New interinstitutional, multimodal presurgical evaluation protocol associated with improved seizure freedom for poorly defined cases of focal epilepsy in children

Solon Schur Montreal Neurological Institute and Hospital, McGill University Health Center, Department of Neurology and Neurosurgery, McGill University;

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Jeremy T. Moreau McConnell Brain Imaging Centre, Department of Neurology and Neurosurgery, Montreal Neurological Institute, McGill University;
Department of Pediatric Surgery, Division of Neurosurgery, Montreal Children’s Hospital, Montreal, Quebec, Canada;

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Hui Ming Khoo Department of Neurosurgery, Osaka University Graduate School of Medicine, Suita, Japan;

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Andreas Koupparis Montreal Neurological Institute, McGill University;

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Elisabeth Simard Tremblay Division of Neurology and Department of Clinical Neurophysiology, Montreal Children’s Hospital;

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Kenneth A. Myers Division of Neurology and Department of Clinical Neurophysiology, Montreal Children’s Hospital;

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Bradley Osterman Division of Neurology and Department of Clinical Neurophysiology, Montreal Children’s Hospital;

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Bernard Rosenblatt Division of Neurology and Department of Clinical Neurophysiology, Montreal Children’s Hospital;

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Jean-Pierre Farmer Department of Pediatric Surgery, Division of Neurosurgery, Montreal Children’s Hospital, Montreal, Quebec, Canada;

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Christine Saint-Martin Pediatric Radiology, Montreal Children’s Hospital, McGill University;

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Sophie Turpin Division of Nuclear Medicine, Medical Imaging, CHU Ste-Justine and Montreal Children’s Hospital; and

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Jeff Hall Montreal Neurological Institute and Hospital, McGill University Health Center, Department of Neurology and Neurosurgery, McGill University;

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Andre Olivier Montreal Neurological Institute and Hospital, McGill University Health Center, Department of Neurology and Neurosurgery, McGill University;

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Andrea Bernasconi Neuroimaging of Epilepsy Laboratory, Montreal Neurological Institute, McGill University, Montreal, Quebec, Canada

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Neda Bernasconi Neuroimaging of Epilepsy Laboratory, Montreal Neurological Institute, McGill University, Montreal, Quebec, Canada

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Sylvain Baillet Montreal Neurological Institute, McGill University;

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Francois Dubeau Montreal Neurological Institute and Hospital, McGill University Health Center, Department of Neurology and Neurosurgery, McGill University;

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Jean Gotman Montreal Neurological Institute, McGill University;

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Roy W. R. Dudley Montreal Neurological Institute and Hospital, McGill University Health Center, Department of Neurology and Neurosurgery, McGill University;
Department of Pediatric Surgery, Division of Neurosurgery, Montreal Children’s Hospital, Montreal, Quebec, Canada;

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OBJECTIVE

In an attempt to improve postsurgical seizure outcomes for poorly defined cases (PDCs) of pediatric focal epilepsy (i.e., those that are not visible or well defined on 3T MRI), the authors modified their presurgical evaluation strategy. Instead of relying on concordance between video-electroencephalography and 3T MRI and using functional imaging and intracranial recording in select cases, the authors systematically used a multimodal, 3-tiered investigation protocol that also involved new collaborations between their hospital, the Montreal Children’s Hospital, and the Montreal Neurological Institute. In this study, the authors examined how their new strategy has impacted postsurgical outcomes. They hypothesized that it would improve postsurgical seizure outcomes, with the added benefit of identifying a subset of tests contributing the most.

METHODS

Chart review was performed for children with PDCs who underwent resection following the new strategy (i.e., new protocol [NP]), and for the same number who underwent treatment previously (i.e., preprotocol [PP]); ≥ 1-year follow-up was required for inclusion. Well-defined, multifocal, and diffuse hemispheric cases were excluded. Preoperative demographics and clinical characteristics, resection volumes, and pathology, as well as seizure outcomes (Engel class Ia vs > Ia) at 1 year postsurgery and last follow-up were reviewed.

RESULTS

Twenty-two consecutive NP patients were compared with 22 PP patients. There was no difference between the two groups for resection volumes, pathology, or preoperative characteristics, except that the NP group underwent more presurgical evaluation tests (p < 0.001). At 1 year postsurgery, 20 of 22 NP patients and 10 of 22 PP patients were seizure free (OR 11.81, 95% CI 2.00–69.68; p = 0.006). Magnetoencephalography and PET/MRI were associated with improved postsurgical seizure outcomes, but both were highly correlated with the protocol group (i.e., independent test effects could not be demonstrated).

CONCLUSIONS

A new presurgical evaluation strategy for children with PDCs of focal epilepsy led to improved postsurgical seizure freedom. No individual presurgical evaluation test was independently associated with improved outcome, suggesting that it may be the combined systematic protocol and new interinstitutional collaborations that makes the difference rather than any individual test.

ABBREVIATIONS

EEG = electroencephalography; EZ = epileptogenic zone; FCD = focal cortical dysplasia; fMRI = functional MRI; icEEG = intracranial EEG; IED = interictal epileptiform discharge; MCH = Montreal Children’s Hospital; MEG = magnetoencephalography; MNI = Montreal Neurological Institute; NP = new protocol; OR = odds ratio; PDC = poorly defined case; PP = preprotocol; SEEG = stereo-EEG; SISCOM = subtraction ictal SPECT coregistered to MRI; VBPP = voxel-based postprocessing; VEEG = video-EEG.

OBJECTIVE

In an attempt to improve postsurgical seizure outcomes for poorly defined cases (PDCs) of pediatric focal epilepsy (i.e., those that are not visible or well defined on 3T MRI), the authors modified their presurgical evaluation strategy. Instead of relying on concordance between video-electroencephalography and 3T MRI and using functional imaging and intracranial recording in select cases, the authors systematically used a multimodal, 3-tiered investigation protocol that also involved new collaborations between their hospital, the Montreal Children’s Hospital, and the Montreal Neurological Institute. In this study, the authors examined how their new strategy has impacted postsurgical outcomes. They hypothesized that it would improve postsurgical seizure outcomes, with the added benefit of identifying a subset of tests contributing the most.

METHODS

Chart review was performed for children with PDCs who underwent resection following the new strategy (i.e., new protocol [NP]), and for the same number who underwent treatment previously (i.e., preprotocol [PP]); ≥ 1-year follow-up was required for inclusion. Well-defined, multifocal, and diffuse hemispheric cases were excluded. Preoperative demographics and clinical characteristics, resection volumes, and pathology, as well as seizure outcomes (Engel class Ia vs > Ia) at 1 year postsurgery and last follow-up were reviewed.

RESULTS

Twenty-two consecutive NP patients were compared with 22 PP patients. There was no difference between the two groups for resection volumes, pathology, or preoperative characteristics, except that the NP group underwent more presurgical evaluation tests (p < 0.001). At 1 year postsurgery, 20 of 22 NP patients and 10 of 22 PP patients were seizure free (OR 11.81, 95% CI 2.00–69.68; p = 0.006). Magnetoencephalography and PET/MRI were associated with improved postsurgical seizure outcomes, but both were highly correlated with the protocol group (i.e., independent test effects could not be demonstrated).

CONCLUSIONS

A new presurgical evaluation strategy for children with PDCs of focal epilepsy led to improved postsurgical seizure freedom. No individual presurgical evaluation test was independently associated with improved outcome, suggesting that it may be the combined systematic protocol and new interinstitutional collaborations that makes the difference rather than any individual test.

In Brief

The objective of this study was to test whether a new interinstitutional, multimodal presurgical evaluation protocol was associated with improved seizure freedom for poorly defined cases of focal epilepsy in children. The new systematic protocol, using advanced neuroimaging and electrophysiology tests, was associated with a 1-year postsurgical seizure freedom rate of 91% versus 47% in the preprotocol era. This is a major step forward in improving the care of children with poorly defined focal epilepsy.

Surgery for children with drug-resistant focal epilepsy has become the treatment of choice in well-selected cases, with favorable outcomes for both seizure control and quality of life. The great challenge in identifying good surgical candidates is localizing and delineating the epileptogenic zone (EZ). This is particularly problematic in so-called poorly defined cases (PDCs)1 for which MRI is negative or only a subtle signal abnormality is seen or when pathology is visible but is known to extend beyond what is seen on MRI, such as a focal cortical dysplasia (FCD)2 and tubers of tuberous sclerosis.

Surgery for PDCs is significantly less successful than in cases of radiologically well-defined lesions.3 Presurgical evaluation of such cases to identify the EZ involves at least video-electroencephalography (VEEG) telemetry and 1.5T MRI.4 The European guidelines for presurgical evaluation state that the investigating center should have at least two other methods of epilepsy-specific brain imaging such as FDG-PET, SPECT, and magnetoencephalography (MEG).5 Even the most dedicated epilepsy centers, which have access to some or all of these technologies, may not use them in a systematic fashion. Despite the availability of advanced imaging technologies and rigor with which they are used, this current practice results in only 50%–60% seizure freedom for PDCs after epilepsy surgery.3,612

Evidence and recommendations have suggested that more advanced neuroimaging methods should be used in such difficult cases, but very few studies have examined the impact of changes in presurgical evaluation strategies.13,14 To our knowledge, no study has addressed this question exclusively in PDCs in children. Afforded by a change in the presurgical evaluation protocol at our hospital in recent years, we had the opportunity to study this question. At the Montreal Children’s Hospital (MCH) prior to 2014, 3T MRI has been regularly performed since 2009 along with VEEG monitoring, but functional neuroimaging was performed on a case-by-case basis, while MEG, electroencephalography (EEG)–functional MRI (fMRI), and stereo-EEG (SEEG) were not used at all. In our previous report looking at the use of intraoperative MRI for focal epilepsy, only approximately 30% of patients underwent FDG-PET, SPECT, or intracranial EEG (icEEG)15 (Fig. 1 left). Starting in November 2014, we modified our presurgical evaluation strategy for PDCs and started using a new protocol (Fig. 1 right) involving new collaborations between our hospital and the Montreal Neurological Institute (MNI). Using advanced neuroimaging and electrophysiology technologies across our two centers, we used the following 3-tier presurgical evaluation protocol. We systematically performed VEEG, 3T MRI, and FDG-PET and attempted SPECT and MEG in all patients. When these studies alone did not provide a strong hypothesis regarding the EZ, we performed EEG-fMRI16 and/or advanced voxel-based postprocessing (VBPP) of 3T MRI, depending on the nature of the case.17 Finally, if these combined methods did not define the EZ sufficiently to allow resective surgery (as per multidisciplinary, interinstitutional consensus) but provided a sound EZ hypothesis, we performed icEEG, preferably with SEEG.

FIG. 1
FIG. 1

Comparison between the PP and NP presurgical evaluation strategies. ECoG = electrocorticography. Figure is available in color online only.

The goal of the present study was to examine how our new presurgical evaluation strategy has impacted postsurgical outcomes in PDCs of focal epilepsy. We hypothesized that 1) substantially more patients treated with the new strategy would obtain postsurgical seizure freedom, and 2) some new protocol tests would be associated with improved outcomes.

Methods

Chart review was performed for consecutive patients with PDCs of focal epilepsy for whom the new presurgical evaluation strategy was followed and who underwent resection (i.e., new protocol [NP]) and for the same number of consecutive PDCs who had undergone surgery just before the new strategy was implemented (i.e., preprotocol [PP]). Patients were required to have at least 1 year of follow-up to be included in the study. Well-defined cases (e.g., tumors, cavernous malformations), known multifocal cases, and diffuse hemispheric cases requiring functional hemispherectomies were excluded as well as patients who underwent nonresective surgeries such as corpus callosotomy and vagus nerve stimulator implantation. We reviewed the demographic and clinical characteristics, presurgical evaluation tests, anatomical location of the suspected EZ, resection volume (calculated from postoperative MRI using Brainlab software), pathology results, and surgical complications. For the presurgical evaluation tests that were used in both the NP and PP eras, there were no differences in the technique or equipment used, except that for NP patients, 3T MRI included 3D FLAIR and arterial spin labeling perfusion sequences, and for SPECT, concomitant VEEG was used. Based on chart review, and clarifying with the treating epileptologists in some cases, at 1-year postsurgical follow-up and at last follow-up, we assessed whether patients were completely seizure free (Engel class Ia) or not. STATA 15 (StataCorp) was used for statistical analysis. Results are reported as mean (SD) unless stated otherwise. We used the Student t-test for comparisons of means between the two groups and chi-square test for comparisons of categorical variables. We used Pearson’s correlations to examine the relationships between variables and univariate and multivariate logistic regression analyses to measure associations between variables and outcomes; p < 0.05 was considered statistically significant. The details of the PP and NP presurgical assessments, as well as the details of the neuroimaging and electrophysiology tests, the comprehensive epilepsy conferences, and the surgeries are provided in the Supplementary Information; the two protocols are compared in Fig. 1.

Results

Twenty-two patients in the NP era were compared with 22 patients in the PP era. The mean ages of the NP and PP groups were 112.9 and 99.7 months, respectively (Table 1). Preoperatively, the PP group was, on average, on a regimen of 2.4 antiepileptic drugs, and the NP group was on a regimen of 2.7 antiepileptic drugs. The mean lengths of follow-up were 26.2 months in the NP group and 46.5 months in the PP group (p = 0.001). Intracranial EEG was performed in 7 NP patients (5 SEEGs, 1 grid, and 1 combined grid/depth electrodes) and 4 PP patients (3 grids, 1 combined grid/depth electrodes). In terms of anatomical EZ localization, 45% patients in the PP group and 64% in the NP group had extratemporal epilepsy.

TABLE 1.

Characteristics of the NP and PP groups

NP (n = 22)PP (n = 22)p Value*
Mean age, mos112.9 (88.2–137.8)100 (70–129)0.48
Sex, n (%)>0.99
  Female10 (45)11 (50)
  Male12 (55)11 (50)
EZ location, n (%)0.23
  Temporal8 (36)12 (55)
   Rt6 (27)7 (32)
   Lt2 (9)5 (23)
  Extratemporal14 (64)10 (45)
   Rt frontal6 (27)4 (18)
   Lt frontal5 (23)4 (18)
   Rt parietal0 (0)1 (5)
   Lt parietal1 (5)0 (0)
   Lt temporoparietal2 (9)0 (0)
   Rt occipital0 (0)1 (5)
Seizure freedom at 1 yr, n (%)20/22 (91)10/22 (45)0.001
Seizure freedom at last FU, n (%)18/22 (82)6/22 (27)0.001
Mean no. of preop AEDs 2.7 (2.3–3.1)2.4 (1.92–2.81)0.21
Mean no. of AEDs at last FU1.0 (0.5–1.5)1.6 (1.2–2.1)0.80
Mean no. of tests performed7.9 (6.9–8.8)3.8 (3.3–4.3)0.0001
Study, n (%)
  MRI22 (100)22 (100)
  EEG22 (100)22 (100)
  PET22 (100)16 (73)
  Ictal SPECT17 (77)4 (18)
  Interictal SPECT16 (73)8 (36)
  MEG19 (86)0 (0)
  EEG-fMRI8 (36)0 (0)
  Invasive monitoring7 (32)4 (18)
   SEEG5 (23)0 (0)
   Grids/strips1 (5)3 (14)
   Combined1 (5)1 (5)
  PET/FLAIR coregistration15 (68)0 (0)
  VBPP3 (14)0 (0)
  SISCOM5 (23)0 (0)
Mean FU length, mos26 (20–32)47 (39–54)0.001
Mean vol of resection, cm3 28 (18–38)23 (15–40)0.42
MRI abnormality, n (%)12 (55)15 (68)0.35
Pathology, n (%)
  FCD14 (64)11 (50)0.22
   Ia3 (14)5 (23)
   Ib0 (0)2 (9)
   IIa5 (23)2 (9)
   IIb3 (14)1 (5)
   IIa & IIb2 (9)1 (5)
   IIId1 (5)0 (0)
  Tuberous sclerosis0 (0)4 (18)
  Hippocampal sclerosis3 (14)1 (5)
  Polymicrogyria0 (0)2 (9)
  Gliosis2 (9)2 (9)
  Other3 (14)2 (9)

AED = antiepileptic drug; FU = follow-up.

Mean values are presented as the mean (95% CI). Boldface type indicates statistical significance.

Student t-test or chi-square test.

NP patients underwent more tests than the PP patients, with 7.9 tests on average versus 3.8 tests. Logistic regression analysis found that with every increase in one test, the odds of being seizure free at 1 year postsurgery was increased by a factor of 1.31 (Table 2). When assessing seizure freedom at the end of follow-up, every increase in one test was associated with an odds ratio (OR) of seizure freedom of 1.37. The proportion of patients undergoing FDG-PET, ictal SPECT, interictal SPECT, and icEEG was larger in the NP group than the PP group (Fig. 2). MEG, PET/FLAIR coregistration, EEG-fMRI, subtraction ictal SPECT coregistered to MRI (SISCOM), and MRI VBPP were used only in the NP group.

TABLE 2.

OR of seizure freedom on univariate analysis at 1 year and at the last follow-up

Seizure Freedom at 1 YrSeizure Freedom at Last FU
OR (95% CI) p ValueOR (95% CI) p Value
Age1.00 (0.99–1.01) 0.791.00 (1.00–1.02)0.13
Male sex1.00 (0.28–3.55)>0.991.00 (0.31–3.28)>0.99
Temporal EZ location 0.32 (0.86–1.21)0.090.71 (0.22–2.36)0.58
NP 10.28 (2.24–64.38)0.00412.00 (2.86–50.31)0.001
No. of tests performed 1.31 (0.95–1.80)0.0951.37 (1.02–1.84)0.036
PET5.6 (0.89–35.42)0.072.75 (0.45–16.90)0.28
Ictal SPECT2.06 (0.56–7.61)0.282.6 (0.76–8.9)0.13
Interictal SPECT0.86 (0.24–3.08)0.811.4 (0.42–4.62)0.58
MEG7.85 (1.49–41.35)0.01511.33 (2.55–50.40)0.001
Intracranial recording0.76 (0.18–3.20)0.710.61 (0.16–2.42)0.49
SISCOM2.00 (0.20–19.75)0.553.80 (0.39–37.13)0.25
EEG-fMRI1.5 (0.26–8.58)0.653.00 (0.53–16.90)0.21
PET/FLAIR coregistration11.37 (1.32–98.31)0.0275.7 (1.31–24.53)0.020
FCD1.125 (0.31–4.07)0.864.5 (1.24–16.28)0.022
MRI abnormality0.83 (0.22–3.10)0.790.51 (0.15–1.77)0.29
Mean resection vol0.99 (0.96–1.02)0.440.99 (0.96–1.02)0.44

Boldface type indicates statistical significance.

FIG. 2
FIG. 2

Proportion of patients in the PP and NP groups who underwent each preoperative diagnostic test.

Early outcome data for seizure freedom were obtained at the first neurology clinic visit, which was at least 1 year after surgery; due to discrepancies in 1-year follow-up clinic appointment scheduling, the 1-year outcomes were measured at a mean of 13.6 and 15.9 months for the NP and PP groups, respectively (p = 0.10). In terms of 1-year postsurgical seizure freedom, 20 (90.9%) of 22 NP patients and 10 (45.5%) of 22 PP patients were seizure free (Table 1). Using univariate logistic regression, the OR of seizure freedom in the NP group compared with the PP group at 1 year was 10.28 (Table 2). This finding was confirmed on multivariate logistic regression, controlling for age, sex, temporal location of the EZ, and FCD pathology (Table 3). In terms of postsurgical seizure outcome over the length of our study, 18 (81.8%) of 22 patients in the NP group and 6 (27.3%) of 22 patients in the PP group were seizure free with mean follow-ups of 26 and 47 months, respectively. The OR of seizure freedom in the NP group compared with the PP group was 12.00, at the time of last follow-up.

TABLE 3.

Multivariate logistic regression for OR of seizure freedom at 1 year

OR (95% CI)p Value
Age1.01 (1.00–1.02)0.48
Male sex1.50 (0.30–7.39)0.62
Temporal EZ location0.25 (0.038–1.69)0.16
NP group11.81 (2.00–69.68)0.006
FCD0.77 (0.15–3.91)0.86

Boldface type indicates statistical significance.

Fifteen (68.2%) of 22 patients in the PP group and 12 (54.5%) of 22 patients in the NP group had some form of signal abnormality on 3T MRI. There was no difference in the likelihood of seizure freedom between the patients who had visible abnormalities on MRI and those who did not, and there was no significant difference in the mean volume of resection between the PP (23 cm3) and NP (28 cm3) groups. The volume of resection was not associated with the likelihood of seizure freedom. In terms of pathological diagnosis, 14 (64.0%) patients in the NP group and 11 (50%) in the PP group had FCD (type I, II, or III). While there was no association between the diagnosis of FCD and seizure freedom at 1 year, there was an association between FCD and seizure freedom at the last follow-up. Of note, no NP patients had tuberous sclerosis, while 4 PP patients had this diagnosis; 3 of these 4 patients became seizure free after surgery. The other pathologies found in each group are listed in Table 1.

Using univariate logistic regressions for the OR of seizure freedom for each preoperative testing modality, MEG and PET/FLAIR coregistration were the only variables significantly associated with increased seizure freedom at 1 year as well as at the time of last follow-up (Table 2). All patients whose 3T MRI studies were analyzed with VBPP were seizure free; therefore, logistic regression analysis could not be performed. Age, sex, temporal EZ location, and the other imaging modalities were not significantly associated with improved seizure freedom.

To better characterize the association between MEG, PET/FLAIR, and the protocol group, we calculated Pearson’s correlation coefficients and found that these three variables were greatly associated. The correlation coefficient for the protocol group and MEG was 0.87, for the protocol group and PET/FLAIR coregistration it was 0.71, and for the protocol group and the number of tests it was 0.76. Together, these findings suggest that the protocol group is colinear with MEG, PET/FLAIR coregistration, and the number of tests performed. Therefore, we opted to retain only the protocol group in our multivariate regression model, which controls for age, sex, the location of the EZ, and the pathology; the NP was associated with improved seizure freedom at 1 year (Table 3).

In terms of complications, at 1-year follow-up, 2 patients in the PP group (1 with left hemiparesis and 1 with right foot drop) and 2 patients in the NP group (1 with dysarthria and 1 with left foot drop) had persistent long-term deficits. There were no deaths in either group, and no patients were lost to follow-up.

Discussion

We present evidence that a new multimodal, 3-tier presurgical evaluation protocol involving interinstitutional collaborations has led to improved seizure outcomes for PDCs of focal epilepsy in children. In tier 1, we performed VEEG, 3T MRI, and PET and attempted interictal/ictal SPECT and MEG in each patient. MEG and PET/FLAIR coregistration were significantly associated with increased seizure freedom on univariate logistic regression. MEG was performed at the MNI with concomitant EEG, with the intention of recording interictal epileptiform discharges (IEDs) to align with simultaneous MEG spikes. In addition, 2 of our patients had seizures during overnight MEG recordings, the onset of which was successfully analyzed.18 The combination of these MEG analyses allowed us to collect source-localizing data for all 19 patients who underwent MEG. The protocolized (i.e., obligatory) aspect of MEG testing allowed us to acquire useful data on some patients who would normally be thought of as poor candidates (i.e., no IEDs) and not subjected to MEG. Almost every patient who underwent MEG became seizure free (17 of 19) compared with only half of those who did not (13 of 25). Eight of 22 NP patients had focal abnormalities found by PET/FLAIR coregistration; 6 of these patients underwent final resection based on these findings and all became seizure free without icEEG. Chassoux et al. found an increase of PET localization of FCD type II from 44% to 83% when PET was coregistered with MRI, and > 90% of patients remained seizure free following resections based on PET/FLAIR localization with a mean follow-up of more than 5 years, despite implanting fewer patients with SEEG.19,20 However, in our series, seizure outcomes associated with both MEG and PET/FLAIR coregistration were highly correlated with those of the new protocol group. Hence, it may be that the combined systematic protocol and new interinstitutional collaborations is what makes the difference as opposed to MEG and/or PET/FLAIR themselves.

If tier 1 tests did not sufficiently delineate the EZ, in tier 2, patients underwent EEG-fMRI and/or 3T-MRI VBPP (at the MNI) in a selective manner based on the specific details of the case. EEG-fMRI has been shown to be useful in delineating the EZ in both adults and children.2124 However, it requires relatively abundant IEDs (and periods of inactive background). Therefore, we only performed EEG-fMRI in 8 patients (of the 22 NP patients) who did not have their EZ well delineated after tier 1 tests but did have an adequate frequency of IEDs. In 2 patients, EEG-fMRI findings were highly concordant with MEG source localization; both went on to have focal resections based on these two results without icEEG, and both patients are seizure free at 18 and 36 months postoperatively. In 4 completely MRI-negative cases, EEG-fMRI findings helped to plan SEEG implantations, and 3 of the 4 patients are seizure free 18–24 months postsurgery.

Three-Tesla MRI VBPP involves brain texture analysis with relative intensity and gradient assessments calculated on 3D T1-weighted MRI, which models the increased signal intensity and the gray matter–white matter blurring associated with FCD, respectively.17 These advanced MRI analysis methods were only used when tier 1 tests pointed to a focal abnormality but no lesion was confidently seen on 3T MRI. Only 3 of our 22 NP patients underwent VBPP; in all 3 patients, a suspected FCD was detected. In 2 patients, this helped in planning the intracranial recording, and in 1 patient icEEG was avoided altogether. In all 3 patients, FCD type IIa was found, and all 3 became seizure free. Importantly, all interpretation and conclusions of both the EEG-fMRI and VBPP analyses were made by the experienced clinical research teams performing these tests on a routine basis at the MNI.

If tier 1 and 2 tests did not define the EZ well enough to plan surgery but provided a sound EZ hypothesis, in tier 3 icEEG, preferably SEEG, was performed. Our NP involved a switch from subdural grids to SEEG from the start. We consider that the 3D convolutional anatomical organization of the brain, consisting of deep interfolded gyri and sulci, requires a 3D intracerebral method of epileptic abnormality source localization. However, due to limitations of spatial coverage, a very strong hypothesis is required to plan a successful SEEG implantation. Therefore, all patients included in this study who underwent SEEG implantation were first presented at comprehensive epilepsy conferences at both MCH and MNI to make certain that each was a good candidate. Furthermore, all SEEG implantation schemes (i.e., where exactly to implant the electrodes) were designed in collaboration with epileptologists at the MNI who had a great deal of experience with SEEG on re-review of all data, in particular, the semiology and surface EEG findings. Finally, for each case, regular discussion of the SEEG findings was had with the same experienced team at the MNI on an almost daily basis and during a dedicated SEEG conclusion meeting at the end of the recording period. We speculate that the first two tiers of our NP, along with the absolute requirement for a strong EZ hypothesis for SEEG implantation and dedicated SEEG implantation planning and thorough review with experienced SEEG epileptologists, contributed to our early SEEG success with these challenging cases; 4 of 5 SEEG patients became seizure free after surgery. In addition, these same collaborations forced us to be very selective in terms of which implanted patients would ultimately be offered resective surgery; for the period referred to in this paper, only 6 of 10 patients with SEEG implantations were offered surgery.

We found only two published studies examining a change in presurgical evaluation protocol in children and none specifically looking at PDCs. Belohlavkova et al. studied differences in their epilepsy surgery program between their 2000–2009 and 2010–2017 cohorts.13 More presurgical evaluation tests were performed, SEEG almost completely replaced subdural grids, and more gross-total resections were achieved in the more recent cohort; however, the rate of seizure freedom was not different between the two cohorts.13 We did not examine extent of resection because for PDCs, we feel that gross-total resection cannot be accurately assessed; by definition, MRI studies either are negative or reveal signal abnormalities that represent pathologies that extend beyond what is seen. However, we did examine the volume of resection and found no significant difference between the two groups and no association with seizure outcome. This suggests that the improved NP outcomes were not a product of becoming more surgically aggressive; instead, the NP appears to allow us to better delineate the EZ so that similar resection volumes are more likely to lead to improved outcomes. In the second study, Rubinger et al. reported on the change in presurgical evaluation protocol at the Hospital for Sick Children in Toronto, which occurred in 2008 and involved a switch from 1.5T to 3T MRI and the use of a combination of MEG and FDG-PET.14 The change was associated with a significant improvement in seizure freedom. MEG and icEEG were not used more in their new protocol, and there was no significant difference in the number of abnormalities detected with 3T MRI. PET was used 10 times more often in their new protocol group (34% vs 3%), but the authors did not test whether it was independently associated with improved outcomes.

Limitations

Our study is potentially subject to the limitations of a retrospective chart review, such as selection bias; however, we followed strict inclusion and exclusion criteria to avoid this. In addition, our cohort is relatively small and the follow-up relatively short, especially for the NP patients. We speculate that the small number of surgical cases is partly due to the fact that we have become more selective in offering surgery in recent years. In the NP era, we have been admitting more patients for presurgical evaluation than ever before, yet our number of resective epilepsy surgeries performed per year has not increased greatly; this increased selectivity, which cannot be easily quantified, also likely plays a significant role in the improved surgical outcomes seen here. However, despite our relatively small numbers, we argue that it was important to share this early experience, as it may be beneficial to other clinicians struggling with similar cases. As for the follow-up time, we acknowledge that 1 year is not enough when it comes to postsurgical seizure outcomes. Seizures can recur in the long term despite early postsurgical seizure freedom rates. Bulacio et al. showed that their 1-year seizure freedom rate of 61% for icEEG cases decreased to 33% at 10 years.25 For this reason, we also included long-term seizure outcome results for both the PP and NP groups from the last clinic visit follow-up for all patients. The trouble with this, of course, was that the follow-up was almost double for the patients treated in the previous PP epoch versus those in the more recent NP group. Our 1-year seizure freedom rates of 46% for PP patients and 91% for NP patients decreased to 27% and 82%, respectively. However, it was reassuring that our 26-month seizure freedom rate for the NP group was still much higher than the 1-year seizure freedom rate for the PP group. Another limitation of the paper is that we were not able to elucidate the patient characteristics that improve the value of each presurgical test. That being said, we empirically know that certain patient factors are prerequisites to achieving “informative” results for some of the tests used. For MEG and EEG-fMRI, it is necessary for the patient to have some interictal epileptiform discharges to be used for source localization. SPECT is most beneficial for patients who have regular (but not too frequent) and easily recognizable seizures that last at least 30 seconds, such that a good ictal injection can be achieved. PET hypometabolism can be subtle and thus is most useful when this hypometabolism corresponds to signal and/or structural abnormalities on 3T MRI, particularly the 3D FLAIR sequence. Finally, icEEG, particularly SEEG, requires a strong hypothesis on which to base the electrode trajectory planning.

In addition to the different set of presurgical evaluation tests used, there are other very important differences between the two groups that cannot be easily quantified or compared. As described, the NP involved new formal collaborations between our pediatric epilepsy surgery program at the MCH and experienced epilepsy clinicians and neuroimaging/electrophysiology researchers at the MNI. Some NP patients were presented at seizure conferences in both hospitals, and the patients were discussed on multiple occasions with repeated interrogation of semiology, imaging, and electrophysiology data. Furthermore, there were other changes between the two protocols in terms of personnel involved, training of those personnel, ways of thinking, and clinical practices (see Other Differences Between the PP and NP Groups in the Supplementary Information), which should all be considered potential confounders in this study. Our study was underpowered to decipher which elements contributed most to improved seizure freedom; however, we believe that these new collaborations have been very important not just in localizing the EZ but also in the related aspects of deciding which patients to perform certain tests on, which patients to implant with SEEG, and finally which patients to offer final resective surgery; again, we feel that we have become more selective, particularly in regard to the latter. On the other hand, at least 1 patient who had not been offered surgery after his PP investigations was offered surgery following the NP (and became seizure free). Here, we reported only the patients who went on to have surgery, while a more important question is, “What proportion of all patients investigated ended up being offered surgery and obtaining good outcomes?” This question will be addressed in a subsequent study with larger numbers, which should also help to decipher which of the presurgical evaluation tests are most helpful. Of course, to decrease costs and resources used, as well as to avoid potential complications, it would be beneficial to perform fewer tests for these children, particularly those requiring sedation, ionizing radiation, and icEEG. In particular, we must consider the cost-effectiveness of our new protocol. While a formal cost-benefit ratio analysis is outside the scope of the current study, we have no reason to believe that the well-described cost-effectiveness of epilepsy surgery in other contexts including children would not apply to our protocol, considering the high rate of seizure freedom we have described for our NP cohort especially keeping in mind the potential long-term neurodevelopmental and societal benefits of successful epilepsy surgery in children.2630

We feel that our study is generalizable within reason. First of all, conceptually, it is generalizable in the sense that if a pediatric hospital that performs epilepsy surgery and uses some standard neuroimaging/electrophysiology techniques wants to try using some advanced imaging methods and they collaborate with experts in those advanced techniques and have access to some form of icEEG, they could potentially improve their outcomes. From a more concrete point of view, what we did could be done by any children’s hospital that has access to EEG, 3T MRI, PET, and SPECT; has access to a geographically feasible partner hospital with MEG, EEG-fMRI, and 3T-MRI VBPP; and has access to SEEG and the necessary expertise to plan and interpret these latter four studies. Maybe this scenario is rarer, but we can think of several cities where such capabilities exist. Both scenarios, the conceptual and the concrete, would require significant and sustained human effort in terms of the interest and will to do this, the determination to see it though for each case, and the ability to develop and maintain the necessary interpersonal interactions/relationships/collaborations to discuss each case in detail after each result, and to maintain such a program.

Conclusions

The present study highlights the benefits of a new interinstitutional, multimodal presurgical evaluation strategy for PDCs of focal epilepsy, which includes a standardized battery of baseline neuroimaging/electrophysiology tests and new collaborations that have provided both access to more advanced imaging/electrophysiology modalities and SEEG, as well as the necessary experience and expertise to interpret the results of these tests. At this point, it appears more likely that the switch to a systematic regimen of tests along with the new collaborations and expertise played a greater role in the improved outcomes rather than any individual test.

Acknowledgments

Special thanks to Nassima Addour for her clerical assistance in formatting and submitting the paper, and for obtaining informed consent from the patients and parents to present this report.

This study was funded by Foundation of the Department of Neurosurgery, McGill University (charitable registration no: 73954 0920 RR 0001). Dr. Moreau reports grants from Fonds de Recherche du Québec–Santé, grants from Foundation of Stars, and grants from Canada First Research Excellence Fund, awarded to McGill University for the Healthy Brains, Healthy Lives initiative, during the conduct of the study.

Disclosures

Dr. Khoo: consultant for Zimmer Biomet.

Author Contributions

Conception and design: Dudley. Acquisition of data: all authors. Analysis and interpretation of data: all authors. Drafting the article: Dudley, Schur. Critically revising the article: all authors. Reviewed submitted version of manuscript: all authors. Approved the final version of the manuscript on behalf of all authors: Dudley. Statistical analysis: Schur. Study supervision: Dudley.

Supplemental Information

Online-Only Content

Supplemental material is available with the online version of the article.

Previous Presentations

An abstract of preliminary work of this study was presented at the 42nd Annual Meeting of the American Society of Pediatric Neurosurgeons, Koloa, Hawaii, January 27–February 1, 2019.

References

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    • PubMed
    • Search Google Scholar
    • Export Citation
  • 2

    Mathern GW. Challenges in the surgical treatment of epilepsy patients with cortical dysplasia. Epilepsia. 2009;50(suppl 9):4550.

  • 3

    Krsek P, Maton B, Jayakar P, Dean P, Korman B, Rey G, et al. Incomplete resection of focal cortical dysplasia is the main predictor of poor postsurgical outcome. Neurology. 2009;72(3):217223.

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  • 4

    Go C, Snead OC III. Pharmacologically intractable epilepsy in children: diagnosis and preoperative evaluation. Neurosurg Focus. 2008;25(3):E2.

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    Rosenow F, Bast T, Czech T, Feucht M, Hans VH, Helmstaedter C, et al. Revised version of quality guidelines for presurgical epilepsy evaluation and surgical epilepsy therapy issued by the Austrian, German, and Swiss working group on presurgical epilepsy diagnosis and operative epilepsy treatment. Epilepsia. 2016;57(8):12151220.

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  • 6

    Kim DW, Lee SK, Nam H, Chu K, Chung CK, Lee SY, et al. Epilepsy with dual pathology: surgical treatment of cortical dysplasia accompanied by hippocampal sclerosis. Epilepsia. 2010;51(8):14291435.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 7

    Hauptman JS, Mathern GW. Vagal nerve stimulation for pharmacoresistant epilepsy in children. Surg Neurol Int. 2012;3(4)(suppl 4):S269S274.

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    Hauptman JS, Mathern GW. Epilepsy neurosurgery in children. Handb Clin Neurol.2012;108:881895.

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    Hamiwka L, Jayakar P, Resnick T, Morrison G, Ragheb J, Dean P, et al. Surgery for epilepsy due to cortical malformations: ten-year follow-up. Epilepsia. 2005;46(4):556560.

    • PubMed
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  • 10

    Kral T, von Lehe M, Podlogar M, Clusmann H, Süssmann P, Kurthen M, et al. Focal cortical dysplasia: long term seizure outcome after surgical treatment. J Neurol Neurosurg Psychiatry. 2007;78(8):853856.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 11

    Chern JJ, Patel AJ, Jea A, Curry DJ, Comair YG. Surgical outcome for focal cortical dysplasia: an analysis of recent surgical series. J Neurosurg Pediatr. 2010;6(5):452458.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 12

    Noe K, Sulc V, Wong-Kisiel L, Wirrell E, Van Gompel JJ, Wetjen N, et al. Long-term outcomes after nonlesional extratemporal lobe epilepsy surgery. JAMA Neurol. 2013;70(8):10031008.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 13

    Belohlavkova A, Jezdik P, Jahodova A, Kudr M, Benova B, Maulisova A, et al. Evolution of pediatric epilepsy surgery program over 2000-2017: Improvement of care?. Eur J Paediatr Neurol. 2019;23(3):456465.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 14

    Rubinger L, Chan C, D’Arco F, Moineddin R, Muthaffar O, Rutka JT, et al. Change in presurgical diagnostic imaging evaluation affects subsequent pediatric epilepsy surgery outcome. Epilepsia. 2016;57(1):3240.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 15

    Warsi NM, Lasry O, Farah A, Saint-Martin C, Montes JL, Atkinson J, et al. 3-T intraoperative MRI (iMRI) for pediatric epilepsy surgery. Childs Nerv Syst. 2016;32(12):24152422.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 16

    Gotman J. Epileptic networks studied with EEG-fMRI. Epilepsia. 2008;49(Suppl 3):4251.

  • 17

    Bernasconi A, Bernasconi N, Bernhardt BC, Schrader D. Advances in MRI for ‘cryptogenic’ epilepsies. Nat Rev Neurol. 2011;7(2):99108.

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    Moreau JT, Simard-Tremblay E, Albrecht S, Rosenblatt B, Baillet S, Dudley RWR. Overnight ictal magnetoencephalography. Neurol Clin Pract. Published online August 26, 2020.doi:10.1212/CPJ.0000000000000937

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 19

    Chassoux F, Rodrigo S, Semah F, Beuvon F, Landre E, Devaux B, et al. FDG-PET improves surgical outcome in negative MRI Taylor-type focal cortical dysplasias. Neurology. 2010;75(24):21682175.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 20

    Desarnaud S, Mellerio C, Semah F, Laurent A, Landre E, Devaux B, et al. 18F-FDG PET in drug-resistant epilepsy due to focal cortical dysplasia type 2: additional value of electroclinical data and coregistration with MRI. Eur J Nucl Med Mol Imaging. 2018;45(8):14491460.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 21

    Gotman J, Pittau F. Combining EEG and fMRI in the study of epileptic discharges. Epilepsia. 2011;52(Suppl 4):3842.

  • 22

    Pittau F, Dubeau F, Gotman J. Contribution of EEG/fMRI to the definition of the epileptic focus. Neurology. 2012;78(19):14791487.

  • 23

    Thornton R, Laufs H, Rodionov R, Cannadathu S, Carmichael DW, Vulliemoz S, et al. EEG correlated functional MRI and postoperative outcome in focal epilepsy. J Neurol Neurosurg Psychiatry. 2010;81(8):922927.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 24

    An D, Fahoum F, Hall J, Olivier A, Gotman J, Dubeau F. Electroencephalography/functional magnetic resonance imaging responses help predict surgical outcome in focal epilepsy. Epilepsia. 2013;54(12):21842194.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 25

    Bulacio JC, Jehi L, Wong C, Gonzalez-Martinez J, Kotagal P, Nair D, et al. Long-term seizure outcome after resective surgery in patients evaluated with intracranial electrodes. Epilepsia. 2012;53(10):17221730.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 26

    Sheikh SR, Kattan MW, Steinmetz M, Singer ME, Udeh BL, Jehi L. Cost-effectiveness of surgery for drug-resistant temporal lobe epilepsy in the US. Neurology. 2020;95(10):e1404e1416.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 27

    Langfitt JT. Cost-effectiveness of anterotemporal lobectomy in medically intractable complex partial epilepsy. Epilepsia. 1997;38(2):154163.

  • 28

    Langfitt JT, Holloway RG, McDermott MP, Messing S, Sarosky K, Berg AT, et al. Health care costs decline after successful epilepsy surgery. Neurology. 2007;68(16):12901298.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 29

    Picot MC, Jaussent A, Neveu D, Kahane P, Crespel A, Gelisse P, et al. Cost-effectiveness analysis of epilepsy surgery in a controlled cohort of adult patients with intractable partial epilepsy: a 5-year follow-up study. Epilepsia. 2016;57(10):16691679.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 30

    Widjaja E, Li B, Schinkel CD, Puchalski Ritchie L, Weaver J, Snead OC, et al. Cost-effectiveness of pediatric epilepsy surgery compared to medical treatment in children with intractable epilepsy. Epilepsy Res. 2011;94(1-2):6168.

    • PubMed
    • Search Google Scholar
    • Export Citation

Supplementary Materials

  • Collapse
  • Expand
  • FIG. 1

    Comparison between the PP and NP presurgical evaluation strategies. ECoG = electrocorticography. Figure is available in color online only.

  • FIG. 2

    Proportion of patients in the PP and NP groups who underwent each preoperative diagnostic test.

  • 1

    Lam J, Tomaszewski P, Gilbert G, Moreau JT, Guiot MC, Albrecht S, et al. The utility of arterial spin labeling in the presurgical evaluation of poorly defined focal epilepsy in children. J Neurosurg Pediatr. 2020;27(3):243252.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 2

    Mathern GW. Challenges in the surgical treatment of epilepsy patients with cortical dysplasia. Epilepsia. 2009;50(suppl 9):4550.

  • 3

    Krsek P, Maton B, Jayakar P, Dean P, Korman B, Rey G, et al. Incomplete resection of focal cortical dysplasia is the main predictor of poor postsurgical outcome. Neurology. 2009;72(3):217223.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 4

    Go C, Snead OC III. Pharmacologically intractable epilepsy in children: diagnosis and preoperative evaluation. Neurosurg Focus. 2008;25(3):E2.

  • 5

    Rosenow F, Bast T, Czech T, Feucht M, Hans VH, Helmstaedter C, et al. Revised version of quality guidelines for presurgical epilepsy evaluation and surgical epilepsy therapy issued by the Austrian, German, and Swiss working group on presurgical epilepsy diagnosis and operative epilepsy treatment. Epilepsia. 2016;57(8):12151220.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 6

    Kim DW, Lee SK, Nam H, Chu K, Chung CK, Lee SY, et al. Epilepsy with dual pathology: surgical treatment of cortical dysplasia accompanied by hippocampal sclerosis. Epilepsia. 2010;51(8):14291435.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 7

    Hauptman JS, Mathern GW. Vagal nerve stimulation for pharmacoresistant epilepsy in children. Surg Neurol Int. 2012;3(4)(suppl 4):S269S274.

  • 8

    Hauptman JS, Mathern GW. Epilepsy neurosurgery in children. Handb Clin Neurol.2012;108:881895.

  • 9

    Hamiwka L, Jayakar P, Resnick T, Morrison G, Ragheb J, Dean P, et al. Surgery for epilepsy due to cortical malformations: ten-year follow-up. Epilepsia. 2005;46(4):556560.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 10

    Kral T, von Lehe M, Podlogar M, Clusmann H, Süssmann P, Kurthen M, et al. Focal cortical dysplasia: long term seizure outcome after surgical treatment. J Neurol Neurosurg Psychiatry. 2007;78(8):853856.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 11

    Chern JJ, Patel AJ, Jea A, Curry DJ, Comair YG. Surgical outcome for focal cortical dysplasia: an analysis of recent surgical series. J Neurosurg Pediatr. 2010;6(5):452458.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 12

    Noe K, Sulc V, Wong-Kisiel L, Wirrell E, Van Gompel JJ, Wetjen N, et al. Long-term outcomes after nonlesional extratemporal lobe epilepsy surgery. JAMA Neurol. 2013;70(8):10031008.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 13

    Belohlavkova A, Jezdik P, Jahodova A, Kudr M, Benova B, Maulisova A, et al. Evolution of pediatric epilepsy surgery program over 2000-2017: Improvement of care?. Eur J Paediatr Neurol. 2019;23(3):456465.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 14

    Rubinger L, Chan C, D’Arco F, Moineddin R, Muthaffar O, Rutka JT, et al. Change in presurgical diagnostic imaging evaluation affects subsequent pediatric epilepsy surgery outcome. Epilepsia. 2016;57(1):3240.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 15

    Warsi NM, Lasry O, Farah A, Saint-Martin C, Montes JL, Atkinson J, et al. 3-T intraoperative MRI (iMRI) for pediatric epilepsy surgery. Childs Nerv Syst. 2016;32(12):24152422.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 16

    Gotman J. Epileptic networks studied with EEG-fMRI. Epilepsia. 2008;49(Suppl 3):4251.

  • 17

    Bernasconi A, Bernasconi N, Bernhardt BC, Schrader D. Advances in MRI for ‘cryptogenic’ epilepsies. Nat Rev Neurol. 2011;7(2):99108.

  • 18

    Moreau JT, Simard-Tremblay E, Albrecht S, Rosenblatt B, Baillet S, Dudley RWR. Overnight ictal magnetoencephalography. Neurol Clin Pract. Published online August 26, 2020.doi:10.1212/CPJ.0000000000000937

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 19

    Chassoux F, Rodrigo S, Semah F, Beuvon F, Landre E, Devaux B, et al. FDG-PET improves surgical outcome in negative MRI Taylor-type focal cortical dysplasias. Neurology. 2010;75(24):21682175.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 20

    Desarnaud S, Mellerio C, Semah F, Laurent A, Landre E, Devaux B, et al. 18F-FDG PET in drug-resistant epilepsy due to focal cortical dysplasia type 2: additional value of electroclinical data and coregistration with MRI. Eur J Nucl Med Mol Imaging. 2018;45(8):14491460.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 21

    Gotman J, Pittau F. Combining EEG and fMRI in the study of epileptic discharges. Epilepsia. 2011;52(Suppl 4):3842.

  • 22

    Pittau F, Dubeau F, Gotman J. Contribution of EEG/fMRI to the definition of the epileptic focus. Neurology. 2012;78(19):14791487.

  • 23

    Thornton R, Laufs H, Rodionov R, Cannadathu S, Carmichael DW, Vulliemoz S, et al. EEG correlated functional MRI and postoperative outcome in focal epilepsy. J Neurol Neurosurg Psychiatry. 2010;81(8):922927.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 24

    An D, Fahoum F, Hall J, Olivier A, Gotman J, Dubeau F. Electroencephalography/functional magnetic resonance imaging responses help predict surgical outcome in focal epilepsy. Epilepsia. 2013;54(12):21842194.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 25

    Bulacio JC, Jehi L, Wong C, Gonzalez-Martinez J, Kotagal P, Nair D, et al. Long-term seizure outcome after resective surgery in patients evaluated with intracranial electrodes. Epilepsia. 2012;53(10):17221730.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 26

    Sheikh SR, Kattan MW, Steinmetz M, Singer ME, Udeh BL, Jehi L. Cost-effectiveness of surgery for drug-resistant temporal lobe epilepsy in the US. Neurology. 2020;95(10):e1404e1416.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 27

    Langfitt JT. Cost-effectiveness of anterotemporal lobectomy in medically intractable complex partial epilepsy. Epilepsia. 1997;38(2):154163.

  • 28

    Langfitt JT, Holloway RG, McDermott MP, Messing S, Sarosky K, Berg AT, et al. Health care costs decline after successful epilepsy surgery. Neurology. 2007;68(16):12901298.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 29

    Picot MC, Jaussent A, Neveu D, Kahane P, Crespel A, Gelisse P, et al. Cost-effectiveness analysis of epilepsy surgery in a controlled cohort of adult patients with intractable partial epilepsy: a 5-year follow-up study. Epilepsia. 2016;57(10):16691679.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 30

    Widjaja E, Li B, Schinkel CD, Puchalski Ritchie L, Weaver J, Snead OC, et al. Cost-effectiveness of pediatric epilepsy surgery compared to medical treatment in children with intractable epilepsy. Epilepsy Res. 2011;94(1-2):6168.

    • PubMed
    • Search Google Scholar
    • Export Citation

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