SummaryWe describe our treatment of two boys with continuous spikes and waves during slow wave sleep (CSWS). One of the boys was suffering from non-convulsive status epilepticus and the other from conscious disturbance with automatism. Their ictal EEG readings showed continuous diffuse spike and wave complexes, which were considered to show electrical status. The boys were diagnosed as having CSWS, and were later diagnosed with Landau–Kleffner syndrome (LKS). EEG readings returned to normal on intravenous injection of flunitazepam (FZP) at a dose of 0.02mg/kg, suggesting that FZP is an effective treatment for CSWS

Fujino, Osamu

Fujita, Takehisa

Hashimoto, Kiyoshi

Hirata, Kiyotaka

Kawakami, Yasuhiko

Kuwabara, Kentaro

Matsumoto, Yoshiaki

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Treatment with flunitrazepam of continuous spikes and waves during slow wave sleep (CSWS) in children 

Seizure (2007) 16, 190—192
www.elsevier.com/locate/yseizCASE REPORTS
Treatment with flunitrazepam of continuous
spikes and waves during slow wave sleep
(CSWS) in children
Yasuhiko Kawakami a,*, Yoshiaki Matsumoto b, Kiyoshi Hashimoto a,
Kentaro Kuwabara a, Kiyotaka Hirata c, Takehisa Fujita a,
Osamu Fujino aaDepartment of Pediatrics, Nippon Medical School Tama Nagayama Hospital, 1-7-1 Nagayama Tama,
Tokyo 206-8512, Japan
bDepartment of Clinical Pharmacokinetics, College of Pharmacy, Nihon University, Funabashi,
Chiba 274-8555, Japan
cDepartment of Pharmacy, Nippon Medical School, Tokyo 113-8602, Japan
Received 8 October 2004; received in revised form 11 November 2005; accepted 31 October 2006KEYWORDS
Continuous spikes and
waves during slow wave
sleep (CSWS);
Flunitazepam (FZP);
Landau—Kleffner
syndrome (LKS)
Summary We describe our treatment of two boys with continuous spikes and waves
during slow wave sleep (CSWS). One of the boys was suffering from non-convulsive
status epilepticus and the other from conscious disturbance with automatism. Their
ictal EEG readings showed continuous diffuse spike and wave complexes, which were
considered to show electrical status. The boys were diagnosed as having CSWS, and
were later diagnosed with Landau—Kleffner syndrome (LKS). EEG readings returned to
normal on intravenous injection of flunitazepam (FZP) at a dose of 0.02 mg/kg,
suggesting that FZP is an effective treatment for CSWS.
# 2006 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.Introduction
Flunitrazepam (FZP) is commonly used clinically for
the induction of anesthesia.1 It has also been
reported that intravenous injection of FZP relieves
prolonged seizures.2 Epilepsy with continuous spikes
and waves during slow wave sleep (CSWS) is an
unclassified condition3 observed mainly in cases of* Corresponding author. Tel.: +81 42 371 2111;
fax: +81 42 372 7377.
E-mail address: kawakami@nms.ac.jp (Y. Kawakami).
1059-1311/$ — see front matter # 2006 British Epilepsy Association
doi:10.1016/j.seizure.2006.10.013refractory epilepsy. In this report, we describe our
treatment of two boys with CSWS. Informed consent
was obtained prior to treatment.Case reports
Patient 1: N.K., 9-year-old male (Fig. 1)
The patient’s developmental milestones were
normal until he experienced non-convulsive status
epilepticus at the age of 9 years and nine months.. Published by Elsevier Ltd. All rights reserved.
CSWS in children, treated with FZP 191
Figure 1 Nine-year-old male. (A) Waking EEG showed irregular spikes and waves. The bilateral arrow indicates the
period during which his eyes were open. Paroxysmal discharges were inhibited by eye opening. (B) EEG of non-REM sleep
revealed a CSWS pattern. (C) After intravenous FZP administration, epileptiform discharges disappeared. Calibration,
50 mV, 1 s.His speech deteriorated dramatically, and his IQ
score of WISC-R declined to 54. Waking EEG
records showed diffuse spike and wave complexes
which were attenuated by eye opening (Fig. 1A).
Continuous bursts of slow spike and wave com-
plexes occurred without any clinical symptoms
during non-REM sleep (Fig. 1B). He was diagnosed
as having CSWS. An intravenous injection of FZP at
a dose of 0.02 mg/kg brought his EEG readings
back to normal (Fig. 1C). Brain images (CT and
MRI) were also normal. He was treated thereafter
with oral FZP (0.002 mg/kg/day) for 2 weeks and a
longer course of valpronic acid, and followed a
satisfactory course including gradual recovery of
his mental development. He finally graduatedfrom elementary school and then junior high
school.
Patient 2: C.K., 7-year-old male (Fig. 2)
This patient had a history of simple febrile seizures (1
year). From the age of 7 years and nine months, he
suffered lost consciousness with automatism for sev-
eral minutes early each morning; he also had dysar-
thria, sometimes spoke meaninglessly, and suffered
from decreased perception. However, he was able to
go to school by himself and experienced no aphasia.
Sleep EEG readings recorded at our clinic revealed
diffuse spike and wave complexes which were con-
sidered to show electrical status (Fig. 2A). He was
192 Y. Kawakami et al.
Figure 2 Seven-year-old male. (A) EEG showed diffuse irregular spikes and waves. (B) Immediately after intravenous
FZP administration (arrow) epileptiform discharges disappeared. (C) Twenty minutes after FZP administration, inhibition
of paroxysmal discharges was still observed. Calibration, 50 mV, 1 s.diagnosed as having CSWS. An intravenous injection
of FZPat a dose of 0.02 mg/kg returned EEG readings
to normal (Fig. 2B), and they stayed in the normal
range for more than 20 min (Fig. 2C). The patient
woke up 30 min after the injection, and his responses
to subsequent questions were appropriate. His brain
images (CT, MRI and SPECT) were normal. He was
treated thereafter in the same way as Patient 1. He
regained smooth speech patterns and completed
elementary school satisfactorily.Discussion
Epilepsy with CSWS is defined by Tassinari et al.4 and
epileptic seizures with CSWS are thought to be
intractable even with polytherapy involving antie-
leptic drugs.5 Several reports had documented the
potent anticonvulsive effects of FZP in animals6 and
humans,2,7 so we decided to try it on two patients
with CSWS.Wewere able to demonstrate its efficacy
in inhibiting electrical status on EEG. Long-term use
of FZP is likely to result in side effects (intolerance,
drowsiness, etc), but it seems to be a good reliever
of ictal states with CSWS. It has been reported that
some patients with CSWS can be regarded as
Landau—Kleffner syndrome (LKS) sufferers.8,9
Indeed, it is suspected that CSWS syndrome and
LKS may well be two sides of the same coin.5
Because of their satisfactory long-term outcomes,
we diagnosed the two present cases as having LKS.5
Although no previous reports have indicated the use
of FZP for CSWS, we suggest from our experience
with the two cases described here that it may be a
beneficial treatment.Acknowledgments
We are grateful to Professors Yoshitaka Fukunaga
and Timothy D. Minton of Nippon Medical School for
reviewing the manuscript.References
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Treatment with flunitrazepam of continuous spikes and waves during slow wave sleep (CSWS) in children

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