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Brain & Development xxx (2017) xxx–xxx

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Case Report

Successful corpus callosotomy for Doose syndrome


Sotaro Kanai a, Tohru Okanishi a,⇑, Mitsuyo Nishimura b, Kentaro Iijima c,
Takuya Yokota a, Tomohiro Yamazoe c, Ayataka Fujimoto c, Hideo Enoki a,
Takamichi Yamamoto c
a
Department of Child Neurology, Seirei-Hamamatsu General Hospital, 2-12-12 Sumiyoshi, Hamamatsu, Shizuoka 430-8558, Japan
b
Laboratory of Neurophysiology, Seirei-Hamamatsu General Hospital, 2-12-12 Sumiyoshi, Hamamatsu, Shizuoka 430-8558, Japan
c
Comprehensive Epilepsy Center, Seirei-Hamamatsu General Hospital, 2-12-12 Sumiyoshi, Hamamatsu, Shizuoka 430-8558, Japan

Received 16 March 2017; received in revised form 6 June 2017; accepted 7 June 2017

Abstract

Doose syndrome (epilepsy with myoclonic-atonic seizures) is an epilepsy syndrome with an incidence of approximately 1–2% of
childhood-onset epilepsies. Although this syndrome is associated with multiple types of generalized seizures, the diagnosis is based
on the presence of myoclonic-atonic seizures. Eighteen percent of patients have refractory seizures and intellectual disabilities. There
have, however, been a few reports on the efficacy of surgical treatment for Doose syndrome.
We describe a case of Doose syndrome in a 10-year-old boy. He developed generalized tonic–clonic seizures at 3 years 8 months
of age and subsequently developed myoclonic-atonic, myoclonic, and tonic seizures. The frequent myoclonic seizures were refractory
to multiple antiepileptic medications. His cognitive development was moderately delayed. Anterior four fifths corpus callosotomy
was performed at 8 years 5 months of age. His seizures, especially myoclonic seizures, were markedly reduced. He was given vagus
nerve stimulation therapy at 9 years and 1 month of age, which led to complete resolution of the myoclonic seizures. Corpus cal-
losotomy can be a good treatment strategy in patients with Doose syndrome with medically refractory generalized seizures.
Ó 2017 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

Keywords: Doose syndrome; Epilepsy with myoclonic-atonic seizures; Myoclonic seizures; Corpus callosotomy; Vagus nerve stimulation

1. Introduction approximately 1–2% of childhood-onset epilepsies.


Although these patients can develop multiple types of
Doose syndrome is an epilepsy syndrome that was generalized seizures, the diagnosis is based on the pres-
first reported in 1970 as ‘‘centrencephalic myoclonic- ence of myoclonic-atonic seizures. The seizures are gen-
astatic petit mal” [1]. This syndrome was otherwise erally refractory to antiepileptic medication. The
known as myoclonic-astatic epilepsy, and was redefined seizure-free ratio in each antiepileptic medication ranges
in 2010 by the International League Against Epilepsy as from 0% to 36%. Cognitive impairment affects 20–74%
‘‘epilepsy with myoclonic-atonic seizures” [2]. Doose of the patients with Doose syndrome [3]. An electroen-
syndrome is relatively common, with an incidence of cephalogram (EEG) demonstrates a 2–5 Hz syn-
chronous spike and wave, and polyspike and wave
complexes with abnormal parietal theta activities,
⇑ Corresponding author. Fax: +81 53 475 7596. although most of the posterior background rhythms
E-mail addresses: okanishipediatrics@gmail.com, t.okanishi@sis. and sleep architecture could be considered generally
seirei.or.jp (T. Okanishi). normal for age. This can help to distinguish children

http://dx.doi.org/10.1016/j.braindev.2017.06.001
0387-7604/Ó 2017 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

Please cite this article in press as: Kanai S et al. Successful corpus callosotomy for Doose syndrome. Brain Dev (2017), http://dx.doi.org/
10.1016/j.braindev.2017.06.001
2 S. Kanai et al. / Brain & Development xxx (2017) xxx–xxx

with Doose syndrome from those with LGS, in whom 2. Case report
the EEG is much more abnormal with little or no nor-
mal background activity [3]. Brain magnetic resonance A 10-year-old boy developed febrile generalized
imaging (MRI) shows no abnormality. tonic–clonic (GTC) seizures at the age of 3 years
Antiepileptic medications such as valproate, ethosux- 8 months. One week after the febrile seizure, he devel-
imide, and lamotrigine are beneficial for controlling the oped daily myoclonic-atonic seizures. GTC seizures,
seizures [4–6]. For the refractory patients, a ketogenic myoclonic seizures, and tonic seizures also appeared
diet has been reported to be efficacious [4,6,7]. Recently, after the onset. He was treated with valproate, lamotrig-
a few reports described vagus nerve stimulation (VNS) ine, and clobazam, which controlled the myoclonic-
therapy, which led to complete resolution of seizures atonic seizures. Other antiepileptic medications, includ-
in two patients [8,9]. However, there has been no ing zonisamide, topiramate, carbamazepine, nitraze-
detailed report of open cranial surgery for the pam, and levetiracetam, were administered for the
syndrome. other types of seizures, and were partially effective in
Corpus callosotomy (CC) is a valuable palliative sur- reducing the frequencies.
gical option for cases of medically refractory epilepsy, The patient was referred to our hospital at the age of
especially in cases that include drop attacks [10,11]. 8 years 3 months. Brain MRI showed no suspicious
CC is typically used in patients with diffuse or multifocal epileptogenic lesions. The patient’s Tanaka-Binet intel-
epileptic discharges resulting in generalized seizures [11]. lectual test score was 45. Scalp video EEG monitoring
There have been only a few reports of CC for children for 24 h showed dominantly bilateral parietal 6–7 Hz
with refractory myoclonic seizures. theta activity that was not attenuated by eye opening,
Here, we present a case of a child with Doose syn- and diffuse 1.5–2 Hz high-amplitude spike and wave
drome, whose myoclonic seizures were refractory to burst interictally (Fig. 1). Bilateral myoclonic seizures
multiple antiepileptic medications. CC markedly with frontal dominant high-amplitude spike or poly-
decreased seizure frequency. spike and waves were captured approximately one

Fig. 1. The interictal EEG showed (a) bilateral parietal dominant theta activity that was not attenuated by eye opening, (b) diffuse 1.5–2 Hz high-
amplitude spike and wave burst.

Please cite this article in press as: Kanai S et al. Successful corpus callosotomy for Doose syndrome. Brain Dev (2017), http://dx.doi.org/
10.1016/j.braindev.2017.06.001
S. Kanai et al. / Brain & Development xxx (2017) xxx–xxx 3

Fig. 2. The ictal EEG of myoclonic seizure. Bilateral muscular contractions on electromyogram (arrow) occurred simultaneously for 0.2 s associated
with polyspikes.

hundred times during drowsiness to light sleep (Fig. 2).


Tonic and GTC seizures were also seen. From the clin-
ical course and the EEG findings, we diagnosed him as
having Doose syndrome.
The parents did not want diet therapy. The patient
subsequently had anterior four fifths CC at the age of
8 years 5 months (Fig. 3). His myoclonic seizures mark-
edly decreased to a few times a month. We added VNS
therapy for his residual seizures at the age of 9 years
1 month. Interictal EEG did not show any epileptiform
discharges at the age of 10 years 6 months. At the last
follow-up at the age of 10 years 10 months, only simple
partial seizures once a month remained with valproate,
lamotrigine, and levetiracetam. Although the Tanaka-
Binet intelligence score was 44 and had not improved,
the parents were satisfied that his concentration for
Fig. 3. The head computed tomography soon after anterior four fifth
study was improved compared to the status before CC.
corpus callosotomy (arrow).

3. Discussion seizures, which were refractory to multiple antiepileptic


medications. CC markedly reduced those seizures, and
Our patient showed frequent myoclonic seizures dur- additional VNS therapy led to complete resolution of
ing drowsiness to light sleep, as well as tonic and GTC his residual myoclonic seizures.

Please cite this article in press as: Kanai S et al. Successful corpus callosotomy for Doose syndrome. Brain Dev (2017), http://dx.doi.org/
10.1016/j.braindev.2017.06.001
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Seizure and intellectual outcomes are variable in References


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CC can be a valuable surgical option for children with
medically refractory generalized seizures in Doose
syndrome.

Please cite this article in press as: Kanai S et al. Successful corpus callosotomy for Doose syndrome. Brain Dev (2017), http://dx.doi.org/
10.1016/j.braindev.2017.06.001