Pediatric Neurology 129 (2022) 48e54

Contents lists available at ScienceDirect

:
Pediatric Neurology
journal homepage: www.elsevier.com/locate/pnu

Research Paper

Localizing and Lateralizing Value of Seizure Onset Pattern on Surface

EEG in FCD Type II
Titaporn Thamcharoenvipas, MD a, b, Yukitoshi Takahashi, MD, PhD a, c, d, *,
Nobusuke Kimura, MD a, Kazumi Matsuda, MD a, Naotaka Usui, MD, PhD a
a
National Epilepsy Center, NHO Shizuoka Institute of Epilepsy and Neurological Disorders, Shizuoka, Japan
b
Division of Neurology, Department of Pediatrics, Faculty of Medicine, Prince of Songkla University, Songkhla, Thailand
c
Department of Pediatrics, Gifu University School of Medicine, Gifu, Japan
d
School of Pharmaceutical Sciences, University of Shizuoka, Shizuoka, Japan

a r t i c l e i n f o a b s t r a c t

Article history: Background: Surface ictal electroencephalographic (EEG) monitoring has an important role in the pre-
Received 15 October 2021 surgical evaluation of patients with focal cortical dysplasia (FCD). This study aimed to examine the
Accepted 27 January 2022 characteristics of seizure onset pattern (SOP) on surface ictal EEG. This information will be useful for
Available online 4 February 2022
invasive monitoring planning.
Methods: We reviewed 290 seizures from 31 patients with intractable seizures related to FCD type II (6
Keywords:
patients with FCD IIa and 25 patients with FCD IIb). We categorized the SOPs into five patterns and
Seizure onset pattern
evaluated the relationships between the SOPs and the location and pathology of the FCD II subtype.
Surface EEG monitoring
Focal cortical dysplasia
Results: The most common SOP was no apparent change (39.0%), followed by rhythmic slow wave and
Epileptic focus repetitive spikes/sharp waves. The SOP of rhythmic slow wave was associated with FCD II in the temporal
Localization lobe (P < 0.001), and the SOP of no apparent change was associated with FCD II in the occipital lobe
(P ¼ 0.012). The SOPs of rhythmic slow waves and fast activity were most common in FCD IIa, P < 0.001
and 0.031, respectively. The repetitive spikes/sharp waves SOP was the most common pattern in FCD IIb
(P < 0.001). The surface SOPs provided correct localization and lateralization of epileptic foci in FCD in
62.1% and 62.7%, respectively. In 61.3% of the patients, over 50% of the SOPs in each patient indicated
accurate localization.
Conclusions: SOPs in surface EEG monitoring are beneficial for presurgical evaluation and lead to
localization of epileptic foci and pathologic subtypes of FCD.
© 2022 The Author(s). Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND
license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

Introduction

Ethics statement: We confirm that we have read the journal's position on issues
involved in ethical publication and affirm that this report is consistent with those
guidelines.
Declaration of Competing Interests: This study was funded in part by grants-in-
aid for Scientific Research I (15K09634, 18K0765, and 21K07788); MHLW Research
program on rare and intractable diseases, Grant number JPMH20FC1039; Research
on Rare and Intractable Diseases Unit of the Ministry of Heath, Labour and Welfare,
Japan; Health and Labour Sciences Research Grants for Comprehensive Research on
Disability Health and Welfare, Japan (H26- nanchitou-ippan-051, H29- nanchitou-
ippan-010); AMED under Grant Number JP18lk0201069s0502; and grants from the
Japan Epilepsy Research Foundation.
* Communications should be addressed to: Dr. Takahashi; National Epilepsy
Center; NHO Shizuoka Institute of Epilepsy and Neurological Disorders; Urush-
iyama 886; Aoi-ku, 420-8688 Japan.
E-mail address: takahashi-ped@umin.ac.jp (Y. Takahashi).
Focal cortical dysplasia (FCD) is one of the common causes of
medically intractable focal epilepsy1-6 and is considered to have
intrinsic epileptogenicity in some forms of FCD.7-12
FCDs can be classified as FCD I with architectural abnormalities,
FCD II with the presence of dysmorphic neurons and balloon cells,
and FCD III associated with other pathologies.13 Dysmorphic neu-
rons in the histopathology of FCD II are believed to be responsible
for epileptogenesis.
Many previous studies have reported that appropriate surgical
resection of FCDs achieved seizure-free rates of 45% to 75%14-24 at
one to two years, and preserved or improved development.23-25 A
good surgical outcome depends on complete resection of the

https://doi.org/10.1016/j.pediatrneurol.2022.01.008
0887-8994/© 2022 The Author(s). Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
T. Thamcharoenvipas, Y. Takahashi, N. Kimura et al.
epileptogenic lesions associated with FCD.15,20,21,26,27 Because the
epileptogenic zone usually extends beyond the lesions depicted on
magnetic resonance imaging (MRI), the actual epileptogenic zone
needs to be diagnosed by other modalities including ictal electro-
encephalography (EEG), positron emission tomography, and/or
ictal single-photon emission computed tomography in presurgical
evaluation.
In comprehensive presurgical evaluation, intracranial EEG
monitoring is the gold standard to identify the ictal seizure onset
zone, but this examination is available only in tertiary neurological
or level 4 epilepsy centers. In general neurological or epilepsy
centers, ictal scalp EEG recording with simultaneous video moni-
toring and MRI are the essential noninvasive initial presurgical
evaluations to provide fundamental screening for surgical candi-
dates. Ictal scalp EEG recording with simultaneous video moni-
toring allows evaluation of multiple habitual seizures for semiology
and corresponding ictal EEG patterns.
There have been only a few studies focusing on surface ictal EEG
seizure onset patterns (SOPs) in patients with FCD II. We conducted
this study to investigate the benefits and limitations of the infor-
mation obtained from surface EEG SOPs around the onset of sei-
zures, and the localizing and lateralizing value of SOPs in patients
with FCD II with medical refractory seizure. We analyzed the
relationship between the characteristics of SOPs and the FCD II
subtype. These findings will provide fundamental data and di-
rections to guide epileptologists in the efficient screening of sur-
gical candidate patients in this group.
Methods
Case selection
We selected patients with focal onset epilepsy who met all of
the following: (1) presurgical evaluation by MRI (including T1-
weighted, T2-weighted, and fluid-attenuated inversion recovery
sequences) and/or functional neuroimaging studies (including
arterial spin labeling, single-photon emission computed tomogra-
phy, and positron emission topography) showing a single focal
abnormality, suggesting FCD without dual pathology; (2) having
had at least one clinical habitual seizure captured by surface EEG
monitoring; (3) histopathological confirmation of FCD IIa by
architectural disorganization with dysmorphic neurons, or FCD IIb
by architectural disorganization with dysmorphic neurons and
balloon cells; and (4) postsurgical seizure outcome of Engel class I
for at least 2 years of follow-up. Patients with a history of prior
brain surgery or one or more seizures with incomplete data (such
as ictal EEG recordings without video recording, or incomplete
tracing) were excluded. The MRI and functional neuroimaging
studies were evaluated by two pediatric neurologists (T.T. and Y.T.).
This study was approved by the Ethics Committee of the Na-
tional Epilepsy Center, NHO Shizuoka Institute of Epilepsy and
Neurological Disorders, Japan.
EEG recording and analysis
Two pediatric neurologists (T.T. and Y.T.) reviewed all ictal scalp
EEG recordings of each patient. The SOPs on the surface EEGs of the
patients were determined by visual inspection with variable
montages including referential, transverse, and anterior-posterior
(A-P) bipolar montages using a 10-20 electrode placement. In
some patients, the SOPs were verified by additional temporal scalp
electrodes (F9, F10) and/or sphenoid electrodes (Sp1, Sp2). Records
with incomplete data of surface ictal video-EEG recording, data of
uncertain seizures, or data with massive artifacts were excluded
from further analysis.
49
Pediatric Neurology 129 (2022) 48e54
Ictal EEG seizure onset pattern
An ictal SOP was defined as apparent EEG changes just before
the appearance of clinical ictal symptoms. This study classified ictal
SOPs into the following five patterns (Fig 1A-E):
1. Background suppression: activity <10 mV in amplitude over all
electrodes (generalized suppression) or over 1 to 3 electrodes, in
a unilateral hemisphere, longer than two seconds (focal
suppression)
2. Repetitive spikes/sharp waves: three or more epileptiform dis-
charges in sequence, longer than two seconds
3. Rhythmic slow wave: less than beta range activity, longer than
two seconds
4. Fast activity: beta or greater than beta range activity, longer than
two seconds
5. No apparent change: undetectable or unclear ictal activity by
visual inspection
Definitions of localization and lateralization
We defined localization and lateralization as follows.
Localization
We investigated all SOPs preceding the appearance of clinical
ictal symptoms and judged the localization of SOPs relative to the
location of the FCD. The diagnostic values of the SOPs were clas-
sified as follows:
1. Correct localization: focus suggested by SOP found in the same
lobe as the FCD with or without midline propagation (Fz, Cz, or
Pz).
2. False localization: focus suggested by SOP found in other lobes
or the contralateral side of the FCD with or without midline
propagation, or in bilateral lobes.
3. Undetermined localization: no focus suggested by SOP:
3.1. Midline localization: focus suggested by SOP found at
midline region with or without bilateral spread.
3.2. SOP indicating generalized suppression.
Lateralization
We investigated all SOPs and classified the lateralization of ictal
change relative to the location of the FCD. The lateralizing values of
the SOPs were classified as follows:
1. Correct lateralization: focus suggested by SOP correct, in the
ipsilateral hemisphere of the FCD, regardless of the lobe.
2. False lateralization: focus suggested by SOP incorrect, in the
contralateral hemisphere of FCD, regardless of the lobe, with or
without midline propagation.
3. Undetermined lateralization: (1) SOP found in midline (Fz, Cz, or
Pz), (2) SOP of no apparent change, and (3) SOP indicating
generalized suppression.
Statistical analysis
The data were summarized using descriptive statistics. Fisher
exact test and chi-square test were used to analyze associations
between ictal SOP and location or pathology of FCD. A P value less
than 0.05 was considered to be statistically significant. All analyses
were performed using R program version 3.5.3.28
T. Thamcharoenvipas, Y. Takahashi, N. Kimura et al. Pediatric Neurology 129 (2022) 48e54

FIGURE 1. Typical seizure onset patterns (SOPs) in surface ictal EEG recordings. (A) Background suppression (generalized [A-1] and focal [A-2]); (B) repetitive spikes/sharp waves;
(C) rhythmic slow wave; (D) fast activity; (E) no apparent change. The color version of this figure is available in the online edition.

Results
Among 1410 patients with intractable epilepsy who underwent
epilepsy surgery at the Shizuoka Institute of Epilepsy and Neuro-
logical Disorders between February 1984 and March 2017, we
investigated a total of 290 epileptic seizures in 31 patients who
fulfilled the selection and exclusion criteria (Table 1); 83.9% of the
study patients had an FCD in the frontal lobe, and 80% had the
pathologic subtype of FCD IIb.
Seizure onset patterns and anatomical location of FCD
frequent SOP was no apparent change (39.0%), the second was
rhythmic slow wave (24.8%), and then repetitive spikes/sharp
waves (18.6%) and fast activity (13.8%) (Table 2). Background sup-
pression SOPs were observed in 3.8% of the patients, but no patients
were compatible with Lennox-Gastaut syndrome.
In patients with a frontal lobe FCD II, the most common SOPs
were no apparent change (38.5%), repetitive spikes/sharp waves
(20.6%), and rhythmic slow wave (21.8%) (Table 2). In patients with
temporal lobe FCD II, the significantly predominant SOP was
rhythmic slow wave (61.0%, P < 0.001). In patients with occipital
lobe FCD II, the significantly predominant SOP was no apparent
change (80%, P ¼ 0.012).

The location of the FCD II lesion was the frontal lobe in 26 pa- Histological classification of FCD II and seizure onset patterns
tients (257 seizures), the temporal lobe in three patients (23 sei-
zures), and the occipital lobe in two patients (10 seizures). The Among the 31 patients (total 290 seizures) classified by histo-
average number of ictal EEGs analyzed per patient was 6 (4, 10) pathological subtype, six patients had FCD IIa and 25 patients had
(median, interquartile range). Among the 290 seizures, the most FCD IIb.
In FCD IIa (85 seizures), SOPs of rhythmic slow wave and fast
activity were dominant, and rhythmic slow wave (43.5%, P < 0.001)
and fast activity (21.2%, P < 0.031) had significantly higher rates
TABLE 1.
Demographic and Clinical Data of Study Patients (n ¼ 31)
than in FCD IIb (Fig 2). In FCD IIb (205 seizures), the dominant SOPs
were no apparent change (42.4%) and repetitive spikes/sharp waves
Demographic Data Values
(25.9%) and the SOP of repetitive spikes/sharp waves was more
Sex (male/female) 22/9 frequent than in FCD IIa (1.2%) (P < 0.001).
Age at seizure onset, mean ± S.D. (range), y 4.8 ± 3.0 (0.7-15.0)
Age at EEG monitoring, mean ± S.D. (range), y 21.4 ± 13.1 (4.3-57.7)
Frequency of recorded seizures, median (IQR), 6 (4, 10) Localizing and lateralizing rates of seizure onset patterns
no. of seizures
Age at surgery, mean ± S.D. (range), y 22.4 ± 13.3 (4.0-57.7) The details of the localizing and lateralizing SOP values in 177
Follow up duration, mean ± S.D. (range), y 6.9 ± 3.7 (2.0-15.0)
seizures (excepting no apparent changes SOPs) are shown in
Location of FCD II lesion in MRI, no. of patients (%) 31
Frontal lobe 26 (83.9) Table 3. Correct localization of SOPs to the location of the FCD II was
Parietal lobe 0 (0) found in 62.1% of the seizures, with accuracy rates ranging from
Temporal lobe 3 (9.7) 52.9% to 100% in the various lobes. The overall false SOP localizing
Occipital lobe 2 (6.4) rate was 20.3%. The most frequent false localizing SOP was bilateral
Number of seizures analyzed, no. (%) 290
Frontal lobe FCD 257 (88.6)
simultaneous EEG change (72.2%, 26 of 36 seizures) followed by
Temporal lobe FCD 23 (7.9) contralateral EEG change in the homotopic lobe (19.4%, seven of 36
Occipital lobe FCD 10 (3.5) seizures) (Table 3).
Pathologic diagnosis of FCD II, no. of patients (%) 31 The false localizing rate was 41.2% in temporal lobe FCD II SOPs
FCD type IIa 6 (19.4)
and 18.3% in frontal lobe FCD IIs (P ¼ 0.051). Contralateral homo-
FCD type IIb 25 (80.6)
topic lobe localization among the false localizations was more
Abbreviations: frequent in patients with temporal lobe FCD II than in patients with
EEG ¼ Electroencephalography
FCD ¼ Focal cortical dysplasia
frontal lobe FCD II (P ¼ 0.001). For temporal lobe FCD II, EEG
IQR ¼ Interquartile range changes in the contralateral temporal lobe contributed to the
MRI ¼ Magnetic resonance imaging relatively high false localization rate. The midline localizing SOP
50
T. Thamcharoenvipas, Y. Takahashi, N. Kimura et al.
TABLE 2.
Seizure Onset Pattern and Location of Focal Cortical Dysplasia Type II of 290 Seizures (n, (%))
Location of FCD in MRI Background Suppression Repetitive Spikes/Sharp Waves (%) Rhythmic Slow Wave (%) Fast Activity (%) No Apparent Change (%) Total
(%)
Frontal 10 (3.9) 53 (20.6)
Temporal 1 (4.3) 1 (4.3)
Occipital - -
Total 11 (3.8) 54 (18.6)
Abbreviations:
FCD ¼ Focal cortical dysplasia
MRI ¼ Magnetic resonance imaging
SOP ¼ Seizure onset pattern
*
P value < 0.001, compared with other lobes, by Fisher exact test.
y
P value ¼ 0.012, compared with other lobes, by Fisher exact test.
pattern was observed only in frontal lobe FCD IIs (14.6%), which
reduced the localizing value of SOPs in this location.
For lateralizing values, the overall rate of correct lateralization
was 62.7%, ranging from 58.8% to 100% for FCD II in the various
lobes. The overall false lateralizing rate was 5.1% in 177 seizures.
The predominant false lateralizing SOP was EEG change in the
contralateral homotopic lobe, occurring at a rate of 77.8% (seven of
nine seizures), and was most frequent in temporal lobe FCD II. The
false lateralization rate in frontal FCD II was significantly lower
(P value < 0.001), and significantly higher (P value < 0.001) in
temporal FCD II than in the other lobes. Undetermined lateraliza-
tion of SOPs excepting no apparent change was found in 34.7% of
frontal lobe FCD II and in 11.8% of temporal lobe FCD IIs
(P value > 0.05).
Ratio of correct localization of SOPs at the same lobe as FCD/total
numbers of SOPs recorded in each patient (correct R-EFs)
The median frequency of the recorded seizures in this study was
6 (4, 10 [median, interquartile range]) per patient, and each patient
may have had a single or multiple SOPs, so we tried to evaluate the
accuracy of all SOPs (including correct localized SOPs, false local-
ized SOPs, and undetermined SOPs) in each patient by calculating
the correct SOP-EFs, which was defined as the ratio of correct lo-
calizations among all seizures in each patient.
Among the 31 patients, four patients (12.9%) showed a single
type of SOP and 27 patients showed multiple SOPs, with various
correct R-EFs (ratio of correct localization of SOPs at the same lobe
as FCD/total numbers of SOPs recorded in each patient). After
calculating the correct R-EFs for each patient, 19 of the 31 patients
(61.3%) showed SOPs with more than 50% correct R-EFs in surface
EEG monitoring (Table 4).
FIGURE 2. Ictal seizure onset patterns corresponding to pathologic classification of FCD type II of 290 seizures in 31 patients. aP value < 0.001, bP value ¼ 0.031 compared with other
FCD types, by Fisher exact test; cP value < 0.001 compared with other FCD types, by chi-square test. FCD, focal cortical dysplasia; SOP, seizure onset pattern; BS, background
suppression; spikes, repetitive spikes/sharp waves; slow, rhythmic slow wave; FA, fast activity; No, no apparent change. The color version of this figure is available in the online
edition.
51
Pediatric Neurology 129 (2022) 48e54
Seizures
56 (21.8) 39 (15.2) 99 (38.5) 257
14* (61.0) 1 (4.3) 6 (26.1) 23
2 (20%) - 8y (80) 10
72 (24.8) 40 (13.8) 113 (39.0) 290
In patients with frontal lobe FCD II, only one patient showed no
SOP-EFs in surface EEG monitoring (correct R-EF, 0%), but 25 of 26
patients (96.2%) showed at least one SOP with correct localization.
In patients with temporal lobe FCD II, all three patients showed
correct R-EFs at rates of greater than 50% in surface EEG monitoring.
In patients with occipital lobe FCD II, both patients showed less
than 25% correct R-EF in surface EEG monitoring.
Discussion
Variety and significance of SOPs in surface EEG monitoring for
presurgical evaluation
This is the first study characterizing surface SOPs in a large
number of patients with pathologically confirmed FCD type II. In all
the seizures studied, the most common SOP was no apparent
change, followed by rhythmic slow wave and repetitive spikes/
sharp waves. Our findings were quite different from those of some
other studies. For example, according to the surface SOP study in 18
patients with MRI-diagnosed FCD by Seifer et al.,29 70% of the SOPs
were fast activity and 20% were rhythmic sharp waves/spikes. The
predominance of no apparent change SOP in our study might be
attributed to the definition of SOPs in our study, which was limited
before appearance of clinical symptoms. Some patients in our study
had a long latency from the onset of epilepsy to the presurgical
evaluation, resulting in the evolutional expansion of the epilepto-
genic zone. Subsequently, SOPs might change from fast activity to
slow wave. We will confirm this hypothesis by examining the re-
lationships between SOPs and the characteristics of FCD (distance
from brain surface, volume, etc.) in an upcoming study.
Although the finding of a high prevalence of no apparent change
SOPs (approximately 40%) among the patients with FCD in our
T. Thamcharoenvipas, Y. Takahashi, N. Kimura et al. Pediatric Neurology 129 (2022) 48e54

TABLE 3.
Localizing and Lateralizing Values of Seizure Onset Patterns Across FCD Type II Locations of 177 Seizures

Localization and Lateralization Frontal Lobe n ¼ 158 Temporal Lobe n ¼ 17 Occipital Lobe n ¼ 2 Total n ¼ 177

Localization
Correct localizing SOP, n (%) 99 (62.7) 9 (52.9) 2 (100.0) 110 (62.1)
Ipsilateral and same lobe (focal) 88 (55.7) 9 (52.9) 2 (100.0) 99 (55.9)
Ipsilateral þ midline in same lobe (regional) 11 (7.0) - - 11 (6.2)
False localizing SOP, n (%) 29 (18.3) 7 (41.2) - 36 (20.4)
Bilateral simultaneous 25 (15.7) 1 (5.9) - 26 (14.7)
Contralateral homotopic lobe 2* (1.3) 5* (29.4) - 7 (4.0)
Other lobes - 1 (5.9) - 1 (0.6)
Midline with spreading to contralateral side 2 (1.3) - - 2 (1.1)
Undetermined SOP, n (%) 30 (19.0) 1 (5.9) - 31 (17.5)
Midline 23 (14.6) - - 23(13.0)
Generalized suppression 7 (4.4) 1 (5.9) - 8 (4.5)
Lateralization
Correct lateralizing SOP, n (%) 99 (62.7) 10 (58.8) 2 (100.0) 111 (62.7)
Ipsilateral and same lobe (focal) 88 (55.7) 9 (52.9) 2 (100.0) 99 (55.9)
Ipsilateral þ midline in same lobe (regional) 11 (7.0) - - 11 (6.2)
Ipsilateral other lobe - 1 (5.9) - 1 (0.6)
False lateralizing SOP, n (%) 4y (2.6) 5z (29.4) - 9 (5.1)
Contralateral side in homotopic lobe 2 (1.3) 5 (29.4) - 7 (4.0)
Contralateral side in other lobe - - - -
Midline with spreading to contralateral side 2(1.3) - - 2 (1.1)
Undetermined SOP, n (%) 55 (34.7) 2 (11.8) - 57 (32.2)
Bilateral simultaneous 25 (15.7) 1 (5.9) - 26 (14.6)
Midline 23 (14.6) - - 23 (13.0)
Generalized suppression 7 (4.4) 1 (5.9) - 8 (4.6)

Abbreviations:
FCD ¼ Focal cortical dysplasia
SOP ¼ Seizure onset pattern
*
P value ¼ 0.001 comparison between frontal and temporal lobes by Fisher exact test.
y
P value < 0.001.
z
P value < 0.001, compared with other lobes by Fisher exact test.

study was unexpected, this finding is important to remind neu-
rologists of the limitations of a surface video-EEG SOP in the pre-
surgical evaluation of patients with FCD. Although 40% of the
seizures in our patients with FCD II showed no apparent change in
SOP, after repeated surface video-EEGs, 96.8% of the patients had at
least one correct localization of SOPs at the same lobes as FCD in
their surface EEG monitoring and 61.3% had SOPs with more than
50% correct R-EFs. Adding comprehensive presurgical evaluations
with brain images, all the patients in our study achieved a post-
surgical seizure outcome of Engel class I, even in patients with
correct R-EFs at rates lower than 50%. Therefore, even in patients
with a low percent of correct R-EFs, it is imperative to perform
presurgical evaluation in combination with other modalities.
Location of FCD affects SOP
We found two significant associations between SOPs and the
location of an FCD II. First, the rhythmic slow wave pattern was
associated with a temporal lobe FCD II (P < 0.001) (Table 2). Other
studies have reported SOPs of rhythmic temporal alpha or theta
activity in 49% to 94% of patients with mesial temporal lobe epi-
lepsy (TLE).30-34 Patients with temporal lobe FCD usually have le-
sions in the lateral temporal lobes. Therefore, temporal lesions
including mesial temporal sclerosis and FCD tend to show a
rhythmic slow wave pattern on an ictal surface EEG. We need
further histologic studies on mesial temporal sclerosis and FCD II to
confirm the reason for these common rhythmic slow patterns.
Second, no apparent change was the dominant SOP in patients
with occipital lobe FCD II (80% of SOPs, P ¼ 0.012). However, pre-
vious studies of occipital lobe epilepsy regardless of the etiologies
reported that ictal SOPs were fast activity or generalized repetitive
epileptiform discharges32,35 or localized in the occipital region35,36
with brief focal occipital suppression occasionally occurring pre-
ceding fast activity.37 Therefore, SOPs in the occipital lobe may
occur with no apparent change before onset of ictal symptoms,
followed by fast activities, etc. We need further studies in many
patients with occipital SOPs to clarify this point because of the
small number of patients in this study.

TABLE 4.
Ratio of Correct Localizations of SOPs at the Same Lobe as FCD/Total Numbers of SOPs Recorded in Each Patient

Location of FCD in MRI Correct R-EF* (%)

>75% (n, (%)) 75%-51% (n, (%)) 50%-26% (n, (%)) 25%-1% (n, (%)) 0% (n, (%))

Frontal (n ¼ 26) 10/26 (38.5) 6/26 (23.1) 6/26 (23.1) 3/26 (11.5) 1/26 (3.8)
Temporal (n ¼ 3) 2/3 (66.7) 1/3 (33.3) - - -
Occipital (n ¼ 2) - - - 2/2 (100.0) -
Total (n ¼ 31) 12/31 (38.7) 7/31 (22.6) 6/31 (19.4) 5/31 (16.1) 1/31 (3.2)

Abbreviations:
Correct R-EF ¼ Ratio of correct localizations of SOPs at the same lobe of FCD/total numbers of SOPs (correct, false, and undetermined localizations) recorded in each patient
FCD ¼ Focal cortical dysplasia
SOP ¼ Seizure onset pattern
*
No statistical significance compared by Fisher exact test.

52
T. Thamcharoenvipas, Y. Takahashi, N. Kimura et al.
Subtype of FCD II affects SOPs
Some of the patients in our study showed characteristic SOPs in
relation to pathologic types. In FCD IIa, SOPs of rhythmic slow
waves (43.5%) and fast activity (21.2%) were observed at signifi-
cantly higher rates than in FCD IIb, whereas in FCD IIb, the SOP of
repetitive spikes/sharp waves was more frequent than in FCD IIa.
We speculate that the difference in characteristic SOPs between
FCD IIa and FCD IIb may be due to differences in pathology such as
the composition of dysplastic neurons, differences in networks, and
altered synaptic transmission. One of the histologic differences
between FCD IIa and FCD IIb is the presence of balloon cells in FCD
IIb, which have a glutamate buffering effect, resulting in decreased
spread of epileptic activities.9,38 Relatively little spread of ictal ac-
tivity in FCD IIb may have contributed to the predominant SOP of no
apparent change.
Correct localization and lateralization rates of SOPs
The overall correct localizing and lateralizing rates of SOP were
both approximately 60% in patients with frontal or temporal FCD.
Seifer et al.29 reported a correct localization rate of scalp EEGs in
MRI-diagnosed FCDs of 50%. Compared with previous studies of
SOP in focal epilepsy regardless of pathology, our study, which
focused on focal epilepsy due to FCD II, found better localizing and
lateralizing rates. Elwan et al.39 reported a correct localization rate
of 60% and correct lateralization rate of 87.5%. The lower correct
localizing and lateralizing rates in our study may be causally related
to our definition of SOP as an EEG change just before the appear-
ance of ictal symptoms and our strict criteria for defining locali-
zation and lateralization.
False localization and lateralization values of SOPs
The false localizing rate of SOPs in temporal lobe FCDs in our
study was 41.2%, and the false localizations were mainly found in
the SOP of EEG change in contralateral temporal lobes (29.4%).
Previous studies in TLE reported that ictal propagation from one
side to the other was quite common and could be observed in
surface and invasive EEGs.33,40-43 These findings suggest that ictal
EEGs of TLE frequently show false contralateral homotopic foci. This
phenomenon may be related to deep interhemispheric
commissures.
The SOPs of frontal lobe FCD II had more frequent midline lo-
calizations (14.6%) and a lower success rate of lateralizing (34.7%)
results than with FCD IIs in the temporal lobes. A previous study on
frontal lobe epilepsy regardless of pathology showed localized
scalp EEG SOPs in only 30% to 40% of the cases.44 Some studies
attributed the lower correct localizing rate of scalp EEG SOPs in
frontal lobe epilepsy to prompt propagation of ictal discharges to
the contralateral hemisphere and the frequent association of
movement artifacts.44-48 In our study, SOPs in frontal lobe FCD IIs
showed a small proportion of contralateral propagation (15.7%),
which may have resulted in higher correct localization; this may
have been due to evaluation of SOPs just before the appearance of
ictal symptoms. A study of SOPs before the appearance of ictal
symptoms may be helpful in lateralizing the epileptogenic zone.
Surface ictal EEGs had a significant localization power
(approximately 60%), and their false lateralization rates were 2.6%
to 29.4%. This finding suggests that localization of SOPs by surface
EEG monitoring may be able to usefully contribute to the deter-
mination of the optimal site for intracranial mapping or investi-
gation. In addition, 61.3% of our patients had correct R-EFs above
50% for SOPs recorded by surface EEG monitoring, indicating that
certain types of surface SOPs can play an important role in
53
Pediatric Neurology 129 (2022) 48e54
accurately identifying the epileptic zone in noninvasive presurgical
evaluation.
Limitations
This study had several limitations. First, the small numbers of
patients with FCD in the parietal or occipital lobes limits the sta-
tistical reliability. Second, we enrolled only patients with good
surgical outcomes, because we wanted to evaluate the relationship
between foci suggested by SOP and localization of FCD. Further
studies including patients with fair or poor surgical outcomes are
needed to further elucidate the characteristics and significance of
scalp SOPs in the presurgical evaluation of refractory epilepsy
associated with FCD II. Third, we did not examine the SOPs of pa-
tients with lesional epilepsy other than FCD II. We must await
further studies about the relationship between SOPs and other le-
sions to reach firmer conclusions concerning the characteristic
SOPs in patients with FCD II. Fourth, in the 1990s, some patients had
to wait many years from the disease onset to the presurgical
investigation, because they could not be properly evaluated until
the launch of the 3.0-T MRI in Japan. These long latency periods
from the onset of epilepsy to the EEG monitoring might have
affected the SOPs.
Implication of findings and future directions
Our results suggest that surface EEG monitoring in patients with
refractory epilepsy related to FCD II can provide much useful pre-
surgical information, especially in a finding of repetitive spikes/
sharp waves SOPs, which may indicate the epileptogenic zone of
possible FCD IIb, or a finding of SOPs of rhythmic slow wave and fast
activity, which may indicate the epileptogenic zone of a possible
FCD IIa. An SOP of no apparent change in a surface EEG recording is
not a contraindication for surgery.
Larger studies of SOPs in patients with pathologically confirmed
FCD II are needed to provide more accurate data to identify corre-
lations between SOPs and pathologic findings in this group of
patients.
Conclusion
A surface ictal SOP is one of the noninvasive presurgical as-
sessments available in general neurology centers and can play an
important role in confirming localization and lateralization of
epileptic foci in patients with FCD II with few false lateralizations.
Acknowledgments
The authors thank Dr. Akihiko Kondo and Dr. Takayasu Tottori,
neurosurgeons at the National Epilepsy Center, Shizuoka Institute
of Epilepsy and Neurological Disorders, who performed epilepsy
surgeries and cared for the patients, and to all the doctors at the
Center for providing patient care. The authors also thank Nannapat
Pruphetkaew, statistical consultant of the Epidemiology Unit, Fac-
ulty of Medicine, Prince of Songkla University for data analysis.
References
1. Leventer RJ, Phelan EM, Coleman LT, Kean MJ, Jackson GD, Harvey AS. Clinical
and imaging features of cortical malformations in childhood. Neurology.
1999;53:715e722.
2. Barkovich AJ, Guerrini R, Kuzniecky RI, Jackson GD, Dobyns WB.
A developmental and genetic classification for malformations of cortical
development: update 2012. Brain. 2012;135:1348e1369.
3. Guerrini R, Sicca F, Parmeggiani L. Epilepsy and malformations of the cerebral
cortex. Epileptic Disord. 2003;5:S9eS26.
T. Thamcharoenvipas, Y. Takahashi, N. Kimura et al.
4. Lee SK, Kim DW. Focal cortical dysplasia and epilepsy surgery. J Epilepsy Res.
2013;3:43e47.
5. Kuzniecky R, Murro A, King D, et al. Magnetic resonance imaging in childhood
intractable partial epilepsies: pathologic correlations. Neurology. 1993;43:
681e687.
6. Kim YH, Kang HC, Kim DS, et al. Neuroimaging in identifying focal cortical
dysplasia and prognostic factors in pediatric and adolescent epilepsy surgery.
Epilepsia. 2011;52:722e727.
7. Bast T, Oezkan O, Rona S, et al. EEG and MEG source analysis of single and
averaged interictal spikes reveals intrinsic epileptogenicity in focal cortical
dysplasia. Epilepsia. 2004;45:621e631.
8. Battaglia G, Colciaghi F, Finardi A, Nobili P. Intrinsic epileptogenicity of
dysplastic cortex: converging data from experimental models and human pa-
tients. Epilepsia. 2013;54:33e36.
9. Boonyapisit K, Najm I, Klem G, et al. Epileptogenicity of focal malformations
due to abnormal cortical development: direct electrocorticographic-
histopathologic correlations. Epilepsia. 2003;44:69e76.
10. Namer IJ, Valenti-Hirsch MP, Scholly J, Lannes B, Imperiale A, Hirsch E. Hy-
permetabolism during resting-state FDG-PET suggesting intrinsic epi-
leptogenicity in focal cortical dysplasia. Clin Nucl Med. 2014;39:993e995.
11. O'Brien TJ, So EL, Cascino GD, et al. Subtraction SPECT coregistered to MRI in
focal malformations of cortical development: localization of the epileptogenic
zone in epilepsy surgery candidates. Epilepsia. 2004;45:367e376.
12. Otsubo H, Iida K, Oishi M, et al. Neurophysiologic findings of neuronal
migration disorders: intrinsic epileptogenicity of focal cortical dysplasia on
electroencephalography, electrocorticography, and magnetoencephalography.
J Child Neurol. 2005;20:357e363.
13. Blümcke I, Thom M, Aronica E, et al. The clinicopathologic spectrum of focal
cortical dysplasias: a consensus classification proposed by an ad hoc Task Force
of the ILAE Diagnostic Methods Commission. Epilepsia. 2011;52:158e174.
14. Hader WJ, Mackay M, Otsubo H, et al. Cortical dysplastic lesions in children with
intractable epilepsy: role of complete resection. J Neurosurg. 2004;100:110e117.
15. Kloss S, Pieper T, Pannek H, Holthausen H, Tuxhorn I. Epilepsy surgery in
children with focal cortical dysplasia (FCD): results of long-term seizure
outcome. Neuropediatrics. 2002;33:21e26.
16. Tassi L, Colombo N, Garbelli R, et al. Focal cortical dysplasia: neuropathological
subtypes, EEG, neuroimaging and surgical outcome. Brain. 2002;125:
1719e1732.
17. Fauser S, Schulze-Bonhage A, Honegger J, et al. Focal cortical dysplasias: sur-
gical outcome in 67 patients in relation to histological subtypes and dual pa-
thology. Brain. 2004;127:2406e2418.
18. Fauser S, Essang C, Altenmuller DM, et al. Long-term seizure outcome in 211
patients with focal cortical dysplasia. Epilepsia. 2015;56:66e76.
19. Kral T, Clusmann H, Blumcke I, et al. Outcome of epilepsy surgery in focal
cortical dysplasia. J Neurol Neurosurg Psychiatry. 2003;74:183e188.
20. Alexandre Jr V, Walz R, Bianchin MM, et al. Seizure outcome after surgery for
epilepsy due to focal cortical dysplastic lesions. Seizure. 2006;15:420e427.
21. Hamiwka L, Jayakar P, Resnick T, et al. Surgery for epilepsy due to cortical
malformations: ten-year follow-up. Epilepsia. 2005;46:556e560.
22. Choi SA, Kim SY, Kim H, et al. Surgical outcome and predictive factors of epi-
lepsy surgery in pediatric isolated focal cortical dysplasia. Epilepsy Res.
2018;139:54e59.
23. Park CK, Kim SK, Wang KC, et al. Surgical outcome and prognostic factors of
pediatric epilepsy caused by cortical dysplasia. Childs Nerv Syst. 2006;22:
586e592.
24. Kwon HE, Eom S, Kang HC, et al. Surgical treatment of pediatric focal cortical
dysplasia: clinical spectrum and surgical outcome. Neurology. 2016;87:
945e951.
25. Kimura N, Takahashi Y, Shigematsu H, et al. Developmental outcome after
surgery in focal cortical dysplasia patients with early-onset epilepsy. Epilepsy
Res. 2014;108:1845e1852.
54
Pediatric Neurology 129 (2022) 48e54
26. Krsek P, Maton B, Jayakar P, et al. Incomplete resection of focal cortical
dysplasia is the main predictor of poor postsurgical outcome. Neurology.
2009;72:217e223.
27. Kim DW, Lee SK, Chu K, et al. Predictors of surgical outcome and pathologic
considerations in focal cortical dysplasia. Neurology. 2009;72:211e216.
28. Team RC. R: A language and environment for statistical computing Vienna,
Austria. Available at: https://www.R-project.org/; 2020. Accessed July 14, 2021.
29. Seifer G, Blenkmann A, Princich JP, et al. Noninvasive approach to focal cortical
dysplasias: clinical, EEG, and neuroimaging features. Epilepsy Res Treat.
2012;2012:736784.
30. Williamson PD, French JA, Thadani VM, et al. Characteristics of medial temporal
lobe epilepsy: II. Interictal and ictal scalp electroencephalography, neuropsy-
chological testing, neuroimaging, surgical results, and pathology. Ann Neurol.
1993;34:781e787.
31. Risinger MW, Engel Jr J, Van Ness PC, Henry TR, Crandall PH. Ictal localization of
temporal lobe seizures with scalp/sphenoidal recordings. Neurology. 1989;39:
1288e1293.
32. Foldvary N, Klem G, Hammel J, Bingaman W, Najm I, Luders H. The localizing
value of ictal EEG in focal epilepsy. Neurology. 2001;57:2022e2028.
33. Tatum WOt. Mesial temporal lobe epilepsy. J Clin Neurophysiol. 2012;29:
356e365.
34. Ebner A, Hoppe M. Noninvasive electroencephalography and mesial temporal
sclerosis. J Clin Neurophysiol. 1995;12:23e31.
35. Adcock JE, Panayiotopoulos CP. Occipital lobe seizures and epilepsies. J Clin
Neurophysiol. 2012;29:397e407.
36. Beaumanoir A. Infantile epilepsy with occipital focus and good prognosis. Eur
Neurol. 1983;22:43e52.
37. Babb TL, Halgren E, Wilson C, Engel J, Crandall P. Neuronal firing patterns
during the spread of an occipital lobe seizure to the temporal lobes in man.
Electroencephalogr Clin Neurophysiol. 1981;51:104e107.
38. Abdijadid S, Mathern GW, Levine MS, Cepeda C. Basic mechanisms of epi-
leptogenesis in pediatric cortical dysplasia. CNS Neurosci Ther. 2015;21:
92e103.
39. Elwan S, Alexopoulos A, Silveira DC, Kotagal P. Lateralizing and localizing value of
seizure semiology: comparison with scalp EEG, MRI and PET in patients suc-
cessfully treated with resective epilepsy surgery. Seizure. 2018;61:203e208.
40. Gloor P, Salanova V, Olivier A, Quesney LF. The human dorsal hippocampal
commissure. An anatomically identifiable and functional pathway. Brain.
1993;116:1249e1273.
41. Lieb JP, Engel Jr J, Babb TL. Interhemispheric propagation time of human hip-
pocampal seizures. I. Relationship to surgical outcome. Epilepsia. 1986;27:
286e293.
42. Mintzer S, Cendes F, Soss J, et al. Unilateral hippocampal sclerosis with
contralateral temporal scalp ictal onset. Epilepsia. 2004;45:792e802.
43. Spencer SS, Marks D, Katz A, Kim J, Spencer DD. Anatomic correlates of
interhippocampal seizure propagation time. Epilepsia. 1992;33:862e873.
44. Kellinghaus C, Luders HO. Frontal lobe epilepsy. Epileptic Disord. 2004;6:
223e239.
45. Salanova V, Morris 3rd HH, Van Ness PC, Luders H, Dinner D, Wyllie E. Com-
parison of scalp electroencephalogram with subdural electrocorticogram re-
cordings and functional mapping in frontal lobe epilepsy. Arch Neurol.
1993;50:294e299.
46. Quesney LF. Preoperative electroencephalographic investigation in frontal lobe
epilepsy: electroencephalographic and electrocorticographic recordings. Can J
Neurol Sci. 1991;18:559e563.
47. Swartz BE, Walsh GO, Delgado-Escueta AV, Zolo P. Surface ictal electroen-
cephalographic patterns in frontal vs temporal lobe epilepsy. Can J Neurol Sci.
1991;18:649e662.
48. Laskowitz DT, Sperling MR, French JA, O'Connor MJ. The syndrome of frontal
lobe epilepsy: characteristics and surgical management. Neurology. 1995;45:
780e787.