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Adrenocorticotropic Hormone versus
Pulsatile Dexamethasone in the Treatment
of Infantile Epilepsy Syndromes
Edda Haberlandt, MD, Christine Weger, MD, Sara Baumgartner Sigl, MD,
Markus Rauchenzauner, MD, Sabine Scholl-Bu
¨rgi, MD, Kevin Rosta
´sy, MD,
and Daniela Karall, MD
For treatment of intractable epilepsies, there are no data
comparing conventional adrenocorticotropic hormone
and pulsatile corticoid therapy with dexamethasone. A
retrospective comparison of efficacy was therefore con-
ducted for both forms of application. Between 1989 and
2001, a series of 11 children with West syndrome and
3 with Lennox-Gastaut syndrome were treated with adreno-
corticotropic hormone (group 1); between 2003 and 2006, 7
children with West syndrome, 5 with electrical status
epilepticus during slow sleep, and 2 with Lennox-Gastaut
syndrome were treated with pulsatile corticoid therapy
(group 2). In group 1 (n= 14), 9/11 West syndrome patients
became seizure free, but none with Lennox-Gastaut syn-
drome (0/3). In group 2 (n= 14), 4/7 West syndrome patients
became seizure-free, 1/2 with Lennox-Gastaut syndrome
exhibited seizure-frequency reduction, and 2/5 patients
with electrical status epilepticus during slow-wave sleep
exhibited significant improvement according to electro-
encephalograms. In West syndrome, pulsatile corticoid
therapy was an effective alternative treatment to adrenocor-
ticotropic hormone, whereas in Lennox-Gastaut syndrome
in general steroids did not lead to a significant seizure reduc-
tion. In electrical status epilepticus during slow-wave sleep,
treatment with pulsatile corticoid therapy seems to be
effective and should be investigated in a larger group of
patients. Ó2010 by Elsevier Inc. All rights reserved.
Haberlandt E, Weger C, Baumgartner Sigl S, Rauchenzauner
M, Scholl-Bu¨ rgi S, Rosta´ sy K, Karall D. Adrenocorticotropic
hormone versus pulsatile dexamethasone in the treatment of
infantile epilepsy syndromes. Pediatr Neurol 2010;42:21-27.
Introduction
In 1950, adrenocorticotropic hormone was used for the
first time for therapy-resistant epilepsies, by Klein and
Livingston [1], and in 1968 Sorel [2] reported successful
use of adrenocorticotropic hormone in treatment of chil-
dren with West syndrome. In 1959, successful treatment
of infantile spasms with adrenocorticotropic hormone or
oral steroids was reported by Dumermuth [3]. Later on,
other epileptic syndromes such as Lennox-Gastaut syn-
drome and electrical status epilepticus during slow-wave
sleep were occasionally treated with adrenocorticotropic
hormone [4].
Numerous studies have been reported on the treatment of
infantile spasms and other therapy-resistant epilepsies in
childhood. Most, however, are uncontrolled and retrospec-
tive. For steroids, there still is no agreed upon protocol for
the treatment of intractable infantile epilepsies. National
and regional strategy recommendations differ substantially
in regard to application form, duration, dosing, and the
choice of steroids [5,6].
Recently, pulsatile corticoid therapy has become avail-
able as an alternative treatment to adrenocorticotropic
hormone. Only a few reports are available on efficacy
and adverse-effect profile for high-dose pulsatile dexa-
methasone therapy in children [7,8]. Reported here is
a retrospective study of both efficacy and the adverse-
effect profile of adrenocorticotropic hormone vs pulsa-
tile corticoid therapy with dexamethasone in the treat-
ment of children with West syndrome, Lennox-Gastaut
syndrome, and electrical status epilepticus in slow-wave
sleep.
From the Department of Pediatrics, Division of Neuropediatrics and
Inherited Metabolic Disorders, Medical University of Innsbruck,
Innsbruck, Austria.
Communications should be addressed to:
Dr. Haberlandt; Department of Pediatrics; Division of Neuropediatrics and
Inherited Metabolic Disorders; Medical University of Innsbruck;
Anichstrasse 35; A-6020 Innsbruck, Austria.
E-mail: edda.haberlandt@uki.at
Received February 2, 2009; accepted July 13, 2009.
Ó2010 by Elsevier Inc. All rights reserved.
doi:10.1016/j.pediatrneurol.2009.07.011 0887-8994/10/$—see front matter
Haberlandt et al: ACTH and Steroids in Epilepsies 21
Methods
Charts of 28 patients with intractable epilepsy treated with ACTH or ste-
roids between 1989-2006 at the University Children’s Hospital, Medical
University of Innsbruck, were analyzed retrospectively. Inclusion criteria
were diagnosis of an intractable epilepsy (West syndrome, electrical status
epilepticus in slow-wave sleep, Lennox-Gastaut syndrome) and treatment
with either adrenocorticotropic hormone or pulsatile corticoid therapy with
dexamethasone. Diagnoses were classified according to international crite-
ria for diagnosis of epilepsy [9]. Exclusion criteria were steroid treatment
due to other reasons, change of anticonvulsant treatment during steroid
treatment (in group 1 accepted only), or severe adverse effects such as ma-
lignant hypertonus or intractable infections leading to cessation of treat-
ment. Initially, all patients were treated with oral anticonvulsants.
Table 1. Baseline and response characteristics for two treatment groups in 28 patients with infantile epilepsy syndromes
Sex
Start
of Tx
Age at Start
of Tx Etiology
Time Interval,
Dx to Tx
EEG*
Response, %
Seizure
†
Response, %
Time Interval to
Response, EEG
Time Interval to
Response, Seizures
Group 1: Adrenocorticotropic Hormone (n= 14)
West Syndrome(n = 11)
M 2001 5 mo Idiopathic 14 weeks 100 100 6 weeks 8 weeks
M 2001 6 mo Idiopathic 4 weeks 100 100 2 weeks Immediate
M 2001 7 mo Idiopathic 4 weeks 100 100 4 weeks 4 weeks
M 1989 10 mo Symptomatic 4 weeks 50 100 2 weeks Immediate
M 1889 10 mo Symptomatic 4 weeks 50 100 3 weeks Immediate
F 1990 7 mo Symptomatic 2 weeks 50 100 4 weeks 4 weeks
F 1991 5 mo Symptomatic 32 weeks 0 100 No response 6 weeks
M 1997 10 mo Symptomatic 16 weeks 100 100 1 week Immediate
M 1997 7 mo Symptomatic 8 weeks 50 0 2 weeks No response
F 1998 4 mo Symptomatic 16 weeks 0 50 No response Immediate
M 2001 9 mo Symptomatic 6 weeks 50 100 2 weeks 2 weeks
Lennox-Gastaut Syndrome (n=3)
M 1992 20 mo Cryptogenic 8 weeks 50 50 2 weeks Not clear
M 1998 2 yr 9 mo Cryptogenic 16 weeks 50 50 1.5 weeks 4 weeks
F 2000 2 yr 10 mo Cryptogenic 8 weeks 0 0 No response No response
Group 2: Pulsatile Corticoid Therapy With Dexamethasone (n= 14)
West Syndrome (n = 7)
M 2003 7 mo Idiopathic 8 weeks 100 100 1 week 1 week
M 2005 6 mo Idiopathic 20 weeks 100 100 16 weeks 4 weeks
F 2004 6 mo Symptomatic 4 weeks 100 100 1 week 1 week
M 2006 8 mo Symptomatic 1 week 100 50 8 weeks 12 weeks
F 2003 6 mo Cryptogenic 16 weeks 50 100 1 week 4 weeks
M 2005 22 mo Cryptogenic 1 weeks 0 50 No response 1 week
F 2005 4 mo Cryptogenic 1 week 0 50 No response 1 week
Lennox-Gastaut Syndrome(n=2)
M 2004 13 mo Cryptogenic 48 weeks 0 50 No response 1 week
M 2005 2 yr Cryptogenic 12 weeks 100 50 8 weeks 8 weeks
Electrical Status Epilepticus During Slow Sleep (n=5)
M 2005 4 yr 6 mo Symptomatic 20 weeks 0 50 No response 1 week
M 2005 5 yr Idiopathic 60 weeks 100 100 1 week 4 weeks
M 2005 4 yr 4 mo Idiopathic 52 weeks 0 100 No response 1 week
M 2005 8 yr 5 mo Idiopathic 96 weeks 100 100 16 weeks 4 weeks
M 2006 5 mo Cryptogenic 144 weeks 50 100 4 weeks 1 week
* EEG response was categorized as 100% (good responder), 50% (responder), and 0% (nonresponder). In West syndromes, 100% indicates that
hypsarrhythmia resolved or only minimal epileptiform activity was left; in Lennox-Gastaut syndromes and electrical status epilepticus during slow-wave
sleep, a 100% responder was defined as having no or only minimal epileptiform activity. A 50% responder in West syndrome had no hypsarrhythmia, but
still exhibited clear epileptiform activity; in Lennox-Gastaut syndrome and electrical status epilepticus during slow-wave sleep, a 50% EEG responder had
a decrease of at least 50% in epileptiform activity, but otherwise still exhibited all the hallmarks of the respective epileptic syndrome. The 0% category for
nonresponders was defined as from no reduction to less than 50% reduction of epileptiform activity.
†
Seizure response was categorized as 100% (seizure free), 50% (responder), and 0% (nonresponder), for complete cessation of seizures, at least 50%
reduction of seizure frequency but short of seizure freedom, and no change in seizure frequency, respectively.
Abbreviations:
Dx = Diagnosis
Tx = Treatment
22 PEDIATRIC NEUROLOGY Vol. 42 No. 1
Treatment with adrenocorticotropic hormone or pulsatile corticoid therapy
was started, if there was no seizure control or no effect on the electroen-
cephalograph (EEG).
Group 1 was treated between 1989 and 2001 with adrenocorticotropic
hormone following the scheme of Ko¨nigsteiner Arbeitskreis, a German
working group of epileptologists [10]. For weeks 1 and 2, 15-20 IU/day
of synthetic corticotropin (Novartis Synacthen Depot) was given intramus-
cularly; this was increased by another 20 IU/day every 2 weeks, up to
a maximum of 120 IU/day in case of therapy-resistant seizures. In case
of response, the dose was reduced by 20 IU/day every 2 weeks thereafter.
EEG recordings with sleep were performed every 10-14 days. All patients
treated with adrenocorticotropic hormone received standard antibiotic pro-
phylaxis (mostly with trimethoprim) and had regular laboratory monitoring
of electrolytes and blood sugar, blood pressure, and kidney function, as
well as cardiac assessment.
In 2003, because of similar treatment effect but fewer adverse effects,
pulsatile corticoid therapy was introduced at the study hospital. Patients
treated between 2003 and 2006 received pulsatile corticoid therapy as 20
mg/m
2
dexamethasone i.v. daily, given for 3 days, with an interval of 4
weeks between each cycle [11]. Every patient received at least five cycles.
Electroencephalography with sleep activity was performed before and after
every cycle. No prophylactic antibiotics were administered.
All patients were treated with informed parental consent. All parents
were advised to seek medical attention for any infection or disease during
treatment with steroids. The observational period was at least 6 months af-
ter treatment with steroids.
The EEG response was evaluated and divided into three categories as
percentages: 100%, good responder; 50%, responder; and 0%, nonre-
sponder. For West syndrome, a 100% responder was defined as having
hypsarrhythmia resolved or only minimal epileptiform activity remaining.
In Lennox-Gastaut syndromes and electrical status epilepticus during slow-
wave sleep, a 100% responder was defined as having no or only minimal
epileptiform activity. A 50% responder in West syndrome had no hypsar-
rhythmia, but still exhibited clear epileptiform activity. In Lennox-Gastaut
syndrome and electrical status epilepticus during slow-wave sleep, a 50%
EEG responder had a greater than 50% decrease in epileptiform activity,
but still had all the hallmarks of the respective epileptic syndrome. A non-
responder was defined as exhibiting no reduction or up to less than 50%
reduction in epileptiform activity.
Seizure frequency was similarly divided into three categories: 100%,
seizure free (complete cessation of seizures); 50%, responder ($50% but
<100% reduction in seizure frequency); and 0%, nonresponder (no change
in seizure frequency).
For both treatment groups, the time interval to response of EEG or sei-
zure frequency was considered as immediate if response was between day 1
and day 4. Data are presented in a descriptive statistical manner.
Group 1 (n= 14; 10 male, 4 female) comprised 11 patients with West
syndrome and 3 patients with Lennox-Gastaut syndrome; the median age
was 12 months (range, 4-34 months). Group 2 (n= 14; 11 male, 3 female)
comprised 7 patients with West syndrome, 2 with Lennox-Gastaut syn-
drome, and 5 with electrical status epilepticus during slow-wave sleep;
the median age was 32 months (range, 4-101 months). Baseline character-
istics are given in Table 1.
Results
Changes in EEG
Comparison of the two treatment options regarding gen-
eral effectiveness on EEG abnormalities revealed a better
response in group 1 (100% response in 4/14, 50% response
in 7/14 patients, and 0% response in 3/14 patients) (Fig 1;
Table 1). In group 2, a smaller proportion of patients fell
in the middle response group: 7/14 patients exhibited
100% response, but 5/14 exhibited 0% response, and only
2/14 exhibited 50% response. That is, 11/14 patients ex-
hibited 100% or 50% response on EEG with adrenocortico-
tropic hormone (group 1), compared with 9/14 patients with
pulsatile corticoid therapy (group 2). The nonresponders for
group 2 were two patients with electrical status epilepticus
during slow-wave sleep, two patients with West syndrome,
and one patient with Lennox-Gastaut syndrome (Table 1).
In group 1, a 100% response on EEG was seen in 4/11 pa-
tients with West syndrome; 5/11 responded 50% and 2/11
were non responders. In group 1, 0/3 patients with Len-
nox-Gastaut syndrome had 100% response; 2/3 had 50% re-
sponse, and 1/3 patients had no response. In group 2, 4/7
patients with West syndrome had 100% response on
EEG, 1/7 had 50% response, and 2/7 had no response. In
group 2, considering together the two patients with Len-
nox-Gastaut syndrome and the five patients with electrical
status epilepticus during slow-wave sleep, 3/7 had 100%
response, 1/7 had 50% response, and 3/7 had no response
(Table 1).
Changes in Seizure Frequency
In group 1, 9/14 patients became seizure free, 3/14 had
partial seizure reduction, and 2/14 fell in the nonresponder
group (Fig 2;Table 1). In group 2, 8/14 patients became sei-
zure free, and 6/14 patients had partial seizure reduction,
there was no nonresponder (Fig 2;Table 1).
Changes in Seizure Frequency in the Individual
Syndromes
Seizure freedom in adrenocorticotropic hormone treat-
ment of West syndrome was achieved in 9/11 patients;
the other two were a 50% responder and a nonresponder.
No patient with Lennox-Gastaut syndrome was seizure
free after adrenocorticotropic hormone treatment (Fig 3;
Table 1).
Pulsatile corticoid therapy treatment led to seizure free-
dom in 5/7 patients with West syndrome and to 50%
response in 2/7. For patients with either Lennox-Gastaut
syndrome and electrical status epilepticus during slow-
4
77
2
3
5
0
1
2
3
4
5
6
7
patients
100% response 50% response no response
EEG response
ACTH PCT
Figure 1. Electroencephalographic (EEG) response to adrenocorticotro-
pic hormone (ACTH) and pulsatile corticoid therapy (PCT) with dexa-
methasone in two groups of infantile epilepsy syndrome patients (n=14
in each group).
Haberlandt et al: ACTH and Steroids in Epilepsies 23
wave sleep, 4/7 achieved seizure freedom and 3/7 were 50%
responders (of the 5 patients with electrical status
epilepticus in slow-wave sleep, 4 benefited with seizure-
freedom) (Fig 4;Table 1).
Time Interval to Change in EEG
In group 1, 4/11 patients with West syndrome had 100%
EEG response, but this was not immediate. In group 1 over-
all, 7/14 patients exhibited response within 1-2 weeks, and
another 3 patients responded in 3 or 4 weeks; only one
patient responded in 6 weeks, after which period no further
patient responded.
In group 2, 4/7 patients with West syndrome had 100%
EEG response, 2 of them immediately (after the first pulse,
day 1-3). A positive response was observed up to week 8
after the third pulse of pulsatile corticoid therapy (Table 1).
Time Interval to Change in Seizure Frequency
In group 1, 9/11 patients with West syndrome achieved
seizure freedom, and out of these 4/9 responded immedi-
ately (day 1-4). Seizure freedom was achieved after 2 weeks
for 1 patient, 4 weeks for 2 patients, 6 weeks for 1 patient,
and 8 weeks for 1 patient.
In group 2, 4/7 patients with West syndrome achieved
seizure freedom, 2 after the first cycle and 2 others after 4
weeks (Table 1).
Adverse-Effects Profile
In group 1 (adrenocorticotropic hormone), adverse
effects included hypertension in 10/14 patients (9 of these
10 had normal echocardiography, and 1 had myocardial
hypertrophy), myocardial hypertrophy diagnosed by echo-
cardiography in 8/14 patients (7 of these 8 without and 1
with hypertension). Electrolyte abnormalities were seen in
8/14 (6 with low potassium, 1 each with low calcium and
low phosphate), elevation of liver enzymes in 5/14, Cush-
ing syndrome in 3/14, bacterial infections in 3/14, viral
infections in 1/14, and oral candidiasis in 2/14 (Table 2).
Further adverse effects included cerebral atrophy (1/14),
melena (1/14), fatigue (1/14), hirsutism (1/14), acne
(1/14), and increase of appetite (1/14).
In group 2 (pulsatile corticoid therapy), adverse effects
included elevated liver enzymes in 7/14 patients, viral
infections in 7/14, oral candidiasis in 3/14, generalized
exanthema or erythema in 4/14, and fatigue in 2/14. In
addition, hepatomegaly, acne, hypertension, myocardial
0
1
2
3
4
5
6
7
8
9
seizure free responder non responder
seizure response to ACTH
WS LGS
patients
Figure 3. Seizure response to adrenocorticotropic hormone (ACTH) in
patients with West Syndrome (WS) (n= 11) or Lennox-Gastaut Syndrome
(LGS) (n= 3). Seizure free was defined as complete cessation of seizures;
responder, as $50% reduction of seizure frequency but less than complete
cessation; nonresponder, as no change in seizure frequency.
9
8
3
6
2
0
0
1
2
3
4
5
6
7
8
9
patients
seizure free responder non responder
seizure response
ACTH PCT
Figure 2. Seizure response to adrenocorticotropic hormone (ACTH) and
pulsatile corticoid therapy (PCT) with dexamethasone in two groups of in-
fantile epilepsy syndrome patients (n= 14 in each group). Seizure free was
defined as complete cessation of seizures; responder, as $50% reduction
of seizure frequency but less than complete cessation; nonresponder, as no
change in seizure frequency.
0
10
20
percentage
30
40
50
60
70
seizure free responder non responder
seizure response to PCT
WS LGS/ESES
Figure 4. Seizure response to pulsatile corticoid therapy (PCT) with
dexamethasone in patients with West Syndrome (WS) (n= 7) and in pa-
tients with Lennox-Gastaut Syndrome or electrical status epilepticus in
slow sleep (LGS/ESES) (n= 7). Seizure free was defined as complete ces-
sation of seizures; responder, as $50% reduction of seizure frequency but
less than complete cessation; nonresponder, as no change in seizure
frequency.
24 PEDIATRIC NEUROLOGY Vol. 42 No. 1
hypertrophy, and electrolyte abnormalities were seen in one
patient each (Table 2).
Discussion
Treatment with adrenocorticotropic hormone and ste-
roids is an option for intractable infantile epilepsies. The
mechanism for how steroids influence seizure activity is
still unknown. The increase of serum levels of cortisol, di-
rect effect on brain, and suppression of cortical and hypo-
thalamic corticotropin-releasing hormone levels have
been discussed as potential mechanisms (corticotropin-
releasing hormone is a potential convulsant in rats) [12],
along with reduced cerebral blood circulation, reduction
of cerebral edema, increase of glucose levels, change of
protein metabolism, and acceleration of intracerebral
enzyme activity [13]. Recent findings suggest that brain-
adrenal axis dysfunction plays an important role [14].
Clear therapeutic strategies concerning administration of
steroids are lacking. Studies differ in dosages and therapy
periods, and prospective studies are rare [5,6]. Observations
differ substantially, and comparison between studies is not
valid. Results have differed for several studies comparing
effectiveness of high and low dosage of adrenocorticotropic
hormone and oral steroids for treatment of West syndrome.
Reports from older studies indicated better effectiveness
and higher response rates for adrenocorticotropic hormone
than for steroids, but newer studies could not confirm sig-
nificant differences [15-19]. In 1998, Yamamoto et al.
[20] reported successful treatment with adrenocorticotropic
hormone vs steroids for infantile epilepsies in a small study
population (5 patients in each group). In 2002, nine children
with infantile spasms were treated with pulsatile steroid
therapy, with a good result in five patients [8].
To summarize, no individual treatment has demonstrated
superiority in the treatment of infantile spasms [21], but
early administration of steroids after the second week of
hypsarrhythmia is relevant for controlling seizures and pro-
vides a better cognitive outcome [22,23]. It was this back-
ground that spurred the present study of the efficacy and
adverse-effects profile of adrenocorticotropic hormone
and pulsatile corticoid therapy with dexamethasone in the
treatment of infantile epilepsy syndromes.
Considering the 100% and 50% responses together, both
treatment options exhibited high and comparable effective-
ness on EEG: 11/14 in group 1 (78%) and 9/14 in group 2
(64%) (Fig 1;Table 1). Similarly, Gupta et al. [24] reported
EEG response in 50-75% of subjects treated with adreno-
corticotropic hormone or continuous steroid treatment.
Most group 2 patients (9/14) had EEG improvement with
pulsatile corticoid therapy, and the proportion with 100%
improvement on EEG was greater in group 2 than in group
1 (7/14 vs 4/14). Most group 2 patients exhibited either
100% EEG response or no response at all (Fig 1;Table
1). Thus, pulsatile steroid therapy is a treatment option for
West syndrome (4/7 were 100% responders), as well as
for Lennox-Gastaut syndrome or electrical status epilepti-
cus during slow-wave sleep (1/2 and 2/4, respectively,
were 100% responders).
Seizure response for both therapy options was likewise
comparable. Adrenocorticotropic hormone treatment re-
sulted in seizure freedom in 9/14 patients (64%), pulsatile
corticoid therapy in 8/14 patients (57%) (Fig 2;Table 1).
Additionally, the proportion of responders with 50% sei-
zure reduction was similar for the two groups (3/14 for
group 1 and 6/14 for group 2). For comparison, seizure free-
dom of 54-100% of patients treated with steroids is reported
elsewhere [25].
In terms of seizure response for the different epilepsy
syndromes, 10/11 West syndrome patients treated with ad-
renocorticotropic hormone treatment (group 1) had a good
seizure response, and 9 of the 10 achieved seizure freedom
(Fig 3;Table 1). Seizure freedom after adrenocorticotropic
hormone in West syndrome was reported for up to 54% of
patients by Riikonen [13] and for 100% by Snead et al. [15].
In contrast, the three group 1 patients with Lennox-Gastaut
syndrome exhibited a lesser seizure response to adrenocor-
ticotropic hormone: no patients achieved seizure freedom, 2
patients were 50% responders, and 1 was a nonresponder
(Fig 3;Table 1). In a study of Lennox-Gastaut syndrome pa-
tients, Yamatogi et al. [26] observed good response, with
seizure freedom, but a high proportion of relapse; they con-
cluded that effectiveness of adrenocorticotropic hormone
for Lennox-Gastaut syndrome is uncertain.
Treatment with pulsatile steroid therapy with dexameth-
asone (group 2) resulted in similar seizure response rates for
Table 2. Adverse-effects profile for two treatment groups in 28
patients with infantile epilepsy syndromes
Adverse Effect
ACTH,
no. of patients
PCT,
no. of patients
Sample size n=14 n=14
Infections, viral 1 7
Infections, bacterial 3 0
Infections, viral, repeated 0 3
Hepatomegaly 0 1
Elevation of liver enzymes 5 7
Electrolyte imbalance 8 1
Fatigue 2 2
Increase of appetite 1 0
Cushing syndrome 3 0
Myocardial hypertrophy 8 1
Hypertension 10 1
Oral candidiasis 2 3
Exanthema, erythema 0 4
Acne 1 1
Hirsutism 1 0
Melena 1 0
Cerebral atrophy 1 0
None 1 1
Death 0 0
Abbreviations:
ACTH = Adrenocorticotropic hormone
PCT = Pulsatile corticoid therapy with dexamethasone
Haberlandt et al: ACTH and Steroids in Epilepsies 25
West syndrome and for Lennox-Gastaut syndrome or elec-
trical status epilepticus during slow-wave sleep in our study
group (Fig 4;Table 1), exhibiting good anticonvulsive ef-
fect of pulsatile steroid therapy. In general, clinical seizures
were reduced more frequently with pulsatile corticoid ther-
apy, even though EEG did not exhibit clear response in all
cases (Table 1).
In terms of time to response, the present data demonstrate
that EEG response to pulsatile steroid therapy is possible up
to the 3rd therapy cycle (week 8-10). One patient had imme-
diate clearing within the first week (Table 1), but response
was observed up to week 8-10, after the third pulse of pul-
satile steroid therapy, suggesting that re-evaluation of pul-
satile steroid therapy after 3 months seems advisable.
Yamamoto et al. [20] demonstrated response of all patients
to oral steroids (dexamethasone palmitate) given once
a week (study groups with 5 patients), so one could hypoth-
esize that reduction of cycle interval could increase effec-
tiveness of pulsatile steroid therapy treatment. Also,
treatment with adrenocorticotropic hormone resulted in im-
mediate response in 5/11 patients with West syndrome, but
in one case the response took up to week 8 (Table 1).
Mackay et al. [27] described an average response to adreno-
corticotropic hormone after 2 weeks, which is comparable
to the present findings. After 8 weeks of treatment with ad-
renocorticotropic hormone, patients who had not responded
continued to exhibit no response (Table 1). It can therefore
be recommended that adrenocorticotropic hormone be
stopped after 8 weeks if there is no response.
Severe adverse effects such as hypertension and bacte-
rial infections are described under treatment with adreno-
corticotropic hormone [6,19,20]. Hypertension was the
main adverse effect of adrenocorticotropic hormone treat-
ment, affecting 10/14 group 1 patients (71%) (Table 2). In
contrast, with pulsatile corticoid therapy only 1/14 group 2
patients (7%) developed hypertension. Riikonen and Don-
ner [28] reported hypertension in 11/17 patients treated
with adrenocorticotropic hormone, similar to the present
findings.
In group 2, uncomplicated and recurrent viral infections
were the main adverse effects (5/14 patients; 36%). In a pro-
spective study, Riikonen and Donner [28] reported infec-
tions in 18-43% during adrenocorticotropic hormone
treatment, with dosage dependency. In the present study,
despite prophylactic antibiotic therapy, 3/14 group 1 pa-
tients (21%) developed severe bacterial infections. Oral
fungus was observed in 3/14 group 2 patients (21%). In
group 1, 3/14 patients (21%) developed Cushing syndrome,
whereas Verhelst et al. [29] reported Cushing syndrome in
19% of steroid-treated patients. For adrenocorticotropic
hormone, all adverse effects were reversible after treatment
was stopped, including the myocardial hypertrophy in 8/14
patients (57%), as reported previously [30]. No child in ei-
ther group died because of intractable infection from immu-
nosuppression related to steroid treatment. Nevertheless,
severe adverse effects of treatment with adrenocorticotropic
hormone are a burden to parents and children. In contrast,
pulsatile steroid therapy produces less severe adverse
effects and is thus more tolerable.
In conclusion, in West syndrome, pulsatile steroid ther-
apy with dexamethasone seems to be an effective alternative
treatment to adrenocorticotropic hormone. For Lennox-
Gastaut syndrome, treatment with steroids does not seems
to be very effective in general. For electrical status epilepti-
cus during slow-wave sleep, treatment with pulsatile corti-
coid therapy seems to be effective and worth a trial.
Results of this retrospective study are limited for several
reasons: the study groups are small, because indication for
adrenocorticotropic hormone or pulsatile steroid therapy is
limited to rare diagnoses. The frequency of diagnosis differs
between the two study groups, another limitation to data
comparison. The time lag between diagnosis and treatment
also differs between groups. Prospective trials with larger
patient groups would be needed to confirm these clinical
observations.
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