.53 0.79
Baseline developmental Scores
Cognitive 60.6 10.3 58.2 8.0 0.2
Language 58.6 12.8 55.9 11.7 0.3
Motor 53.5 13.4 50.9 9.1 0.3
Spasm load (clusters per day) 4.91 3.2 5.06 2.4 0.8
Abbreviations:
ACTH ¼ Adrenocorticotropic hormone
SD ¼ Standard deviation
* P value obtained for assessing significant differences between the two treatment arms in relation to baseline characteristics (chi-square test used for categorical data;
independent t test used for quantitative data).

high-dose ACTH (150 IU/m2/day) regime.8 Outcomes re-
ported with low-dose regimes (ranging between 41.6% and
60%), on the other hand, are more comparable.7,21,22 The
better response could also be explained by longer duration
of therapy as in some trials.21 Preparations of ACTH used
also vary; natural ACTH used in the United States,23 whereas
synthetic ACTH is used in European and Japanese trials.
Because the chemical composition is different in the natural
and synthetic products, a better response may be seen with
natural ACTH. Response to ACTH may also vary in different
ethnic groups. West syndrome amongst the Japanese seems
to respond better to pyridoxine than to ACTH.24

TABLE 2.
Comparison of Primary and Secondary Outcome Measures Between Prednisolone and ACTH Treatment Groups

Outcome Measures Prednisolone ACTH P-value Risk Ratio Absolute Risk Number
(N ¼ 48) (N ¼ 49) Reduction Needed
to Treat
Spasm cessation on 14th day, no. (%) 28 (58.3%) 18 (36.7%) 0.03 1.59 (1.02-2.46) 0.22 (0.02-0.39) 5 (3-57)
Electroclinical response on 14th day, no. (%) (no spasms 21 (43.75%) 9 (18.4%) 0.007 2.38 (1.22-4.66) 0.25 (0.07-0.42) 4 (2-14)
and no hypsarrhythmia)
Spasm cessation on 42nd day, no. (%) 32 (66.7%) 20 (40.8%) 0.01 1.63 (1.1-2.42) 0.26 (0.06-0.43) 4 (2-17)
Spasm freedom for consecutive 28 days in those with 15 (31.3%) 6 (12.2%) 0.008 2.55 (1.08-6.03) 0.19 (0.03-0.35) 5 (3-40)
electroclinical response on 14th day, no. (%)
Reduction of spasms by >50% in those not controlled 12 (66.7%) 12 (38.7%) 0.059 1.72 (0.99-2.99) 0.28 (0.01-0.51) 4 (2-117)
by day 14, no. (%)*
No. of days taken for control of spasms, mean  SD 3.85  2.4 8.65  3.7 0.001 4.8 (2.99-6.61)
Abbreviations:
ACTH ¼ Adrenocorticotropic hormone
SD ¼ Standard deviation
* Prednisolone group ¼ 18 (excludes 2 missing data); ACTH group ¼ 31.
198 J. Wanigasinghe et al. / Pediatric Neurology 53 (2015) 193e199

TABLE 3.
Comparison of Side Effects Experienced by Participants in the Prednisolone (N ¼ 48) and ACTH (N ¼ 49) Groups

Side Effect Prednisolone ACTH Level of Significance*

No. % No. %
Increased appetite 28 73.7 19 43.2 0.005
Weight gain 19 50.0 14 31.8 0.09
Frequent crying spells 16 42.1 11 25.0 0.1
Drowsiness 4 10.5 7 15.9 0.48
Cushingoid features 8 21.1 9 20.5 0.95
Insomnolence 3 7.9 2 4.5 0.53
Lethargy 2 5.3 2 4.5 0.88
Reduction in social behavior 2 5.3 1 2.3 0.47
Abdominal distension 8 21.1 0 0 0.001*
Hypertension 1 2.6 1 2.3 0.92
Increased susceptibility to infectiony 0 0.0 1 2.3 0.35
Irritability 8 21.1 5 11.4 0.23
Nausea 1 2.6 1 2.3 0.92
Vomiting 2 5.3 1 2.3 0.47
Diarrhea 2 5.3 3 6.8 0.77
Dyspepsia 2 5.3 2 4.5 0.88
Electrolyte imbalances 2 5.3 0 0.0 0.12
* Because of multiple comparisons, the level of significance was adjusted to P < 0.00294 by Bonferroni correction: aadjusted ¼ a/c, where a is the overall experiment-wise
alpha (0.05); c is the number of comparisons made (17).
y
Increased susceptibility to infection was assessed by history examination to look for presence of fever, any evidence of local or systemic infection.

We have detailed the comparison of adverse effects for the
two treatment arms because this should an important
consideration when determining effectiveness of a therapy.
In clinical practice, the experienced adverse effects of high-
dose ACTH are many and include several life-threatening
complications such as high blood pressure, cardiomyopa-
thy, and heart failure.25 On the contrary, in the trial that used a
high dose of ACTH (150 IU/m2/day), the description of adverse
effects was limited to irritability and increased appetite. This
appears to be an under reporting, considering the list of
adverse effects noted in our trial, which used a lower dose of
ACTH and for a much shorter duration of therapy.8
Conclusions
The highlight of our findings is that prednisolone (10 mg
four times daily for 14 days) if used as a first-line therapy,
would result in an absolute risk reduction of 22% of children
with West Syndrome, compared with ACTH therapy. This
should guide pediatricians and pediatric neurologists all
over the world in making the choice to use prednisolone as
a form of first-line treatment for treatment of spasms. The
impact of this finding is enormous, particularly in relation
to affordability, both at country and individual level. This
will be felt mostly in countries where other options (ACTH
or vigabatrin) remain unavailable. The infection rate expe-
rienced with this protocol being low also facilitates exper-
imenting with this protocol with greater confidence. The
more frequently experienced side effects of irritability,
frequent crying, and cushingoid features are not life-
threatening and typically resolve after discontinuation of
medication.
This clinical trial was part funded by the Sri Lanka Medical Association (grant
number: CT/2010), which is the oldest medical professionals’ organization in the
country. We wish to thank the staff of the University unit and staff of the electro-
encephalograph department at Lady Ridgeway Hospital for their contribution. We
wish to thank Compumendics Ltd (Australia) for donating the electroencephalo-
graph recording equipment.
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