Surgical management of temporal lobe tumor related epilepsy in children

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1 J Neurosurg (Pediatrics 3) 102: , 2005 Surgical management of temporal lobe tumor related epilepsy in children OGUZ ÇATALTEPE, M.D., GÜZIDE TURANLI, M.D., DILEK YALNIZOGLU, M.D., MERAL TOPÇU, M.D., AND NEJAT AKALAN, M.D. Departments of Neurosurgery and Pediatric Neurology, Hacettepe University Medical School, Ankara, Turkey; and Division of Neurosurgery, UMass Memorial Medical Center, Worcester, Massachusetts Object. Slow-growing, low-grade temporal lobe tumors are one of the most common causes of epilepsy in children. Although there are numerous consistent features in this patient group, consensus about the management and surgical approach is lacking. In this study the authors review the clinical, pathological, and radiological features as well as outcome data obtained in 29 pediatric patients with temporal lobe tumor related epilepsy and discuss the surgical treatment strategies. Methods. In patients who presented with intractable seizures secondary to mass lesions and underwent comprehensive epilepsy workup, the tumor was resected and the diagnosis confirmed by pathological examination. A minimum follow-up period of 16 months was required. Medical records were reviewed for details of seizure type and duration, electrophysiological data, imaging studies, operative notes, pathological examination reports, and follow-up data. The surgical approach was as follows. The lesionectomy with/without cortical resection was performed in all cases of lateral temporal tumors. Lesionectomy was performed with/without cortical resection in cases of basal temporal tumors if the mesial structures were radiologically normal. Mesial temporal tumors were excised, as were the remaining mesial temporal structures in the nondominant hemisphere; however, if the tumor was in the dominant hemisphere, lesionectomy was performed only if the remaining mesial structures were radiologically normal. Twenty-nine patients between 2 and 18 years of age were identified. Most tumors were located in the mesial temporal lobe. All patients underwent resection of the tumor with or without mesial and cortical structures. The most common pathological entity was dysembryoplastic neuroepithelial tumor. Sixty-nine percent of the patients remained seizure free (Engel Class I) and 14% experienced significant improvement (Engel Class II) after surgery. Outcome was better in the patients who underwent gross-total tumor resection. Conclusions. Mesially located low-grade neoplasms were the most frequently observed mass lesions in children with temporal tumor related epilepsy in this series. Resection of the tumor with or without amygdalohippocampectomy provides a high rate of seizure-free outcome. It is the author s opinion that temporal lobe tumors should be managed based on the subgroups defined by their anatomical locations. If the tumor is located in or in proximity to eloquent cortex, we recommend functional magnetic resonance imaging and invasive monitoring techniques to map the eloquent cortex and epileptogenic zone, thereby tailoring the resection. KEY WORDS brain neoplasm temporal lobe tumor epilepsy pediatric neurosurgery S Abbreviations used in this paper: DNET = dysembryoplastic neuroepithelial tumor; EEG = electroencephalography; MR = magnetic resonance. 280 INCE Hughlings-Jackson s report 15 in the 1880s, it has been known that seizures may be the only manifestation of a brain tumor. Supratentorial tumors constitute 10 to 40% of the pathological substrates in patients undergoing surgery for a seizure disorder. 2,7,20,29 Temporal lobe tumors, especially low-grade gliomas, are among the most common causes of seizures in patients referred for epilepsy surgery. 9,16,18,19,25 Although we still do not know the exact pathophysiology of tumor-induced seizures or their true incidence among patients with epilepsy, our understanding of temporal lobe tumors as a distinct clinicopathological group has improved in the last decade, partly due to the advent of neuroimaging modalities, such as MR imaging. It has become apparent that temporal lobe tumors seen in patients with epilepsy exhibit numerous consistent features including the following: young age, well-differentiated histological characteristics, close association with the limbic system, a distinctive growth pattern, and an indolent biological nature with seizures as the only neurological symptom. 2 5,7,13,20,26,29,32 Despite these common features, the management strategy is controversial including whether to perform surgical intervention or radiological observation, or to conduct lesionectomy alone or lesionectomy with resection of the surrounding epileptogenic cortex and/or amygdalohippocampectomy. Treatment of pediatric patients presents additional challenges, and there are only a few published pediatric series in the literature. 3,8,16,18,19,25 To address these issues focusing on pediatric patients, we retrospectively reviewed 29 patients with epilepsy who presented with temporal tumor related seizures and underwent surgery between 1996 and 2003 at Hacettepe University

2 Temporal lobe tumor related epilepsy Hospitals. We discuss the treatment strategies undertaken in these patients. Clincal Material and Methods Hospital records were reviewed for the following inclusion criteria: 1) seizure as a main presenting sign; 2) neuroimaging-documented mass lesion in the temporal lobe; 3) resection of the lesion; 4) pathological tissue confirmation; and 5) a minimum 16-month follow-up period. All patients underwent comprehensive pre- and postsurgical workups including a thorough seizure history, neurological examinations, neuroimaging studies, routine EEG recordings, noninvasive continuous EEG/video monitoring, and neuropsychological evaluation. Patient charts, neurophysiological data, operative notes, and pathology reports were reviewed and summarized. Preoperative and postoperative neuroimaging studies were re-reviewed by the authors to verify the location of the lesion with respect to gyral anatomy and limbic structures, as well as to evaluate the lesion and limbic structure characteristics, such as signal intensity, mass effect on adjacent brain tissue, and volume loss. All patients underwent either total or subtotal tumor resection with or without mesial and neocortical excision. Complete tumor extirpation was determined by reviewing operative reports and postoperative MR images. Follow-up examination results were obtained from patient charts. Postoperatively, all patients continued to receive anticonvulsant medications before attempting gradual drug withdrawal. Thereafter, gradual drug tapering was attempted in patients who had been seizure free. The frequency of pre- and postoperative seizures was compared using the seizure frequency during the most recent year prior to surgery and the latest follow-up data after surgery. Postoperative seizure outcome was categorized using the Engel classification. 10 Results We studied data obtained in 29 children who underwent surgery for a temporal lobe tumor related seizure disorder. Nine patients were female and 20 were male, whose mean age was 10.5 years (range 2 18 years). Age at seizure onset ranged from 8 months to 12 years (mean 6.1 years). In 79% of the patients seizure history was greater than 2 years. All patients presented with seizure disorder, and six experienced other symptoms such as memory difficulties and visual field defects. All but three experienced complex partial seizures with or without secondary generalized seizures. Neurological status was normal in 82% of the patients. Forty-one percent of the patients underwent long-term noninvasive EEG/video monitoring. Interictal epileptogenic abnormalities, consisting of sharp waves and spikes, were evident in 63% of the patients. The lateralizing value of the interictal EEG was 70% and the localizing value was 55% in this group. Ictal EEG findings indicated a lateralizing value in 80% of the patients, whereas the localizing value was 40%. Ten patients underwent preoperative neuropsychological tests and three underwent Wada testing. We considered undertaking Wada and neuropsychological tests in all cases for which we planned resecting mesial structures; however, they could not be performed in some cases because of the patient s young age or limited cooperation. We did not use functional MR imaging because it was not available at our institution during the study period. All patients underwent MR imaging, whereas computerized tomography scanning was performed in 12 patients. Fourteen (48%) of the 29 tumors originated in mesial temporal structures, nine (31%) in the basal temporal region including the fusiform and inferior temporal gyri (T-3), and six were localized in the lateral temporal region including the superior and middle temporal gyri (T-1 and T-2). None of the mesial temporal tumors crossed the collateral sulcus. Enhancement of the lesion was observed in 21% of the patients after contrast administration. Magnetic resonance imaging revealed intratumoral microcystic components in six patients. Hypointensity/isointensity and hyper-/isointensity were common on T 1 - and T 2 -weighted MR images, respectively, but in some cases the signal intensity and homogeneity varied. Gross-total tumor removal was achieved in 62% of the patients, whereas in 38% it was subtotal. The surgical strategy was tumor excision alone in six patients (20%), tumor removal and anterior temporal lobectomy sparing the mesial structures in 11 patients (37.9%), and tumor resection and anterior temporal lobectomy with amygdalohippocampectomy in 12 patients (41.4%). Between 1996 and 1999, the resection procedure involved anterior excision of 3.5 to 4 cm of the temporal lobe and sparing of the superior temporal gyrus. Since then we have undertaken a very limited resection of anterior temporal lobe, which includes almost the temporal pole alone in some cases of mesial and basal temporal tumors just to obtain a better exposure to the tumor. Although we still describe this as anterior temporal lobectomy in our series, its only purpose was to create better exposure. The postoperative complication rate was 17.2%: temporary hemiparesis in two cases, wound infection in one, and superior quadrant defects in four. There were no major deficits and the mortality rate was 0%. Dysembryoplastic neuroepithelial tumor (Figs. 1 and 2) was the most common (48.2%) histopathological diagnosis. Other histopathological diagnoses included ganglioglioma (13.7%; Fig. 3), pilocytic astrocytoma (13.7%), oligodendroglioma (10.3%), pleomorphic xanthoastrocytoma (6.8%), and low-grade glial tumor (6.8%; Fig. 4). Focal cortical dysplasia or neuronal heterotopia was present in 20.6% of the pathological specimens, mostly derived from DNETs. Ipsilateral hippocampal sclerosis as a component of dual disease was observed in two patients. The mean follow-up duration was 31 months (range months). Postoperatively 69% of the patients were seizure free (Engel Class I). In an additional four patients we observed a significant improvement in seizure frequency (Engel Class II). Overall, good postoperative seizure control was demonstrated in 83% of the cases (Tables 1 and 2). Two patients with Engel Class III outcome underwent reassessment and repeated operation. In one case the residual tumor was removed and in the other case the hippocampus was resected. The first patient continued to suffer from seizures after the second surgery, whereas in the second patient seizures resolved (follow-up period 6 months only). In eight patients antiepilepsy medication was gradually reduced and stopped after a minimum 2-year seizure-free period. In two patients typical seizures recurred and they 281

3 O. Çataltepe, et al. FIG. 1. Case 22. Preoperative MR images obtained in a 10-year-old girl with a large mesial temporal mass (DNET); axial T 2 -weighted (left), sagittal T 1 -weighted (center), and coronal T 2 -weighted images (right). started on a regimen of antiepilepsy medications. Three additional patients have tapered their medication intake without any seizures and plan to stop all medications in the near future. Discussion Primary brain tumors are present in 10 to 40% of patients with epilepsy undergoing surgical treatment for intractable seizures. 3,5 In two large series from the Montreal Neurological Institute, 15 to 20% of surgically treated epilepsy patients harbored mass lesions and 74% of the tumors were gliomas. 27,28 In these and some other series, temporal lobe tumors were found to be the largest group among tumor-related epilepsy cases with a rate of 38 to 76%. 4 6,13,27 With the advent of neuroimaging techniques, especially MR imaging, slow-growing low-grade neoplasms located in the temporal lobe have been detected with increasing frequency as a substrate for seizure disorder among epilepsy patients. Although there are a large number of series involving tumor-related epilepsy cases, most comprise adult patients. Although temporal lobe tumors are one of the most common pathological entities in children with epilepsy, besides cortical dysplasia, there are very few temporal lobe tumor related epilepsy series focused on the pediatric age group. 16,18 At our institution, temporal tumor related epilepsy cases constituted 40% of our pediatric epilepsy surgery cases during the time of this study. In this report we describe our experience with these cases and discuss our surgical approach. It is our opinion that temporal lobe tumors are not homogeneous lesions and patients outcome can be improved, especially regarding seizure management, if the surgical approach is based on the subgroups defined by the anatomical location of the lesion. We use different surgical approaches in mesial, basal, and lateral temporal tumors and we also approach tumors located in dominant hemisphere differently from those in the nondominant hemisphere. If the tumor is located in the mesial temporal lobe in the nondominant hemisphere, we resect all mesial temporal structures in addition to tumor even if the tumor is shown not to involve the remaining mesial structures on neuroimaging studies. For example, we perform tumor resection and complete hippocampectomy in cases of amygdala tumors in which there is a neuroimaging-documented healthy-looking hippocampus if neuropsychological tests imply no risk. If the tumor is in the dominant hemisphere, we undertake lesionectomy only if remaining mesial structures appear normal on neuroimaging studies; however, if the tumor infiltrates all mesial temporal structures in the dominant hemisphere, we perform Wada and neuropsychological testing to gather more information regarding potential risks of resection. Subsequently, we proceed to excise mesial structures if the risks are acceptable. We group the tumors involving fusiform and inferior tem- FIG. 2. Case 22. Postoperative axial (left), sagittal (center), and coronal (right) T 1 -weighted MR images. 282

4 Temporal lobe tumor related epilepsy FIG. 3. Case 21. Preoperative (left) and postoperative (right) sagittal MR images obtained in a 15-year-old boy with a mesial temporal mass originating in the amygdala (ganglioglioma). poral gyri together as basal temporal tumors and perform lesionectomy only if the mesial structures are radiologically normal, which is the case in general except for highgrade tumors or dual pathological entities. In cases involving these dual pathological entities, we recommend performing Wada and neuropsychological tests first and then performing amygdalohippocampectomy if they are not functionally dominant. These two groups of patients combined constitute the most controversial group among cases of temporal lobe tumors. Therefore, the surgical approach should be carefully tailored individually considering the electrophysiological, radiological/neuroimaging, and functional characteristics of the case. In the subgroup of lateral temporal tumors that includes superior and middle temporal gyri, our surgical approach is more straightforward: we undertake lesionectomy with or without the resection of the surrounding cortex. If the tumor is located in or in proximity to eloquent cortex, especially on the dominant side, we recommend functional MR imaging and periand intraoperative invasive monitoring as well as stimulation studies to map the eloquent cortex, epileptogenic zone, and their relationship with the lesion. The extent of the resection should be tailored in these cases based on the data obtained from these studies. Although invasive monitoring is not a routine part of our pre- and perioperative assessment in this patient group, it may be indicated in some cases such as those involving discordant radiological/neuroimaging, electrophysiological, and clinical data. We believe that it may be also useful in cases with dual pathological entities, especially if the lesion involves the dominant hemisphere and if it covers or is in proximity to eloquent cortex and mapping is necessary. We also use invasive monitoring if postoperative status is Engel Class III to IV and reassessment of the patient indicates that the seizure onset is still in the surgical site. A Distinct Clinicopathological Group Epilepsy patients with temporal lobe tumors as the substrate of seizures exhibit certain distinctive characteristics. One group 11,13,29,31 has reported their vast experience with these cases in several papers and described temporal lobe tumors associated with intractable seizures as a distinct clinicopathological group. They stated that the tumor related seizures frequently occur in a young host and that the biological behaviors of these tumors were strikingly indolent. They have reported on 65 patients in whom extended follow-up data (mean 17.2 years) were obtained, and there was only one death due to tumor in this series. Interestingly, there has been a male predominance observed in several series, including our own. The incidence of affected males in the study by Ianelli, et al., 16 was 73% compared with a rate of 70% in our series. Cortical localization of these tumors is a distinctive neuroimaging feature; up to 91% of tumors were found in a peripheral position, within or adjacent to the gray white junction or hippocampus. 6,13 Our MR imaging findings were also consistent with these results, with 69% of the tumors located peripherally. Another interesting finding is the frequent involvement of mesial temporal structures. Forty-eight percent of the tumors originated in mesial temporal structures in our series, including the amygdala and hippocampus. An additional 31% of the tumors were localized in the basal temporal region, and the remaining lesions were in the lateral temporal neocortex. The incidence of mesially located temporal lobe tumors was 43% in the series published by Zaatreh, et al. 31 Numerous distinctive characteristics have been reported, especially by Spencer s group 4,13,31 in epilepsy patients with gliomas including the following: a well-differentiated pattern, an indolent biological nature, young age, long history of seizure disorder (typically the only manifestation), normal neurological examination, long-term survival, and favorable outcome after surgery. The characteristics of our series were highly consistent with these distinctive traits. Therefore, we concur with previous reports that temporal lobe tumors associated with chronic epilepsy have some characteristics that justify setting them apart as a distinct clinicopathological group. This is extremely relevant when determining an appropriate therapeutic approach for these patients. Pathological Substrate It is well known that the vast majority of tumors among epilepsy patients are low-grade gliomas. 4,21 There are, however, discrepancies regarding the frequency of the histological tumor subtypes in this patient population. Although ganglioglioma was the most common single pathological entity (38 49%) followed by low-grade astrocytoma in some series, 18,24,30 another group found that low-grade astrocytoma was the most frequently seen disease (44%), followed by oligodendroglioma (30%), 10 and a different group 283

5 O. Çataltepe, et al. reported that DNET was the most common pathological entity (87%). 20 Zaatreh, et al., 31 reported on 68 patients, both adult and children, with temporal lobe tumor related epilepsy. They found low-grade astrocytoma to be the most common pathological entity (45.6%) followed by ganglioglioma (21.2%) and oligodendroglioma (17.6%). In our series, DNETs were the most common tumor type (48%), followed by low-grade astrocytoma (13%) and ganglioglioma (13%). In our study we also found that 20.6% of the temporal lobe tumor specimens contained an additional disease entity: cortical dysplasia or neuronal heterotopia in the surrounding brain tissue. We agree with Morris, et al., 24 that the discrepancies concerning the incidence of subtypes may be related to the use of different pathological criteria for the diagnosis of these controversial tumors. Surgical Strategy The epileptogenic mechanism of tumor related epilepsy is unclear. The proposed mechanisms include direct pressure and irritation in the cortical tissue, gliosis, and disrupted vascularization in the surrounding cortex; some morphological neuronal alterations in cellular levels; changes in the level of neurotransmitters; and so-called denervation hypersensitivity. 4,7,11,18,20 Regardless of the mechanism, the primary goal of surgical treatment in these patients is to control the seizures and resect the tumor while preserving cognitive and motor functions. These dual therapeutic goals necessitate determining the spatial relationship between the epileptogenic zone and the lesion. In addition, one must determine the causative relationship between the tumor and seizure disorder because structural lesions that are not a source of epileptic activity may be observed. 1,2,4 Undertaking a comprehensive preoperative evaluation of these patients, including video/eeg monitoring, is of critical importance for clarifying the spatial relationship between the epileptogenic zone and the lesion, as well as verifying the causative relationship between epilepsy and the tumor. The optimal surgical approach for these lesions remains controversial. To prevent future seizures some surgeons have recommended isolated resection of the tumor, whereas others have suggested additional resection of surrounding epileptogenic tissue and/or mesial structures by using electrocorticographic guidance. 2,5,9 Among those recommending resection of epileptogenic zones, the extent of tissue removal and resection margins is debated. When the tumor and epileptogenic zone are not colocalized, the issue becomes more complex. Jooma, et al., 17 retrospectively reviewed data obtained in 30 patients in whom seizures were due to temporal mass lesions and found that those treated with lesionectomy alone experienced significantly lower seizure-free outcomes compared with those who underwent electrophysiologically guided resection of the lesion and epileptogenic focus. In contrast, Khajavi, et al., 18 found in their pediatric patients that seizure-free outcome correlated with the extent of tumor resection but not with additional excision of the surrounding epileptogenic zone. They concluded that perhaps resection of the entire tumor removes the primary epileptogenic drive or eliminates enough epileptogenic tissue beyond a critical mass required to generate clinical seizures. Another controversy concerns the extent of tumor resection. Blume, et al., 3 reported seizure-free outcomes in 88% of their cases after gross-total resection, whereas only 25% of patients were seizure free after a subtotal resection. Several other authors have published results similar to those in our series. 5,18 We achieved gross-total resection in 62% of patients. Although the size of our patient popula- FIG. 4. Case 18. Preoperative (upper) and postoperative (lower) sagittal (left) and coronal (right) MR images obtained in a 14-year-old girl with a very large left temporal mass (pleomorphic xanthoastrocytoma). 284

6 Temporal lobe tumor related epilepsy TABLE 1 Demographic and treatment data obtained in 29 patients with temporal lobe tumor related epilepsy* Age (yrs), Seizure Case No. Sex Duration (mos) Tumor Location Op (extent) FU (mos) Engel Class 1 13, M 3 DNET mesial les, ATL, & AHC (GT) 16 I 2 8, M 6 GG & CD mesial les, ATL, & AHC (GT) 38 I 3 6, M 4 DNET basal les & ATL (GT) 19 I 4 10, F 6 DNET & CD basal les & ATL (GT) 16 I 5 5, M 3 oligo mesial les, ATL, & AHC (ST) 18 I 6 2, M 1 PA mesial les, ATL, & AHC (ST) 20 II 7 7, M 3 PA mesial les, ATL, & AHC (GT) 19 III 8 4, M 1 PA mesial les, ATL, & AHC (GT) 17 I 9 18, M 16 DNET lat les & ATL (GT) 26 I 10 11, M 9 LGA mesial les & ATL (ST) 60 III 11 12, M 8 PX lat les & ATL (ST) 32 I 12 6, M 2 DNET & CD basal les & ATL (ST) 28 III 13 14, M 11 PA lat les & ATL (ST) 81 III 14 4, F 2 DNET mesial les & ATL (GT) 17 I 15 11, M 8 DNET & CD basal les & ATL (GT) 34 I 16 14, F 8 DNET basal les & ATL (ST) 84 III 17 12, M 8 DNET lat les (GT) 78 I 18 14, F 2 PX basal les (GT) 19 II 19 15, F 13 DNET basal les (GT) 36 I 20 18, F 14 DNET & HS mesial les, ATL, & AHC (GT) 33 I 21 15, M 8 GG mesial les, ATL, & AHC (ST) 17 II 22 10, F 6 DNET & CD mesial les, ATL, & AHC (GT) 19 I 23 11, M 6 oligo lat les (GT) 21 I 24 13, M 9 oligo mesial les, ATL, & AHC (GT) 30 I 25 9, M 2 GG mesial les, ATL, & AHC (GT) 22 I 26 18, F 6 GG basal les & ATL (ST) 16 II 27 4, M 1 LGA, HS, & CD mesial les, ATL, & AHC (ST) 22 I 28 6, M 4 DNET lat les (GT) 32 I 29 15, F 10 DNET basal les (ST) 30 I * AHC = amygdalohippocampectomy; ATL = anterior temporal lobectomy; CD = cortical dysplasia; FU = follow up; GG = ganglioglioma; GT = gross-total; HS = hippocampal sclerosis; les = lesionectomy; LGA = low-grade astrocytoma; oligo = oligodendroglioma; PA = pilocytic astrocytoma; PX = pleomorphic xanthoastrocytoma; ST = subtotal. tion is too limited to allow a statistically significant comparison between these two groups, in the gross-total resection group the seizure-free outcome rate was much higher than that in the subtotal group (88% compared with 36%). Other authors have reported favorable outcomes even in patients who had undergone incomplete tumor resection. Kirkpatrick, et al., 20 reported incomplete resection in 71% of patients with temporal lobe tumor related epilepsy with a seizure-free outcome rate of 81%. Possibly the favorable outcome in incomplete resection can be attributed to the decreasing volume of critical epileptogenic mass and to interrupting critical seizure propagation pathways. 31 It is also possible, however, that even if a seizure-free outcome is present for some time, increasing epileptogenic mass secondary to tumor regrowth and/or redeveloped propagation pathways may cause the recurrence of seizures in the long term. Therefore, we believe that gross-total resection should be the goal of surgery to decrease the risk of tumor recurrence and to achieve a long-term seizure-free outcome. The accessibility of the lesion and its relation with the eloquent cortex, however, will determine the limits of the resection. From a surgical point of view, another controversial issue is resection of mesial temporal structures in addition to the tumor. Using depth electrodes Mathern, et al., 23 found that in patients with temporal lobe lesions, ictal EEG onset started or first propagated in the mesial temporal contacts in 94% of the patients. Their findings strongly indicated that mesial structures are capable of generating independent seizures. It may be also speculated that hippocampi are often epileptogenic in these patients because of abnormal synaptic reorganization of the hippocampi induced by seizures secondary to temporal tumors. Once the primary lesion is removed, however, the continuity of this epileptogenic capability is unknown. Indeed, there is no clear evidence that the hippocampi in patients with tumor-associated epilepsy are morphologically abnormal. 18 On the other hand, there are convincing data regarding surgical strategy if there is a dual pathological entity and hippocampal atrophy associated with a temporal lobe tumor. Morris, et al., 24 recommended hippocampal resection if additional hippocampal atrophy was evident on MR imaging. Cascino, et al., 8 concluded that stereotactic tumor resection alone yielded unsatisfactory results in cases of temporal lobe epilepsy with a dual pathological entity. They also found that MR imaging identified hippocampal atrophy predicted unsatisfactory seizure outcome after lesionectomy alone. Therefore, they recommended temporal lobectomy including resection of the hippocampus and tumor in dual pathological entity cases. The incidence of dual disease varies in the literature. Drake, et al., 9 found mesial temporal sclerosis in 56% of pediatric patients with temporal lobe tumors in their series. After identifying two patients with neuroimagingdocumented dual disease in our series, we resected the amygdala and hippocampus along with the tumor in both cases. Hippocampal sclerosis was confirmed in pathologi- 285

7 O. Çataltepe, et al. cal examinations in both cases; however, the surgical strategy is unclear when electrophysiological evidence of epileptogenic activity conflicts with radiological evidence of normal mesial structures in cases involving temporal tumor related epilepsy. Fried, et al., 13 have suggested that the mesial structures should be resected with the tumor in patients with mesial temporal lesions and early seizure onset. Mesial structures, however, may be preserved in patients with lateral lesions and late-onset seizures. 12,13 Zaatreh, et al., 31 resected the mesial structure when tumor was involved and gauged the extent of hippocampal resection depending on exact tumor location, lesion size, preoperative neuropsychological findings, and the MR imaging appearance of the hippocampus. Currently, there are no convincing data with which to define a clear surgical strategy. Our current approach is to resect both the amygdala and hippocampus in mesially originating tumors in the nondominant side even if tumor involvement is not clear on MR imaging. We found tumor extension in the hippocampus and parahippocampus, in two cases in which tumors originated in the amygdala, on histological examinations despite a radiologically/neuroimaging normal-appearing hippocampus. On the other hand, we found a histologically normal hippocampus in two other patients with radiologically similar tumors. As a result, the relevant literature TABLE 2 Summary of clinical variables and outcomes No. of Cases Engel Seizure Outcome Class Variable I II III IV seizure duration (yrs) age (yrs) tumor location mesial basal lat pathological entity DNET GG PA oligo LGA PX cortical dysplasia yes no hippocampal sclerosis yes no op type les les & ATL les, ATL, & AHC extent of resection ST GT including our study does not clarify the mesial extent of surgical management in patients with temporal lobe tumor related epilepsy and, thus, more data are needed to devise the optimal surgical strategy. Surgery-Related Outcome The prognosis after tumor related epilepsy surgery is much better than that after nonlesional epilepsy surgery, especially when tumors are localized in the temporal lobe. In several other series investigators have also reported seizure-free outcome in more than 80% of patients. 4,5,7,13,14,20 As we have discussed, the main predictor for long-term seizure control in these patients is gross-total resection of the tumor. Khajavi, et al., 18 concluded that only the completeness of the tumor resection determines seizure outcome in children. Zaatreh, et al., 31 reached a similar conclusion in a series including both adults and children. Another interesting finding was recently reported by Luyken, et al. 22 In a mixed group of epilepsy patients with brain tumors (including all brain regions in both children and adults) they found that the tumor type was also correlated with seizure outcome. Greater than 90% of patients with ganglioglioma and oligodendroglioma experienced seizure-free outcomes, whereas those with pilocytic astrocytoma and Grade II astrocytoma had worse seizure-free outcomes (61 and 66%, respectively). They explained this difference by the higher rate of residual tumors and significantly longer duration of seizures in the astrocytoma group. They also found the following factors to be associated with poorer seizure control: longer duration of epilepsy, additional EEG focus, additional hippocampal sclerosis or cortical dysplasia, and incomplete tumor resection. In our study, 69% of our patients had a seizure-free outcome (Engel Class I) and an additional 14% had significant improvement in the frequency and severity of the seizures (Engel Class II). We believe that the surgical failure in these cases should be addressed following further assessment. In patients with Engel Grade III to IV, we offer neuroimaging and electrophysiological reassessment with MR imaging and noninvasive monitoring. If we observe a residual tumor or residual mesial structure and the seizure onset is correlated with these areas, we propose repeated operation for removal of the residue. If the tumor resection is satisfactory and we did not purposefully resect mesial structures in the first surgery, but the new electrophysiological data still localize the seizure onset zone to the surgical site, we then accept the patient as a candidate for invasive monitoring. Finally, if the invasive monitoring locates the seizure onset to the mesial structures and the risk is acceptable, we then recommend the resection of the mesial structures. Conclusions Low-grade neoplasms are the most frequently observed mass lesions in children with temporal tumor related epilepsy. The surgical goal should be gross-total resection of the tumor. 21 The approach in each case should be based on the MR imaging findings and the anatomical localization of the tumor as well as electrophysiological findings. Magnetic resonance imaging plays a critical role in determining the presence of a dual pathological entity and anatomical extent of the lesion as well as in choosing an adequate sur- 286

8 Temporal lobe tumor related epilepsy gical strategy. Lesionectomy alone is the correct surgical approach in patients harboring a lesion localized in the lateral temporal region. Mesial structures should be resected if there is mesial sclerosis and any tumor involvement in this area, if the risk of surgery is acceptable. A limited anterior temporal lobectomy can be performed to provide a better access to the tumor or if the epileptogenic area is much larger than the tumor itself. The chance of seizure-free outcome in this patient group is very high. In the event of an unsatisfactory seizure outcome, the patient should undergo reevaluation to determine the completeness of tumor resection and the epileptogenic zone. Acknowledgement We thank Dr. Dara Brodsky for her help in preparation of the article. References 1. Awad IA, Rosenfeld J, Ahl J, Hahn JF, Luders H: Intractable epilepsy and structural lesions of the brain: mapping, resection strategies, and seizure outcome. 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