Multimodality imaging in the surgical
treatment of children with
J.H. Seo, MD
K. Holland, MD, PhD
D. Rose, MD
L. Rozhkov, MS
H. Fujiwara, BS
A. Byars, PhD
T. Arthur, MD
T. DeGrauw, MD, PhD
J.L. Leach, MD
M.J. Gelfand, MD
L. Miles, MD
F.T. Mangano, DO
P. Horn, PhD
K.H. Lee, MD
Objectives: To evaluate the diagnostic value of individual noninvasive presurgical modalities and
to study their role in surgical management of nonlesional pediatric epilepsy patients.
Methods: We retrospectively studied 14 children (3–18 years) with nonlesional intractable focal epi-
lepsy. Clinical characteristics, surgical outcome, localizing features on 3 presurgical diagnostic tests
(subtraction peri-ictal SPECT coregistered to MRI [SISCOM], statistical parametric mapping [SPM]
analysis of [18F] FDG-PET, magnetoencephalography [MEG]), and intracranial EEG (iEEG) were re-
Concordance of localization between each test and iEEG was scored as follows: 2 ? lobar concor-
each patient was measured by the summation of concordance scores for all 3 tests.
Results: Seven (50%) of 14 patients were seizure-free for at least 12 months after surgery. One
(7%) had only rare seizures and 6 (43%) had persistent seizures. MEG (79%, 11/14) and
SISCOM (79%, 11/14) showed greater lobar concordance with iEEG than SPM-PET (13%, 3/14)
(p ? 0.05). SPM-PET provided hemispheric lateralization (71%, 10/14) more often than lobar
localization. Total concordance score tended to be greater for seizure-free patients (4.7) than for
non–seizure-free patients (3.9).
Conclusions: Our data suggest that MEG and SISCOM are better tools for lobar localization than
SPM analysis of FDG-PET in children with nonlesional epilepsy. A multimodality approach may
improve surgical outcome as well as selection of surgical candidates in patients without MRI
ECoG ? electrocorticogram; FCD ? focal cortical dysplasia; iEEG ? intracranial EEG; MEG ? magnetoencephalography;
MSI ? magnetic source localization; SISCOM ? subtraction peri-ictal SPECT coregistered to MRI; SPM ? statistical para-
togenic zone is reasonably localized with noninvasive presurgical evaluation.1-3Among available
Presence of visible MRI lesion not only warrants surgical candidacy, but also predicts a favorable
surgical outcome.4-7Recent advances with high-resolution MRI may reveal the presence of brain
lesions not previously detected. However, some patients continue to have no detectable lesions on
MRI, despite the suggestion of a focal epileptogenic zone on seizure semiology and scalp EEG.
When no lesion is seen on MRI, other noninvasive functional imaging modalities have been
employed: peri-ictal SPECT and subsequent subtraction image coregistered to MRI (SISCOM)
may visualize increased blood flow at the time of seizure8,9; 2-deoxy-2-(18F)fluoro-D-glucose PET
(FDG-PET) and subsequent voxel-based analysis using statistical parametric mapping (SPM) may
visualize the areas of decreased metabolism10; and magnetoencephalography (MEG)/magnetic
source localization (MSI) may reveal the source of interictal/ictal epileptic discharges.11Although
From the Division of Pediatric Neurology (J.H.S., K.H., D.R., L.R., H.F., A.B., T.A., T.D., P.H., K.H.L.), Department of Radiology (J.L.L.,
M.J.G.), Department of Pathology (L.M.), and Division of Pediatric Neurosurgery (F.T.M.), Cincinnati Children’s Hospital Medical Center,
University of Cincinnati College of Medicine; and Department of Mathematical Sciences (P.H.), University of Cincinnati, Cincinnati, OH.
Study funding: Supported in part by the NIH (R01NS062756).
Disclosure: Author disclosures are provided at the end of the article.
Address correspondence and
reprint requests to Dr. Ki Hyeong
Lee, Division of Pediatric
Neurology, Cincinnati Children’s
Hospital Medical Center,
University of Cincinnati College
of Medicine, 3333 Burnet
Avenue, Cincinnati, OH
Copyright © 2010 by AAN Enterprises, Inc.
the diagnostic sensitivity and specificity of these
individual modalities have been studied sepa-
rately in various epilepsy groups,12there have
been few studies on the diagnostic yield of indi-
vidual noninvasive modalities and the value of
combined multimodality imaging in the nonle-
sional epilepsy population. The purpose of this
individual noninvasive presurgical modalities
with intracranial EEG (iEEG) as a gold stan-
dard, and to study whether a multimodal ap-
proach contributes to improved surgical
outcome in nonlesional pediatric epilepsy.
METHODS Standard protocol approval, registration,
and patient consent. The study was approved by the institu-
tional review board at Cincinnati Children’s Hospital Medical
Center. Patient consent was not required in this retrospective
Subjects. We retrospectively reviewed medical records of chil-
dren with medically intractable focal epilepsy who underwent
presurgical evaluation in the comprehensive epilepsy center at
the Cincinnati Children’s Hospital Medical Center between Oc-
tober 2006 and October 2009. Our standard presurgical evalua-
tion included detailed history and clinical examination, scalp
video-EEG monitoring, MRI with dedicated high-resolution
imaging for epilepsy patients, FDG-PET scans, ictal/interictal
SPECT, and MEG/MSI. Invasive EEG was recommended for
further localization of ictal onset zone or to map eloquent corti-
ces. Of 256 patients with presurgical evaluation during the study
period, we identified 46 patients who had normal or nonspecific
MRI. Of these 46, 25 patients underwent iEEG and subsequent
resective epilepsy surgery. Fourteen of the 25 patients met the
inclusion criteria as follows: 1) were 18 years of age or younger at
time of surgery; 2) had normal or nonspecific findings on preop-
erative MRI; 3) underwent all multimodality evaluations includ-
ing SISCOM, SPM-PET, and MEG; 4) had iEEG and
subsequent resective epilepsy surgery; and 5) had follow-up of at
least 12 months postsurgery (figure 1). Eleven patients were ex-
cluded because they failed ictal SPECT (n ? 2), MEG (n ? 2),
or had a short follow-up duration without test failures (n ? 7)
(table e-1 on the Neurology®Web site at www.neurology.org).
Presurgical evaluation: Noninvasive functional imag-
ing studies. Imaging protocols. MRI was performed at 3 T (10
patients) or 1.5 T (4 patients). The details used for the MRI proto-
cols are included in the supplementary data. Imaging studies were
tion in neuroradiology) with 15 years of experience in epilepsy im-
aging (J.L.L.). Analysis of imaging was performed in a 2-step
process. Initially, the imaging studies were reviewed blinded to clin-
ical history (other than intractable epilepsy), results of other tests,
and to resection location. The studies were then re-reviewed with
knowledge of all additional clinical history, EEG results, additional
tion on postoperative imaging studies). No subject had a clearly
defined lesion on MRI. Examinations were classified (after final re-
view) as normal (10 patients), nonspecific findings (volume loss or
but nondiagnostic (subtle gyral morphology asymmetry on same
side as surgery, but without clear focal cortical thickening, altered
cortical signal, or gray matter white matter blurring, 1 patient; sub-
tle subcortical white matter increased signal without cortical thick-
ening or cortical increased signal seen only on final imaging review,
1 patient). One patient had postsurgical changes in the region of a
prior right temporal lobectomy, but no imaging abnormality in the
region of the new resection site (right temporal and parietal lobes).
supplementary data (appendix e-1: Methods).
Neuropsychological evaluation. Neuropsychological evalu-
ation was done preoperatively, as well as 12 months postopera-
tively, by a board-certified pediatric neuropsychologist, and
included the Bayley Scales of Infant and Toddler Development,
Figure 1 Flow diagram of patient selection
F/U ? follow-up; iEEG ? intracranial EEG.
Neurology 76January 4, 2011
third edition,13for the youngest patient. For the other patients,
either the Wechsler Intelligence Scale for Children (fourth edi-
tion) or the Wechsler Adult Intelligence Scale (third or fourth
edition) were used, based upon the age of the patient.14,15
Invasive video/EEG monitoring. Following a multidisci-
plinary surgical conference in which all noninvasive evaluation
data were reviewed, extraoperative iEEG monitoring was recom-
mended if the noninvasive data were incongruent or divergent,
no causative lesion was seen on MRI, or eloquent cortex was
involved. Extraoperative monitoring was performed using sub-
dural strip and grid electrodes. Placement of intracranial elec-
trodes was guided by noninvasive localization and further
tailored by intraoperative electrocorticogram (ECoG). Continu-
ous video iEEG was recorded using the Stellate systems (128-
channel 16-bit A/D and sampling frequency 2 KHz; Natus
Medical Inc., San Carlos, CA). Primary ictal onset zone included
the area covered by the first electrodes that showed an EEG onset
pattern preceding clinical behavior. Secondary spread zone was
defined as the area neighboring the primary ictal onset zone
which showed an EEG spread pattern during a seizure.
Surgical resection. The resection margin was determined us-
ing iEEG ictal onset zone (primary ictal onset zone plus second-
ary spread zone) sparing eloquent cortex (language and motor).
If indicated, facial motor cortex or primary sensory cortex was
included in the resection margin after extensive discussion with
the patients and their parents. Multiple subpial transection was
performed on the primary motor or language cortex when the
area was clearly included in the epileptogenic zone. Postresection
intraoperative ECoG was performed in all cases to assess residual
epileptiform discharges at the resection margins. Further resec-
tion was recommended only when we identified burst of repeti-
tive spikes longer than 5 seconds, high frequency oscillations, or
frank electrographic seizures.
Evaluation of surgical outcome. Postoperative seizure out-
come was evaluated by review of outpatient visits or telephone con-
tacts. Seizure outcome was classified based on the system proposed
by Engel et al.2: Class I ? seizure-free; Class II more than 90%
reduction; Class III more than 50% reduction; and Class IV less
than 50% reduction or unchanged. Seizure outcome data were re-
ported as of the date of latest available follow-up.
Pathology. Pathology was initially reviewed by several pediat-
ric pathologists, and then it was blindly reviewed by a single
pediatric neuropathologist (L.M.) specifically for this study. His-
topathology of focal cortical dysplasia (FCD) was classified using
Palmini’s classification16as follows: 1A, architectural abnormal-
ity only; 1B, architectural abnormality plus giant or immature
neurons; IIA, architectural abnormality with dysmorphic neu-
rons without balloon cells; IIB, architectural abnormality with
dysmorphic neurons and balloon cells.
Analysis and statistics. Localization of individual presurgical
tests including SISCOM, SPM-PET, and MEG was determined
for lobar location by visual analysis. Comparison of localization
between each test and primary ictal onset area on iEEG led to
concordance scores as follows: 2 ? lobar concordance; 1 ?
hemispheric concordance; 0 ? discordance or nonlocalization.
Table 1Clinical characteristics and surgical outcome of 14 patients
Patient Sex/age, ySeizure semiology
F/16Tingling sensation in R arm,
head, eye deviating to L
L H L frontal corticectomy ?
22I FCD IA SMA syndrome
F/14 Staring, head turning
to R, L hand automatism
L H L frontal corticectomy 15I FCD IB SMA syndrome
M/8 Staring followed by GTCNot lateralizingR frontal corticectomy ?
17 IIFrontal: FCD IB;
temporal: FCD IA;
F/9Tonic, atonic, myoclonic Not lateralizingR frontal corticectomy ?
28IV FCD IA Transient motor
F/18 Staring, speaking
L temporal L lateral temporal
23I NA Transient naming
M/14Head turning to RNot lateralizingL frontal corticectomy15IFCD IB—
M/17Numbness on L forearm,
head turning to L
R HR frontal corticectomy21 IIIFCD IA—
F/14 Staring, followed by
GT (R ? L)
Not lateralizingL parietal corticectomy14I NA—
F/14 Myoclonic (R ? L)L HL frontal corticectomy12I FCD IB—
M/3Staring, turning to R R HR temporal lobectomy 24IIIFCD IB;
F/13 GTCR HR frontal lobectomy 25III FCD IB—
F/11 Staring with R hand
R HR parietal corticectomy ?
15IV FCD IB;
Not lateralizing L frontal corticectomy32 III NA—
M/14Staring, head and eyes
version to R
L HL frontal corticectomy ?
12I FCD IIA;
Abbreviations: FCD ? focal cortical dysplasia; GT ? generalized tonic seizure; GTC ? generalized tonic-clonic seizure; H ? hemispheric; MST ? multiple
subpial transsection; NA ? not available; NL ? normal; SMA ? supplementary motor area.
Neurology 76January 4, 2011
Lobar concordance was present if the test localization indicated
the same lobar region as iEEG; hemispheric concordance if the
same hemisphere; otherwise, the findings were considered dis-
cordant or nonlocalizing. Total concordance score in each pa-
tient was measured by the summation of concordance scores for
all 3 tests.
Fisher exact test was used to evaluate the relationship be-
tween total concordance score and postsurgical seizure outcome.
For the purpose of the statistical analysis, outcome was dichoto-
mized as seizure-free (Class I) or non–seizure-free (Class II, III,
and IV) and the total concordance score was classified as low
(0–2), medium (3–4), or high (5–6).
RESULTS Patients. Fourteen patients met the inclu-
sion criteria for this study. Their clinical characteris-
tics and surgical outcomes are summarized in table 1.
The mean age at surgery was 12.6 years (3–18 years).
The mean duration of epilepsy was 7.3 years (2.5–13
years). Based on ictal scalp EEG and clinical semiol-
ogy, we were able to localize the possible epilepto-
genic zone in only 1 of 14 patients (7%) and to
lateralize the epileptogenic hemisphere in an addi-
tional 8 patients (57%). The mean length of postop-
erative follow-up was 20 months (12–32 months).
Clinical outcome. Overall seizure-free outcome in the
25 patients with negative MRI who had resective sur-
gery during the study period was 48% (12/25).
Among 14 patients who met the study inclusion cri-
teria, 50% (7/14) were seizure-free: 1 (7%) had rare
seizures (Engel Class II) and 6 (43%) had persistent
seizures (Class III and IV). No patient experienced
permanent neurologic deficit (table 1).
There was no significant difference between preop-
erative and postoperative neuropsychological test scores
on a population basis (table e-2). Four patients demon-
at follow-up than at presurgical examination. Two pa-
tients demonstrated scores that were 12 and 13 points
lower. The remainder of the patients was either not as-
sessed on both presurgical and postsurgical occasions or
demonstrated changes of less than 10 points.
Level of concordance with iEEG: SISCOM, SPM-PET,
and MEG. Details of localization of each test and their
concordance scores compared with iEEG are listed in
both SISCOM and MEG showed lobar concordance
with iEEG in 9 (64%) patients. SPM-PET showed lo-
bar concordance with iEEG in 3 (21%) patients, but
additional 10 (71%) patients. MEG and SISCOM
showed higher lobar concordance with iEEG than
SPM-PET (p ? 0.05, sign test). The sum of concor-
dance scores across all 14 patients was 24 for MEG, 23
for SISCOM, and 13 for SPM-PET.
Relationship between test concordance and surgical
outcome. The total concordance scores for individual
patients and their surgical outcomes are also shown
Table 2 Localization concordance between each functional imaging test and intracranial EEG
L F, T72L F L T1 L F2 L F25I
L F, T, P88 L FL T1 L F, P2 L F25I
Bi–R F, T82 R F, TL F, T, R F0 Both O, R P0Both T, O00II
R F, T, P100 R F L P0 R F, P2 R P13 IV
L F, T76 L TBoth F, L T1L T2 L T25I
L F, T, P 112 L FL T, both F1 L T, F2L F25I
R F 128R F L F, T0 R F2 R F24III
L F, T, P 122L P Both F, T0 R F, T, L P0 L P22I
L F, T, P92L F, P L F, T1 L F, P2 L F, P25I
R F, T78 R T R F, T1 R T2 R F14III
R F62R F R F2 R F2 R F26 III
L F, T, P86 R F, P, TR F, P2 R T, O1 R F, T25 IV
L F 102 R FR T1 R F2 R F25 III
L F, T, P 104 L F, T L F, T2 L F2 L F26I
Abbreviations: Bi ? bilateral hemispheric; F ? frontal; iEEG ? intracranial EEG; MEG ? magnetoencephalography; O ? occipital; P ? parietal; SISCOM ?
subtraction peri-ictal SPECT coregistered to MRI; SPM ? statistical parametric mapping; T ? temporal.
aComparison of localization between each test and intracranial EEG led to concordance scores as follows: 2 ? lobar concordance; 1 ? hemispheric
concordance; and 0 ? discordance or nonlocalization.
bTotal concordance score in each patient was measured by the summation of concordance scores for all 3 tests.
cTotal concordance score in each test was measured by the summation of concordance scores for all 14 patients.
Neurology 76January 4, 2011
in table 2. Total concordance score tended to be
greater for the seizure-free group compared with
the non–seizure-free group (Class II, III, IV): the aver-
age of total concordance scores was 4.7 in the
seizure-free group, while the score was 3.9 in the non-
seizure-free group. The difference did not reach
When both SISCOM and MEG showed lobar con-
cordance with iEEG (SISCOM ? MEG ? 4), seizure-
free outcome was 67% (6/9), while that of the rest
(SISCOM ? MEG ?4) was 20% (1/5) (p ? 0.27,
tion in addition to the lobar concordance between
SISCOM and MEG (SISCOM ? MEG ? SPM-PET
?5), the surgical outcome increased to 75% (6/8), while
17% (1/6) (p ? 0.10, Fisher exact test). Two illustrative
Pathology. Pathology was available in 11 patients and
FCD was found in all 11 patients. Ten patients were
classified as Palmini type I (3 IA/7 IB); one patient
was classified as IIA. There were 2 cases where the
reviewers disagreed: the blinded reviewer identified
FCD type IA and the other review diagnosed subpial
gliosis. In 3 patients, the volume of specimen was not
sufficient for pathologic diagnosis.
DISCUSSION Absence of an MRI lesion not only
discourages consideration of a patient for surgical
candidacy, but is also associated with poor surgical
outcome. In our study, the overall seizure-free out-
come was 50% when all 3 noninvasive modalities
were used. This seizure-free outcome compares well
with other published
epilepsy.6,11,17-21Although seizure-free outcome in
these challenging patients is still lower than in the
Figure 2 Patient 14 with all concordant presurgical tests (total sum ? 6) and seizure-free outcome
A 14-year-old boy with focal epilepsy since age 4 years. Scalp EEG disclosed frequent interictal spikes in left hemisphere,
especially in left anterior temporal areas. MRI was normal. (A) Magnetoencephalography showed maximal source activity in
left inferior frontal region. (B) Subtraction peri-ictal SPECT coregistered to MRI demonstrated increased perfusion in left
frontal region. (C) Statistical parametric mapping–PET showed hypometabolism involving left frontal and temporal region.
(D) Intracranial EEG revealed ictal onset in left lateral temporal and inferior frontal areas (red circles). The patient became
seizure-free following left frontal corticectomy and left anterior temporal lobectomy at 12 months of follow-up. Pathology
revealed type IIA focal cortical dysplasia in both frontal and temporal lobes without hippocampal sclerosis.
Neurology 76January 4, 2011
lesional focal epilepsy group, high seizure burdens
and frequently associated cognitive dysfunction
should be weighed in favor of surgical consideration.
There are several noninvasive localization tests
available to help detect epileptogenic foci in nonle-
sional epilepsy. Most recently, SISCOM, MEG, and
FDG-PET have become more widely available.
However, most epilepsy centers may not have access
to all of these modalities, therefore, there are few
studies directly comparing all 3 tests with iEEG and
surgical outcome in the same patients. The current
study shows that both SISCOM and MEG have bet-
ter lobar concordance with iEEG than SPM-PET.
This is consistent with recent studies showing that
SISCOM and MSI had a high predictive value for
localizing seizures with iEEG.22,23Although FDG-
PET has been shown to be useful in temporal lobe
epilepsy,24its diagnostic value in nonlesional neocor-
tical epilepsy is less clear.25,26We used SPM analysis
in an attempt to eliminate some of the subjectivity
required with visual analysis and to control for differ-
ences in expertise and experience between readers.27
Using SPM analysis of FDG-PET, the lobar concor-
dance rate with iEEG was lower for FDG-PET than
the other modalities. The extent of hypometabolism
on FDG-PET is often larger than the true epilepto-
genic zone, and often extends beyond one lobe into
an adjacent lobe. In addition, the epileptogenic zone
is often observed in the periphery of hypometabolism
rather than in the center.28As a result, FDG-PET
may be more often lateralizing than localizing to a
single lobe. In fact, FDG-PET successfully lateralized
seizure onset zone in 71% (10/14) of our patients.
PET and iEEG lateralization disagreed in 4 patients;
Figure 3 Patient 3 with all discordant presurgical tests (total sum ? 0) and non–seizure-free outcome
An 8-year-old boy with focal epilepsy since 1 year of age. Scalp EEG disclosed consistent focal slowing over right temporal
area with multifocal interictal spikes. The patient had 3-step surgery including bilateral subdural grid placement as the first
step, because of discordant test results. (A) Magnetoencephalography showed maximal source localization in both tempo-
ral lobes. (B) Subtraction peri-ictal SPECT coregistered to MRI showed increased perfusion in multifocal areas. (C) Statisti-
cal parametric mapping–PET demonstrated multifocal areas of hypometabolism. (D) Ictal onset zone was found in right
frontal and temporal areas (red circles), which lead to multiple corticectomy involving both frontal and temporal lobes. The
IB FCD in right frontal lobe and type IA FCD in right temporal lobe.
Neurology 76 January 4, 2011
3 had a Class III or IV outcome. Therefore, discor-
dant FDG-PET with other noninvasive tests may be
associated with poor surgical outcome in nonlesional
epilepsy. Similar findings have been reported in adult
temporal lobe epilepsy.29
Our data support the role of multimodal ap-
proach in presurgical evaluation of nonlesional epi-
lepsy. First, multimodality imaging allowed us to
extend the surgical treatment to patients who could
not be considered good candidates without the tests.
Based on ictal scalp EEG and clinical semiology, we
were able to localize the possible epileptogenic zone
in only 1 out of 14 patients (7%, 1/14) and to later-
alize the epileptogenic hemisphere in an additional 8
patients (57%, 8/14). Without multimodality ap-
proach, 36% of patients (5/14) with poor lateraliza-
tion may have been discouraged from epilepsy
surgery. Second, we were able to refine the hypothe-
sis on the possible epileptogenic zone and therefore
to reduce the size of craniotomy and number of sub-
dural electrodes. In our series, 57% of patients with
lateralizing but nonlocalizing seizure onset may have
required diffuse hemispheric iEEG coverage without
the multimodal tests. Third, high concordance score
across these tests tended to be associated with favor-
able surgical outcome even though it did not reach
statistical significance, probably due to small sample
size. This agrees with a previous study demonstrating
that positivity of all tests including MSI, FDG-PET,
and ictal SPECT predicts increased odds for seizure-
free outcome after surgery.22
Histologic examination revealed that all 11 pa-
tients with available pathology had focal cortical dys-
plasia. FCD type I was noted in 91% (10/11) of
patients in this study. In previous reports, type I
FCD was often associated with negative MRI and
poor surgical outcome while type II FCD was associ-
ated with more visible MRI findings and better out-
come.30Higher incidence of FCD in our series than
previous series of nonlesional epilepsy17and the pres-
ence of disagreement between the initial and second
reviewer (18%, 2/11) suggest that there exists some
variability of diagnostic threshold for FCD.
We recognize that there are limitations to this
study. First, this is a single-center retrospective re-
view, which is subject to selection bias given specific
referral patterns. It is possible that more difficult
cases of nonlesional epilepsy may have been discour-
aged from surgical consideration by the patients’ pri-
mary neurologists. Second, our study did not analyze
the cost-benefit aspect of this multimodality ap-
proach. With surging health care costs, many epi-
lepsy centers may not offer all available noninvasive
tests. However, considering the long-term financial
burden of caring for intractable epilepsy patients, this
multimodality approach may be justified. Long-term
follow-up of this patient population may provide fur-
ther answers. Third, we applied SPM analysis of
FDG-PET using a normal adult template. Even
though SPM-PET has been reported to be useful in
evaluating children over 6 years,31small differences
in the pattern of glucose metabolism may occur espe-
cially during late childhood and adolescence. Devel-
opment of a normal pediatric template needs to be
undertaken to apply SPM analysis more widely in the
pediatric group, especially in children less than 6
years of age. Finally, we compared individual presur-
gical tests with iEEG to evaluate their diagnostic ac-
curacy. Even though iEEG is considered the gold
standard to map the ictal onset zone, sampling error
is still possible, especially in nonlesional cases. There-
fore, we tried to differentiate between the primary
ictal onset zone vs the secondary spread zone based
on iEEG pattern. Another shortcoming of using
iEEG as the gold standard is that the placement of
iEEG is to some degree influenced by the presurgical
tests and thus the iEEG findings are not completely
independent from the 3 presurgical tests.
Although combined multimodality imaging ap-
proach could enhance our ability to localize the epi-
leptogenic zone in nonlesional focal epilepsy,
extraoperative iEEG cannot be completely avoided
presently. Aside from the exact localization of the
epileptogenic zone, the extent of curative resection
may not be accurately determined without proper
iEEG monitoring and cortical stimulation mapping.
A larger prospective study may be necessary to eluci-
date the role of multimodality imaging in this se-
lected group of patients.
Statistical analysis was conducted by Dr. Paul Horn.
The authors thank Dr. Dong Soo Lee at Seoul National University for
sharing the normal FDG-PET template acquired at his institution.
Dr. Seo reports no disclosures. Dr. Holland-Bouley has received a speaker
honorarium from Ortho-McNeil-Janssen Pharmaceuticals, Inc. and re-
ceives research support from the NIH/NINDS (R01NS062756 [PI]). Dr.
Rose reports no disclosures. L. Rozhkov has 2 patents pending re: The
technology of operating cylinder-rod kinematic couples by means of high-
pressure gases. Dr. Byars receives research support from Novartis, the
NIH (NICHHD 5R01HD38578 [coinvestigator] and NIDCD
5R01DC007186 [coinvestigator]), the US Department of Defense, and
the US Department of Health & Human Services/National Institute of
Child Health & Development. H. Fujiwara reports no disclosures. Dr.
Arthur’s spouse owns stock in General Electric. Dr. DeGrauw may accrue
revenue on a patent re: Co-enzyme Q10 assay in blood; and receives
research support from the FDA. Dr. Leach and Dr. Gelfand report no
disclosures. Dr. Miles serves on the editorial board of Pediatric and Devel-
opmental Pathology. Dr. Mangano reports no disclosures. Dr. Horn serves
on a scientific advisory board for the Cincinnati Children’s Hospital Med-
ical Center and receives royalties from the publication of Reference Inter-
Neurology 76January 4, 2011
vals: A User’s Guide (American Association of Clinical Chemistry Press, Download full-text
2005). Dr. Lee reports no disclosures.
Received March 2, 2010. Accepted in final form September 8, 2010.
1. Cascino GD. Surgical treatment for extratemporal epi-
lepsy. Curr Treat Options Neurol 2004;6:257–262.
2. Engel J Jr VNP, Rasmussen T, Ojemann LM. Outcome
with Respect to Epileptic Seizures, 2nd ed. New York:
Raven Press; 1993.
3. Wyllie E, Comair YG, Kotagal P, Bulacio J, Bingaman W,
Ruggieri P. Seizure outcome after epilepsy surgery in chil-
dren and adolescents. Ann Neurol 1998;44:740–748.
4. Mohamed A, Wyllie E, Ruggieri P, et al. Temporal lobe epi-
lepsy due to hippocampal sclerosis in pediatric candidates for
epilepsy surgery. Neurology 2001;56:1643–1649.
5. Paolicchi JM, Jayakar P, Dean P, et al. Predictors of out-
come in pediatric epilepsy surgery. Neurology 2000;54:
6. Siegel AM, Jobst BC, Thadani VM, et al. Medically intrac-
table, localization-related epilepsy with normal MRI: pre-
surgical evaluation and surgical outcome in 43 patients.
7.Zentner J, Hufnagel A, Ostertun B, et al. Surgical treat-
ment of extratemporal epilepsy: clinical, radiologic, and
histopathologic findings in 60 patients. Epilepsia 1996;37:
8. Lewis PJ, Siegel A, Siegel AM, et al. Does performing im-
age registration and subtraction in ictal brain SPECT help
localize neocortical seizures? J Nucl Med 2000;41:1619–
9. O’Brien TJ, So EL, Mullan BP, et al. Subtraction SPECT
co-registered to MRI improves postictal SPECT localiza-
tion of seizure foci. Neurology 1999;52:137–146.
10. Chugani DC, Chugani HT. New directions in PET neu-
roimaging for neocortical epilepsy. Adv Neurol 2000;84:
11. RamachandranNair R, Otsubo H, Shroff MM, et al. MEG
predicts outcome following surgery for intractable epilepsy
in children with normal or nonfocal MRI findings. Epilep-
12. Spencer SS, Theodore WH, Berkovic SF. Clinical applica-
tions: MRI, SPECT, and PET. Magn Reson Imaging
13. Bayley N. Bayley Scales of Infant and Toddler Develop-
ment, third ed. San Antonio: The Psychological Corpora-
14. Wechsler D. Wechsler Intelligence Scale for Children,
fourth ed. San Antonio: The Psychological Corporation;
15. Wechsler D. Wechsler Adult Intelligence Scale, fourth ed.
San Antonio: The Psychological Corporation; 2008.
16.Palmini A, Najm I, Avanzini G, et al. Terminology and
classification of the cortical dysplasias. Neurology 2004;
Chapman K, Wyllie E, Najm I, et al. Seizure outcome after
epilepsy surgery in patients with normal preoperative
MRI. J Neurol Neurosurg Psychiatry 2005;76:710–713.
Cohen-Gadol AA, Wilhelmi BG, Collignon F, et al. Long-
term outcome of epilepsy surgery among 399 patients with
nonlesional seizure foci including mesial temporal lobe
sclerosis. J Neurosurg 2006;104:513–524.
Cukiert A, Buratini JA, Machado E, et al. Results of sur-
gery in patients with refractory extratemporal epilepsy with
normal or nonlocalizing magnetic resonance findings in-
vestigated with subdural grids. Epilepsia 2001;42:889–
Jayakar P, Dunoyer C, Dean P, et al. Epilepsy surgery in
patients with normal or nonfocal MRI scans: integrative
strategies offer long-term seizure relief. Epilepsia 2008;49:
Lee SK, Lee SY, Kim KK, Hong KS, Lee DS, Chung CK.
Surgical outcome and prognostic factors of cryptogenic
neocortical epilepsy. Ann Neurol 2005;58:525–532.
Knowlton RC, Elgavish RA, Bartolucci A, et al. Functional
imaging: II: prediction of epilepsy surgery outcome. Ann
Knowlton RC, Elgavish RA, Limdi N, et al. Functional
imaging: I. Relative predictive value of intracranial electro-
encephalography. Ann Neurol 2008;64:25–34.
Carne RP, O’Brien TJ, Kilpatrick CJ, et al. MRI-negative
PET-positive temporal lobe epilepsy: a distinct surgically
remediable syndrome. Brain 2004;127:2276–2285.
Henry TR, Sutherling WW, Engel J Jr, et al. Interictal
cerebral metabolism in partial epilepsies of neocortical ori-
gin. Epilepsy Res 1991;10:174–182.
Swartz BE, Halgren E, Delgado-Escueta AV, et al. Neuro-
imaging in patients with seizures of probable frontal lobe
origin. Epilepsia 1989;30:547–558.
Kim YK, Lee DS, Lee SK, Chung CK, Chung JK, Lee
MC. (18)F-FDG PET in localization of frontal lobe epi-
lepsy: comparison of visual and SPM analysis. J Nucl Med
Juhasz C, Chugani DC, Muzik O, et al. Is epileptogenic
cortex truly hypometabolic on interictal positron emission
tomography? Ann Neurol 2000;48:88–96.
Choi JY, Kim SJ, Hong SB, et al. Extratemporal hypome-
tabolism on FDG PET in temporal lobe epilepsy as a pre-
dictor of seizure outcome after temporal lobectomy. Eur
J Nucl Med Mol Imaging 2003;30:581–587.
Krsek P, Maton B, Korman B, et al. Different features of
histopathological subtypes of pediatric focal cortical dys-
plasia. Ann Neurol 2008;63:758–769.
Muzik O, Chugani DC, Juhasz C, Shen C, Chugani HT.
Statistical parametric mapping: assessment of application
in children. Neuroimage 2000;12:538–549.
Neurology 76January 4, 2011