Levetiracetam Monotherapy in Newly
Diagnosed Cryptogenic West Syndrome
Hakan Gümüş, MD, Sefer Kumandaş, MD, and Hüseyin Per, MD
The combination of axial spasms in clusters, hypsar-
rhythmia, and psychomotor delay beginning in the first
year of life defines West syndrome. Adrenocorticotrophic
hormone remains the choice of treatment for many
neurologists. Recent controlled studies support vigaba-
trin as first-line therapy, and open-label studies suggest
that topiramate, lamotrigine, and zonisamide may be
useful in treating spasms. Studies regarding the efficacy
and safety of such treatments often come from small,
uncontrolled trials and are often inconclusive. Levetirac-
etam is effective for treating localization-related epilepsy,
but it is uncertain whether it is effective for treating West
syndrome. To evaluate the efficacy of levetiracetam
monotherapy in newly diagnosed cryptogenic West syn-
drome, levetiracetam was used initially in the treatment
of five patients with cryptogenic West syndrome. On
admission, levetiracetam (30 mg/kg) tablets were crushed
and administered via nasogastric tube. Two patients were
seizure free, two patients experienced a 50% reduction in
seizure frequency, and one patient had no improvement
in seizure frequency. There were no relapses in the two
patients at 6 months after the cessation of seizures. It
appears that levetiracetam may be effective in the initial
treatment of selected patients with cryptogenic West
syndrome. © 2007 by Elsevier Inc. All rights reserved.
Gümüş H, Kumandaş S, Per H. Levetiracetam monotherapy
in newly diagnosed cryptogenic West syndrome. Pediatr
Neurol 2007;37:350-353.
Introduction
In 1841, West described infantile spasms as a unique
seizure type with associated devastating developmental
consequences in his own son [1]. West syndrome is a
devastating, age-dependent epileptic encephalopathy char-
From Department of Pediatric Neurology, Erciyes University School
of Medicine, Kayseri, Turkey.
350 PEDIATRIC NEUROLOGY Vol. 37 No. 5
doi:10.1016/j.pediatrneurol.2007.06.019 ● 0887-8994/07/$—see front matter
acterized by a triad of infantile spasm, hypsarrhythmia,
and (in the majority) psychomotor retardation [2-5]. West
syndrome is a type of epilepsy specific to infancy. It
affects half the infants with severe epilepsy, one in
2000-4000 live born, of whom 60% are boys. Onset peaks
in the first year of life. The disease combines features of a
triad, with sudden axial muscle contraction occurring in
clusters, psychomotor delay or deterioration, and major
diffuse paroxysmal activity on the electroencephalogram.
Most patients become free of spasms before 5 years of age,
although a majority of children are left with other seizure
types and cognitive or motor delay (or both); behavior
troubles are also common [6-9].
The etiologic classification of West syndrome may also
be confusing. The etiology of West syndrome has been
classified as symptomatic, cryptogenic, and idiopathic.
The most readily defined group is symptomatic, which
consists of infants who have clinical signs, neuroimaging,
or other laboratory results that define a specific underlying
condition. Symptomatic cases account for more than 80%
of the cases. New gene defects associated with the CDKL5
(cyclin-dependent kinase-like 5; previously STK9, serine/
threonine kinase 9) and ARX (aristaless related homeobox-
gene mutation) genes are associated with West syndrome
[10].
Because of the poor prognosis of West syndrome,
treatment is usually initiated quickly and aggressively
after diagnosis, often at the risk of serious side effects,
with the hope of changing the natural history of the
disease. There is an ongoing debate about which treat-
ments are best for West syndrome, with the most popular
current treatments being in the forms of adrenocorticotro-
phic hormone, oral corticosteroids (such as prednisolone
or prednisone), valproic acid, and vigabatrin. Other treat-
ments include pyridoxine or pyridoxal phosphate; nitraz-
epam (benzodiazepines); topiramate; and lamotrigine, fel-
bamate, and zonisamide [11].
Communications should be addressed to:
Dr. Gümüş; Department of Pediatric Neurology; Erciyes University
School of Medicine; Kayseri 38039, Turkey.
E-mail: hakgumus@erciyes.edu.tr
Received January 11, 2007; accepted June 20, 2007.
© 2007 by Elsevier Inc. All rights reserved.
 Levetiracetam has recently been approved for adjunc-
tive therapy in the treatment of partial onset and general-
ized seizures. Lagae et al. [12] also reported that leveti-
racetam was effective in refractory childhood epilepsy
syndrome with a significant effect on myoclonic seizures.
However, the effectiveness of levetiracetam as a single
agent in newly diagnosed cryptogenic West syndrome is
currently unknown.
Patients and Methods
Five infants with newly diagnosed West syndrome were admitted to
the Erciyes University hospital from January 2005 to September 2006.
All patients had typical clinical spasms (flexions, extensions, or both) and
electroencephalographic changes of hypsarrhythmia or modified hypsar-
rhythmia. Informed consent was obtained from the parents. The study
had full approval from the local Research Ethics Committee.
On admission, levetiracetam (30 mg/kg) tablets were crushed and
administered via nasogastric tube. The following day, the patients
continued on levetiracetam at a dose of 25 mg/kg twice a day, and the
dose was adjusted every 5 to 7 days depending on the clinical response.
The dose was increased every 5 and 7 days until seizures ceased or the
maximal dose (60 mg/kg/day) was reached. If levetiracetam failed to
control seizures after a trial of at most 4 weeks, it was replaced by
adrenocorticotropin therapy.
Electroencephalography was performed before and at the end of the
trial. Seizure frequency was determined by parental or nursing observa-
tion (or both). A response to therapy was defined as cessation of spasms
and disappearance of the hypsarrhythmic electroencephalographic pat-
tern and reduction in seizure frequency to 50% or less. During leveti-
racetam treatment, patients were carefully monitored for the development
of side effects. Blood and urine samples were obtained twice a week for
routine laboratory examination.
In this study, children were classified as cryptogenic if they fulfilled
the following criteria: (a) no known associated etiology, (b) normal
development and neurological examination before onset of spasms, (c)
no previous seizure, and (d) normal computed tomography and magnetic
resonance image findings.
Results
Clinical profiles of five infants (3 male, 2 female) are
given in Table 1. The age of onset ranged from 4 to 9
months (mean, 6.4 months). All of the patients were
classified as cryptogenic. The mean time interval be-
tween the occurrence of first spasms and the start of
levetiracetam therapy (i.e., treatment lag; Table 1) was
5.8 weeks (range, 3 weeks to 5 months). Electroen-
Table 1. Clinical and demographic characteristics
Age at Time of Seizure Dose,
Patient Onset, mo Control, day mg/kg
1 4 12 45
2 6 17 50
3 5 18 60
4 8 — 50
5 9 21 45
In all cases, etiology was cryptogenic.
* Spasm was bilateral in all cases.
cephalographic findings include disorganized back-
ground, high amplitude slow and sharp waves, and
multifocal spikes over all areas of the brain in all
patients.
Two of the five patients (patients 1 and 2) became
seizure free, with disappearance of the hypsarrhythmic
electroencephalographic pattern. In both of the responders,
seizures disappeared within a few days (12-17 days)
of starting treatment. Repeated electroencephalography
showed a well-organized background rhythm with no
evidence of seizure activity. Two of the five patients
(patient 3 and 5) had reduction in seizure frequency to
⬎50% and patient 4 had no improvement in seizure
frequency. In non-responder and partial responder pa-
tients, hypsarrhythmia or modified hypsarrhythmia per-
sisted in electroencephalography. The nonresponders (pa-
tients 3 and 5) were treated with adrenocorticotrophic
hormone and have shown complete resolution of spasms
and disappearance of the hypsarrhythmic electroencepha-
lographic pattern. Mean levetiracetam dose was 50 mg/kg/
day. The patients remained free of clinical seizures for 9
months.
Discussion
West syndrome is characterized by flexor and extensor
spasms, hypsarrhythmia, and developmental regression.
Adrenocorticotrophic hormone is the most effective drug
in controlling seizures but has frequent and severe, some-
times life threatening side effects. In addition, adrenocor-
ticotrophic hormone efficacy is often transient, and long-
term benefits are controversial [13]. Among conventional
antiepileptic drugs, valproate and benzodiazepines have
been found to be effective in controlled clinical trials of
spasms [14]. However, a potential for fatal hepatic failure
in children is a major concern associated with valproate
administration [15]. The benzodiazepines diminish seizure
activity only temporarily and usually require additional
medications. There remains a need for more effective
alternative therapy with reduced adverse effects.
With major advances in understanding of the basic
neuropathology, neuropharmacology, and neurophysiol-
ogy of epilepsy, several novel antiepileptic drugs have
Treatment
Duration, Treatment
mo Type of Spasm* Lag
6 Flexor 3 wk
5 Flexor 1 mo
9 Mixed 2 mo
10 Mixed 5 mo
7 Extensor 5 wk
Gümüş et al: Effect of Levetiracetam in West Syndrome 351
been developed and marketed in recent years [16]. Some
therapeutic trials with these new antiepileptic drugs have
been attempted. Vigabatrin has been used as both add-on
and monotherapy in the treatment of West syndrome. The
results showed that vigabatrin was effective in controlling
spasms, especially in patients with tuberous sclerosis [17].
Lamotrigine has also been reported to be beneficial in
West syndrome [18]. Hurst and Rolan [19], using felbam-
ate, reported successful treatment of three children with
West syndrome. Pyridoxine or pyridoxal phosphate, ni-
trazepam, topiramate, and zonisamide may be used for the
treatment of West syndrome [11].
Levetiracetam has a broad spectrum of activity and is
useful for most seizure types. It is especially effective in the
treatment of juvenile myoclonic epilepsy. Levetiracetam is
available as a tablet or in suspension. The suspension form is
not available in Turkey. The half-life is short, but the duration
of efficacy is longer. Twice-daily dosing is required. The
initial dose in children is 10 to 20 mg/kg, and the target dose
is 40 to 60 mg/kg. Levetiracetam does not metabolize in the
liver. Metabolism occurs in the blood, and excretion is in
the urine. It does not interfere with the metabolism of other
drugs and has no life-threatening side effects. The most
commonly reported side effects associated with the use of
levetiracetam are central nervous system effects, including
somnolence and fatigue [20].
Although double-blind placebo-controlled clinical trials
and uncontrolled studies have demonstrated the efficacy of
levetiracetam in adults, only a few studies have examined the
usefulness of this drug in treating childhood epilepsy [21].
Kossoff et al. [22] reported that the use of high-dose
levetiracetam was beneficial in Landau-Kleffner syn-
drome. Hirsch et al. [23] reported the positive effects of
levetiracetam when used in monotherapy in six patients
with idiopathic generalized epilepsy. De Los Reyes et al.
[24] also reported the beneficial effects of levetiracetam in
Lennox-Gastaut syndrome. Lawlor et al. [25] used leveti-
racetam in an 11-month-old infant and reported it to be
beneficial in symptomatic West syndrome.
Rossetti and Bromfield [26] reported 23 patients with
status epilepticus treated with levetiracetam. In this study, the
median daily dose of levetiracetam was 2000 mg. Ten
patients (43%) were seizure free. Frost et al. [27] treated 22
patients, all younger than 2 years old when treatment started
(range, 2 days to 21 months). The maximum dose used varied
from 15 to 144 mg/kg. The study included different types of
epilepsy, including West syndrome. Of the 20 patients
observed in their follow-up, 11 had more than 50% reduction
in the number of seizures (including 6 with more than 90%
reduction) and 4 were free of seizures. Only one patient
stopped treatment because of side effects. These findings
support the good tolerability of rapid titration and of high
doses of levetiracetam in childhood.
Nonetheless, published data concerning the use of
levetiracetam monotherapy in infants with cryptogenic
West syndrome are very limited. Opp et al. [28] reported
13 patients (6.2%) who were seizure free and 39 (18.7%)
352 PEDIATRIC NEUROLOGY Vol. 37 No. 5
who responded with a seizure reduction of more than 50%
following the introduction of levetiracetam.
With treatment of 15 children with serious, resistant
generalized epilepsies such as West syndrome and
Lennox-Gastaut syndrome, severe myoclonic epilepsy,
and others, Buyse et al. [29] reported a 45% overall
decrease in the number of seizures using levetiracetam.
They also reported the best results with generalized
tonic-clonic and myoclonic seizures.
In the present study, levetiracetam was administered to
five patients newly diagnosed with West syndrome. Overall,
two of the five infants became seizure free and two patients
experienced reduction of seizure frequency by more than
50%. One patient did not respond to levetiracetam therapy.
The present findings suggest that levetiracetam mono-
therapy can be effective in treating newly diagnosed
cryptogenic West syndrome. To our knowledge, this is the
first reported study using levetiracetam monotherapy for
newly diagnosed cryptogenic West syndrome. Further
trials are required to confirm our results, define longer-
term outcome, and identify characteristics of responders.
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