Brain & Development xxx (2017) xxx–xxx

www.elsevier.com/locate/braindev

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.

Doose syndrome is an epilepsy syndrome that was
first reported in 1970 as ‘‘centrencephalic myoclonic-
astatic petit mal” [1]. This syndrome was otherwise
known as myoclonic-astatic epilepsy, and was redefined
in 2010 by the International League Against Epilepsy as
‘‘epilepsy with myoclonic-atonic seizures” [2]. Doose
syndrome is relatively common, with an incidence of
⇑ Corresponding author. Fax: +81 53 475 7596.
E-mail addresses: okanishipediatrics@gmail.com, t.okanishi@sis.
seirei.or.jp (T. Okanishi).
Although these patients can develop multiple types of
generalized seizures, the diagnosis is based on the pres-
ence of myoclonic-atonic seizures. The seizures are gen-
erally refractory to antiepileptic medication. The
seizure-free ratio in each antiepileptic medication ranges
from 0% to 36%. Cognitive impairment affects 20–74%
of the patients with Doose syndrome [3]. An electroen-
cephalogram (EEG) demonstrates a 2–5 Hz syn-
chronous spike and wave, and polyspike and wave
complexes with abnormal parietal theta activities,
although most of the posterior background rhythms
and sleep architecture could be considered generally
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
the EEG is much more abnormal with little or no nor-
mal background activity [3]. Brain magnetic resonance
imaging (MRI) shows no abnormality.
Antiepileptic medications such as valproate, ethosux-
imide, and lamotrigine are beneficial for controlling the
seizures [4–6]. For the refractory patients, a ketogenic
diet has been reported to be efficacious [4,6,7]. Recently,
a few reports described vagus nerve stimulation (VNS)
therapy, which led to complete resolution of seizures
in two patients [8,9]. However, there has been no
detailed report of open cranial surgery for the
syndrome.
Corpus callosotomy (CC) is a valuable palliative sur-
gical option for cases of medically refractory epilepsy,
especially in cases that include drop attacks [10,11].
CC is typically used in patients with diffuse or multifocal
epileptic discharges resulting in generalized seizures [11].
There have been only a few reports of CC for children
with refractory myoclonic seizures.
Here, we present a case of a child with Doose syn-
drome, whose myoclonic seizures were refractory to
multiple antiepileptic medications. CC markedly
decreased seizure frequency.
2. Case report
A 10-year-old boy developed febrile generalized
tonic–clonic (GTC) seizures at the age of 3 years
8 months. One week after the febrile seizure, he devel-
oped daily myoclonic-atonic seizures. GTC seizures,
myoclonic seizures, and tonic seizures also appeared
after the onset. He was treated with valproate, lamotrig-
ine, and clobazam, which controlled the myoclonic-
atonic seizures. Other antiepileptic medications, includ-
ing zonisamide, topiramate, carbamazepine, nitraze-
pam, and levetiracetam, were administered for the
other types of seizures, and were partially effective in
reducing the frequencies.
The patient was referred to our hospital at the age of
8 years 3 months. Brain MRI showed no suspicious
epileptogenic lesions. The patient’s Tanaka-Binet intel-
lectual test score was 45. Scalp video EEG monitoring
for 24 h showed dominantly bilateral parietal 6–7 Hz
theta activity that was not attenuated by eye opening,
and diffuse 1.5–2 Hz high-amplitude spike and wave
burst interictally (Fig. 1). Bilateral myoclonic seizures
with frontal dominant high-amplitude spike or poly-
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
4 S. Kanai et al. / Brain & Development xxx (2017) xxx–xxx
Seizure and intellectual outcomes are variable in
Doose syndrome. Eighteen percent of patients have
refractory seizures and intellectual disabilities [4]. The
ketogenic diet is a widely reported therapy and may,
in fact, be the most efficacious [4,6,7]. Efficacy of surgi-
cal treatment for Doose syndrome is unclear for the
refractory cases. Caraballo et al. reported clinical
courses in 69 patients with Doose syndrome [7]. In the
study, five patients underwent VNS implantation, and
three showed seizure reduction greater than 50%. Two
other case reports described VNS therapy leading to
complete resolution of myoclonic, atonic, and absence
seizures [8,9]; one patient later presented serious brady-
cardia. To our knowledge, there has been only a single
case of CC for Doose syndrome, which was briefly
described in Caraballo’s retrospective study and did
not show the effectiveness.
CC is a palliative surgical option for cases of medi-
cally refractory epilepsy without resectable epileptic foci
[10]. This procedure has a role in alleviating various
types of seizures, with the best efficacy in drop attacks
and generalized seizures, including absence, atonic,
myoclonic, and GTC seizures. Kasasbeh et al. reported
that CC for children with refractory myoclonic seizures
resulted in complete resolution in more than half of the
cases [11]. We therefore expected that CC could be effec-
tive in the present case, because the main seizure type in
this patient was myoclonic seizures. From this case
study, we cannot evaluate the efficacy of CC for
myoclonic-atonic seizure, which is the most characteris-
tic type in Doose syndrome.
In conclusion, we report the a case of a child with
Doose syndrome with refractory myoclonic, tonic, and
GTC seizures, which were markedly reduced after CC.
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
References
[1] Doose H, Gerken H, Leonhardt R, Volzke E, Volz C. Centren-
cephalic myoclonic-astatic petit mal. Clinical and genetic inves-
tigations (in German). Neuropediatrics 1970;2:59–78.
[2] Berg AT, Berkovic SF, Brodie MJ, Buchhalter J, Cross JH, van
Emde Boas W, et al. Revised terminology and concepts for
organization of seizures and epilepsies: report of the ILAE
commission on classification and terminology, 2005–2009. Epilep-
sia 2010;51:676–85.
[3] Kelley SA, Kossoff EH. Doose syndrome (myoclonic-astatic
epilepsy): 40 years of progress. Dev Med Child Neurol
2010;52:988–93.
[4] Oguni H, Tanaka T, Hayashi K, Funatsuka M, Sakauchi M,
Shirakawa S, et al. Treatment and long-term prognosis of
myoclonic-astatic epilepsy of early childhood. Neuropediatrics
2002;33:122–32.
[5] Wallace SJ. Myoclonus and epilepsy in childhood: a review of
treatment with valproate, ethosuximide, lamotrigine and zon-
isamide. Epilepsy Res 1998;29:147–54.
[6] Kilaru S, Bergqvist AG. Current treatment of myoclonic astatic
epilepsy: clinical experience at the Children’s Hospital of
Philadelphia. Epilepsia 2007;48:1703–7.
[7] Caraballo RH, Chamorro N, Darra F, Fortini S, Arroyo H.
Epilepsy with myoclonic atonic seizures: an electroclinical study
of 69 patients. Pediatr Neurol 2013;48:355–62.
[8] Fan PC, Peng SS, Yen RF, Shieh JY, Kuo MF. Neuroimaging
and electroencephalographic changes after vagus nerve stimula-
tion in a boy with medically intractable myoclonic astatic
epilepsy. J Formos Med Assoc 2014;113:258–63.
[9] Cantarı́n-Extremera V, Ruı́z-Falcó-Rojas ML, Tamarı́z-Martel-
Moreno A, Garcı́a-Fernández M, Duat-Rodriguez A, Rivero-
Martı́n B. Late-onset periodic bradycardia during vagus nerve
stimulation in a pediatric patient. A new case and review of the
literature. Eur J Paediatr Neurol 2016;20:678–83.
[10] Maehara T, Shimizu H. Surgical outcome of corpus callosotomy
in patients with drop attacks. Epilepsia 2001;42:67–71.
[11] Kasasbeh AS, Smyth MD, Steger-May K, Jalilian L, Bertrand M,
Limbrick DD. Outcomes after anterior or complete corpus
callosotomy in children. Neurosurgery 2014;74:17–28.