J Neurosurg (4 Suppl Pediatrics) 104:265–268, 2006

Absence epilepsy associated with moyamoya disease
Case report
KEN-ICHIRO KIKUTA, M.D., PH.D., YASUSHI TAKAGI, M.D., PH.D.,
YOSHIKI ARAKAWA, M.D., PH.D., SUSUMU MIYAMOTO, M.D., PH.D.,
AND NOBUO HASHIMOTO, M.D., PH.D.
Department of Neurosurgery, Kyoto University Graduate School of Medicine, Kyoto, Japan

PThe authors present the case of a 6-year-old girl with typical absence epilepsy induced by hyperventilation associated with moyamoya disease (MMD). A diffuse 3-Hz spike-and-wave complex induced by hyperventilation was apparent on an electroencephalogram, and her seizures were intractable to medication. Significant ischemia in the bilateral
frontal lobes was present. The epilepsy disappeared after superficial temporal artery–middle cerebral artery anastomosis
with encephalomyosynangiosis on both sides. In the treatment of children with intractable absence epilepsy, the possibility of underlying MMD and indications that revascularization surgery may be needed should be taken into consideration.
KEY WORDS • absence epilepsy • hyperventilation • moyamoya disease •
electroencephalogram • revascularization • pediatric neurosurgery

M

OYAMOYA disease is considered a progressive ste-

noocclusive disease at the terminal portion of bilateral ICAs accompanied by the development of
moyamoya vessels.1,20 Although abnormal electroencephalographic findings such as the “re–build up” phenomenon
are often observed in pediatric patients, epileptic-type MMD
affects only a small percentage of children with MMD.6,8,13,19
Absence epilepsy is characterized behaviorally by a paroxysmal, abrupt-onset loss of consciousness and a termination
associated with a bilateral, synchronous, 3-Hz spike-andwave complex on an EEG, which can usually be induced
by hyperventilation.10 Although juvenile absence epilepsy is
generally considered benign because remission of seizures
can be achieved in most cases by monotherapy with antiepileptic drugs, some refractory cases do exist.10 We present
a case of MMD that was initially thought to be a refractory
case of typical juvenile absence epilepsy.
Case Report
History and Examination. This 6-year-old girl presented
in January 2002 having suffered recurrent syncopal episodes lasting several seconds, approximately five times a
day since 2001. The attacks were accompanied by ocular
Abbreviations used in this paper: EEG = electroencephalogram;
ICA = internal carotid artery; MMD = moyamoya disease; rCBF =
regional cerebral blood flow; rCVR = regional cerebrovascular reserve; SPECT = single-photon emission computerized tomography;
99m
Tc-ECD = technetium 99m–ethylcysteinate dimer.

J. Neurosurg: Pediatrics / Volume 104 / April, 2006

abduction and urinary incontinence, and often occurred
when she ate or went to bed. The attacks were not accompanied by automatism (such as orofacial twitches) or cognitive impairment. At 4 years of age she had experienced
episodes of bilateral motor weakness in her legs, induced by
hyperventilation. She was taken to a pediatrician who rendered a diagnosis of juvenile absence epilepsy on the basis
of an EEG obtained in August 2001 that revealed a typically diffuse 3-Hz spike-and-wave discharge induced by hyperventilation (Fig. 1A). In spite of daily oral administration
of high-dose sodium valproate (up to 1800 mg), the incidence of seizures increased inversely, reaching 10 times per
day; the child was taken to another hospital for further examination. A magnetic resonance imaging study performed
in November 2001 demonstrated a small brain infarction at
the left frontal lobe (Fig. 2A), and findings from a cerebral
angiography study in November 2001 revealed stenoocclusive changes at the terminal portions of the bilateral ICA
and the presence of moyamoya vessels at the base of the
brain (Fig. 2B–E). A diagnosis of MMD was made, and antiplatelet therapy with 81 mg of aspirin a day was started.
The girl presented to our hospital for surgical treatment in
January 2002. Results of a 99mTc-ECD SPECT study the
same month showed decreased rCBF in the bilateral frontal
lobes (Fig. 2F), and decreased rCVR in the same region was
revealed on an acetazolamide challenging study (Fig. 2G).
Operation and Postoperative Course. The patient underwent superficial temporal artery–middle cerebral artery
anastomosis with encephalomyosynangiosis on the right
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K. Kikuta, et al.

FIG. 1. A: A preoperative EEG obtained in August 2001 showing a diffuse 3-Hz spike-and-wave complex induced by
hyperventilation. An absence seizure was induced 64 seconds after hyperventilation began (arrow). B: A postoperative
EEG in the nonmedicated patient from March 2005 showing mild buildup without induction of a spike-and-wave complex under hyperventilation. The absence seizure was not induced by hyperventilation, and the arrow indicates 90 seconds after hyperventilation began.

side in January, and on the left side in March 2002. Medication with 81 mg of aspirin and 600 mg of sodium valproate a day continued postoperatively. The success of the
bypass surgeries and improvement in rCBF and rCVR were
confirmed on cerebral angiograms (Fig. 3A and B) and on
99m
Tc-ECD SPECT images (Fig. 3C and D) in July 2002.
The child discontinued the use of aspirin in September
2002 and sodium valproate in January 2005.
The patient has been free from either seizures or transient
ischemic attacks for more than 2 years since her surgery,
and experiences no restriction in activities of daily life. On
an EEG obtained in March 2005, a 3-Hz spike-and-wave
complex was not induced by hyperventilation, although the
patient was taking no medication (Fig. 1B).
Discussion
Although several abnormal findings on EEGs have been
reported in patients with epileptic-type MMD (such as resting regional slow waves, diffuse inactive patterns, paroxysmal slow bursts, or epileptic discharges), patients with
MMD and absence epilepsy exhibiting typical 3-Hz spikeand-wave complexes on EEGs have not been reported previously.6,8,12,13,17 The prevalence of MMD in Japan has been
reported as 3.16 per 100,000 persons,22 and the incidence of
MMD in combination with epilepsy has been reported to be
6 to 12.5% of the group suffering from the disease as a
whole.13,18 The prevalence of epilepsy in children and adolescents ranges from 5 to 15 per 100,000 persons, and 10 to
15% of these present with absence epilepsy.2 Thus, the
prevalence of epileptic MMD is 0.19 to 0.4 per 100,000 persons and that of absence epilepsy 0.5 to 2.3 per 100,000 persons. The prevalence of MMD in combination with absence
epilepsy as garnered from epidemiological data is roughly
0.0000009 to 0.0000089 per 100,000 persons, which is quite
low.
In MMD, the degree of brain ischemia is generally more
severe in pediatric patients than in adults because the demand for cerebral blood flow is rather high in children.11
266

FIG. 2. A: A magnetic resonance image obtained in November
2001 demonstrating an ischemic lesion at the left frontal lobe. B–E:
Angiograms (right anteroposterior view) obtained in November 2001
showing stenoocclusive changes at the terminal portions of the bilateral ICAs and the presence of moyamoya vessels at the base of the
brain (anteroposterior views of the right [B] and left [C] ICA and lateral views of the right [D] and left [E] ICA). F: A 99mTc-ECD
SPECT study from January 2002 demonstrating decreased rCBF in
the bilateral frontal lobes and reduced rCVR revealed by acetazolamide challenging in the same region (G).

J. Neurosurg: Pediatrics / Volume 104 / April, 2006

Absence epilepsy and moyamoya disease
cure for the seizures in our patient could be accomplished by
revascularization without valproate; however, the possibility exists that improvement of the seizures could have been
achieved with revascularization alone. Early revascularization surgery is recommended in patients with epileptic-type
MMD when seizures are intractable to medication.
Absence epilepsy can usually be cured by monotherapy
with antiepileptic drugs; however, in some refractory cases
patients exhibit atypical absence seizures or other generalized seizure forms.10 In our patient, neither automatism nor
focal seizures were present, both of which are often observed in patients with atypical absence seizures. Therefore,
an initial diagnosis of typical absence epilepsy was made by
a pediatrician, despite past episodes of transient ischemic
attacks. In the treatment of pediatric patients with intractable absence epilepsy, the possibility of underlying MMD
should be considered.
FIG. 3. Right (A) and left (B) external carotid artery angiograms
obtained in the patient in July 2002 demonstrating extensive blood
supply to the brain via a bypass. A postoperative 99mTc-ECD SPECT
study obtained on the same day shows the recovery of rCBF (C) and
rCVR (D) in the bilateral frontal lobes.

Conclusions
This is the first reported case of absence epilepsy associated with MMD. Ischemia in the frontal lobes enhanced by
hyperventilation was probably related to the occurrence of
epilepsy, and the seizures resolved with revascularization
surgery.

Abnormal findings on EEGs such as the re–build up phenomenon after hyperventilation are also usually observed in
pediatric patients only.6,8,19 The occurrence of the re–build
up phenomenon after hyperventilation is frequently seen in
the region where rCBF or rCVR was reduced, indicating a
close relationship between this phenomenon and brain ischemia.3,5,9,14,16,21 Based on these findings, brain ischemia is
thought to be significantly involved in abnormalities detected on EEGs obtained in patients with MMD.
The pathogenesis of absence epilepsy remains unclear.10,15
Some authors posit that decreased rCBF in the frontal lobes
enhanced by hyperventilation is implicated.4,7 In our case, a
preoperative SPECT study revealed decreased rCBF and
rCVR in the bilateral frontal lobes. After our patient’s revascularization surgeries, the ischemia in her bilateral frontal
lobes improved. Neither the absence epilepsy nor the 3-Hz
spike-and-wave complex on our patient’s EEGs appeared to
be induced by hyperventilation during the time she was not
receiving medication. It is highly probable that ischemia in
the frontal lobes enhanced by hyperventilation was related
to the occurrence of absence epilepsy in this case.
Revascularization surgery was beneficial for the control
of epilepsy in this case. Nakase, et al.,13 have reported that
the clinical features of epileptic-type MMD are similar to
those of ischemic-type MMD. In their research, a patient
age of less than 1 year and the presence of major ischemic
lesions indicated a poor prognosis; early revascularization
surgery was particularly recommended for patients with
these risk factors. Robertson and colleagues17 reported the
case of a 13-year-old girl with MMD who exhibited partial
seizures induced by the Valsalva maneuver. They speculated that cerebral hypoperfusion induced by the maneuver had
caused the seizures, which were resolved not by medication
but by bilateral extracranial–intracranial synangiosis. In a
surgical procedure for epilepsy such as an amygdalohippocampectomy, postoperative therapy with antiepileptic drugs
is recommended for approximately 2 years to achieve complete remission of seizures.23 Hence, we did not think that a

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J. Neurosurg: Pediatrics / Volume 104 / April, 2006

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Manuscript received May 13, 2005.
Accepted in final form January 6, 2006.
Address reprint requests to: Ken-ichiro Kikuta, M.D., Ph.D., Department of Neurosurgery, Kyoto University Graduate School of
Medicine, 54 Kawaharacho, Shogoin, Sakyo-ku, Kyoto 606-8507,
Japan. email: kikuta@kuhp.kyoto-u.ac.jp.

J. Neurosurg: Pediatrics / Volume 104 / April, 2006