Академический Документы
Профессиональный Документы
Культура Документы
The combination of axial spasms in clusters, hypsar- acterized by a triad of infantile spasm, hypsarrhythmia,
rhythmia, and psychomotor delay beginning in the first and (in the majority) psychomotor retardation [2-5]. West
year of life defines West syndrome. Adrenocorticotrophic syndrome is a type of epilepsy specific to infancy. It
hormone remains the choice of treatment for many affects half the infants with severe epilepsy, one in
neurologists. Recent controlled studies support vigaba- 2000-4000 live born, of whom 60% are boys. Onset peaks
trin as first-line therapy, and open-label studies suggest in the first year of life. The disease combines features of a
that topiramate, lamotrigine, and zonisamide may be triad, with sudden axial muscle contraction occurring in
useful in treating spasms. Studies regarding the efficacy clusters, psychomotor delay or deterioration, and major
and safety of such treatments often come from small, diffuse paroxysmal activity on the electroencephalogram.
uncontrolled trials and are often inconclusive. Levetirac- Most patients become free of spasms before 5 years of age,
etam is effective for treating localization-related epilepsy, although a majority of children are left with other seizure
but it is uncertain whether it is effective for treating West types and cognitive or motor delay (or both); behavior
syndrome. To evaluate the efficacy of levetiracetam troubles are also common [6-9].
monotherapy in newly diagnosed cryptogenic West syn- The etiologic classification of West syndrome may also
drome, levetiracetam was used initially in the treatment be confusing. The etiology of West syndrome has been
of five patients with cryptogenic West syndrome. On classified as symptomatic, cryptogenic, and idiopathic.
admission, levetiracetam (30 mg/kg) tablets were crushed The most readily defined group is symptomatic, which
and administered via nasogastric tube. Two patients were consists of infants who have clinical signs, neuroimaging,
seizure free, two patients experienced a 50% reduction in or other laboratory results that define a specific underlying
seizure frequency, and one patient had no improvement condition. Symptomatic cases account for more than 80%
in seizure frequency. There were no relapses in the two of the cases. New gene defects associated with the CDKL5
patients at 6 months after the cessation of seizures. It (cyclin-dependent kinase-like 5; previously STK9, serine/
appears that levetiracetam may be effective in the initial threonine kinase 9) and ARX (aristaless related homeobox-
treatment of selected patients with cryptogenic West gene mutation) genes are associated with West syndrome
syndrome. © 2007 by Elsevier Inc. All rights reserved. [10].
Because of the poor prognosis of West syndrome,
Gümüş H, Kumandaş S, Per H. Levetiracetam monotherapy treatment is usually initiated quickly and aggressively
in newly diagnosed cryptogenic West syndrome. Pediatr after diagnosis, often at the risk of serious side effects,
Neurol 2007;37:350-353. 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
Introduction current treatments being in the forms of adrenocorticotro-
phic hormone, oral corticosteroids (such as prednisolone
In 1841, West described infantile spasms as a unique or prednisone), valproic acid, and vigabatrin. Other treat-
seizure type with associated devastating developmental ments include pyridoxine or pyridoxal phosphate; nitraz-
consequences in his own son [1]. West syndrome is a epam (benzodiazepines); topiramate; and lamotrigine, fel-
devastating, age-dependent epileptic encephalopathy char- bamate, and zonisamide [11].
From Department of Pediatric Neurology, Erciyes University School Communications should be addressed to:
of Medicine, Kayseri, Turkey. 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.
350 PEDIATRIC NEUROLOGY Vol. 37 No. 5 © 2007 by Elsevier Inc. All rights reserved.
doi:10.1016/j.pediatrneurol.2007.06.019 ● 0887-8994/07/$—see front matter
Levetiracetam has recently been approved for adjunc- cephalographic findings include disorganized back-
tive therapy in the treatment of partial onset and general- ground, high amplitude slow and sharp waves, and
ized seizures. Lagae et al. [12] also reported that leveti- multifocal spikes over all areas of the brain in all
racetam was effective in refractory childhood epilepsy patients.
syndrome with a significant effect on myoclonic seizures. Two of the five patients (patients 1 and 2) became
However, the effectiveness of levetiracetam as a single seizure free, with disappearance of the hypsarrhythmic
agent in newly diagnosed cryptogenic West syndrome is electroencephalographic pattern. In both of the responders,
currently unknown. seizures disappeared within a few days (12-17 days)
of starting treatment. Repeated electroencephalography
Patients and Methods showed a well-organized background rhythm with no
evidence of seizure activity. Two of the five patients
Five infants with newly diagnosed West syndrome were admitted to (patient 3 and 5) had reduction in seizure frequency to
the Erciyes University hospital from January 2005 to September 2006. ⬎50% and patient 4 had no improvement in seizure
All patients had typical clinical spasms (flexions, extensions, or both) and
electroencephalographic changes of hypsarrhythmia or modified hypsar-
frequency. In non-responder and partial responder pa-
rhythmia. Informed consent was obtained from the parents. The study tients, hypsarrhythmia or modified hypsarrhythmia per-
had full approval from the local Research Ethics Committee. sisted in electroencephalography. The nonresponders (pa-
On admission, levetiracetam (30 mg/kg) tablets were crushed and tients 3 and 5) were treated with adrenocorticotrophic
administered via nasogastric tube. The following day, the patients hormone and have shown complete resolution of spasms
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.
and disappearance of the hypsarrhythmic electroencepha-
The dose was increased every 5 and 7 days until seizures ceased or the lographic pattern. Mean levetiracetam dose was 50 mg/kg/
maximal dose (60 mg/kg/day) was reached. If levetiracetam failed to day. The patients remained free of clinical seizures for 9
control seizures after a trial of at most 4 weeks, it was replaced by months.
adrenocorticotropin therapy.
Electroencephalography was performed before and at the end of the
trial. Seizure frequency was determined by parental or nursing observa- Discussion
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-
West syndrome is characterized by flexor and extensor
racetam treatment, patients were carefully monitored for the development spasms, hypsarrhythmia, and developmental regression.
of side effects. Blood and urine samples were obtained twice a week for Adrenocorticotrophic hormone is the most effective drug
routine laboratory examination. in controlling seizures but has frequent and severe, some-
In this study, children were classified as cryptogenic if they fulfilled times life threatening side effects. In addition, adrenocor-
the following criteria: (a) no known associated etiology, (b) normal
development and neurological examination before onset of spasms, (c)
ticotrophic hormone efficacy is often transient, and long-
no previous seizure, and (d) normal computed tomography and magnetic term benefits are controversial [13]. Among conventional
resonance image findings. antiepileptic drugs, valproate and benzodiazepines have
been found to be effective in controlled clinical trials of
Results spasms [14]. However, a potential for fatal hepatic failure
in children is a major concern associated with valproate
Clinical profiles of five infants (3 male, 2 female) are administration [15]. The benzodiazepines diminish seizure
given in Table 1. The age of onset ranged from 4 to 9 activity only temporarily and usually require additional
months (mean, 6.4 months). All of the patients were medications. There remains a need for more effective
classified as cryptogenic. The mean time interval be- alternative therapy with reduced adverse effects.
tween the occurrence of first spasms and the start of With major advances in understanding of the basic
levetiracetam therapy (i.e., treatment lag; Table 1) was neuropathology, neuropharmacology, and neurophysiol-
5.8 weeks (range, 3 weeks to 5 months). Electroen- ogy of epilepsy, several novel antiepileptic drugs have
Treatment
Age at Time of Seizure Dose, Duration, Treatment
Patient Onset, mo Control, day mg/kg mo Type of Spasm* Lag
1 4 12 45 6 Flexor 3 wk
2 6 17 50 5 Flexor 1 mo
3 5 18 60 9 Mixed 2 mo
4 8 — 50 10 Mixed 5 mo
5 9 21 45 7 Extensor 5 wk