HK J Paediatr (new series) 2013;18:178-181

Presurgical Evaluation of Epileptogenic Focus in
Temporal Lobe Epilepsy by 11C-Flumazenil PET and123
I-Iomazenil SPECT: A Case Report
G IMATAKA, M OGINO, S SAKAMOTO, O ARISAKA

Abstract

Meticulous neuroradiological evaluations, including 123I-iomazenil (IMZ) single photon emission computed
tomography (SPECT) and 11C-flumazenil (FMZ) positron emission tomography (PET), preoperatively
disclosed epileptogenic foci in a 16-year-old boy with temporal lobe epilepsy. Interictal scalp
electroencephalography showed spikes in the left temporal region. Left hippocampal sclerosis was seen
on magnetic resonance imaging. Hypoperfusion in the entire left temporal lobe was seen on 99mTc ethylcysteinate dimer (ECD) SPECT. Hypometabolism over most of the left temporal lobe was apparent on
18
F-fluorodeoxyglucose (FDG) PET. An area of hypoperfusion dominating the left temporal lobe wasidentified on 123I-IMZ SPECT. A low-uptake area in the left temporal lobe was seen on 11C-FMZ PET.
Anteromedial temporal lobectomy and multiple subpial transection with intraoperative electrocorticography
resulted in satisfactory seizure outcomes. Use of 123I-IMZ SPECT and 11C-FMZ PET appeared todemonstrate the epilepsy focus more localised than 99mTc ECD SPECT and 18F-FDG PET.

Key words

Hippocampal sclerosis; Positron emission tomography (PET); Single photon emission computed
tomography (SPECT)

Introduction
For surgery in patients with refractory intractableepilepsy, presurgical diagnosis of the epileptogenic
focus has the greatest impact on the surgical outcome.

Department of Pediatrics, Dokkyo Medical University Schoolof Medicine, Shimotsuga, Tochigi, JapanG IMATAKAO ARISAKA

MD
MD

Department of Neurosurgery, Dokkyo Medical University
School of Medicine, Tochigi, Japan
M OGINOMDPET Center, Dokkyo Medical University Hospital, Tochigi,Japan
S SAKAMOTOMD

Correspondence to: Dr G IMATAKA
Received November 29, 2012

Both magnetic resonance imaging and ictal video
encephalographic monitoring are thought to beessential before surgery, 1 although the latter requires
the patient to be available until a seizure occurs. 2
Diagnosis of the epileptogenic focus using
intracranial electroencephalography (EEG) is thought
to be highly accurate, but is quite invasive andrequires patient's uncomfortable obligation. 1,3 Many
reports have shown that various neuroradiologicaldiagnostic modalities using radioisotopes (RIs) cancorrectly detect epileptogenic foci, offering a lessinvasive alternative to patients. Recently, 123I-iomazenil(IMZ) single photon emission computed tomography(SPECT) has seen practical application 4 and the
diagnostic value of 11 C-flumazenil (FMZ) positronemission tomography (PET) has also been studied, 5although few reports concerning th ese imaging
m o d a l i t i e s ha v e b e e n p u b l i s h e d i n J ap an . We
performed 123I-IMZ SPECT and 11C-FMZ PET as well as
99m
Tc ethyl-cysteinate dimer (ECD) SPECT and18
F-fluorodeoxyglucose (FDG) PET for presurgicaldiagnosis in a case of temporal lobe epilepsy. We

Imataka et al

successfully detected the epileptic focus interictally before
surgery and present the case herein, along with the clinicalcourse.

Case Report
The case pertains to a 16-year-old boy without any
history of febrile seizures or family history of epilepsy. At
3 years old, he suffered complex partial seizures that
rendered him immobile and impaired awareness. At 4 years
old, these seizures often turned into secondary generalised
seizures, which were temporarily controlled bycarbamazepine. After reaching 5 years of age, the patient
suffered oral automatism followed by extended periods ina twilight state. Magnetic resonance imaging (MRI) at thattime did not reveal any abnormalities. Clonazepam andzonisamide were added, but seizures remaineduncontrolled. From 12 years old, the patient often engagedin quarrels resulting from his memory disorder.
Gabapentine and topiramate were concomitantly
administered, but proved completely ineffective. A senseof fear and depersonalisation, in addition to abdominal
discomfort, appeared from 14 years of age. EEG showedinterictal spikes in the left temporal region (Figure 1). We
had two complex partial seizures (CPSs) with postictal nose
wiping during overnight video tape recorder (VTR)-EEG
recordings, both of which originated from his left
sphenoidal and anterior temporal leads. VTR showed that
he touched his nose by his left hand after seizures. MRI
demonstrated left hippocampal sclerosis (Figure 2a). Lefttemporal lobe epilepsy associated with hippocampal
sclerosis was diagnosed. No functional MRI studies wereperformed.
WISC-III examinations performed two years before
surgery showed the score below the general average, VIQ
71, PIQ 60 and TIQ 62, respectively. Among them he wasespecially poor at vocabulary and verbal expression. He
successfully graduated from his junior high school.
Hypoperfusion throughout the entire left temporal lobe
was seen on 99mTc ECD SPECT (Figure 2b), although123I-IMZ SPECT disclosed hypoperfusion restricted to themedial portion of the left temporal lobe (Figure 2c).
Hypometabolism was observed in a broad area across theentire left temporal lobe on 18F-FDG PET (Figure 2d). The
hypometabolic area was seen to predominantly involvethe inner side of the left temporal lobe on 11C-FMZ PET(Figure 2e). According to a presurgical RI study, 123I-IMZS P E CT an d 11 C - F M Z P ET s h o w e d m o r e fo c a l179

accumulations than 99mTc ECD SPECT and 18F-FDG PET.
Based on these findings, the seizure focus wasdetermined to be located in the vicinity of the head of thehippocampus on the inner side of the left temporal region.
Electrocorticography (ECoG)-guided epilepsy surgery was
performed without invasive monitoring using intracranialelectrodes. Intraoperative ECoG showed spikes not onlyon the inner side of the temporal lobe, but also in thetemporal pole, posterior cortex, amygdaloid body, and headof the hippocampus. In addition to medial temporal
lobectomy, multiple subpial transection (MST) wasperformed on the lateral surface of the temporal lobe.
Although he has occasional simple partial seizures and rare
CPS after surgery, his family is quite satisfied with thisoutcome. His status is categorised as Engel class IIB/ILAE
class 3.

Discussion
Clarifying the focus of localisation-related seizures prior
to epilepsy surgery is essential. However, reaching a proper
diagnosis of the focus based solely on the state of theseizures is often difficult.6 For accurate diagnosis, EEG isinevitable, but interictal single EEG offers a detection rateof only 55.5% even with activators such as hyperpnoea,
photic stimulation, and sleep.7 Digital EEG with video
monitoring is thus often recorded for a long period using

Figure 1 Interictal electroencephalography at 14 years old.
Spikes are apparent in the left temporal region.

Presurgical Evaluation of Epileptogenic Focus in TLE

180(a)

(b)

(c)

(d)

(e)

Figure 2 (a) Brain fluid-attenuated inversion recovery (spin echo: echo time, 105.0 msec; repetition time, 9000 msec) magnetic resonanceimaging of the brain at 14 years old, showing left hippocampal sclerosis. (b) An area of hypoperfusion is observed over the entire left
temporal lobe on 99mTc ethyl-cysteinate dimer single photon emission computed tomography (SPECT). (c) The area of hypoperfusion
dominates the inner side of the left temporal lobe on 123I-iomazenil SPECT. (d) A hypometabolic area is seen over a broad area
across the entire left temporal lobe on 18F-fluorodeoxyglucose positron emission tomography (PET). (e) The hypometabolic area
dominates the inner side of the left temporal lobe on 11C-flumazenil PET.Imataka et al

intracranial electrodes,1-3 although this is quite an invasive
procedure for patients. In recent years, 123I-IMZ SPECT
has been introduced to visualise benzodiazepine receptors
and is now approved and applied clinically in Japan. The
usefulness of this method has been reported.4 Moreover,
PET with 11C-FMZ, a central benzodiazepine receptor
antagonist, has shown diagnostic usefulness.5Although interictal EEG recordings showed left
anterotemporal abnormal discharges and coronal MRI(FLAIR) suggested higher intensity in his left medialtemporal region, his left hippocampus seemed relatively
smaller. It did not exclude the possibility of the rightpathology. It may require invasive EEG recordings, which
was not suitable for him. We, including his family, wanted
to skip invasive modalities and performed theseinvestigations. The examinations performed in this study,
using four different RI substances, all suggestedabnormalities in the left temporal region. Among thesemodalities, the results with IMZ and FMZ nicely matched
the MRI findings of left hippocampal sclerosis and theepileptic focus detected intraoperatively. Use of 123I-IMZ
SPECT and 11C-FMZ PET appeared to demonstrate theepilepsy focus more localised than 99mTc ECD SPECT and18F-FDG PET.
Anterior temporal lobectomy remains one of the standard
surgical methods for mesial temporal lobe epilepsy. As
intraoperative ECoG showed residual spikes on the lateralsurface of the temporal lobe, multiple subpial transection(MST) was added on the superior and middle temporal gyri.
The importance of intraoperative ECoG has been describedin many reports,8 and in this case suggested a remainingfocus. Outcomes for this patient have proven satisfactory
to date, although only 1 year has passed since surgery.
In the present case, no intellectual deterioration wasobserved and the patient was able to enter high school withmental stabilisation after surgery. Taking into consideration
the relatively poor quality of life for this patient, withfrequent intractable complex partial seizures sincechildhood, surgery may have been indicated at an earlier
age. MRI at 5 years old probably appeared normal due tothe limited resolution available at the time. However, MRI
performed 9 years later clearly showed left hippocampal
sclerosis. According to Wiebe et al, seizures were controlled

181

in 8 of 40 cases in which drug treatment was administered,but for the other 32 cases in which epilepsy surgery wasperformed, seizures disappeared in 58% within 1 year.9
Koepp et al reported that for intractable temporal lobe
epilepsy with normal MRI findings, 11C-FMZ PET clearlyvisualizes the seizure foci.10 Identifying the epileptic focus
using 11C-FMZ PET and/or 123I-IMZ SPECT proactively isimportant even in the absence of abnormalities on MRI.
Epilepsy surgery should always be kept in mind for patientswith intractable temporal lobe epilepsy.

References
1.

Berg AT, Vickrey BG, Langfitt JT, et al; Multicenter Study ofEpilepsy Surgery. The multicenter study of epilepsy surgery:recruitment and selection for surgery. Epilepsia 2003:44:142533.
2. Engel J Jr, Wiebe S, French J, et al. Practice parameter: temporal
lobe and localized neocortical resections for epilepsy. Epilepsia
2003:44:741-51.
3. McNally KA, Paige AL, Varghese G, et al. Localizing value of
ictal-interictal SPECT analyzed by SPM (ISAS). Epilepsia 2005:
46:1450-64.
4. Kaneko K, Sasaki M, Morioka T, et al. Presurgical identificationof epileptogenic areas in temporal lobe epilepsy by 123Iiomazenil SPECT: a comparison with IMP SPECT and FDG PET.
Nucl Med Commun 2006:27:893-9.
5. Hammers A, Koepp MJ, Labbe C, et al. Neocortical abnormalitiesof [11C]-flumazenil PET in mesial temporal lobe epilepsy.
Neurology 2001:56:897-906.
6. Ochs R, Gloor P, Quesney F, Ives J, Olivier A. Does head-turning
during a seizure have lateralizing or localizing significance?
Neurology 1984:34:884-90.
7. Marsan CA, Zivin LS. Factors related to the occurrence of typicalparoxysmal abnormalities in the EEG records of epileptic
patients. Epilepsia 1970:11:361-81.
8. Imataka G, Ogino M, Nakagawa E, Yamanouchi H, Arisaka O.
Electroencephalography-guided resection of dysembryoplastic
neuroepithelial tumor: case report. Neurol Med Chir (Tokyo)
2008:48:318-21.
9. Wiebe S, Blume WT, Girvin JP, Eliasziw M; Effectiveness andEfficiency of Surgery for Temporal Lobe Epilepsy Study Group.
A randomized, controlled trial of surgery for temporal-lobe
epilepsy. N Engl J Med 2001:345:311-8.
10. Koepp MJ, Hammers A, Labbe C, Woermann FG, Brooks DJ,Duncan JS. 11C-flumazenil PET in patients with refractory
temporal lobe epilepsy and normal MRI. Neurology 2000;54:332-9.