CLINICAL ARTICLE

J Neurosurg 136:512–522, 2022

Predictors of surgical outcome in focal cortical dysplasia

and its subtypes
Sita Jayalakshmi, DM,1 Sudhindra Vooturi, PhD,1 Rammohan Vadapalli, MD,2
Sailaja Madigubba, MD,3 and Manas Panigrahi, MCh4
Departments of 1Neurology, 2Radiology, 3Pathology, and 4Neurosurgery, Krishna Institute of Medical Sciences,
Secunderabad, India

OBJECTIVE The authors analyzed predictors of surgical outcome in patients with focal cortical dysplasia (FCD) and its
ILAE (International League Against Epilepsy) subtypes after noninvasive multimodal evaluation and calculated time to
first seizure.
METHODS Data of 355 patients with refractory epilepsy, confirmed FCD pathology, and 2–13 years of postsurgical
follow-up were analyzed to determine the predictive roles of clinical, EEG, imaging, and surgical factors that influence
seizure freedom.
RESULTS The mean ± SD age at surgery was 20.26 ± 12.18 years. In total, 142 (40.0%) patients had daily seizures and
90 (25.3%) had multiple seizure types. MRI showed clear-cut FCD in 289 (81.4%) patients. Pathology suggested type I
FCD in 27.3% of patients, type II in 28.4%, and type III in 42.8% of patients. At latest follow-up, 72.1% of patients were
seizure free and 11.8% were seizure free and not receiving antiepileptic drugs. Among the subtypes, 88.8% of patients
with type III, 69.3% with type II, and 50.5% with type I FCD were seizure free. Multiple seizure types, acute postoperative
seizures (APOS), and type I FCD were predictors of persistent seizures, whereas type III FCD was the strongest predic-
tor of seizure freedom. Type I FCD was associated with daily seizures, frontal and multilobar distribution, subtle findings
on MRI, incomplete resection, and persistent seizures. Type II and III FCD were associated with clear-cut lesion on MRI,
regional interictal and ictal EEG onset pattern, focal pattern on ictal SPECT, complete resection, and seizure freedom.
Type III FCD was associated with temporal location, whereas type I and II FCD were associated with extratemporal loca-
tion. Nearly 80% of patients with persistent seizures, mostly those with type I FCD, had their first seizure within 6 months
postsurgery.
CONCLUSIONS Long-term seizure freedom after surgery can be achieved in more than two-thirds of patients with FCD
after noninvasive multimodal evaluation. Multiple seizure types, type I FCD, and APOS were predictors of persistent sei-
zures. Seizures recurred in about 80% of patients within 6 months postsurgery.
https://thejns.org/doi/abs/10.3171/2020.12.JNS203385
KEYWORDS focal cortical dysplasia; epilepsy surgery; seizure freedom; types of FCD; long-term follow-up

F
ocal cortical dysplasia (FCD) is the most common
malformation of cortical development (MCD), caus-
ing drug-resistant epilepsy (DRE). FCD is notorious
for intrinsic epileptogenicity.1–4 FCD is the most common
pathology in children and the third most common etiology
in adults undergoing epilepsy surgery.2,3 High-resolution
MRI has increased the rate of detection of FCD and early
resection.5 Detection of FCD on MRI is higher in patients
with severe pathology (type II FCD), and this has been
associated with better surgical outcome.6 Furthermore,
FDG-PET and ictal SPECT are complementary to MRI
for FCD localization, especially in patients with type I
FCD and patients with subtle findings on MRI.7 Complete
resection of FCD is a major prognostic factor for seizure
freedom,8 and histopathologic characteristics predict post-
surgical prognosis.5
Pathologic grade or type of FCD correlates with surgi-
cal outcome. Patients with type II FCD have higher rates
of seizure freedom after resective surgery, particularly
those with type IIb.2,9,10 However, Keene et al.11 and Kloss
et al.12 reported no differences in postsurgical outcomes
between patients with different subtypes of FCD. Fauser

ABBREVIATIONS AED = antiepileptic drug; APOS = acute postoperative seizures; ATL-AH = anterior temporal lobectomy with amygdalohippocampectomy; DRE = drug-
resistant epilepsy; ETLE = extratemporal lobe epilepsy; FCD = focal cortical dysplasia; ILAE = International League Against Epilepsy; MCD = malformation of cortical devel-
opment; TLE = temporal lobe epilepsy.
SUBMITTED September 4, 2020. ACCEPTED December 30, 2020.
INCLUDE WHEN CITING Published online July 30, 2021; DOI: 10.3171/2020.12.JNS203385.

512 J Neurosurg Volume 136 • February 2022 ©AANS 2022, except where prohibited by US copyright law

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et al.13 reported that patients with type I FCD and mild
MCD had better outcomes than those with severe forms
of FCD. In a long-term follow-up study, the same authors
reported that seizure freedom was significantly greater in
patients with unilobar FCD, complete resection of lesion,
age ≤ 18 years at surgery, and shorter duration of epilepsy,
whereas age > 18 years at surgery was a negative predic-
tive factor.14 In a meta-analysis, seizure freedom was as-
sociated with partial seizures, temporal location, detection
on MRI, type II FCD, and complete resection.8 Most stud-
ies included patients with type I and type II FCD or few
cases of type III FCD.
The aim of the present study was to investigate the roles
of clinical, EEG, imaging, and surgical predictive factors
for seizure freedom after surgery for FCD in patients with
DRE evaluated with a noninvasive multimodal protocol.
We also investigated the influence of International League
Against Epilepsy (ILAE) subtype of FCD on postopera-
tive seizure freedom and time to first seizure.
Methods
Patients
Of 987 patients who underwent epilepsy surgery be-
tween January 2005 and December 2019, we analyzed the
data of 355 consecutive patients who underwent surgery
for DRE and had a pathological diagnosis of FCD. The
inclusion criteria were 1) pathological diagnosis of type
I, II, or III FCD in the surgical specimen and 2) at least
2 years of postsurgical follow-up. Patients with tuber-
ous sclerosis, hemispherical dysplasia, and periventricu-
lar nodular heterotopia and those who required invasive
EEG monitoring were excluded from the study. Data on
presurgical, surgical, and postsurgical variables were col-
lected with an approved data collection form. Follow-up
consisted of patient visits and telephone calls. Follow-up
assessment was done at 3, 6, and 12 months postsurgery,
and then every year for at least 10 years or longer. The
study was approved by our institutional ethics committee.
Patients were included in the study after informed consent
was obtained from the patient or caregiver.
Presurgical Evaluation
All patients underwent presurgical evaluation with 3-T
MRI brain and video-EEG, as well as structured neuro-
psychological and developmental assessments. FDG-PET
with PET-MRI fusion was done in 262 patients, whereas
ictal SPECT was done in 157 patients. MRI was done
using a 3-T scanner (Ingenia 3T, Philips Healthcare) as
part of our epilepsy protocol; details were discussed in
a previous publication.7 MRI abnormalities were classi-
fied as either clear-cut FCD or subtle FCD (the brain was
apparently normal or the lesion was indistinct on MRI,
and FCD was detected retrospectively after PET-MRI
fusion). Functional MRI was used to evaluate lateraliza-
tion of language, memory, and motor functions for select
patients.
Prolonged video-EEG monitoring was done until at
least two seizures were recorded. Interictal spikes were
classified as unilateral (if 75% of spikes were confined to
the side of the lesion), bilateral, and multifocal. Seizure
Jayalakshmi et al.
semiology was classified as lateralized, nonlateralized,
and contralateral. Patterns on ictal EEG included focal,
regional, hemispheric, generalized, and contralateral.15
Regional onset on ictal EEG, lateralized semiology, and
unilateral spikes were compared with the other param-
eters in each FCD group.
FDG-PET was performed in all 156 patients with ex-
tratemporal lobe epilepsy (ETLE), as well as 106 patients
with temporal lobe epilepsy (TLE) and subtle findings on
MRI or no concordance between findings on MRI and
ictal EEG. PET-MRI fusion was performed using Syngo
Multimodality Workplace software (Siemens). The fusion
images were analyzed in all three projections. Metabolism
on PET was classified as focal (confined to the lesion/lobe)
hypometabolism or hypermetabolism or as normal metab-
olism. The extent of hypometabolism or hypermetabolism
was classified as lateralized if the PET abnormality was
beyond one lobe but in the same hemisphere. Findings
were classified as not informative if PET was normal or
inconclusive. For data analysis, patients with focal hypo-
metabolism and hypermetabolism were considered as one
group and compared with the rest.
Ictal SPECT was performed in 157 patients with TLE,
ETLE with subtle findings on MRI, or lack of concordance
between MRI and ictal EEG or MRI and FDG-PET. Dur-
ing video-EEG monitoring, SPECT images were obtained
with the Millennium MG system (GE Healthcare). Hyper-
perfusion on ictal SPECT was classified as focal (confined
to the lesion/lobe) or lateralized (beyond one lobe but in
the same hemisphere). Patients with focal hyperperfusion
and the rest were separated into two groups for analysis.
Surgery
Patients were approved for surgery after consensus was
reached regarding the surgical procedure at a multidis-
ciplinary conference that reviewed multimodality data.
Consensus was reached when concordance was observed
between at least two or more imaging modalities (clear-cut
lesion on MRI, localized pattern on FDG-PET, or local-
ized pattern on ictal SPECT; Figs. 1 and 2). All patients
with subtle findings on MRI were evaluated with FDG-
PET and ictal SPECT and underwent surgery, if both were
concordant. Surgical procedures included focal resection
(lesionectomy/lobectomy), multilobar resection, anterior
temporal lobectomy with amygdalohippocampectomy
(ATL-AH), and posterior disconnection. Neuronavigation
with MRI and FDG-PET data was used to confirm FCD
location during surgery.
Intraoperative ECoG was performed before and af-
ter resection under optimal anesthetic conditions. ECoG
results were graded as a score from 1 to 5.16 An ECoG
score of 2 to 5 was considered abnormal, and these regions
were included within the resected zone. During focal re-
section of a clear-cut lesion, the FCD was resected along
with at least 1 cm of circumferential cortex, and resection
was extended in noneloquent cortical regions if postresec-
tion ECoG showed epileptiform activity. In patients with
subtle findings on MRI, resection of the abnormality on
FDG-PET was performed with neuronavigation and ex-
tended on the basis of ECoG results. In patients with a
lesion that was close to or overlapping with the motor cor-
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Jayalakshmi et al.

FIG. 1. A patient with drug-resistant TLE and a right-sided subtle temporal abnormality (arrows) on 3D T1-weighted axial MR (A)
and 3D coronal FLAIR (B) images. Axial (C) and coronal (D) FDG-PET images show right-sided temporal hypometabolism, and
an axial ictal SPECT image (E) reveals right-sided temporal hyperperfusion. Interictal EEG (F) shows right-sided anterior and mid-
temporal spikes, and ictal EEG (G) is suggestive of right-sided hemispheric ictal onset. The patient underwent right-sided ATL-AH
and was seizure free for 42 months. The pathological diagnosis was type Ib FCD. Figure is available in color online only.

FIG. 2. A patient with drug-resistant frontal lobe epilepsy and a subtle prefrontal abnormality (arrows) on a 3D T1-weighted axial
MR image (A). Axial (B) and coronal (C) FDG-PET and PET-MRI fusion (E) images show left-sided mesial frontal hypometabo-
lism, and an axial ictal SPECT image (D) reveals left-sided frontal hyperperfusion. Interictal EEG (F) shows left-sided rhythmic
frontocentral (F3-C3) spikes, and ictal EEG (G) is suggestive of left-sided frontocentral onset. After left-sided, ECoG-guided
mesial frontal and prefrontal resection, the child was seizure free for more than 8 years. Histopathological examination was sug-
gestive of type IIa FCD. Figure is available in color online only.

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tex, the boundaries were defined with direct intraoperative
cortical stimulation under general anesthesia.
Pathologic Examination
A trained neuropathologist examined the resected tis-
sue, and FCD was classified as type I, II (including types
IIa and IIb), or III (including types IIIa, IIIb, IIIc, and
IIId) according to the ILAE classification system.17 Type I
FCD was characterized by isolated lesions, which present
with either radial and/or tangential dyslamination of the
neocortex. Type II FCD was characterized by isolated le-
sions with cortical dyslamination and dysmorphic neurons
without (type IIa) or with (IIb) balloon cells. Type III FCD
includes type IIIa (type I FCD with hippocampal sclero-
sis), type IIIb (type I FCD with glial or glioneuronal tu-
mor), type IIIc (type I FCD with cerebral vascular malfor-
mation), and type IIId (type I FCD with any other lesion
acquired during early life, such as those due to trauma,
ischemic injury, and encephalitis).
Postsurgical Evaluation and Outcome
Seizures that occurred within 7 days after surgery were
classified as acute postoperative seizures (APOS). All pa-
tients underwent EEG, neuropsychological evaluation at 3
months and 1 year, and brain MRI at 1 year postsurgery.
Completeness of resection was analyzed by comparison of
presurgical and postsurgical MRI data, but only for patients
with clear-cut FCD on MRI. Antiepileptic drugs (AEDs)
were continued unchanged through 1 year after surgery
and then down-titrated sequentially over a few months in
seizure-free patients. Outcome at the latest follow-up was
assessed (according to the ILAE classification system)
and categorized as class 1 (seizure free) or persistent sei-
zures.18 Patients who had seizures during AED reduction
but remained seizure free after AED was restarted were
considered seizure free. In patients with persistent seizures
following surgery, the time to first seizure was recorded.
Statistical Analysis
We confirmed data homogeneity, and all continuous
variables were expressed as mean ± SD and categorical
variables were expressed as number (percentage). The
primary outcome of the statistical analysis was seizure
freedom at latest follow-up. Accordingly, the study cohort
was divided into groups on the basis of seizure freedom,
FCD type, and FCD location (temporal vs extratemporal).
Intergroup comparison of categorical variables was done
using the Fisher’s exact test, whereas the independent Stu-
dent t-test was used for comparison of continuous vari-
ables. After univariate analysis, the variables that were
significantly different between groups (based on seizure
freedom) were included in logistic regression analysis to
evaluate predictors of seizure freedom.
The other outcome of interest was time to first seizure.
Because duration of follow-up ranged from 2 to 13 years,
Kaplan-Meier curves were used to show time to first sei-
zure for patients with the various types of FCD. Data
analysis was done using SPSS for Windows version 20.0
(IBM Corp.). A p value ≤ 0.05 was considered statistically
significant.
Jayalakshmi et al.
Results
Demographic and Clinical Variables
Of 355 included patients, 159 (44.8%) were women.
The mean ± SD age at onset of epilepsy was 9.71 ± 8.51
years, and the mean duration of epilepsy was 10.85 ± 8.22
years. The mean age at surgery was 20.26 ± 12.18 years.
Family history of epilepsy was reported by 68 (19.2%) pa-
tients, 72 (20.3%) had febrile convulsions, 49 (13.8%) had
a history of status epilepticus, and 53 (14.9%) had delayed
development. Aura was reported by 124 (34.9%) patients,
and 142 (40.0%) had daily seizures and 90 (25.3%) had
multiple seizure types.
Sensitivity of Various Diagnostic Modalities
Interictal EEG showed regional epileptiform discharg-
es in 229 (64.5%) patients, and 216 (60.8%) had regional
onset on ictal EEG. Seizure semiology was lateralized in
271 (76.3%) patients. The combination of semiology and
surface EEG data showed localization in 319 (89.9%) pa-
tients. MRI showed clear-cut FCD in 289 (81.4%) patients.
MRI showed a subtle abnormality in 66 (18.6%) patients,
and the lesion was identified after FDG-PET and MRI fu-
sion. Concordance between MRI and surface EEG data
was achieved in 78.5% (227) of patients, and concordance
between MRI and combined surface EEG and semiology
data was achieved in 92.3% (267) of patients with clear-
cut FCD and 78.78% (52) with subtle findings on MRI. Of
258 (72.7%) patients who underwent interictal FDG-PET,
230 (89.1%) had hypometabolism and 21 (8.1%) had hy-
permetabolism. Focal pattern on FDG-PET was observed
in 204 (77.9%) patients. Of the 157 patients who under-
went ictal SPECT, focal hyperperfusion was noted in 119
(75.8%) patients.
Surgical Procedures and Pathological Analysis
The most common surgery performed was ATL-
AH in 149 (42.0%) patients, followed by focal resection
in 143 (40.3%). Resection involved the temporal lobe in
199 (56.1%) patients, frontal in 102 (28.7%), parietal in 17
(4.8%), and occipital in 10 (2.8%) patients. Multilobar re-
section was done in 27 (7.6%) patients. FCD was close to
an eloquent cortex in 36 (10.1%) patients. There were no
deaths, but 35 (9.8%) patients had postsurgical complica-
tions, including 22 with transient motor weakness, 10 with
language disturbance, and 2 with hemianopia. One patient
had persistent foot drop, and 2 had hemianopia after pos-
terior disconnection.
Histopathological results were suggestive of type I
FCD in 97 (27.3%) patients, type II in 101 (28.4%) (IIa in
58 patients and IIb in 43), type IIIa in 116 (32.6%), type
IIIb in 17 (4.7%), type IIIc in 4 (1.1%), and type IIId in 15
(4.2%). Five (1.4%) patients had mixed type I/II FCD with
oligodendroglia hyperplasia. Complete resection of FCD
was done in 255 of 289 (88.2%) patients with clear-cut le-
sion on MRI.
Outcomes
Postsurgical follow-up ranged from 2 to 13 years. At
the latest follow-up, 256 (72.1%) patients were seizure free
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Jayalakshmi et al.
(ILAE class 1), and an additional 53 (14.9%) had > 90%
seizure reduction (ILAE class 2 and 3) and 23 (6.5%) had
50% seizure reduction (ILAE class 4). Five patients had
running-down phenomenon, with postoperative seizure
through 3 weeks postsurgery and maintenance of long-
term seizure freedom. Forty-two (11.8%) patients were not
receiving AEDs.
Predictors of Outcome
Analysis of the factors that influence seizure freedom
showed that mean age at onset (p = 0.007), duration of
epilepsy (p = 0.031), and age at surgery (p = 0.001) were
greater in patients who were seizure free (Table 1). Great-
er percentage of patients with persistent seizures had
daily seizures and multiple seizure types (both p ≤ 0.001)
than patients who were seizure free. Seizure freedom was
significantly associated with clear-cut MRI lesion (p =
0.006), lateralized seizure semiology (p = 0.005), and re-
gional interictal (p = 0.035) and ictal (p = 0.052) EEG on-
set pattern. A significantly greater proportion of seizure-
free patients had concordant findings between MRI and
ictal EEG compared with patients with persistent seizures
(56.6% vs 42.4%, p = 0.018). Patterns on FDG-PET and
ictal SPECT were distributed equally between groups (p
> 0.05).
Seizure freedom was associated with FCD location in
the temporal lobe (p ≤ 0.001), type III FCD (p ≤ 0.001),
and complete resection (p ≤ 0.001), whereas frontal (p ≤
0.001) and multilobar (p = 0.023) location, APOS (p ≤
0.001), resection close to an eloquent cortex (p ≤ 0.001),
and type I FCD (p ≤ 0.001) were associated with persistent
seizures (Table 1 and Fig. 3).
On multiple logistic regression analysis of outcome,
type III FCD was the strongest predictor of seizure free-
dom (β = 6.79, 95% CI 1.83–25.18, p = 0.004), whereas
predictors of persistent seizures were type I FCD (β
= 5.28, 95% CI 1.71–16.22, p = 0.004), multiple seizure
types (β = 0.35, 95% CI 0.12–0.99, p = 0.048), and APOS
(β = 0.29, 95% CI 0.11–0.80, p = 0.017).
Comparison of FCD Subtypes
Comparison of study variables among patients with
various types of FCD (I, II, and III) showed that more
children had type I FCD (45.4%), whereas type III FCD
was more common in adults. Early age at onset (< 2 years)
and presence of multiple seizure types were associated
with type I and II FCD when compared with type III FCD.
FCD was clear-cut on MRI in 92.8% of patients with type
III FCD, 82.2% of those with type II, and 61.9% of those
with type I FCD (Table 2).
Lateralized semiology, regional interictal and ictal
EEG onset pattern, and focal pattern on ictal SPECT were
more common in patients with type III FCD, followed by
patients with type II FCD. Type I FCD was associated
with frontal and multilobar location. Complete resection
of FCD (in patients with clear-cut lesion on MRI) was
achieved in 96.5% of patients with type III FCD, 69.3%
with type II, and 49.5% with type I. A significantly greater
number of patients with type I FCD had APOS (42.3%). At
the latest follow-up, 88.8% of patients with type III FCD,
516 J Neurosurg Volume 136 • February 2022
69.3% with type II, and 50.5% with type I were seizure
free. Of the 42 patients who were seizure free and not re-
ceiving AEDs, 30 (71.4%) had type III FCD, 9 (21.4%) had
type II, and 3 (7.14%) had type I FCD.
Comparison of FCD Location
Significantly greater percentages of patients with TLE
had clear-cut FCD on MRI (p = 0.039), lateralized semiol-
ogy (p = 0.002), regional interictal and ictal EEG onset
pattern (both p ≤ 0.001), and focal pattern on ictal SPECT
(p = 0.035) than patients with ETLE (Table 3). Nearly one-
third of patients with ETLE had onset of epilepsy at an
early age (p ≤ 0.001), multiple seizure types (p = 0.041),
and delayed development (p ≤ 0.001). Seizure frequency
was greatest among patients with ETLE, of whom 62.8%
had daily seizures prior to surgery (p ≤ 0.001). Type III
FCD was associated with TLE (p ≤ 0.001), whereas type
I and II FCD were associated with ETLE (p ≤ 0.001). Of
patients with FCD in the temporal lobe, nearly 84% were
seizure free and 15.6% were not receiving AEDs.
Time to First Seizure According to FCD Subtype
Chronological analysis with Kaplan-Meier curves of
time to first seizure among the 99 patients with persistent
seizures showed that 18 (18.19%) patients had their first
postoperative seizure within 1 week after surgery. An ad-
ditional 63 (63.63%) patients reported their first seizure
within 6 months after surgery; the majority of these pa-
tients (33 [52.3%]) had type I FCD (Fig. 4).
Discussion
In the current study, we have described and analyzed
the factors that affected long-term seizure outcomes after
surgery for DRE and FCD in a large single-center cohort.
Our results demonstrate that epilepsy surgery led to sei-
zure freedom in 72% of patients. Type III FCD was the
strongest predictor of seizure freedom. Multiple seizure
types, APOS, and type I FCD were predictors of persistent
seizures. About 80% of patients with persistent seizures,
mostly those with type I FCD, had their first seizure with-
in 6 months postsurgery.
The novelty of the present study is that all included
patients underwent noninvasive multimodal evaluation
and surgery when there was concordance between at least
two imaging modalities (brain MRI, FDG-PET, and ictal
SPECT). As suggested by Rathore and Radhakrishnan,
epilepsy surgery programs in low- and middle-income
countries should be customized and tailored instead of
merely duplicating the patterns and protocols of epilepsy
surgery programs in Western countries.19 In countries with
limited resources, where patients and their caregivers bear
the cost of medical care, the majority of patients cannot
afford the expensive, invasive EEG evaluations required
for presurgical evaluation.
Favorable seizure outcome after epilepsy surgery was
reportedly observed in 80% of patients with lesional epi-
lepsy, such as epilepsy due to primary brain tumor or
vascular malformation.5 However, the efficacy of surgi-
cal treatment was less favorable for patients with FCD,
with only 33%–75% of patients becoming seizure free.5
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TABLE 1. Comparison of presurgical and surgical variables according to seizure outcome (n = 355)
Variable Seizure Free (n = 256) Persistent Seizure (n = 99) p Value
Women 109 (42.6) 50 (50.5) 0.192
Age at surgery, yrs 21.5 ± 12.2 16.8 ± 11.3 0.001
<2 3 (1.2) 6 (6.1) 0.016
3–12 62 (24.2) 34 (34.3) 0.062
13–18 52 (20.3) 21 (21.2) 0.883
>18 139 (54.3) 38 (38.4) 0.009
Age at onset, yrs 10.5 ± 8.9 7.7 ± 6.7 0.007
Age <2 yrs 40 (15.7) 29 (29.3) 0.007
Duration of epilepsy, yrs 11.4 ± 8.4 9.3 ± 7.4 0.031
Febrile convulsion 57 (22.3) 15 (15.3) 0.183
Aura 109 (42.7) 15 (15.3) <0.001
Normal IQ 195 (76.5) 55 (55.6) <0.001
Psychiatric/behavioral problems 161 (62.9) 60 (60.6) 0.715
Delayed development 27 (11.2) 26 (28.0) <0.001
Daily seizure 84 (32.8) 58 (58.6) <0.001
Clear-cut lesion on MRI 218 (85.2) 71 (71.7) 0.006
Focal pattern on ictal SPECT (n = 157) 78 (77.2) 41 (73.2) 0.566
Focal pattern on FDG-PET (n = 262) 136 (80.0) 68 (73.9) 0.277
Onset pattern on interictal EEG
Regional 174 (68.0) 55 (55.6) 0.035
Hemispherical 44 (17.2) 13 (13.1) 0.421
Generalized 8 (3.1) 14 (14.1) 0.003
Bilateral/multifocal 30 (11.7) 17 (17.2) 0.220
Seizure semiology
Lateralized 206 (80.5) 65 (65.7) 0.005
Generalized 40 (15.6) 30 (30.3) 0.002
Bilateral 3 (1.2) 3 (3.0) 0.354
Contralateral 6 (2.3) 1 (1.0) 0.678
Multiple seizure types 42 (16.4) 48 (48.5) <0.001
Onset pattern on ictal EEG
Regional 164 (64.3) 52 (52.5) 0.052
Hemispherical 32 (12.5) 10 (10.1) 0.587
Generalized 36 (14.1) 33 (33.3) <0.001
Contralateral 4 (1.6) 2 (2.0) 0.672
Multifocal 19 (7.5) 2 (2.0) 0.076
Concordance btwn MRI & ictal EEG 145 (56.6) 42 (42.4) 0.018
FCD type
I 49 (22.1) 48 (52.2) <0.001
II 70 (31.5) 31 (33.7) 0.791
III 103 (46.4) 13 (14.1) <0.001
Location of FCD
Temporal 166 (64.8) 33 (33.3) <0.001
Frontal 58 (22.7) 44 (44.4) <0.001
Parietal 12 (4.7) 5 (5.1) >0.99
Occipital 6 (2.3) 4 (4.0) 0.474
Multilobar 14 (5.5) 13 (13.1) 0.023
Type of resection
Lesionectomy 92 (35.9) 51 (51.5) 0.008
ATL-AH 125 (48.8) 24 (24.2) <0.001
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TABLE 1. Comparison of presurgical and surgical variables according to seizure outcome (n = 355)
Variable Seizure Free (n = 256) Persistent Seizure (n = 99) p Value
Type of resection (continued)
Lobectomy 8 (3.1) 6 (6.1) 0.227
Multilobar resection 15 (5.9) 12 (12.1) 0.071
Posterior disconnection 1 (0.4) 2 (2.0) 0.189
Lesionectomy w/ ATL-AH 15 (5.9) 4 (4.0) 0.606
Resection close to eloquent cortex 14 (5.5) 22 (22.2) <0.001
Complete resection 214 (98.2) 41 (57.7) <0.001
APOS 46 (18.0) 44 (44.4) <0.001
Values are shown as number (percentage) or mean ± SD unless indicated otherwise.

In a meta-analysis of 2014 patients with FCD, Engel class I
(seizure-free) outcome after surgery was reported in mean
± SD 55.8% ± 16.2% of patients.8 In the current study, 72%
of patients were seizure free at latest follow-up. Complete-
ness of resection was associated with seizure freedom in
the current study. Incomplete resection is an independent,
important prognostic factor for poor surgical outcome.20
Complete resection of radiological abnormality is a sig-
nificant predictor of seizure freedom, and the odds of good
seizure control were about 6 times higher among patients
who underwent complete resection than those who did
not.4 FCD with dysplastic neurons is intrinsically epilep-
togenic; hence, the presence of any residual tissue after
resection will result in postsurgical seizures. FCD was
close to an eloquent cortex in 10% of patients and was a
predictor of persistent seizures in the current cohort. Such
patients often undergo subtotal resection to avoid the risk
of unacceptable postoperative neurological deficit.3 Subtle
or normal findings on MRI are often associated with dif-
ficulty to define the epileptogenic zone, which often results
in incomplete resection.5
Even in patients with clear-cut abnormality on MRI
who undergo epilepsy surgery for FCD, seizure outcome
is worse than those who undergo surgery because of other
focal lesional epilepsy syndromes.5 The rate of seizure
freedom for patients with clear-cut FCD on MRI was
85% in the current study, which is better than the rate of
80% reported for patients who underwent resection for fo-
cal epilepsy. Our better outcome may be due to the use
of multimodal diagnostic evaluation, which was reported
previously.7
Fauser et al.13,14 have reported that unilobar resection
is more successful than multilobar resection, but a meta-
analysis reported that temporal resection is associated
with seizure freedom.8 The current study reports that fron-
tal and multilobar FCD were associated with poor seizure
outcome, whereas FCD located in the temporal lobe was
associated with seizure freedom. Fauser et al.21 reported
that younger age at epilepsy surgery was an important
positive predictive factor, whereas age at surgery did not
influence seizure freedom in a meta-analysis.8 In the cur-
rent study, although type III FCD was a strong predictor of

FIG. 3. Comparison of rates of seizure freedom across various study variables (n = 355).

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 Jayalakshmi et al.

TABLE 2. Comparison of study variables according to FCD subtype (n = 350)

Variable Type I (n = 97) Type II (n = 101) Type III (n = 152)
Women 49 (50.5) 48 (48.0) 58 (38.4)
Age at surgery, yrs 17.13 ± 9.31 18.68 ± 12.28* 24.67 ± 12.22†
Age at onset <2 yrs 31 (32.0) 26 (25.7)* 10 (6.6)†
Febrile convulsion 8 (8.2) 15 (14.9)* 47 (31.0)†
Aura 23 (23.7) 30 (29.7)* 70 (46.1)†
Delayed development 29 (29.9) 17 (16.8) 5 (3.3)†
Daily seizure 50 (51.5) 60 (59.4)* 32 (21.1)†
Multiple seizure types 44 (45.4) 32 (31.7)* 11 (7.2)†
Regional onset on interictal EEG 43 (44.3)‡ 69 (68.3)* 111 (73.5)
Lateralized semiology 68 (70.1) 73 (72.3)* 128 (84.2)†
Regional onset on ictal EEG 41 (42.3)‡ 62 (61.4) 111 (73.5)†
Clear-cut lesion on MRI 60 (61.9)‡ 83 (82.2)* 141 (92.8)†
Focal pattern on ictal SPECT (n = 155) 43/64 (67.2)‡ 41/51 (80.4) 34/40 (85.0)†
Focal pattern on FDG-PET (n = 240) 70/95 (73.6) 75/94 (79.7) 42/51 (82.3)
Location of FCD
Temporal 28 (28.9) 34 (33.7)* 137 (90.1)†
Frontal 39 (40.2) 50 (49.5)* 11 (7.2)†
Parietal 8 (8.2) 9 (8.9) 0 (0.0)
Occipital 3 (3.1) 5 (5.0) 2 (1.3)
Multilobar 19 (19.6) 3 (3.0)* 2 (1.3)†
Resection close to eloquent cortex 16 (16.5) 15 (14.9)* 5 (3.3)†
Complete resection 46 (49.5)‡ 70 (69.3)* 136 (96.5)†
APOS 41 (42.3)‡ 27 (26.7)* 20 (13.2)†
Seizure free 49 (50.5)‡ 70 (69.3)* 135 (88.8)†
Not receiving AEDs 3 (3.1) 9 (8.9) 30 (19.7)†
Values are shown as number (percentage) or mean ± SD unless indicated otherwise.
* Significant difference between type II and type III FCD (p < 0.05).
† Significant difference between type I and type III FCD (p < 0.05).
‡ Significant difference between type I and type II FCD (p < 0.05).

seizure freedom, multiple seizure types, APOS, and type I
FCD were predictors of persistent seizures.
In the current study, we report that regional interictal
and ictal EEG onset patterns were more frequent in pa-
tients with type III FCD, followed by those with type II
FCD, and associated seizure freedom. Patterns on FDG-
PET and ictal SPECT did not influence outcomes. In com-
parison, Kim et al. reported that secondarily generalized
tonic-clonic seizures were associated with poor surgical
outcome, but results of MRI, scalp EEG, FDG-PET, and
ictal SPECT were not associated with surgical outcomes.20
Rowland et al. reported no association between EEG and
seizure freedom.8 Notably, all patients in the current study
underwent surgery after noninvasive multimodality evalu-
ation and their outcomes were comparable to those of pa-
tients who underwent invasive evaluation.20,21
FCD epileptogenicity is often associated with patho-
logical severity, resulting in different characteristics relat-
ed to the epileptogenic network. Tassi et al. reported that
isolated type I FCD is characterized by frequent seizures,
negative findings on MRI, frequent frontal or multilobar
involvement, and worse postsurgical outcome when com-
pared with type I FCD associated with other lesions.22 In
the current study, we report that type I FCD was associat-
ed with daily seizures, subtle abnormality on MRI, gener-
alized seizures, generalized interictal and ictal EEG onset
pattern, and frontal and multilobar distributions. Further-
more, type I FCD was associated with risk of incomplete
resection and increased risk of persistent seizures, whereas
type II and III FCD were associated with clear-cut lesion
on MRI, regional interictal and ictal EEG onset pattern,
focal pattern on ictal SPECT, significantly greater chance
of complete resection, and seizure freedom. In a large
multicenter cohort study, patients with type I FCD or mild
MCD had the worst seizure outcomes, with only 50% be-
ing free from disabling seizures.23 FCD localization to a
lobe or presence of widespread epileptogenic network does
influence surgical outcome. Type I FCD is generally more
widespread than type II FCD. FDG-PET is more sensitive
than MRI for evaluation of FCD, and use of multimodal-
ity imaging improves the chance of seizure freedom after
surgery.7 Kim et al.20 also reported that patients with FCD
of severe pathology (type II) had higher chances of com-
plete resection of FCD and subsequent seizure freedom.
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Jayalakshmi et al.

TABLE 3. Comparison of study variables between patients with ETLE and TLE (n = 355)
Variable ETLE (n = 156) TLE (n = 199) p Value
Age at surgery, yrs 17.47 ± 11.13 23.26 ± 11.98 <0.001
Age of onset <2 yrs 48 (30.8) 21 (10.6) <0.001
Febrile convulsion 18 (11.5) 54 (27.2) <0.001
Aura 31 (19.9) 93 (46.8) <0.001
Delayed development 43 (27.6) 10 (5.0) <0.001
Daily seizure 98 (62.8) 44 (22.1) <0.001
Multiple seizure types 26 (38.8) 6 (17.6) 0.041
Clear-cut lesion on MRI 119 (76.3) 170 (85.4) 0.039
Focal pattern on ictal SPECT (n = 157) 61 (68.5) 58 (85.3) 0.035
Focal pattern on FDG-PET (n = 224) 117 (75.0) 53 (77.9) 0.735
Regional onset on interictal EEG 78 (50.0) 151 (75.9) <0.001
Lateralized semiology 104 (66.7) 167 (83.9) 0.002
Regional onset on ictal EEG 74 (47.4) 142 (71.7) <0.001
FCD type on histopathology
I 69 (45.7) 28 (14.1) <0.001
II 67 (44.4) 34 (17.1) <0.001
III 15 (9.9) 137 (68.8) <0.001
Complete resection 93 (78.2) 162 (95.3) <0.001
APOS 54 (30.6) 36 (18.1) <0.001
Seizure freedom 90 (57.7) 166 (83.4) <0.001
Not receiving AEDs 11 (7.1) 31 (15.6) 0.013
Values are shown as number (percentage) or mean ± SD unless indicated otherwise.

FIG. 4. Comparison of times to first seizure among patients with different types of FCD.

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However, Fauser et al. reported that FCD types were not
correlated with postoperative seizure freedom.14 As sug-
gested by Hauptman and Mathern,3 if EEG cannot localize
type I FCD and MRI shows normal findings, noninvasive
tools are required to identify the lesion, detect the borders
of the lesion for histopathological analysis, and determine
whether the lesion involves the functional cerebral cortex.
In a large surgical series, patients with FCD represent-
ed 30% of the population, and those with type III FCD
represented about 10%.10 Type III FCD is characterized
by dyslamination with normal neurons (type I FCD) ad-
jacent to another principal lesion.10 Type IIIa FCD occurs
adjacent to hippocampal sclerosis, with the qualification
that the FCD must be in the temporal lobe near the hippo-
campus. Type IIIa FCD is not a dual-pathology condition,
which occurs when patients with hippocampal sclerosis
have a second principal lesion affecting the brain, includ-
ing type II FCD. In the current study, we report that most
patients with type III FCD were older than 18 years at
surgery, probably because type III FCD is an acquired le-
sion. Essentially, MRI showed a clear-cut lesion in 92.8%
of patients with type III FCD, which explains the high rate
of seizure freedom of 88.8% for this group. As reported
previously, the surgical results and clinical profiles of pa-
tients with type IIIb FCD were similar to those of patients
with isolated epilepsy-associated tumors, but not those of
patients with coexisting FCD.24 Likewise, similar rates of
seizure freedom were reported for patients with type IIIa
FCD and those with isolated hippocampal sclerosis.25–27 In
a small cohort of 69 patients with FCD, type III FCD was
associated with poor surgical outcome; however, these re-
sults cannot be generalized because only 15 patients with
FCD type III were included.28 Only limited studies are
available on the surgical outcomes of patients with type
III FCD.22,29
In the current study, about 80% of patients with persis-
tent seizure, most of whom had type I FCD, had their first
seizure within 6 months postsurgery. This is similar to the
previously reported mean of 4 months until postsurgical
seizure recurrence in patients with FCD.30 Fauser et al.13,14
reported that 21% of their study cohort were not receiv-
ing AEDs, and a further 37% had a relevant reduction in
AEDs from polytherapy to monotherapy. In the current
study, 11.8% of patients were seizure free and not receiv-
ing AEDs at latest follow-up.
Strengths and Limitations
The aim of this study was to analyze variables across
various ILAE subtypes of FCD; however, the substantial
number of patients with type III FCD, especially those
with type IIIa, may have influenced our findings. The find-
ings of the current study may have potential implications
in improving the feasibility of surgery for FCD after non-
invasive evaluation, especially in countries with limited
resources.
Conclusions
Long-term seizure freedom after surgery may be
achieved in more than two-thirds of patients with refracto-
ry epilepsy and FCD who undergo evaluation with a non-
Jayalakshmi et al.
invasive protocol. Multiple seizure types, type I FCD, and
APOS were predictors of persistent seizures. About 80%
of patients with persistent seizures, mostly those with type
I FCD, had their first seizure within 6 months postsurgery.
Type I FCD was associated with daily seizures, subtle ab-
normality on MRI, generalized seizures, generalized in-
terictal and ictal EEG onset pattern, frontal and multilobar
distribution, incomplete resection, and increased risk of
persistent seizures; type II and III FCD were associated
with clear-cut lesion on MRI, regional interictal and ictal
EEG onset pattern, focal pattern on ictal SPECT, and sig-
nificantly greater chances of complete resection and sei-
zure freedom.
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Disclosures
The authors report no conflict of interest concerning the materi-
als or methods used in this study or the findings specified in this
paper.
Author Contributions
Conception and design: Jayalakshmi, Panigrahi. Acquisition of
data: all authors. Analysis and interpretation of data: Jayalakshmi,
Vooturi, Madigubba. Drafting the article: Vadapalli. Critically
revising the article: Jayalakshmi, Panigrahi. Reviewed submitted
version of manuscript: Jayalakshmi, Panigrahi. Approved the final
version of the manuscript on behalf of all authors: Jayalakshmi.
Statistical analysis: Vooturi. Administrative/technical/material
support: Vadapalli.
Correspondence
Sita Jayalakshmi: Krishna Institute of Medical Sciences, Secun-
derabad, Telangana State, India. sita_js@hotmail.com.
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