Epilepsy Research (2014) 108, 937—944
journal homepage: www.elsevier.com/locate/epilepsyres
Outcome of intracranial electroencephalography monitoring and surgery in magnetic resonance imaging-negative temporal lobe epilepsy Ricky W. Lee a,1, Marietta M. Hoogs c, David B. Burkholder a, Max R. Trenerry c, Joseph F. Drazkowski e, Jerry J. Shih f, Karey E. Doll f, William O. Tatum IV f, Gregory D. Cascino a, W. Richard Marsh d, Elaine C. Wirrell a, Gregory A. Worrell a,b, Elson L. So a,∗ a
Department of Neurology, Mayo Clinic, Rochester, MN, United States Department of Physiology and Biomedical Engineering, Mayo Clinic, Rochester, MN, United States c Department of Psychiatry and Psychology, Mayo Clinic, Rochester, MN, United States d Department of Neurologic Surgery, Mayo Clinic, Rochester, MN, United States e Department of Neurology, Mayo Clinic Hospital, Phoenix, AZ, United States f Department of Neurology, Mayo Clinic, Jacksonville, FL, United States b
Received 23 December 2013; received in revised form 26 February 2014; accepted 16 March 2014 Available online 27 March 2014
KEYWORDS Epilepsy surgery; Intracranial electroencephalography; Normal magnetic resonance imaging;
Summary We evaluated the outcomes of intracranial electroencephalography (iEEG) recording and subsequent resective surgery in patients with magnetic resonance imaging (MRI)negative temporal lobe epilepsy (TLE). Thirty-two patients were identified from the Mayo Clinic Epilepsy Surgery Database (Arizona, Florida, and Minnesota). Eight (25.0%) had chronic iEEG monitoring that recorded neocortical temporal seizure onsets; 12 (37.5%) had mesial temporal seizure onsets; 5 (15.6%) had independent neocortical and mesial temporal seizure onsets; and 7 (21.9%) had simultaneous neocortical and mesial seizure onsets. Neocortical temporal lobe
Abbreviations: AVLT, Auditory Verbal Learning Test; BNT, Boston Naming Test; ECoG, electrocorticography; EEG, electroencephalographic, electroencephalography; iEEG, intracranial electroencephalography; IQR, interquartile range; MRI, magnetic resonance imaging; PET, positron emission tomography; SISCOM, subtraction ictal SPECT coregistered to MRI; SPECT, single-photon emission computed tomography; TLE, temporal lobe epilepsy. ∗ Corresponding author at: Department of Neurology, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, United States. Tel.: +1 507 284 8917; fax: +1 507 284 2107. E-mail address: [email protected] (E.L. So). 1 Now with University of Arkansas for Medical Sciences, Central Arkansas Veterans Healthcare System, Little Rock, AR, United States. http://dx.doi.org/10.1016/j.eplepsyres.2014.03.013 0920-1211/© 2014 Elsevier B.V. All rights reserved.
938 Temporal lobe epilepsy
R.W. Lee et al. seizure semiology was the only factor significantly associated with neocortical temporal seizure onsets on iEEG. Only 33.3% of patients who underwent lateral temporal neocorticectomy had an Engel class 1 outcome, whereas 76.5% of patients with iEEG-guided anterior temporal lobectomy that included the amygdala and the hippocampus had an Engel class 1 outcome. Limitations in cohort size precluded statistical analysis of neuropsychological test data. © 2014 Elsevier B.V. All rights reserved.
Introduction The role of surgical resection has been well established in medically intractable temporal lobe epilepsy (TLE) (Wiebe et al., 2001; Yoon et al., 2003; Cohen-Gadol et al., 2006; Schmidt and Stavem, 2009). Seizure-free outcome rates after resective surgery average around 70—80% in patients with hippocampal atrophy and concordant interictal and ictal electroencephalographic (EEG) discharges (Berkovic et al., 1995; Cascino, 2004). Unfortunately, the success rate is much lower in patients with non-lesional TLE (Berkovic et al., 1995; Holmes et al., 2000; Chapman et al., 2005; Tatum et al., 2008; Bell et al., 2009). Given the fact that mesial temporal structures are important for memory, physicians may be more reluctant to recommend anterior temporal lobectomy, which includes the mesial temporal structures, when no structural abnormality is identified on magnetic resonance imaging (MRI). In these complicated patients, intracranial EEG (iEEG) monitoring is often required to guide temporal lobe resection. Because increased complication rates are related to longer monitoring and a greater number of electrodes being implanted, the extent of electrode implantation for iEEG should be determined judiciously and should be limited to reduce the risk of complications (Hamer et al., 2002). The prognostic value of interictal spiking in intraoperative electrocorticography (ECoG) remains controversial. Luther et al. (2011) reported that intraoperative ECoG can be useful in a subset of patients with TLE and non-lesional MRI. However, other authors could not find correlation between seizurefree outcomes and complete resection of irritative zone on ECoG (Schwartz et al., 1997; San-juan et al., 2011; Wray et al., 2012). Therefore, the role of chronic extraoperative iEEG monitoring in patients with MRI-negative TLE remains important and deserves further study. The purpose of this study was to determine the yield of extraoperative iEEG monitoring in patients with MRI-negative TLE. In addition, we sought to determine the outcome of subsequent resective surgery in these patients.
Materials and methods Patient population This study was approved by the Mayo Clinic Institutional Review Board. Patients were identified from the epilepsy surgery databases at Mayo Clinic, Jacksonville, Florida (January 1, 2005—December 31, 2012), Mayo Clinic, Rochester, Minnesota (January 1, 2000—December 31, 2012), and Mayo Clinic, Scottsdale, Arizona (January 1, 2000—December 31, 2012).
Noninvasive presurgical evaluations Charts were reviewed to determine patient characteristics, including age at surgery, duration of epilepsy, seizure risk factors, history of status epilepticus, and treatment history. All patients had routine interictal scalp EEG and continuous video scalp EEG monitoring to record seizures. Clinical ictal semiology was classified as favoring either mesial TLE or neocortical TLE localization. Studies have shown that ipsilateral limb automatism, contralateral dystonic posturing, oroalimentary automatisms, psychic phenomenon, and viscerosensory auras are more commonly seen in mesial TLE (French et al., 1993; Dupont et al., 1999; Villanueva and Serratosa, 2005; Tatum, 2012). In contrast, early aphasia, vestibular symptoms, auditory phenomena, and visual hallucinations have been associated with the temporal neocortex (Gloor et al., 1982; Bercovici et al., 2012; Kennedy and Schuele, 2012). The scalp interictal and ictal epileptiform discharges were categorized on the basis of their location (anterior, posterior, or diffuse). High-resolution MRI was performed according to a dedicated institutional epilepsy protocol (15 patients with a 1.5-Tesla scanner and 16 patients with a 3-Tesla scanner; 1 patient had MRI of indeterminate magnet strength at an external institution). Quantitative analysis of the hippocampal volumes was also obtained if subtle hippocampal asymmetry was appreciated during visual interpretation of the MRIs. The final designation of a nonlesional brain MRI was based on the consensus of a multidisciplinary team of neuroradiologists, epileptologists, and neurosurgeons. Subtraction ictal SPECT (single-photon emission computed tomography) coregistered to MRI (SISCOM), positron emission tomography (PET), or both were performed in patients for whom more information was needed for seizure localization. Three patients underwent fMRI for language and motor mapping. Language tasks performed during fMRI mapping were reading, semantic decision, silent word generation, and sentence comprehension.
Neuropsychological evaluations A presurgical neuropsychological evaluation was routinely performed; however, only a subset of patients completed a postsurgical neuropsychological evaluation. Patients included in the current study with both presurgical and postsurgical neuropsychological testing completed the postsurgical evaluation within approximately 6 months of surgery. Select neuropsychological testing results that were reviewed focused on verbal learning and memory, and on confrontation naming as measured by the Auditory
Intracranial electroencephalography monitoring and surgery in MRI-negative TLE Verbal Learning Test (AVLT) and the Boston Naming Test (BNT), respectively. Patients with indeterminate language lateralization, and those likely to be at risk for significant postoperative memory decline, underwent Wada testing through our practice or at an external institution.
Invasive presurgical evaluations, surgery, and outcomes All patients had both depth electrodes and subdural grids implanted extensively over the temporal lobe to differentiate between mesial and neocortical seizure foci. Subdural grids were placed over the lateral temporal neocortex with additional strip electrodes to sample the anterior and subtemporal regions. Stereotactic depth electrodes were placed orthogonally approaching the amygdala and hippocampus to record the mesial temporal activity. A median of 58 (interquartile range [IQR], 50—64) electrode contacts were implanted over the temporal lobe for seizure location. Electrical cortical stimulation mapping was performed in 14 patients to delineate the language, motor, and/or sensory cortex. The patients were asked to perform reading and confrontation naming tasks during the language mapping session. The iEEG-guided anterior temporal lobectomies in our cohort had more extensive lateral temporal neocortex resection than our standard anterior temporal lobectomies not guided by iEEG. The extent of iEEG-guided anterior temporal lobectomies in our cohort was 50—80 mm of neocortex in nondominant lobe surgeries or 30—45 mm in dominant temporal lobe surgeries. In comparison, the standard anterior temporal lobectomies not guided by iEEG removed 45—50 mm of neocortex in the nondominant lobe surgeries or 30—35 mm in dominant temporal lobe surgeries. Seizure outcomes were assessed according to the Engel classification (Engel et al., 1993).
Statistical analysis Data entry and statistical analysis were performed using statistical software (IBM SPSS Statistics 19; IBM Corp). A 2-sided Fisher exact test was used in the analysis of categorical data. P values less than .05 were considered statistically significant.
Results Demographic characteristics A total of 32 patients (3 patients from Arizona, 5 from Florida, and 24 from Minnesota) fit our inclusion criteria. Characteristics of these patients are summarized in Table 1. More than half of the cohort had at least 1 seizure risk factor. Three patients had a history of status epilepticus. The median age at surgery was 32 years (IQR, 23—40 years). Our patients had a long history of seizures, averaging 9.5 years (IQR, 4.5—18 years). They also had a high seizure burden, with a median seizure frequency of 5 (IQR, 2.5—10.0) seizures per month.
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Table 1 Demographic characteristics of 32 patients with magnetic resonance imaging-negative temporal lobe epilepsy who underwent intracranial electroencephalography monitoring and surgery. Characteristic
No. (%)a
Age at surgery, median (IQR), y Duration of epilepsy prior to surgery, median (IQR), y Seizure frequency per month, median (IQR), No. Female sex Seizure risk factors Family history of epilepsy History of meningitis or encephalitis History of head trauma resulting in loss of consciousness History of status epilepticus History of febrile seizures AEDs tried, median (range), No. Patients with VNS
32 (23—40) 9.5 (4.5—18) 5 (2.5—10) 18 (56) 6 (19) 6 (19) 8 (25) 3 0 6 3
(9) (0) (2—10) (9)
Abbreviations: AEDs, antiepileptic drugs; IQR, interquartile range; VNS, vagus nerve stimulator. a Values are number (percentage) unless indicated otherwise.
Noninvasive presurgical evaluations Because mesial temporal structures are important for memory, we aimed to identify prognostic factors for predicting exclusively neocortical seizure focus on iEEG so mesial temporal structures could be spared during resective surgery (Table 2). The only factor found to be statistically significant was neocortical temporal semiology (3/3 with vs 5/24 without) (P = .01). Neither posterior scalp interictal epileptiform discharges (P = .25) nor ictal (P = .15) epileptiform discharges were found to have significant association with neocortical temporal seizure onsets recorded on iEEG. PET was performed in 22 patients, with 13 PET studies showing concordant temporal lobe hypometabolism. Eighteen patients underwent SISCOM, which showed 12 patients to have concordant temporal lobe localization. Because statistical parametric mapping-based analysis was not performed on our SISCOM and PET imagings, neither of these functionalimaging modalities was reliable in distinguishing between neocortical and mesial temporal seizure foci.
Neuropsychological evaluation In our cohort, only 41% (13/32) had presurgical and postsurgical neuropsychological assessments. Nine of these 13 patients had dominant TLE, whereas 4 patients had nondominant TLE. Since limitations in cohort size precluded statistical analyses of neuropsychological test data, we elected to qualitatively examine outcomes in patients with dominant TLE. This decision was largely based on the knowledge that patients undergoing dominant temporal lobectomy are at greater risk for cognitive decline (Trenerry et al., 1993; Rausch et al., 2003; Bell et al., 2009). Figs. 1—3 depict the neuropsychological performances presurgically and postsurgically for patients with dominant TLE for whom
940 Table 2
R.W. Lee et al. Factors predicting neocortical temporal seizure focus on intracranial electroencephalography monitoring. Exclusive neocortical temporal seizure focus (No./total [%])
Predictor factor
Yes
No
P Value
Neocortical temporal semiology Interictal posterior scalp EEG dischargesa Ictal posterior scalp EEG discharges
3/3 (100) 2/4 (50) 3/6 (50)
5/24 (21) 6/28 (21) 5/26 (19)
.01 .25 .15
Abbreviation: EEG, electroencephalography. a Posterior discharges: P9 or P10 scalp EEG electrodes.
Figure 1 Presurgical and postsurgical total learning scores on the Auditory Verbal Learning Test (AVLT) for the 8 patients with dominant temporal lobe epilepsy who underwent resective surgery.
complete data were available. Six patients who underwent anterior temporal lobectomy of the dominant hemisphere completed both the AVLT and the BNT during presurgical and postsurgical evaluations. Two patients who underwent corticectomy in the dominant hemisphere completed the AVLT at both evaluations, and 3 patients completed the BNT at both evaluations.
Figure 3 Presurgical and postsurgical Boston Naming Test scores for the 9 patients with dominant temporal lobe epilepsy who underwent resective surgery.
The 2 patients who underwent corticectomy in the dominant hemisphere showed relatively stable presurgical and postsurgical verbal learning and memory, whereas the 6 patients who underwent dominant hemisphere temporal lobectomy demonstrated reduced total learning, and variable outcomes in delayed retention. As might be expected, patients with higher presurgical delayed retention appeared to show greater decline compared to patients with lower presurgical delayed retention. Confrontation naming outcomes were variable in both corticectomy (n = 3) and anterior temporal lobectomy patients (n = 6).
Invasive presurgical evaluations, surgery, and outcomes
Figure 2 Presurgical and postsurgical retention scores on the Auditory Verbal Learning Test (AVLT) for the 8 patients with dominant temporal lobe epilepsy who underwent resective surgery.
The iEEGs of patients in this study were continuously recorded for a median (IQR) of 6 (5.25—9) days. Depending on the baseline seizure frequency, the antiepileptic medication dosage was reduced by one-third to one-half on the first day of recording. Subsequent medication adjustments were based on the result of the previous 24 hours’ recording. There was typically no set goal number of seizures to be recorded, although there were general expectations that were influenced foremost by safety concerns, the localizing value of seizures already recorded, and sometimes the inability of patients to tolerate the implanted electrodes. The median (IQR) number of seizures recorded was 4.5 (3—7) seizures.
Intracranial electroencephalography monitoring and surgery in MRI-negative TLE
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Table 3 Summary of intracranial electroencephalography monitoring and surgery outcomes in 32 patients with magnetic resonance imaging-negative temporal lobe epilepsy. iEEG finding
No. of patients
Engel class 1 outcome, No./total (%)a
Neocortical temporal onset Mesial temporal onset Independent mesial and neocortical temporal onset Simultaneous mesial and neocortical temporal onset
8 12 5 7
2/6 (33)b 7/10 (70)b NAc 6/7 (86)
Abbreviations: iEEG, intracranial electroencephalography; NA, not applicable. a Either corticectomy or anterior temporal lobectomy with amygdalohippocampectomy guided by iEEG evaluation; does not include patients with palliative surgery or no surgery. b Two patients did not undergo resective surgery. c No patient underwent resective surgery.
Of the 8 patients found to have neocortical temporal seizure onsets on iEEG, 5 had left temporal seizure foci and 3 had right temporal seizure foci (Table 3). No complications were associated with iEEG in this group. One of these 8 patients did not undergo resective surgery because the eloquent cortex overlapped the ictal onset zone. A second patient had a palliative lateral temporal neocorticectomy to reduce seizure burden. In this patient, resective surgery was limited by the language cortex. The remaining 6 patients had neocorticectomy. Two of the 6 patients (33%) were seizure free (Engel class 1 outcome), whereas the rest of the patients (4/6 [67%]) had significant seizure improvement (Engel class 2 outcome). Although functional cortical stimulation mapping was performed before neocorticectomy in these 6 cases, 2 patients had transient aphasia after resection. Pathology showed mild cortical dysplasia in 1 patient and nonspecific gliosis in 6 patients. The iEEG monitoring recorded mesial temporal seizure onsets in 12 patients. Eleven of the 12 had left temporal seizure foci, whereas 1 had right temporal seizure focus. Anterior temporal lobectomy with amygdalohippocampectomy was offered to all patients. Because of the risk of cognitive impairment, 2 patients declined resective surgery. Seven of 10 (70%) patients who underwent resective surgery had Engel class 1 outcomes. Of the other 3 patients, 2 had Engel class 2 outcomes and 1 had an Engel class 4 outcome. Pathology showed mesial temporal sclerosis in 1 patient, cortical dysplasia in 1 patient, and nonspecific gliosis in 8 patients. No patient in this group had complications from iEEG monitoring or resective surgery. Independent mesial and neocortical temporal seizure onsets were recorded in 5 patients. Because of the risk of cognitive impairment, 3 patients declined resective surgery. The other 2 patients underwent palliative surgery to reduce seizure burden. Pathology showed nonspecific gliosis in both patients. None of the 5 patients who underwent iEEG monitoring had complications, and neither of the 2 patients who underwent resective surgery had complications. In 7 patients, the iEEG monitoring showed simultaneous mesial and neocortical temporal seizure onset. During the iEEG monitoring, 1 patient had transient aphasia from subdural hemorrhage beneath the neocortical temporal grid electrode. All 7 patients underwent anterior temporal lobectomy with amygdalohippocampectomy (6 on the left, 1 on the right). One patient experienced transient aphasia
after resection of seizure focus despite functional electrical cortical mapping that was performed before the resective surgery. Overall, 6 of 7 patients (86%) had Engel class 1 outcomes. The other patient had an Engel class 4 seizure outcome. Pathology showed mesial temporal sclerosis in 1 patient and nonspecific gliosis in 6 patients.
Discussion Studies have shown that epilepsy surgery can be effective in patients with MRI-negative TLE. However, the reported success rate of 40—60% is much lower than that for patients with MRI-apparent structural abnormality concordant with the seizure onset zone (Berkovic et al., 1995; Cohen-Gadol et al., 2006; Bell et al., 2009; Vale et al., 2012). In addition, language and memory function are often supported by regions found in close proximity to the epileptogenic zone, making physicians more reluctant to recommend anterior temporal lobectomy in these challenging patients. Therefore, iEEG monitoring is often pursued to better define the epileptogenic zone and the eloquent cortex, especially when the dominant hemisphere is involved. In our study, most (26/32 [81%]) of the intracranial electrode implantations were performed in the dominant hemisphere. Overall, only 1 patient (3%) experienced a clinically significant complication from iEEG monitoring, which is comparable to the overall rates of 3—27% reported in previous series of mostly firsttime intracranial electrode implantations (Schiller et al., 1998; Hamer et al., 2002; Van Gompel et al., 2008; Wong et al., 2009). Data are limited on the yield of iEEG monitoring for recording the neocortical seizure focus in patients with MRInegative TLE. In a smaller single-center study of 16 patients, Luther et al. (2011) showed that a neocortical temporal seizure focus was recorded in 25% of iEEG recordings, which is corroborated by what we found in our study. However, another study by Immonen et al. (2010) reported a much lower yield of 10%. This difference is most likely related to differences in the cohorts and evaluation methodologies of Immonen et al.’s study and ours. In 50% of our patients, 3Tesla MRI was performed. However, most (62/64 [97%]) of the patients in Immonen et al.’s study were imaged with 1-Tesla or 1.5-Tesla MRI scanners, which have lower sensitivity for detecting lesions. In addition, only subdural strip electrodes were used in Immonen et al.’s iEEG evaluations,
942 which record from a more limited brain area than that recorded with subdural grid electrodes. In our study, neocortical temporal lobe seizure semiology was the only factor associated with recording neocortical temporal seizure onsets. Our small sample size may have limited our ability to identify prognostic factors. However, many of the listed electroclinical features more commonly seen in neocortical TLE can also occur in mesial TLE (O’Brien et al., 1996; Gil-Nagel and Risinger, 1997; Lee et al., 2003). Therefore, these symptoms and signs usually do not permit unequivocal diagnosis of mesial vs lateral neocortical TLE. Both ictal semiologic features and scalp EEG morphology have previously been reported to be valuable in distinguishing between mesial temporal and lateral temporal epilepsy. In their review of the literature, Bercovici et al. (2012) have summarized many semiologic features that favored one epilepsy type over another, such as the more frequent and earlier secondary generalization of the focal seizures seen with lateral neocortical epilepsy. Ebersole and Pacia (1996) have observed that an initial, regular 5- to 9-Hz inferotemporal rhythm on the scalp EEG was associated with hippocampal-onset seizures, whereas 2- to 5-Hz lateralized activity was associated with seizures originating in temporal neocortex. It would have been valuable for us to determine whether similar distinctions in ictal semiology and scalp EEG could be made in our subjects. Unfortunately, 2 of the 3 separate systems of video-EEG recordings that were used during the study period are no longer operational for reviewing the ictal recordings, and the EEG reports do not consistently contain specific data regarding these observations. Resective surgery in patients with MRI-negative neocortical TLE can be challenging. A standard anterior temporal resection is likely to spare a substantial amount of the posterior and superior lateral temporal lobe, which may be involved in seizure initiation. Therefore, these patients may continue to have seizures after standard anterior temporal lobectomy. Our results showed that even corticectomy guided by iEEG monitoring had a low seizure freedom rate of 33%, similar to previously reported rates of 40—50% (Hong et al., 2002; Luther et al., 2011). One of our patients who initially underwent focal corticectomy targeting a neocortical temporal seizure onset zone continued to have seizures, but subsequently became seizure-free following a standard anterior temporal lobectomy. This scenario raises the possibility that the true epileptogenic zone could be more widespread than the ictal onset zone in some patients. A restricted resection, such as a topectomy or lateral temporal neocorticectomy, may not be adequate to render some patients seizure-free. The phenomenon of ‘‘secondary epileptogenesis’’ could also play a role in the low long-term surgical success rates in our neocortical TLE patients (Morrell, 1985; Najm et al., 2013). Hippocampal sclerosis has been reported after generalized convulsions (VanLandingham et al., 1998; Briellmann et al., 2001) or neocortical epilepsy (Worrell et al., 2002). It is conceivable that the mesial temporal structures acquire secondary epileptogenicity as a result of the ictal discharge propagated from the lateral cortex. Although all of our patients had non-lesional findings on MRI, as determined by the multidisciplinary consensus, subtle pathology may not have been detected by high-resolution MRI. Since the intracranially placed electrodes in our cohort covered only the temporal
R.W. Lee et al. lobe, the possibility of temporal lobe-plus epilepsy, or extratemporal lobe epilepsy mimicking TLE (Ryvlin and Kahane, 2005; Barba et al., 2007), may partly explain the low rate of seizure freedom in our neocortical TLE patients. Previous studies have shown that 40—60% of patients with TLE and normal MRI become seizure-free after anterior temporal lobectomy (Berkovic et al., 1995; Cohen-Gadol et al., 2006; Bell et al., 2009; Vale et al., 2012). In these series, iEEG monitoring was not done consistently for seizure localization. Surgical risk to eloquent brain regions was not a predominant issue, whereas it was the reason for intracranial electrode implantation and subsequent limited surgical resections in most of our patients. Some studies using intraoperative electrocorticography have shown successful seizure outcomes for surgery in MRI-negative patients without prolonged extraoperative iEEG monitoring, especially when interictal discharges on electrocorticography were limited to the mesial temporal structures (McKhann et al., 2000; Luther et al., 2011). However, iEEG recording of ictal onset zone is still needed if mesial and lateral or exclusively lateral epileptiform discharges are seen during intraoperative electrocorticography. In our study, we found that anterior temporal lobectomy guided by iEEG can produce an excellent surgical success rate of 86% in patients with simultaneous mesial and lateral ictal onsets on iEEG monitoring. A number of these patients had resection margins well beyond those of our standard anterior temporal lobectomy. Thus, a standard anterior temporal lobectomy may not be sufficient to render all patients seizure free. Previous studies have demonstrated that standard anterior temporal lobectomy with amygdalohippocampectomy of the dominant hemisphere is associated with cognitive decline (Trenerry et al., 1993; Rausch et al., 2003; Bell et al., 2009). This risk is greater in patients with relatively nonatrophic hippocampi (Trenerry et al., 1993, 1996). Due to the small sample size and statistical limits of our study, our neuropsychological data should be interpreted with caution. Our patients who underwent dominant hemisphere focal corticectomy demonstrated relatively stable verbal learning and memory outcomes postsurgically. However, patients who underwent dominant hemisphere standard anterior temporal lobectomy with amygdalohippocampectomy demonstrated a clear trend toward decreased verbal learning outcomes postsurgically, although verbal memory outcomes were variable. Patients with higher verbal memory scores at baseline showed a trend toward decreased performance postsurgically. In comparison, the verbal memory scores appeared to be stable preoperatively and postoperatively in patients with low scores at baseline.
Conclusion In summary, our study has demonstrated the informative role that iEEG evaluations can play in patients with TLE and negative MRI. Anterior temporal lobectomy guided by iEEG in these patients is associated with a high rate of freedom from postsurgical seizures, which is comparable to that in patients with MRI-detected temporal lobe lesions. It is also important to identify neocortical temporal lobe seizure focus in patients with MRI-negative TLE, because surgery
Intracranial electroencephalography monitoring and surgery in MRI-negative TLE that is restricted to the focus and that spares the mesial temporal structures reduces the risk of postsurgical cognitive decline. Nonetheless, these patients have a lower rate of freedom from postsurgical seizures.
Conflict of interest None.
Funding source None.
Acknowledgments We confirm that we have read the Journal’s position on issues involved in ethical publication and affirm that this report is consistent with those guidelines.
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944 Schwartz, T.H., Bazil, C.W., Walczak, T.S., Chan, S., Pedley, T.A., Goodman, R.R., 1997. The predictive value of intraoperative electrocorticography in resections for limbic epilepsy associated with mesial temporal sclerosis. Neurosurgery 40 (February (2)), 302—309. Tatum 4th, W.O., 2012. Mesial temporal lobe epilepsy. J. Clin. Neurophysiol. 29 (October (5)), 356—365. Tatum 4th, W.O., Benbadis, S.R., Hussain, A., Al-Saadi, S., Kaminski, B., Heriaud, L.S., et al., 2008. Ictal EEG remains the prominent predictor of seizure-free outcome after temporal lobectomy in epileptic patients with normal brain MRI. Seizure 17 (October (7)), 631—636. Trenerry, M.R., Jack Jr., C.R., Cascino, G.D., Sharbrough, F.W., So, E.L., 1996. Bilateral magnetic resonance imaging-determined hippocampal atrophy and verbal memory before and after temporal lobectomy. Epilepsia 37 (June (6)), 526—533. Trenerry, M.R., Jack Jr., C.R., Ivnik, R.J., Sharbrough, F.W., Cascino, G.D., Hirschorn, K.A., et al., 1993. MRI hippocampal volumes and memory function before and after temporal lobectomy. Neurology 43 (September (9)), 1800—1805. Vale, F.L., Effio, E., Arredondo, N., Bozorg, A., Wong, K., Martinez, C., et al., 2012. Efficacy of temporal lobe surgery for epilepsy in patients with negative MRI for mesial temporal lobe sclerosis. J. Clin. Neurosci. 19 (January (1)), 101—106 (Epub 2011 December 10). Van Gompel, J.J., Worrell, G.A., Bell, M.L., Patrick, T.A., Cascino, G.D., Raffel, C., et al., 2008. Intracranial electroencephalography with subdural grid electrodes: techniques, complications, and outcomes. Neurosurgery 63 (September (3)), 498—505.
R.W. Lee et al. VanLandingham, K.E., Heinz, E.R., Cavazos, J.E., Lewis, D.V., 1998. Magnetic resonance imaging evidence of hippocampal injury after prolonged focal febrile convulsions. Ann. Neurol. 43 (April (4)), 413—426. Villanueva, V., Serratosa, J.M., 2005. Temporal lobe epilepsy: clinical semiology and age at onset. Epileptic Disord. 7 (June (2)), 83—90. Wiebe, S., Blume, W.T., Girvin, J.P., Eliasziw, M., Effectiveness and Efficiency of Surgery for Temporal Lobe Epilepsy Study Group, 2001. A randomized, controlled trial of surgery for temporallobe epilepsy. N. Engl. J. Med. 345 (August (5)), 311—318. Wong, C.H., Birkett, J., Byth, K., Dexter, M., Somerville, E., Gill, D., et al., 2009. Risk factors for complications during intracranial electrode recording in presurgical evaluation of drug resistant partial epilepsy. Acta Neurochir. (Wien) 151 (January (1)), 37—50 (Epub 2009 January 8). Worrell, G.A., Sencakova, D., Jack, C.R., Flemming, K.D., Fulgham, J.R., So, E.L., 2002. Rapidly progressive hippocampal atrophy: evidence for a seizure-induced mechanism. Neurology 58 (May (10)), 1553—1556. Wray, C.D., McDaniel, S.S., Saneto, R.P., Novotny Jr., E.J., Ojemann, J.G., 2012. Is postresective intraoperative electrocorticography predictive of seizure outcomes in children? J. Neurosurg. Pediatr. 9 (May (5)), 546—551. Yoon, H.H., Kwon, H.L., Mattson, R.H., Spencer, D.D., Spencer, S.S., 2003. Long-term seizure outcome in patients initially seizurefree after resective epilepsy surgery. Neurology 61 (August (4)), 445—450.
journal homepage: www.elsevier.com/locate/epilepsyres
Outcome of intracranial electroencephalography monitoring and surgery in magnetic resonance imaging-negative temporal lobe epilepsy Ricky W. Lee a,1, Marietta M. Hoogs c, David B. Burkholder a, Max R. Trenerry c, Joseph F. Drazkowski e, Jerry J. Shih f, Karey E. Doll f, William O. Tatum IV f, Gregory D. Cascino a, W. Richard Marsh d, Elaine C. Wirrell a, Gregory A. Worrell a,b, Elson L. So a,∗ a
Department of Neurology, Mayo Clinic, Rochester, MN, United States Department of Physiology and Biomedical Engineering, Mayo Clinic, Rochester, MN, United States c Department of Psychiatry and Psychology, Mayo Clinic, Rochester, MN, United States d Department of Neurologic Surgery, Mayo Clinic, Rochester, MN, United States e Department of Neurology, Mayo Clinic Hospital, Phoenix, AZ, United States f Department of Neurology, Mayo Clinic, Jacksonville, FL, United States b
Received 23 December 2013; received in revised form 26 February 2014; accepted 16 March 2014 Available online 27 March 2014
KEYWORDS Epilepsy surgery; Intracranial electroencephalography; Normal magnetic resonance imaging;
Summary We evaluated the outcomes of intracranial electroencephalography (iEEG) recording and subsequent resective surgery in patients with magnetic resonance imaging (MRI)negative temporal lobe epilepsy (TLE). Thirty-two patients were identified from the Mayo Clinic Epilepsy Surgery Database (Arizona, Florida, and Minnesota). Eight (25.0%) had chronic iEEG monitoring that recorded neocortical temporal seizure onsets; 12 (37.5%) had mesial temporal seizure onsets; 5 (15.6%) had independent neocortical and mesial temporal seizure onsets; and 7 (21.9%) had simultaneous neocortical and mesial seizure onsets. Neocortical temporal lobe
Abbreviations: AVLT, Auditory Verbal Learning Test; BNT, Boston Naming Test; ECoG, electrocorticography; EEG, electroencephalographic, electroencephalography; iEEG, intracranial electroencephalography; IQR, interquartile range; MRI, magnetic resonance imaging; PET, positron emission tomography; SISCOM, subtraction ictal SPECT coregistered to MRI; SPECT, single-photon emission computed tomography; TLE, temporal lobe epilepsy. ∗ Corresponding author at: Department of Neurology, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, United States. Tel.: +1 507 284 8917; fax: +1 507 284 2107. E-mail address: [email protected] (E.L. So). 1 Now with University of Arkansas for Medical Sciences, Central Arkansas Veterans Healthcare System, Little Rock, AR, United States. http://dx.doi.org/10.1016/j.eplepsyres.2014.03.013 0920-1211/© 2014 Elsevier B.V. All rights reserved.
938 Temporal lobe epilepsy
R.W. Lee et al. seizure semiology was the only factor significantly associated with neocortical temporal seizure onsets on iEEG. Only 33.3% of patients who underwent lateral temporal neocorticectomy had an Engel class 1 outcome, whereas 76.5% of patients with iEEG-guided anterior temporal lobectomy that included the amygdala and the hippocampus had an Engel class 1 outcome. Limitations in cohort size precluded statistical analysis of neuropsychological test data. © 2014 Elsevier B.V. All rights reserved.
Introduction The role of surgical resection has been well established in medically intractable temporal lobe epilepsy (TLE) (Wiebe et al., 2001; Yoon et al., 2003; Cohen-Gadol et al., 2006; Schmidt and Stavem, 2009). Seizure-free outcome rates after resective surgery average around 70—80% in patients with hippocampal atrophy and concordant interictal and ictal electroencephalographic (EEG) discharges (Berkovic et al., 1995; Cascino, 2004). Unfortunately, the success rate is much lower in patients with non-lesional TLE (Berkovic et al., 1995; Holmes et al., 2000; Chapman et al., 2005; Tatum et al., 2008; Bell et al., 2009). Given the fact that mesial temporal structures are important for memory, physicians may be more reluctant to recommend anterior temporal lobectomy, which includes the mesial temporal structures, when no structural abnormality is identified on magnetic resonance imaging (MRI). In these complicated patients, intracranial EEG (iEEG) monitoring is often required to guide temporal lobe resection. Because increased complication rates are related to longer monitoring and a greater number of electrodes being implanted, the extent of electrode implantation for iEEG should be determined judiciously and should be limited to reduce the risk of complications (Hamer et al., 2002). The prognostic value of interictal spiking in intraoperative electrocorticography (ECoG) remains controversial. Luther et al. (2011) reported that intraoperative ECoG can be useful in a subset of patients with TLE and non-lesional MRI. However, other authors could not find correlation between seizurefree outcomes and complete resection of irritative zone on ECoG (Schwartz et al., 1997; San-juan et al., 2011; Wray et al., 2012). Therefore, the role of chronic extraoperative iEEG monitoring in patients with MRI-negative TLE remains important and deserves further study. The purpose of this study was to determine the yield of extraoperative iEEG monitoring in patients with MRI-negative TLE. In addition, we sought to determine the outcome of subsequent resective surgery in these patients.
Materials and methods Patient population This study was approved by the Mayo Clinic Institutional Review Board. Patients were identified from the epilepsy surgery databases at Mayo Clinic, Jacksonville, Florida (January 1, 2005—December 31, 2012), Mayo Clinic, Rochester, Minnesota (January 1, 2000—December 31, 2012), and Mayo Clinic, Scottsdale, Arizona (January 1, 2000—December 31, 2012).
Noninvasive presurgical evaluations Charts were reviewed to determine patient characteristics, including age at surgery, duration of epilepsy, seizure risk factors, history of status epilepticus, and treatment history. All patients had routine interictal scalp EEG and continuous video scalp EEG monitoring to record seizures. Clinical ictal semiology was classified as favoring either mesial TLE or neocortical TLE localization. Studies have shown that ipsilateral limb automatism, contralateral dystonic posturing, oroalimentary automatisms, psychic phenomenon, and viscerosensory auras are more commonly seen in mesial TLE (French et al., 1993; Dupont et al., 1999; Villanueva and Serratosa, 2005; Tatum, 2012). In contrast, early aphasia, vestibular symptoms, auditory phenomena, and visual hallucinations have been associated with the temporal neocortex (Gloor et al., 1982; Bercovici et al., 2012; Kennedy and Schuele, 2012). The scalp interictal and ictal epileptiform discharges were categorized on the basis of their location (anterior, posterior, or diffuse). High-resolution MRI was performed according to a dedicated institutional epilepsy protocol (15 patients with a 1.5-Tesla scanner and 16 patients with a 3-Tesla scanner; 1 patient had MRI of indeterminate magnet strength at an external institution). Quantitative analysis of the hippocampal volumes was also obtained if subtle hippocampal asymmetry was appreciated during visual interpretation of the MRIs. The final designation of a nonlesional brain MRI was based on the consensus of a multidisciplinary team of neuroradiologists, epileptologists, and neurosurgeons. Subtraction ictal SPECT (single-photon emission computed tomography) coregistered to MRI (SISCOM), positron emission tomography (PET), or both were performed in patients for whom more information was needed for seizure localization. Three patients underwent fMRI for language and motor mapping. Language tasks performed during fMRI mapping were reading, semantic decision, silent word generation, and sentence comprehension.
Neuropsychological evaluations A presurgical neuropsychological evaluation was routinely performed; however, only a subset of patients completed a postsurgical neuropsychological evaluation. Patients included in the current study with both presurgical and postsurgical neuropsychological testing completed the postsurgical evaluation within approximately 6 months of surgery. Select neuropsychological testing results that were reviewed focused on verbal learning and memory, and on confrontation naming as measured by the Auditory
Intracranial electroencephalography monitoring and surgery in MRI-negative TLE Verbal Learning Test (AVLT) and the Boston Naming Test (BNT), respectively. Patients with indeterminate language lateralization, and those likely to be at risk for significant postoperative memory decline, underwent Wada testing through our practice or at an external institution.
Invasive presurgical evaluations, surgery, and outcomes All patients had both depth electrodes and subdural grids implanted extensively over the temporal lobe to differentiate between mesial and neocortical seizure foci. Subdural grids were placed over the lateral temporal neocortex with additional strip electrodes to sample the anterior and subtemporal regions. Stereotactic depth electrodes were placed orthogonally approaching the amygdala and hippocampus to record the mesial temporal activity. A median of 58 (interquartile range [IQR], 50—64) electrode contacts were implanted over the temporal lobe for seizure location. Electrical cortical stimulation mapping was performed in 14 patients to delineate the language, motor, and/or sensory cortex. The patients were asked to perform reading and confrontation naming tasks during the language mapping session. The iEEG-guided anterior temporal lobectomies in our cohort had more extensive lateral temporal neocortex resection than our standard anterior temporal lobectomies not guided by iEEG. The extent of iEEG-guided anterior temporal lobectomies in our cohort was 50—80 mm of neocortex in nondominant lobe surgeries or 30—45 mm in dominant temporal lobe surgeries. In comparison, the standard anterior temporal lobectomies not guided by iEEG removed 45—50 mm of neocortex in the nondominant lobe surgeries or 30—35 mm in dominant temporal lobe surgeries. Seizure outcomes were assessed according to the Engel classification (Engel et al., 1993).
Statistical analysis Data entry and statistical analysis were performed using statistical software (IBM SPSS Statistics 19; IBM Corp). A 2-sided Fisher exact test was used in the analysis of categorical data. P values less than .05 were considered statistically significant.
Results Demographic characteristics A total of 32 patients (3 patients from Arizona, 5 from Florida, and 24 from Minnesota) fit our inclusion criteria. Characteristics of these patients are summarized in Table 1. More than half of the cohort had at least 1 seizure risk factor. Three patients had a history of status epilepticus. The median age at surgery was 32 years (IQR, 23—40 years). Our patients had a long history of seizures, averaging 9.5 years (IQR, 4.5—18 years). They also had a high seizure burden, with a median seizure frequency of 5 (IQR, 2.5—10.0) seizures per month.
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Table 1 Demographic characteristics of 32 patients with magnetic resonance imaging-negative temporal lobe epilepsy who underwent intracranial electroencephalography monitoring and surgery. Characteristic
No. (%)a
Age at surgery, median (IQR), y Duration of epilepsy prior to surgery, median (IQR), y Seizure frequency per month, median (IQR), No. Female sex Seizure risk factors Family history of epilepsy History of meningitis or encephalitis History of head trauma resulting in loss of consciousness History of status epilepticus History of febrile seizures AEDs tried, median (range), No. Patients with VNS
32 (23—40) 9.5 (4.5—18) 5 (2.5—10) 18 (56) 6 (19) 6 (19) 8 (25) 3 0 6 3
(9) (0) (2—10) (9)
Abbreviations: AEDs, antiepileptic drugs; IQR, interquartile range; VNS, vagus nerve stimulator. a Values are number (percentage) unless indicated otherwise.
Noninvasive presurgical evaluations Because mesial temporal structures are important for memory, we aimed to identify prognostic factors for predicting exclusively neocortical seizure focus on iEEG so mesial temporal structures could be spared during resective surgery (Table 2). The only factor found to be statistically significant was neocortical temporal semiology (3/3 with vs 5/24 without) (P = .01). Neither posterior scalp interictal epileptiform discharges (P = .25) nor ictal (P = .15) epileptiform discharges were found to have significant association with neocortical temporal seizure onsets recorded on iEEG. PET was performed in 22 patients, with 13 PET studies showing concordant temporal lobe hypometabolism. Eighteen patients underwent SISCOM, which showed 12 patients to have concordant temporal lobe localization. Because statistical parametric mapping-based analysis was not performed on our SISCOM and PET imagings, neither of these functionalimaging modalities was reliable in distinguishing between neocortical and mesial temporal seizure foci.
Neuropsychological evaluation In our cohort, only 41% (13/32) had presurgical and postsurgical neuropsychological assessments. Nine of these 13 patients had dominant TLE, whereas 4 patients had nondominant TLE. Since limitations in cohort size precluded statistical analyses of neuropsychological test data, we elected to qualitatively examine outcomes in patients with dominant TLE. This decision was largely based on the knowledge that patients undergoing dominant temporal lobectomy are at greater risk for cognitive decline (Trenerry et al., 1993; Rausch et al., 2003; Bell et al., 2009). Figs. 1—3 depict the neuropsychological performances presurgically and postsurgically for patients with dominant TLE for whom
940 Table 2
R.W. Lee et al. Factors predicting neocortical temporal seizure focus on intracranial electroencephalography monitoring. Exclusive neocortical temporal seizure focus (No./total [%])
Predictor factor
Yes
No
P Value
Neocortical temporal semiology Interictal posterior scalp EEG dischargesa Ictal posterior scalp EEG discharges
3/3 (100) 2/4 (50) 3/6 (50)
5/24 (21) 6/28 (21) 5/26 (19)
.01 .25 .15
Abbreviation: EEG, electroencephalography. a Posterior discharges: P9 or P10 scalp EEG electrodes.
Figure 1 Presurgical and postsurgical total learning scores on the Auditory Verbal Learning Test (AVLT) for the 8 patients with dominant temporal lobe epilepsy who underwent resective surgery.
complete data were available. Six patients who underwent anterior temporal lobectomy of the dominant hemisphere completed both the AVLT and the BNT during presurgical and postsurgical evaluations. Two patients who underwent corticectomy in the dominant hemisphere completed the AVLT at both evaluations, and 3 patients completed the BNT at both evaluations.
Figure 3 Presurgical and postsurgical Boston Naming Test scores for the 9 patients with dominant temporal lobe epilepsy who underwent resective surgery.
The 2 patients who underwent corticectomy in the dominant hemisphere showed relatively stable presurgical and postsurgical verbal learning and memory, whereas the 6 patients who underwent dominant hemisphere temporal lobectomy demonstrated reduced total learning, and variable outcomes in delayed retention. As might be expected, patients with higher presurgical delayed retention appeared to show greater decline compared to patients with lower presurgical delayed retention. Confrontation naming outcomes were variable in both corticectomy (n = 3) and anterior temporal lobectomy patients (n = 6).
Invasive presurgical evaluations, surgery, and outcomes
Figure 2 Presurgical and postsurgical retention scores on the Auditory Verbal Learning Test (AVLT) for the 8 patients with dominant temporal lobe epilepsy who underwent resective surgery.
The iEEGs of patients in this study were continuously recorded for a median (IQR) of 6 (5.25—9) days. Depending on the baseline seizure frequency, the antiepileptic medication dosage was reduced by one-third to one-half on the first day of recording. Subsequent medication adjustments were based on the result of the previous 24 hours’ recording. There was typically no set goal number of seizures to be recorded, although there were general expectations that were influenced foremost by safety concerns, the localizing value of seizures already recorded, and sometimes the inability of patients to tolerate the implanted electrodes. The median (IQR) number of seizures recorded was 4.5 (3—7) seizures.
Intracranial electroencephalography monitoring and surgery in MRI-negative TLE
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Table 3 Summary of intracranial electroencephalography monitoring and surgery outcomes in 32 patients with magnetic resonance imaging-negative temporal lobe epilepsy. iEEG finding
No. of patients
Engel class 1 outcome, No./total (%)a
Neocortical temporal onset Mesial temporal onset Independent mesial and neocortical temporal onset Simultaneous mesial and neocortical temporal onset
8 12 5 7
2/6 (33)b 7/10 (70)b NAc 6/7 (86)
Abbreviations: iEEG, intracranial electroencephalography; NA, not applicable. a Either corticectomy or anterior temporal lobectomy with amygdalohippocampectomy guided by iEEG evaluation; does not include patients with palliative surgery or no surgery. b Two patients did not undergo resective surgery. c No patient underwent resective surgery.
Of the 8 patients found to have neocortical temporal seizure onsets on iEEG, 5 had left temporal seizure foci and 3 had right temporal seizure foci (Table 3). No complications were associated with iEEG in this group. One of these 8 patients did not undergo resective surgery because the eloquent cortex overlapped the ictal onset zone. A second patient had a palliative lateral temporal neocorticectomy to reduce seizure burden. In this patient, resective surgery was limited by the language cortex. The remaining 6 patients had neocorticectomy. Two of the 6 patients (33%) were seizure free (Engel class 1 outcome), whereas the rest of the patients (4/6 [67%]) had significant seizure improvement (Engel class 2 outcome). Although functional cortical stimulation mapping was performed before neocorticectomy in these 6 cases, 2 patients had transient aphasia after resection. Pathology showed mild cortical dysplasia in 1 patient and nonspecific gliosis in 6 patients. The iEEG monitoring recorded mesial temporal seizure onsets in 12 patients. Eleven of the 12 had left temporal seizure foci, whereas 1 had right temporal seizure focus. Anterior temporal lobectomy with amygdalohippocampectomy was offered to all patients. Because of the risk of cognitive impairment, 2 patients declined resective surgery. Seven of 10 (70%) patients who underwent resective surgery had Engel class 1 outcomes. Of the other 3 patients, 2 had Engel class 2 outcomes and 1 had an Engel class 4 outcome. Pathology showed mesial temporal sclerosis in 1 patient, cortical dysplasia in 1 patient, and nonspecific gliosis in 8 patients. No patient in this group had complications from iEEG monitoring or resective surgery. Independent mesial and neocortical temporal seizure onsets were recorded in 5 patients. Because of the risk of cognitive impairment, 3 patients declined resective surgery. The other 2 patients underwent palliative surgery to reduce seizure burden. Pathology showed nonspecific gliosis in both patients. None of the 5 patients who underwent iEEG monitoring had complications, and neither of the 2 patients who underwent resective surgery had complications. In 7 patients, the iEEG monitoring showed simultaneous mesial and neocortical temporal seizure onset. During the iEEG monitoring, 1 patient had transient aphasia from subdural hemorrhage beneath the neocortical temporal grid electrode. All 7 patients underwent anterior temporal lobectomy with amygdalohippocampectomy (6 on the left, 1 on the right). One patient experienced transient aphasia
after resection of seizure focus despite functional electrical cortical mapping that was performed before the resective surgery. Overall, 6 of 7 patients (86%) had Engel class 1 outcomes. The other patient had an Engel class 4 seizure outcome. Pathology showed mesial temporal sclerosis in 1 patient and nonspecific gliosis in 6 patients.
Discussion Studies have shown that epilepsy surgery can be effective in patients with MRI-negative TLE. However, the reported success rate of 40—60% is much lower than that for patients with MRI-apparent structural abnormality concordant with the seizure onset zone (Berkovic et al., 1995; Cohen-Gadol et al., 2006; Bell et al., 2009; Vale et al., 2012). In addition, language and memory function are often supported by regions found in close proximity to the epileptogenic zone, making physicians more reluctant to recommend anterior temporal lobectomy in these challenging patients. Therefore, iEEG monitoring is often pursued to better define the epileptogenic zone and the eloquent cortex, especially when the dominant hemisphere is involved. In our study, most (26/32 [81%]) of the intracranial electrode implantations were performed in the dominant hemisphere. Overall, only 1 patient (3%) experienced a clinically significant complication from iEEG monitoring, which is comparable to the overall rates of 3—27% reported in previous series of mostly firsttime intracranial electrode implantations (Schiller et al., 1998; Hamer et al., 2002; Van Gompel et al., 2008; Wong et al., 2009). Data are limited on the yield of iEEG monitoring for recording the neocortical seizure focus in patients with MRInegative TLE. In a smaller single-center study of 16 patients, Luther et al. (2011) showed that a neocortical temporal seizure focus was recorded in 25% of iEEG recordings, which is corroborated by what we found in our study. However, another study by Immonen et al. (2010) reported a much lower yield of 10%. This difference is most likely related to differences in the cohorts and evaluation methodologies of Immonen et al.’s study and ours. In 50% of our patients, 3Tesla MRI was performed. However, most (62/64 [97%]) of the patients in Immonen et al.’s study were imaged with 1-Tesla or 1.5-Tesla MRI scanners, which have lower sensitivity for detecting lesions. In addition, only subdural strip electrodes were used in Immonen et al.’s iEEG evaluations,
942 which record from a more limited brain area than that recorded with subdural grid electrodes. In our study, neocortical temporal lobe seizure semiology was the only factor associated with recording neocortical temporal seizure onsets. Our small sample size may have limited our ability to identify prognostic factors. However, many of the listed electroclinical features more commonly seen in neocortical TLE can also occur in mesial TLE (O’Brien et al., 1996; Gil-Nagel and Risinger, 1997; Lee et al., 2003). Therefore, these symptoms and signs usually do not permit unequivocal diagnosis of mesial vs lateral neocortical TLE. Both ictal semiologic features and scalp EEG morphology have previously been reported to be valuable in distinguishing between mesial temporal and lateral temporal epilepsy. In their review of the literature, Bercovici et al. (2012) have summarized many semiologic features that favored one epilepsy type over another, such as the more frequent and earlier secondary generalization of the focal seizures seen with lateral neocortical epilepsy. Ebersole and Pacia (1996) have observed that an initial, regular 5- to 9-Hz inferotemporal rhythm on the scalp EEG was associated with hippocampal-onset seizures, whereas 2- to 5-Hz lateralized activity was associated with seizures originating in temporal neocortex. It would have been valuable for us to determine whether similar distinctions in ictal semiology and scalp EEG could be made in our subjects. Unfortunately, 2 of the 3 separate systems of video-EEG recordings that were used during the study period are no longer operational for reviewing the ictal recordings, and the EEG reports do not consistently contain specific data regarding these observations. Resective surgery in patients with MRI-negative neocortical TLE can be challenging. A standard anterior temporal resection is likely to spare a substantial amount of the posterior and superior lateral temporal lobe, which may be involved in seizure initiation. Therefore, these patients may continue to have seizures after standard anterior temporal lobectomy. Our results showed that even corticectomy guided by iEEG monitoring had a low seizure freedom rate of 33%, similar to previously reported rates of 40—50% (Hong et al., 2002; Luther et al., 2011). One of our patients who initially underwent focal corticectomy targeting a neocortical temporal seizure onset zone continued to have seizures, but subsequently became seizure-free following a standard anterior temporal lobectomy. This scenario raises the possibility that the true epileptogenic zone could be more widespread than the ictal onset zone in some patients. A restricted resection, such as a topectomy or lateral temporal neocorticectomy, may not be adequate to render some patients seizure-free. The phenomenon of ‘‘secondary epileptogenesis’’ could also play a role in the low long-term surgical success rates in our neocortical TLE patients (Morrell, 1985; Najm et al., 2013). Hippocampal sclerosis has been reported after generalized convulsions (VanLandingham et al., 1998; Briellmann et al., 2001) or neocortical epilepsy (Worrell et al., 2002). It is conceivable that the mesial temporal structures acquire secondary epileptogenicity as a result of the ictal discharge propagated from the lateral cortex. Although all of our patients had non-lesional findings on MRI, as determined by the multidisciplinary consensus, subtle pathology may not have been detected by high-resolution MRI. Since the intracranially placed electrodes in our cohort covered only the temporal
R.W. Lee et al. lobe, the possibility of temporal lobe-plus epilepsy, or extratemporal lobe epilepsy mimicking TLE (Ryvlin and Kahane, 2005; Barba et al., 2007), may partly explain the low rate of seizure freedom in our neocortical TLE patients. Previous studies have shown that 40—60% of patients with TLE and normal MRI become seizure-free after anterior temporal lobectomy (Berkovic et al., 1995; Cohen-Gadol et al., 2006; Bell et al., 2009; Vale et al., 2012). In these series, iEEG monitoring was not done consistently for seizure localization. Surgical risk to eloquent brain regions was not a predominant issue, whereas it was the reason for intracranial electrode implantation and subsequent limited surgical resections in most of our patients. Some studies using intraoperative electrocorticography have shown successful seizure outcomes for surgery in MRI-negative patients without prolonged extraoperative iEEG monitoring, especially when interictal discharges on electrocorticography were limited to the mesial temporal structures (McKhann et al., 2000; Luther et al., 2011). However, iEEG recording of ictal onset zone is still needed if mesial and lateral or exclusively lateral epileptiform discharges are seen during intraoperative electrocorticography. In our study, we found that anterior temporal lobectomy guided by iEEG can produce an excellent surgical success rate of 86% in patients with simultaneous mesial and lateral ictal onsets on iEEG monitoring. A number of these patients had resection margins well beyond those of our standard anterior temporal lobectomy. Thus, a standard anterior temporal lobectomy may not be sufficient to render all patients seizure free. Previous studies have demonstrated that standard anterior temporal lobectomy with amygdalohippocampectomy of the dominant hemisphere is associated with cognitive decline (Trenerry et al., 1993; Rausch et al., 2003; Bell et al., 2009). This risk is greater in patients with relatively nonatrophic hippocampi (Trenerry et al., 1993, 1996). Due to the small sample size and statistical limits of our study, our neuropsychological data should be interpreted with caution. Our patients who underwent dominant hemisphere focal corticectomy demonstrated relatively stable verbal learning and memory outcomes postsurgically. However, patients who underwent dominant hemisphere standard anterior temporal lobectomy with amygdalohippocampectomy demonstrated a clear trend toward decreased verbal learning outcomes postsurgically, although verbal memory outcomes were variable. Patients with higher verbal memory scores at baseline showed a trend toward decreased performance postsurgically. In comparison, the verbal memory scores appeared to be stable preoperatively and postoperatively in patients with low scores at baseline.
Conclusion In summary, our study has demonstrated the informative role that iEEG evaluations can play in patients with TLE and negative MRI. Anterior temporal lobectomy guided by iEEG in these patients is associated with a high rate of freedom from postsurgical seizures, which is comparable to that in patients with MRI-detected temporal lobe lesions. It is also important to identify neocortical temporal lobe seizure focus in patients with MRI-negative TLE, because surgery
Intracranial electroencephalography monitoring and surgery in MRI-negative TLE that is restricted to the focus and that spares the mesial temporal structures reduces the risk of postsurgical cognitive decline. Nonetheless, these patients have a lower rate of freedom from postsurgical seizures.
Conflict of interest None.
Funding source None.
Acknowledgments We confirm that we have read the Journal’s position on issues involved in ethical publication and affirm that this report is consistent with those guidelines.
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