Epilepsia, 51(8):1429–1435, 2010 doi: 10.1111/j.1528-1167.2009.02403.x
FULL-LENGTH ORIGINAL RESEARCH
Epilepsy with dual pathology: Surgical treatment of cortical dysplasia accompanied by hippocampal sclerosis *Dong W. Kim, ySang K. Lee, zHyunwoo Nam, yKon Chu, xChun K. Chung, {Seo-Young Lee, #Geeyoung Choe, and **Hyun K. Kim *Department of Neurology, Konkuk University Medical Center, Seoul, Korea; yDepartment of Neurology, College of Medicine, Seoul National University, Seoul, Korea; zDepartment of Neurology, Seoul Municipal Boramae Hospital, Seoul, Korea; xDepartment of Neurosurgery, College of Medicine, Seoul National University, Seoul, Korea; {Department of Neurology, Kangwon National University Hospital, Chuncheon, Korea; #Department of Pathology, College of Medicine, Seoul National University, Seoul, Korea; and **Department of Neurology, Seoul Municipal Eunpyeong Hospital, Seoul, Korea
SUMMARY Purpose: The presence of two or more epileptogenic pathologies in patients with epilepsy is often observed, and the coexistence of focal cortical dysplasia (FCD) with hippocampal sclerosis (HS) is one of the most frequent clinical presentations. Although surgical resection has been an important treatment for patients with refractory epilepsy associated with FCD, there are few studies on the surgical treatment of FCD accompanied by HS, and treatment by resection of both neocortical dysplastic tissue and hippocampus is still controversial. Methods: We retrospectively recruited epilepsy patients who had undergone surgical treatment for refractory epilepsy with the pathologic diagnosis of FCD and the radiologic evidence of HS. We evaluated the prognostic roles of clinical factors, various diagnostic modalities, surgical procedures, and the severity of pathology.
Approximately one-third of patients with epilepsy are refractory to medical treatment, and epilepsy surgery is an effective therapeutic option in a select subset of these patients. Resection surgery is particularly recommended for certain surgically remediable syndromes, including mesial temporal lobe epilepsy (mTLE), perhaps the most common form of adult epilepsy and often refractory to pharmacotherapy; and neocortical epilepsy, which includes various pathologies with different epileptogenicity (Engel et al., 2003; Tonini et al., 2004; Tellez-Zenteno et al., 2005; Spencer & Huh, 2008)
Accepted September 28, 2009; Early View publication November 16, 2009. Address correspondence to Hyunwoo Nam, Department of Neurology, Seoul Municipal Boramae Hospital, 395, Shindaebang 2 dong, Dongjak Ku, Seoul 156-707, Korea. E-mail:
[email protected] Wiley Periodicals, Inc. ª 2009 International League Against Epilepsy
Results: A total of 40 patients were included, and only 35.0% of patients became seizure free. Complete resection of the epileptogenic area (p = 0.02), and the presence of dysmorphic neurons or balloon cells on histopathology (p = 0.01) were associated with favorable surgical outcomes. Patients who underwent hippocampal resection were more likely to have a favorable surgical outcome (p = 0.02). Conclusions: We show that patients with complete resection of epileptogenic area, the presence of dysmorphic neurons or balloon cells on histopathology, or resection of hippocampus have a higher chance of a favorable surgical outcome. We believe that this observation is useful in planning of surgical procedures and predicting the prognoses of individual patients with FCD patients accompanied by HS. KEY WORDS: Epilepsy surgery, Hippocampal sclerosis, Cortical dysplasia.
Temporal lobe resection for patients with mTLE is the most frequently performed surgical procedure for refractory epilepsy. Hippocampal sclerosis (HS) is the most common underlying pathologic cause of mTLE, and the presence of unilateral HS on presurgical magnetic resonance imaging (MRI) predicts a favorable prognosis for seizure remission following surgery (Radhakrishnan et al., 1998; Jeong et al., 2005). Surgical resection of neocortical epilepsy is more variable and complex. Developmental abnormalities including focal cortical dysplasia (FCD) are frequently found as epileptogenic foci, and other pathologies such as brain tumors and vascular malformations are associated with refractory epilepsy (Janszky et al., 2006; Yun et al., 2006). Surgical outcome in cases of neocortical epilepsy is generally less satisfactory than in patients with mTLE (Engel et al., 2003; Tonini et al., 2004; Tellez-Zenteno et al., 2005; Spencer & Huh, 2008). The presence of two or more epileptogenic pathologies in patients with refractory epilepsy is often observed. This
1429
1430 D. W. Kim et al. so-called ‘‘dual pathology’’ usually refers to the presence of HS together with an additional epileptogenic lesion identified by neuroimaging, but can often include additional microscopic changes revealed only by pathologic examination (Eriksson et al., 2005). Microscopic or macroscopic dysplastic tissues are often observed in association with HS in surgical specimens of otherwise typical patients with mTLE. The clinical implications of the dysplastic lesions in patients with mTLE are controversial (Kasper et al., 2003; Kalnins et al., 2004), but several reports have described the presence of dysplastic lesions as being associated with early seizure onset, high seizure frequency, and poor postsurgical outcomes (Engel, 1992; Bocti et al., 2003; Kelemen et al., 2006). Conversely, pathologic or radiologic evidence of HS is found in a proportion of patients with neocortical epilepsy. The most frequent clinical presentation is the coexistence of HS with a malformation of cortical development, most commonly with FCD (Li et al., 1999; Kral et al., 2003; Srikijvilaikul et al., 2003; Fauser et al., 2004; Siegel et al., 2006). Although it has been suggested that the sclerotic hippocampus as well as dysplastic tissues can be epileptogenic (Fauser & Schulze-Bonhage, 2006), there are few studies describing the surgical treatment of this type of dual pathology, and treatment by resection of both the neocortical dysplastic tissue and hippocampus is still controversial. We investigated the surgical outcome for patients with FCD plus evidence of HS, and examined the prognostic implications of the severity of pathology, clinical factors, surgical procedures, and the results of presurgical diagnostic modalities.
Patients and Methods Patients We studied 40 patients who had undergone surgical treatment for refractory epilepsy with the pathologic diagnosis of FCD and radiologic evidence of HS, at the Seoul National University Hospital between November 1995 and September 2006. We included only patients who had neocortical ictal onsets regardless of the presence of hippocampal ictal onsets; therefore, we excluded patients with mTLE who underwent anterior temporal resection, and had incidental findings of dysplastic tissues in the temporal neocortex. We excluded one patient who had insufficient postoperative follow-up (less than 2 years), and three patients with other types of potentially epileptogenic lesions, including two with ischemic changes, and one the result of trauma. We excluded two patients with other types of malformations of cortical development: one with periventricular heterotopia and with polymicrogyria. All patients had intractable epilepsy, despite taking the appropriate anticonvulsant drugs. We included only patients who had focal resection and excluded patients who had functional hemispherectomy or Epilepsia, 51(8):1429–1435, 2010 doi: 10.1111/j.1528-1167.2009.02403.x
corpus callosotomy. Surgical outcome was described as being either seizure free or not seizure free. Magnetic resonance imaging All patients underwent brain MRI. Standard MRI was performed on a 1.5-T unit (Signa Advantages; General Electric Medical Systems, Milwaukee, WI, U.S.A.), with conventional spin-echo T1-weighted sagittal and T2weighted axial and coronal sequences in all patients. The section thickness and the conventional image gaps were 5 mm and 1 mm. T1-weighted three-dimensional (3D) magnetization-prepared rapid acquisition of gradientecho sequences with 1.5 mm thick sections of the whole brain and T2-weighted fluid-attenuated inversion recovery (FLAIR) images of 3-mm thick sections were also obtained in the oblique coronal plane of the temporal lobe. The angle of oblique coronal imaging was perpendicular to the long axis of the hippocampus. Functional neuroimaging Positron emission tomography (PET) was performed in 38 patients during the interictal period (no seizures for more than 24 h). Axial raw data were obtained using a PET scanner (ECAT EXACT 47; Siemens CTI, Knoxville, TN, U.S.A.) 60 min after the intravenous injection of 18F-fluorodeoxyglucose (FDG, 370 MBq). Spatial resolution was 6.1 mm · 6.1 mm · 4.3 mm. FDG–PET images were assessed visually and by statistical parametric mapping (SPM) analysis, as described previously (Lee et al., 2003). Ictal single photon emission computed tomography (SPECT) was performed in 27 patients during video-EEG (electroencephalography) monitoring. Technetium-99m (99MTc) was mixed with hexamethylpropyleneamine oxime (925 MBq) and injected as soon as a seizure started. Brain SPECT images were acquired within 2 h of the injection. A triple-head rotating gamma camera (Prism 3000; Picker, Cleveland, OH, U.S.A.) was used, equipped with a highresolution fan beam collimator. Interictal SPECT was also performed to identify perfusion changes. Side-by-side visual analysis of interictal and ictal images was performed and the subtraction method was used, as previously described (Lee et al., 2003). The results of FDG–PET and SPECT were defined as localizing if the predominant hyperperfusion area or the predominant hypometabolic zone was confined to the resected lobe, and diffuse or multifocal abnormalities beyond the epileptogenic area were not considered as localizing even when they were within the epileptogenic hemisphere, including the epileptogenic area. Video-EEG monitoring Interictal and ictal scalp EEGs were recorded in all patients using a video-EEG monitoring system, with electrodes placed according to the international 10–20 system, with additional anterior temporal electrodes. In 33 patients
1431 Epilepsy with Dual Pathology for whom other methods gave inconclusive or discordant results, we used a combination of grids and strips for intracranial EEG. The location of electrode grids and strips was determined based on clinical, neurophysiologic, imaging, and scalp EEG data. Intracranial grids and strips were used in various combinations, but always included multiple strips reaching to the parahippocampal gyrus to sample mesial temporal activity. In patients with neocortical epilepsy and a lesion demonstrated on MRI, subdural electrodes were placed over a lesion and the surrounding area including eloquent cortex. In patients with extratemporal epilepsy and no cortical lesion revealed on MRI, the locations of subdural arrays were guided by the results of ictal scalp EEG, FDG-PET, and ictal SPECT studies and semiology. A more widespread overage of the neocortex was conducted in these nonlesional cases. In patients with TLE, ictal EEG was performed in both lateral and mesial temporal areas by using grids and multiple strips to determine from which site seizure onset originated. In some patients, second intracranial EEG monitoring studies were undertaken when initial studies failed to identify ictal-onset zones. Insertion of additional electrodes or repositioning of previous electrodes was done during the second evaluation (Lee et al., 2004). At least three habitual seizures were recorded during scalp and intracranial EEG monitoring. When necessary, preoperative and intraoperative functional mapping and intraoperative electrocorticography were also performed. A localizing pattern of ictal-onset rhythm/interictal spike was defined as a localized ictal rhythm/interictal spike in the electrodes of an epileptogenic lobe or two adjacent electrodes. In patients with multiple areas of ictal-onset rhythm/ interictal spike, we defined as localizing only when the whole areas are finally considered epileptogenic, and did not include when the abnormalities were multilobar within the epileptogenic hemisphere including the epileptogenic area. Surgery and pathology The surgical area was decided based on the clinical symptoms, neuroimaging, and electrophysiologic observations. The resection margin for patients with epilepsy of neocortical origin was defined by (1) the presence of either a discrete lesion visible on MRI with compatible ictal EEG or a massive and exclusive ictal-onset zone confirmed by intracranial EEG; and (2) the absence of an eloquent cortex. Hippocampal resection, as a form of anterior temporal lobectomy with removal of the medial structures—including the amygdala, hippocampus, and parahippocampal gyrus—was performed in patients whose seizures arose from the hippocampus as well as neocortical area or were simultaneously recorded from the hippocampus and neocortical area by intracranial EEG. Although there was a concern that the sclerotic hippocampus could be epileptogenic, we tried to spare hippocampus for better functional outcome when there was no evidence of hippocampal ictal onset, especially when the ictal-onset area was localized to the extratemporal
areas. However, some patients with neocortical TLE or multifocal epilepsy with anterior temporal ictal onsets underwent hippocampal resection as a part of a standard anterior temporal lobectomy procedure, because it is often difficult to differentiate mesial from lateral temporal ictal onsets without recording from depth electrodes in the hippocampus. Complete resection was defined by resection of areas of ictal onset, persistent pathologic delta slowing, >1/s frequent spikes, and the presence of an intermittent gamma wave revealed by intracranial EEG, or resection of the entire MRI-visible neocortical lesion other than hippocampal sclerosis. The diagnosis and classification of the pathology of cortical dysplasia was described according to the system of Palmini and colleagues: ectopically placed neurons only (mild malformation of cortical development [mMCD]), isolated architectural abnormalities (FCD 1A), additional immature or giant neurons (FCD 1B), the presence of dysmorphic neurons (FCD 2A), and additional balloon cells (FCD 2B) (Palmini et al., 2004). All patients with hippocampal resection had pathologic diagnosis of HS. Informed consent was obtained from the patients before surgical treatment, and this protocol was approved by the institutional review board. Statistical tests We compared the clinical characteristics of the seizurefree group with the nonseizure-free group using the Student’s t-test or the Mann-Whitney U test for continuous variables and with a chi-square test or Fisher’s exact test for categorical variables. All analyses were conducted using SPSS version 12.0 (SPSS Inc., Chicago, IL, U.S.A.) and STATA version 9.2 (STATA Corp., College Station, TX, U.S.A.). p < 0.05 was considered significant.
Results Patients and surgical outcomes We studied 26 male and 14 female patients with a mean age at the time of surgery of 26.0 € 11.9 years (range 4– 51 years). The mean age at seizure onset was 11.0 € 6.9 years (range 0.5–32 years), and the mean interval between seizure onset and surgery was 15.0 € 10.6 years (range 1–48 years). A history of febrile convulsions was present in 11 (27.5%) of 40 patients, and 29 (72.5%) of 40 patients experienced secondary generalized tonic–clonic seizures. Of the patients, 7 had frontal lobe epilepsy, 17 had neocortical TLE, 3 had parietal lobe epilepsy, 1 had occipital lobe epilepsy, and 12 had multifocal epilepsy. Interestingly, all patients with multifocal epilepsy had temporal ictal onsets; three patients had frontotemporal, two had temporoparietal, five had temporooccipital, one had fronto-temporooccipital, and one had hemispheric epilepsy. During the follow-up period of more than 2 years, 14 (35.0%) of 40 Epilepsia, 51(8):1429–1435, 2010 doi: 10.1111/j.1528-1167.2009.02403.x
1432 D. W. Kim et al. patients were seizure-free, whereas 26 (65.0%) of 40 patients did not become seizure-free (Fig. 1). Diagnostic sensitivities of various modalities In addition to HS, MRI detected other focal abnormalities in the resected neocortical area in 40.0% of patients. Interictal scalp EEG showed unifocal epileptiform discharges in the resected lobe in 70.0% of patients, and ictal scalp EEG correctly localized these discharges to the resected lobe in 72.5% of patients. FDG–PET showed concordant focal hypometabolism in 81.6% of patients and ictal SPECT showed concordant focal hyperperfusion in 55.6% of patients. Surgical outcome in different pathologic subtypes of FCD Patient pathology revealed 2 patients with the characteristics of mMCD, 20 with FCD 1A, 10 patients with FCD 1B, 5 patients with FCD 2A, and 3 with FCD 2B. Patients were divided into two subgroups: those with mild pathology (mMCD, FCD 1A, and FCD 1B) and those with severe pathology (FCD 2A and 2B). Patients in the severe pathology group had a greater chance of becoming seizure-free than did patients in the mild pathology group (p = 0.01, Table 1). Prognostic factors for seizure-free outcomes Complete resection of the potential epileptogenic area was performed in 24 (60.0%) of 40 patients, with the completeness of resection an important prognostic factor (Table 1). We could not perform complete excision in 16 patients because the epileptogenic zone included portions of the eloquent area in 6 patients, whereas in 10 the epileptogenic area was often multifocal or widespread. Age at surgery, age at onset of epilepsy, duration of epilepsy, sex, seizure frequency, and the presence of febrile convulsions or secondary generalized tonic–clonic seizures were not significant prognostic factors of surgical outcome. The detection of a focal abnormality on the resected area by diagnostic modalities, including the presence of neocortical lesion revealed by MRI, focal interictal epileptiform discharge, a localized ictal-onset zone from scalp EEG, focal hypometabolism on PET, ictal hyperperfusion on ictal SPECT, was not associated with surgical outcome. The performance of an invasive study was also not associated with surgical outcome (Table 1). Surgical outcome following hippocampal resection related to epilepsy syndromes HS was found frequently in patients with neocortical TLE (17 patients) and multifocal epilepsy (12 patients) (Table 2). Hippocampal resection was performed in patients with evidence of hippocampal ictal onsets, but three patients with neocortical TLE and two with multifocal epilepsy underwent hippocampal resection as a part of standard anterior temporal lobectomy without definite hippocampal ictal Epilepsia, 51(8):1429–1435, 2010 doi: 10.1111/j.1528-1167.2009.02403.x
Table 1. Clinical characteristics and outcomes after surgical resection in 40 patients with epilepsy with focal cortical dysplasia plus hippocampal sclerosis and prognostic factors for becoming seizure-free for at least 2 years following surgery Seizure-free (n = 14, 35.0%) Age at operation (year, mean ± SD) Age at onset (year, mean ± SD) Duration of epilepsy (year, mean ± SD) Male/female Seizure frequency per month (mean ± SD) Presence of 2GTCS Presence of FC Complete resection of epileptogenic area Focal MRI lesion Interictal EEG, focal IED Ictal EEG, localized ictal-onset zone PET, focal hypometabolism (n = 38) Ictal SPECT, focal hyperperfusion (n = 27) Performance of intracranial EEG monitoring Severe pathologic characteristicsa Resection of hippocampus
Not seizure-free (n = 26, 65.0%)
p-Value
28.0 ± 10.8
24.9 ± 12.6
0.44
12.7 ± 7.9
10.0 ± 6.3
0.25
15.3 ± 8.8
14.9 ± 11.6
0.90
18/8 20.3 ± 51.3
0.45 0.95
8/6 18.4 ± 46.5 9 6 12
20 5 12
0.39 0.11 0.02
7 10 12
9 18 17
0.34 1.00 0.27
11/12
20/26
0.40
2/6
13/21
0.36
10
23
0.21
6
2
0.01
11
8
0.02
a Severe pathologic characteristics mean the presence of dysmorphic neurons or balloon cells on histopathology. 2GTCS, secondary generalized tonic–clonic seizure; EEG, electroencephalography; FC, febrile convulsion; IED, interictal epileptiform discharge; MRI, magnetic resonance imaging; PET, positron emission tomography; SD, standard deviation; SPECT, single photon emission computed tomography.
Table 2. Surgical outcome and hippocampal resection in relation to epilepsy syndrome
Hippocampal resection Seizure-free
FLE (7)
TLE (17)
PLE (3)
OLE (1)
Multifocal (12)
Total (40)
1
11
1
0
5
18
1
8
0
0
5
14
FLE, frontal lobe epilepsy; TLE, temporal lobe epilepsy; PLE, parietal lobe epilepsy; OLE, occipital lobe epilepsy.
onset, because it was difficult to differentiate neocortical from hippocampal ictal onsets without depth electrodes in the hippocampus. Hippocampal resection was performed in 18 patients (Table 2), and the performance of hippocampal resection was associated with a higher chance of becoming
1433 Epilepsy with Dual Pathology
A
B
C
D
E
Figure 1. An illustrative case: A 31-year-old woman presented with recurrent seizures. Magnetic resonance imaging (MRI) showed right hippocampal sclerosis without cortical abnormality (A). On scalp electroencephalography (EEG), repetitive spikes were observed in the right frontal area (B, circle). She had two types of seizures; she often experienced altered consciousness with motionless staring, with mesial temporal ictal onset on the intracranial EEG (C, arrow). She also experienced hyperactivity with violent behaviors with frontal ictal onset on the intracranial EEG (D, arrow). She underwent standard anterior temporal lobectomy with partial frontal lobectomy (E). Although she did not become seizure-free, the seizure frequency reduced markedly after surgery. Epilepsia ILAE
seizure-free after surgery (p = 0.02, Table 1). Two patients with persistent seizures after neocortical resection sparing hippocampus underwent hippocampal resection as a second operation, and one of them became seizure-free.
Discussion Our study shows that HS is frequently found in association with temporal FCD or multilobar FCD with temporal involvement. The coexistence of HS with temporal FCD is a well-known phenomenon (Srikijvilaikul et al., 2003; Fauser et al., 2004), and the coincidence of such dual temporal lobe pathologies has been regarded as evidence supporting common pathogenic mechanisms during embryogenesis or early development (Cendes et al., 1995). Recent molecular neuropathology studies that focused on developmental aspects of hippocampal organization suggested that HS may be a disorder resulting
from developmental errors (Blumcke et al., 2002). The pathology of FCD, such as the presence of dysmorphic neurons and balloon cells has been observed in the hippocampus of patients with medically intractable mTLE (da Silva et al., 2006; Kim et al., 2008). They noted no correlation between HS and the spread of ictal rhythm of extratemporal origin through the temporal lobe, and suggested that HS may reflect more widespread developmental abnormalities rather than providing evidence for secondary epileptogenesis (Lawn et al., 2000). Alternative explanations for the coexistence of FCD with HS include the secondary development of HS from seizures induced by FCD or seizures resulting from the combined effect of HS and FCD (Eriksson et al., 2005). HS can be demonstrated in animal models of limbic status epilepticus, with many of these animals developing spontaneous recurrent seizures similar to human mTLE (Represa et al., 1995). In humans, the most frequent association with HS is a Epilepsia, 51(8):1429–1435, 2010 doi: 10.1111/j.1528-1167.2009.02403.x
1434 D. W. Kim et al. prolonged febrile convulsion in childhood, and there is some evidence showing that acute symptomatic or prolonged seizures originating from the neocortex can cause hippocampal damage in humans (Briellmann et al., 2005; Mueller et al., 2006; Parmar et al., 2006). However, the development of hippocampal damage in neocortical epilepsy may indicate the presence of a subtle cortical dysplasia in the hippocampus undetected by routine MRI. Only 14 (35%) of 40 of our patients became seizure-free after surgical resection. This seizure-free rate was no better than that reported previously. In most studies, more than half the patients with FCD became seizure-free following surgery (Tassi et al., 2002; Cohen-Gadol et al., 2004; Fauser et al., 2004; Alexandre et al., 2006; Siegel et al., 2006), and approximately 60% of patients with FCD without HS in our previous study (Kim et al., 2009). Poor prognosis in patients with concomitant HS and FCD has been described previously (Kral et al., 2003). This poor prognosis can be explained by either common developmental or secondary epileptogenic mechanisms, because both mechanisms may explain the more widespread and severe epileptogenic abnormalities, which are easily associated with poor surgical outcomes. However, the coexistence of HS and temporal lobe developmental pathology may be just an epiphenomenon, a consequence of white matter atrophy secondary to epilepsy-induced damage (Emery et al., 1997). It is interesting to note that a better surgical outcome was achieved in patients in whom both the dysplastic tissue and the sclerotic hippocampus were removed, regardless of the epileptogenicity of the hippocampus. A similar result has been observed in a study with dual pathology epilepsy with diverse neocortical pathologies (Li et al., 1999). The poorer surgical outcome in patients without hippocampal resection may be related to the incomplete removal of epileptogenic regions, because the atrophic hippocampus might itself be involved in epileptogenicity in dual pathology patients. An electrophysiologic study showed the intrinsic epileptogenicity of both the atrophic hippocampus and the dysplastic lesion, with the hippocampus epileptogenicity strongly correlated with the severity of pathology (Fauser & Schulze-Bonhage, 2006). Although we resected the hippocampus in all patients showing evidence of hippocampal ictal onset, it is possible that the unresected hippocampus might have undetected intrinsic epileptogenicity in some cases because we did not monitor intracranial EEG in all patients. Placement of a depth electrode with prolonged monitoring is often necessary to detect the hippocampal epileptogenicity. The apparent prognostic effect of hippocampal resection may be related to the different location of FCD. Hippocampal resection was performed more frequently in patients with temporal FCD or multilobar FCD with temporal involvement, and it has been shown that patients with temporal FCD have a higher chance of being seizure-free than patients with extratemporal FCD Epilepsia, 51(8):1429–1435, 2010 doi: 10.1111/j.1528-1167.2009.02403.x
(Hirabayashi et al., 1993; Urbach et al., 2002; Fauser et al., 2004; Alexandre et al., 2006). However, the performance of hippocampal resection in all FCD patients with radiologic evidence of HS cannot be justified because it is likely that patients with preserved hippocampal function will experience a significant functional deficit after hippocampal resection, and a proportion of patients may have a chance of becoming seizure-free after a resection that spares hippocampus. Complete resection of MRI-visible lesions or of the epileptogenic regions in the neocortex has been associated with favorable surgical outcome, and patients with severe pathologic features have a greater chance of becoming seizure-free following surgery. The prognostic value of complete resection has been consistently documented (Tassi et al., 2002; Cohen-Gadol et al., 2004; Fauser et al., 2004, 2008; Kim et al., 2009; Krsek et al., 2009), but the prognostic value of the severity of the pathology is controversial because it has been associated with favorable surgical outcomes in some reports (Tassi et al., 2002; Kim et al., 2009), whereas others showed the opposite results (Fauser et al., 2004). The positive prognostic role of severe pathology may be explained by the incomplete surgical resection of the epileptogenic zone in some patients with mild pathology or a greater chance of accurate localization using other diagnostic tools in patients with severe pathology (Kim et al., 2009). Our study suggests that the surgical outcome would be less favorable in FCD patients with HS, and resection of hippocampus after intracranial EEG monitoring should be considered because the sclerotic hippocampus can be epileptogenic in these patients. Complete surgical resection of neocortical lesions identified by MRI or intracranial EEG may be associated with a higher chance of becoming seizure-free, and the severe pathology of FCD may be also associated with a favorable seizure outcome. However, because we studied only a limited number of patients, further studies are needed to completely understand the prognostic and epileptogenic role of HS in FCD patients.
Acknowledgment 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. Disclosure: None of the authors has any conflict of interest to disclosure.
References Alexandre V Jr, Walz R, Bianchin MM, Velasco TR, Terra-Bustamante VC, Wichert-Ana L, Araujo D Jr, Machado HR, Assirati JA Jr, Carlotti CG Jr, Santos AC, Serafini LN, Sakamoto AC. (2006) Seizure outcome after surgery for epilepsy due to focal cortical dysplastic lesions. Seizure 15:420–427. Blumcke I, Thom M, Wiestler OD. (2002) Ammon’s horn sclerosis: a maldevelopmental disorder associated with temporal lobe epilepsy. Brain Pathol 12:199–211.
1435 Epilepsy with Dual Pathology Bocti C, Robitaille Y, Diadori P, Lortie A, Mercier C, Bouthillier A, Carmant L. (2003) The pathological basis of temporal lobe epilepsy in childhood. Neurology 60:191–195. Briellmann RS, Wellard RM, Jackson GD. (2005) Seizure-associated abnormalities in epilepsy: evidence from MR imaging. Epilepsia 46:760–766. Cendes F, Cook MJ, Watson C, Andermann F, Fish DR, Shorvon SD, Bergin P, Free S, Dubeau F, Arnold DL. (1995) Frequency and characteristics of dual pathology in patients with lesional epilepsy. Neurology 45:2058–2064. Cohen-Gadol AA, Ozduman K, Bronen RA, Kim JM, Spencer DD. (2004) Long-term outcome after epilepsy surgery for focal cortical dysplasia. J Neurosurg 101:55–65. da Silva AV, Houzel JC, Targas Yacubian EM, Carrete H Jr, Sakamoto AC, Priel MR, Martins HH, Oliveira I, Garzon E, Stavale JN, da Silva Centeno R, Machado H, Cavalheiro EA. (2006) Dysmorphic neurons in patients with temporal lobe epilepsy. Brain Res 1072:200–207. Emery JA, Roper SN, Rojiani AM. (1997) White matter neuronal heterotopia in temporal lobe epilepsy: a morphometric and immunohistochemical study. J Neuropathol Exp Neurol 56:1276–1282. Engel J Jr. (1992) Update on surgical treatment of the epilepsies. Clin Exp Neurol 29:32–48. Engel J Jr, Wiebe S, French J, Sperling M, Williamson P, Spencer D, Gumnit R, Zahn C, Westbrook E, Enos B. (2003) Practice parameter: temporal lobe and localized neocortical resections for epilepsy: report of the Quality Standards Subcommittee of the American Academy of Neurology, in association with the American Epilepsy Society and the American Association of Neurological Surgeons. Neurology 60:538– 547. Eriksson SH, Nordborg C, Rydenhag B, Malmgren K. (2005) Parenchymal lesions in pharmacoresistant temporal lobe epilepsy: dual and multiple pathology. Acta Neurol Scand 112:151–156. Fauser S, Schulze-Bonhage A, Honegger J, Carmona H, Huppertz HJ, Pantazis G, Rona S, Bast T, Strobl K, Steinhoff BJ, Korinthenberg R, Rating D, Volk B, Zentner J. (2004) Focal cortical dysplasias: surgical outcome in 67 patients in relation to histological subtypes and dual pathology. Brain 127:2406–2418. Fauser S, Schulze-Bonhage A. (2006) Epileptogenicity of cortical dysplasia in temporal lobe dual pathology: an electrophysiological study with invasive recordings. Brain 129:82–95. Fauser S, Bast T, Altenmuller DM, Schulte-Monting J, Strobl K, Steinhoff BJ, Zentner J, Schulze-Bonhage A. (2008) Factors influencing surgical outcome in patients with focal cortical dysplasia. J Neurol Neurosurg Psychiatry 79:103–105. Hirabayashi S, Binnie CD, Janota I, Polkey CE. (1993) Surgical treatment of epilepsy due to cortical dysplasia: clinical and EEG findings. J Neurol Neurosurg Psychiatry 56:765–770. Janszky J, Pannek HW, Fogarasi A, Bone B, Schulz R, Behne F, Ebner A. (2006) Prognostic factors for surgery of neocortical temporal lobe epilepsy. Seizure 15:125–132. Jeong SW, Lee SK, Hong KS, Kim KK, Chung CK, Kim H. (2005) Prognostic factors for the surgery for mesial temporal lobe epilepsy: longitudinal analysis. Epilepsia 46:1273–1279. Kalnins RM, McIntosh A, Saling MM, Berkovic SF, Jackson GD, Briellmann RS. (2004) Subtle microscopic abnormalities in hippocampal sclerosis do not predict clinical features of temporal lobe epilepsy. Epilepsia 45:940–947. Kasper BS, Stefan H, Paulus W. (2003) Microdysgenesis in mesial temporal lobe epilepsy: a clinicopathological study. Ann Neurol 54:501–506. Kelemen A, Barsi P, Eross L, Vajda J, Czirjak S, Borbely C, Rasonyi G, Halasz P. (2006) Long-term outcome after temporal lobe surgery – prediction of late worsening of seizure control. Seizure 15:49–55. Kim SH, Cho YJ, Seok Kim H, Heo K, Lee MC, Lee BI, Seung Kim T, Woo Chang J. (2008) Balloon cells and dysmorphic neurons in the hippocampus associated with epileptic amnesic syndrome: a case report. Epilepsia 49:905–909. Kim DW, Lee SK, Chu K, Park KI, Lee SY, Lee CH, Chung CK, Choe G, Kim JY. (2009) Predictors of surgical outcome and pathologic considerations in focal cortical dysplasia. Neurology 72:211–216.
Kral T, Clusmann H, Blumcke I, Fimmers R, Ostertun B, Kurthen M, Schramm J. (2003) Outcome of epilepsy surgery in focal cortical dysplasia. J Neurol Neurosurg Psychiatry 74:183–188. Krsek P, Maton B, Jayakar P, Dean P, Korman B, Rey G, Dunoyer C, Pacheco-Jacome E, Morrison G, Ragheb J, Vinters HV, Resnick T, Duchowny M. (2009) Incomplete resection of focal cortical dysplasia is the main predictor of poor postsurgical outcome. Neurology 72:217– 223. Lawn N, Londono A, Sawrie S, Morawetz R, Martin R, Gilliam F, Faught E, Kuzniecky R. (2000) Occipitoparietal epilepsy, hippocampal atrophy, and congenital developmental abnormalities. Epilepsia 41:1546–1553. Lee SK, Yun CH, Oh JB, Nam HW, Jung SW, Paeng JC, Lee DS, Chung CK, Choe G. (2003) Intracranial ictal onset zone in nonlesional lateral temporal lobe epilepsy on scalp EEG. Neurology 61:757– 764. Lee SK, Kim KK, Nam H, Oh JB, Yun CH, Chung CK. (2004) Adding or repositioning intracranial electrodes during presurgical assessment of neocortical epilepsy: electrographic seizure pattern and surgical outcome. J Neurosurg 100:463–471. Li LM, Cendes F, Andermann F, Watson C, Fish DR, Cook MJ, Dubeau F, Duncan JS, Shorvon SD, Berkovic SF, Free S, Olivier A, Harkness W, Arnold DL. (1999) Surgical outcome in patients with epilepsy and dual pathology. Brain 122:799–805. Mueller SG, Laxer KD, Cashdollar N, Lopez RC, Weiner MW. (2006) Spectroscopic evidence of hippocampal abnormalities in neocortical epilepsy. Eur J Neurol 13:256–260. Palmini A, Najm I, Avanzini G, Babb T, Guerrini R, Foldvary-Schaefer N, Jackson G, Luders HO, Prayson R, Spreafico R, Vinters HV. (2004) Terminology and classification of the cortical dysplasias. Neurology 62(suppl 3):2–8. Parmar H, Lim SH, Tan NC, Lim CC. (2006) Acute symptomatic seizures and hippocampus damage: DWI and MRS findings. Neurology 66:1732–1735. Radhakrishnan K, So EL, Silbert PL, Jack CR Jr, Cascino GD, Sharbrough FW, O’Brien PC. (1998) Predictors of outcome of anterior temporal lobectomy for intractable epilepsy: a multivariate study. Neurology 51:465–471. Represa A, Niquet J, Pollard H, Ben-Ari Y. (1995) Cell death, gliosis, and synaptic remodeling in the hippocampus of epileptic rats. J Neurobiol 26:413–425. Siegel AM, Cascino GD, Meyer FB, Marsh WR, Scheithauer BW, Sharbrough FW. (2006) Surgical outcome and predictive factors in adult patients with intractable epilepsy and focal cortical dysplasia. Acta Neurol Scand 113:65–71. Spencer S, Huh L. (2008) Outcomes of epilepsy surgery in adults and children. Lancet Neurol 7:525–537. Srikijvilaikul T, Najm IM, Hovinga CA, Prayson RA, Gonzalez-Martinez J, Bingaman WE. (2003) Seizure outcome after temporal lobectomy in temporal lobe cortical dysplasia. Epilepsia 44:1420–1424. Tassi L, Colombo N, Garbelli R, Francione S, Lo Russo G, Mai R, Cardinale F, Cossu M, Ferrario A, Galli C, Bramerio M, Citterio A, Spreafico R. (2002) Focal cortical dysplasia: neuropathological subtypes, EEG, neuroimaging and surgical outcome. Brain 125:1719– 1732. Tellez-Zenteno JF, Dhar R, Wiebe S. (2005) Long-term seizure outcomes following epilepsy surgery: a systematic review and meta-analysis. Brain 128:1188–1198. Tonini C, Beghi E, Berg AT, Bogliun G, Giordano L, Newton RW, Tetto A, Vitelli E, Vitezic D, Wiebe S. (2004) Predictors of epilepsy surgery outcome: a meta-analysis. Epilepsy Res 62:75–87. Urbach H, Scheffler B, Heinrichsmeier T, von Oertzen J, Kral T, Wellmer J, Schramm J, Wiestler OD, Blumcke I. (2002) Focal cortical dysplasia of Taylor’s balloon cell type: a clinicopathological entity with characteristic neuroimaging and histopathological features, and favorable postsurgical outcome. Epilepsia 43:33–40. Yun CH, Lee SK, Lee SY, Kim KK, Jeong SW, Chung CK. (2006) Prognostic factors in neocortical epilepsy surgery: multivariate analysis. Epilepsia 47:574–579.
Epilepsia, 51(8):1429–1435, 2010 doi: 10.1111/j.1528-1167.2009.02403.x
