Pediatric Neurology 50 (2014) 334e336

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

Original Article

Intravenous Methylprednisolone for Intractable Childhood

Epilepsy
Kholoud H. Almaabdi MBBS, Rawan O. Alshehri MBBS, Areej A. Althubiti MBBS,
Zainab H. Alsharef MBBS, Sara N. Mulla MBBS, Dareen S. Alshaer MBBS,
Nouf S. Alfaidi MBBS, Mohammed M. Jan MBChB FRCPC *
Department of Pediatrics, Faculty of Medicine, King Abdulaziz University, Jeddah, Saudi Arabia

abstract
BACKGROUND: Steroids have been used for the treatment of certain epilepsy types, such as infantile spasms;
however, the use in the treatment of other intractable epilepsies has received limited study. We report our
experience with intravenous methylprednisolone in children with epilepsy refractory to multiple antiepileptic
drugs. METHODS: A series of consecutive children were analyzed retrospectively. Patients with infantile spasms,
progressive degenerative, or metabolic disorders were excluded. RESULTS: Seventeen children aged 2-14 (mean 5.3)
years were included. Associated cognitive and motor decits were recognized in 82%. Most children (88%) had
daily seizures and 13 (76%) were admitted previously with status epilepticus. The epilepsy was cryptogenic (un-
known etiology) in 47% and the seizures were mixed in 41%. Intravenous methylprednisolone was given at
15 mg/kg per day followed by a weaning dose of oral prednisolone for 2-8 weeks (mean 3 weeks). Children were
followed for 6-24 months (mean 18). Six (35%) children became completely seizure free; however, three of them
later developed recurrent seizures. At 6 months posttreatment, improved seizure control was noted in 10 (59%)
children. Children with mixed seizures were more likely to have a favorable response than those with one seizure
type (49% vs 31%, P 0.02). No major side effects were noted, and 35% of the parents reported improvements in
their childs alertness and appetite. CONCLUSION: Add-on steroid treatment for children with intractable epilepsy is
safe and may be effective in some children when used in a short course.
Keywords: methylprednisolone, child, intractable, epilepsy, seizure
Pediatr Neurol 2014; 50: 334-336
2014 Elsevier Inc. All rights reserved.

Introduction seizures. They typically require detailed workup, prepara-

Therapeutic options for children with epilepsy refractory
to antiepileptic drug therapy are limited.1 These patients are
subject to more side effects and comorbid cognitive and
behavioral impairments.2-4 Intractability also increases the
risk of physical injury and sudden death.5-7 Therapeutic
options include the ketogenic diet, vagus nerve stimulation,
and surgery.8 These options may not apply to every patient,
particularly infants and younger children with mixed
Article History:
Received November 13, 2013; Accepted in nal form December 12, 2013
* Communications should be addressed to: Dr. Jan; Department of
Pediatrics; King AbdulAziz University Hospital; PO Box 80215; Jeddah
21589, Kingdom of Saudi Arabia.
E-mail address: mmjan@kau.edu.sa
tion, and expensive hospitalization. Steroids therefore may
be an option when other treatments fail or while preparing
patients for other more denitive treatments. Steroids,
particularly adrenocorticotropic hormone (ACTH), have
been frequently used in children with infantile spasms.9
Prednisolone was also reported to have similar efcacy.10-
12
However, their efcacy and tolerability have not been
not clearly established and their mechanism of action re-
mains unknown.13 There are concerns about the safety, cost,
and availability of ACTH when compared with predniso-
lone, particularly in infants and young children.14 A shorter
pulse of intravenous methylprednisolone can be a more
practical and cost-effective alternative.15 Apart from infan-
tile spasms, there are limited reports about the use of
steroids in children with intractable epilepsy. Steroids have

0887-8994/$ - see front matter 2014 Elsevier Inc. All rights reserved.
http://dx.doi.org/10.1016/j.pediatrneurol.2013.12.015
 K.H. Almaabdi et al. / Pediatric Neurology 50 (2014) 334e336 335

been used with variable success in children with epileptic
encephalopathies.16 In this article, we report our experience
with intravenous pulse methylprednisolone for the treat-
ment of children with severe drug-resistant epilepsy.
Methods
A series of consecutive children with refractory epilepsy, who were
treated with steroids between 2007 and 2011, was analyzed retrospec-
tively. Patients were identied through referrals and consultations to the
pediatric neurology service at King Abdulaziz University Hospital, Jed-
dah, Saudi Arabia. King Abdulaziz University Hospital is a multispecialty
adult and pediatric hospital providing tertiary medical care and is the
main teaching center of the western region of the country. The university
hospital review board approved the study protocol. Intractable epilepsy
was dened as recurrent seizures that failed to respond to at least three
antiepileptic drug trials singly or in combination despite of using
maximum doses or doses resulting in therapeutic drug levels.17 Patient-
and disease-related data were collected by chart review; follow-up
phone interviews with a parent were also conducted. All included
patients had difcult and drug-resistant epilepsy with limited other
therapeutic options. Patients with infantile spasms, autoimmune disor-
ders, or progressive degenerative or metabolic disorders were excluded.
Intravenous methylprednisolone was used as an add-on agent to the
other antiepileptic drug therapy during a brief hospitalization. A 3-day
pulse was used followed by a weaning dose of oral prednisolone based
on our acute multiple sclerosis exacerbation treatment protocol.18,19
Follow-up was performed by one pediatric neurologist to document
therapeutic response and occurrence of side effects. Therapeutic
response was recorded as complete (no seizures), good (>50% seizure
reduction), fair (<50% seizure reduction), or none (no response). The
seizure outcome was assessed based on seizure diaries prepared by the
parents during follow-up in our epilepsy clinics. Data were tabulated in
Excel sheets using SPSS 17 (SPSS, Inc., Chicago, IL). Descriptive analyses
were performed and the variables were examined using chi-square
statistics to identify the magnitude of any signicant associations.
children. Electroencephalography before the introduction
of steroids revealed focal or multifocal epileptiform dis-
charges in seven (41%) and generalized epileptiform dis-
charges in 10 (59%) patients. None of the included patients
met the criteria for continuous spike wave in slow-wave
sleep.
Intravenous pulse methylprednisolone was added during
a brief hospitalization to the other antiepileptic drugs,
which ranged from two to ve (mean three) at the time of
enrollment. Initial doses ranged between 13 and 16 (mean
15) mg/kg per day divided every 6 hours for 3 days. Oral
prednisolone was then started at 1-1.2 mg/kg per day once
in the morning for 1 week and then weaned slowly over 2 to
8 weeks (mean 3). The children were followed for 6 to
24 months (mean 18). After pulse therapy, six (35%) chil-
dren became completely seizure free; however, three of
them later recurred. The timing and frequency of clinical
follow-up varied among patients, but all had follow-up at
6 months, as shown in the Figure. Most of those with
favorable response (seven of 10) did so in the initial 2 weeks
of therapy. Patients with mixed seizures were more likely to
have a favorable response when compared with those with
one seizure type (49% vs 31%, P 0.02). No benecial
response was noted in seven (41%) children; however, none
had seizure worsening. Follow-up electroencephalography
recordings, performed 4-6 months after treatment, revealed
no epileptiform discharges in seven (41%) children, all of
whom had a favorable therapeutic response. No major side
effects were noted, specically hypertension or glucosuria.
Six (35%) of the parents reported improvements in their
childs level of alertness and appetite.

Discussion
Results
The study results suggest that pulse steroid therapy is a
Seventeen children with severe drug-resistant epilepsy
useful and well-tolerated option when other antiepileptic
were included. They were 2-14 (mean 5.3) years of age, with drugs fail. Many of our patients had signicant seizure
70% being males. Their epilepsy was diagnosed at the age of
reduction, which is impressive given that they had frequent
3 months to 5 years (mean 38 months). Associated cognitive
seizures of multiple types that failed to respond to many
and motor decits were recognized in 82% and was severe antiepileptic drug trials. This may explain why 41% of our
in eight (47%). All children had medically refractory epilepsy
(having failed multiple antiepileptic drug trials). The keto-
genic diet was not tried in these patients because it is not
available in our center. Most children (88%) had ongoing
daily seizures and 13 (76%) had been admitted previously
with status epilepticus. The epilepsy was of unknown eti-
ology in 47%. The underlying etiologies are summarized in
the Table. The seizures were mixed in seven (41%), primary
generalized tonic clonic in four (23%), partial  secondary
generalizations in three (18%), and myoclonic in three (18%)
patients. Lennox Gastaut syndrome was noted in four (23%)
and Doose syndrome was noted in two (12%) of these

TABLE.
Causes of the intractable epilepsy in the study cohort (n 17)

Diagnosis Number (%)

1: unknown 8 (47)
FIGURE.
2: hypoxic ischemic insult 4 (23)
Seizure outcome at 6 months after the intravenous pulse of methylpred-
3: genetic/syndromic 2 (12)
nisolone shown in percentages of children achieving complete seizure
4: isolated brain malformation 2 (12)
control, >50% seizure reduction, <50% seizure reduction, or no change.
6: postmeningitis 1 (6)
(The color version of this gure is available in the online edition)
336 K.H. Almaabdi et al. / Pediatric Neurology 50 (2014) 334e336
patients had no benet. Other authors have used higher
doses of intravenous methylprednisolone of up to 30 mg/kg
per day for longer duration of time (up to 5 days) with similar
results.20 Clinical improvement was accompanied by the
disappearance of epileptiform discharges on follow-up
electroencephalography. Interestingly, we found that pa-
tients with mixed seizures were more likely to have a favor-
able response than those with one seizure type. Some authors
found that children with high-amplitude spike-slow wave
discharges appear to be the best candidates for intravenous
methylprednisolone pulse therapy.20 Others reported dra-
matic clinical and electroencephalography improvement of
refractory epilepsy secondary to continuous spike and waves
during slow-wave sleep.21,22 In addition to cryptogenic
epileptic encephalopathies, intravenous methylprednisolone
and oral prednisolone have been reported to be effective for
refractory partial epilepsy.23
No major side effects were noted, specically including
hypertension and glucosuria. Even in studies that used
higher doses, side effects were transient.20,23 In fact, 35% of
our parents reported improvements in their childs level of
alertness. This may be related to seizure reduction rather
than a direct drug effect. Of caution is the relapse rate after
initial favorable response which has been reported with
prednisolone.12 We have encountered this in three of the six
patients with complete seizure control who later relapsed.
We therefore presented our 6-month response rate. Limi-
tations of our study include the small sample size, which
failed to identify statistically signicant differences between
different seizure subtypes or specic epilepsy syndromes.
However, we followed our patients for prolonged period
(mean 18 months) to document therapeutic response.
Overall, 59% had sustained improvement at 6 months
follow up. Control beyond 6 months was not presented
because it is not likely to be related to steroid therapy.
We conclude that intravenous pulse methylprednisolone
may be a useful addition in the treatment of some children
with refractory epilepsy. The absence of pharmacokinetic in-
teractions facilitates its use in individuals who are already
taking multiple antiepileptic drugs. This treatment represents
a safe and potentially effective option for treating children with
high seizure frequency unresponsive to standard antiepileptic
drugs. Larger randomized controlled studies are needed in
children to establish the long-term efcacy and safety.
References
1. Kwan P, Brodie MJ. Early identication of refractory epilepsy. N Engl
J Med. 2000;342:314-319.
2. Austin JK, Smith S, Risinger MW, McNehs AM. Childhood epilepsy
and asthma comparison of quality of life. Epilepsia. 1994;35:
608-615.
3. Farwell JR, Dodrill CB, Batzel LW. Neuropsychological abilities of
children with epilepsy. Epilepsia. 1985;26:395-400.
4. Kotagal P, Rothner AD, Erenberg G, Cruse RP, Wyllie E. Complex
partial seizures of childhood onset. Arch Neurol. 1987;44:
1177-1180.
5. Baker GA, Jacoby A, Buck D, Stalgis C, Monnet D. Quality of life of
people with epilepsy: a European study. Epilepsia. 1997;38:353-362.
6. Buck D, Baker GA, Jacoby A. Patients experiences of injury as a
result of epilepsy. Epilepsia. 1997;38:439-444.
7. Harvey AS, Nolan T, Carlin JB. Community-based study of mortality
in children with epilepsy. Epilepsia. 1993;34:597-603.
8. Prassad AN, Stafstrom CF, Holmes GL. Alternative epilepsy thera-
pies: the ketogenic diet, immunoglobulins, and steroids. Epilepsia.
1996;37:S81-S95.
9. Sorel L, Dusaucy-Bauloye A. A propos de 21 cas dhypsarrhythmia de
Gibbs: son traitement spectaculaire par lACTH. Acta Neurol Belg.
1958;58:130-141.
10. Lombroso CT. A prospective study of infantile spasms: clinical and
therapeutic correlations. Epilepsia. 1983;24:135-158.
11. Hrachovy RA, Frost JD, Kellaway PR, Zion TE. Double-blind study of
ACTH versus prednisone therapy in infantile spasms. J Pediatr. 1983;
103:641-645.
12. You SJ, Jung DE, Kim HD, Lee HS, Kang HC. Efcacy and prognosis of
a short course of prednisolone therapy for pediatric epilepsy. Eur J
Paediatr Neurol. 2008;12:314-320.
13. Gupta R, Appleton R. Corticosteroids in the management of the
paediatric epilepsies. Arch Dis Child. 2005;90:379-384.
14. Mackay M, Weiss S, Snead OC. Treatment of infantile spasms: an
evidence-based approach. Int Rev Neurobiol. 2002;49:157-184.
15. Mytinger JR, Quigg M, Taft WC, Buck ML, Rust RS. Outcomes in
treatment of infantile spasms with pulse methylprednisolone.
J Child Neurol. 2010;25:948-953.
16. Watemberg N. The use of steroids in epilepsy: time for a reap-
praisal? Isr Med Assoc J. 2010;12:176-177.
17. Jan MM, Zuberi SA, Alsaihati BA. Pregabalin: preliminary experi-
ence in intractable childhood epilepsy. Pediatr Neurol. 2009;40:
347-350.
18. Jan MM. Childhood multiple sclerosis. J Pediatr Neurol. 2005;3:
131-136.
19. Beck RW, Cleary PA, Trobe JD, et al. The effect of corticosteroids for
acute optic neuritis on the subsequent development of multiple
sclerosis. The Optic Neuritis Study Group. N Engl J Med. 1993;329:
1764-1769.
20. Heyman E, Lahat E, Gandelman-Marton R. Interictal encephalog-
raphy can inuence patient selection for methylprednisolone
therapy in pediatric refractory epilepsy. J Child Neurol. 2012;27:
162-167.
21. Okuyaz C, Aydin K, Gucuyener K, Serdaroglu A. Treatment of elec-
trical status epilepticus during slow-wave sleep with high-dose
corticosteroid. Pediatr Neurol. 2005;32:64-67.
22. Buzatu M, Bulteau C, Altuzarra C, Dulac O, Van Bogaert P. Cor-
ticosteroids as treatment of epileptic syndromes with contin-
uous spike-waves during slow-wave sleep. Epilepsia. 2009;50:
68-72.
23. Sofue A, Naiki M, Yokotsuka T, et al. Effect of corticosteroids in a
twin child with idiopathic localization-related epilepsy. Brain Dev.
2008;30:211-214.