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 Table of Contents  
ORIGINAL ARTICLE
Year : 2016  |  Volume : 53  |  Issue : 2  |  Page : 96-101

Surgical strategy in the management of low-grade brain neoplasm with epilepsy: seizure outcome


Department of Neurosurgery, Ain Shams University, Cairo, Egypt

Date of Submission21-Jan-2016
Date of Acceptance29-Mar-2016
Date of Web Publication2-Jun-2016

Correspondence Address:
Hatem A Sabry
MD, Department of Neurosurgery, Ain Shams University, 11361 Cairo
Egypt
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/1110-1083.183435

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  Abstract 

Background
For 30-50% of patients with brain tumors, epileptic seizures are the presenting clinical sign of a tumor; 10-30% of patients develop seizures later during the disease course. Slow-growing tumors, (i.e. low-grade gliomata) are the most epileptogenic, although the high frequency of epilepsy in these patients might be related to longer survival from low-grade tumors. This study bears on this controversy through a prospective strategy in which patients were treated with excision of lesion together with epileptogenic area around, as defined using intraoperative electrocorticography.
Patients and methods
This is a prospective study designed to treat patients presenting between January 1997 and December 2011 with drug-resistant epilepsy (defined as failure to attain a seizure-free status utilizing adequate trials of two tolerated and appropriate antiepileptic drugs). Surgical procedure consisted of maximal resection of the tumor and any resectable surrounding associated with epileptogenic cortex, identified by means of intraoperative electrocorticography.
Results
Fifty-four patients were operated upon and followed up for a mean of 40 months (range = 6-72 months). Thirty-two tumors (59.2%) were located in the temporal lobe, 15 (27.8%) in the frontal lobe, and seven (13%) in the parietal lobe. The histopathology confirmed low-grade astrocytoma (WHO grade I or II) in 38.9% (n = 21) of patients, oligodendroglioma in 24% (n = 13), ganglioglioma in 20.4% (n = 11), and dysembryoplastic neuroepithelial tumor in 16.7% (n = 9) of patients. Gross total resection was achieved in 64.8% (n = 35) of patients and subtotal resection in 35.2% (n = 19) of patients. There was no death and five patients had permanent deficit. At follow-up, according to Engel's seizure outcome scale, 77.8% (n = 42) of the patients had good seizure control (classes I and II), and, collectively, 90.7% (n = 49) of patients had more than 75% reduction in seizures (class I-III).
Conclusion
In our series, we had a relatively high rate of gross total resection, which was associated with worthwhile seizure control, which compares favorably with a recent work that showed that the extent of resection significantly predicts seizure freedom following surgery. The favorable seizure outcome is tentatively attributed to the fact that all identified areas harboring epileptogenic activity around tumors were resected along with tumor resection.

Keywords: Epilepsy surgery, low-grade glioma, seizure outcome


How to cite this article:
Mustafa MA, Sabry HA, Abdel Latif AM. Surgical strategy in the management of low-grade brain neoplasm with epilepsy: seizure outcome. Egypt J Neurol Psychiatry Neurosurg 2016;53:96-101

How to cite this URL:
Mustafa MA, Sabry HA, Abdel Latif AM. Surgical strategy in the management of low-grade brain neoplasm with epilepsy: seizure outcome. Egypt J Neurol Psychiatry Neurosurg [serial online] 2016 [cited 2021 Apr 23];53:96-101. Available from: http://www.ejnpn.eg.net/text.asp?2016/53/2/96/183435


  Introduction Top


The incidence of brain tumors in people with epilepsy is about 4%. Of patients with brain tumors, the frequency of epilepsy is 30% or more depending on tumor type. For 30-50% of patients with brain tumors, an epileptic seizure is the presenting clinical sign of a tumor; 10-30% develop seizures later during the disease course [1]. Slow-growing tumors - that is, mainly low-grade gliomata - are the most epileptogenic, although the high frequency of epilepsy in these patients might be related to substantially longer survival from low-grade tumors compared with high-grade tumors [2],[3]. The optimal surgical strategies in patients with tumoral epilepsy, particularly those related to lesions in the temporal lobe, remain poorly defined. Some studies suggest lesionectomy as an efficient procedure for appreciable seizure control, whereas others recommend excision of variable amounts or potentially epileptogenic cerebral cortex in addition to the lesion.

The present study bears on the controversy through a prospectively devised strategy in which patients were treated with excision of the lesion together with the epileptogenic area around it as defined with intraoperative electrocorticography (ECoG) [4],[5].


  Patients and methods Top


The descriptive study was designed and approved by Ain Shams University ethical committee to prospectively evaluate a consecutive group of patients with medically intractable seizures who had brain tumors as the etiology of the seizures over a period from January 1997 through December 2011.

A total of 54 patients during the period were enrolled in the study; they were investigated and underwent respective surgery in the Department of Neurosurgery, Ain Shams University, Cairo, Egypt, and in Saudi German Hospital, Jeddah, Saudi Arabia. Patients were considered medically intractable if they have had uncontrollable and disabling seizures for more than 1 year despite the appropriate use of at least two major anticonvulsant medications. Patients whose seizures were not the main presenting symptom even though they had brain tumors as the cause of the seizure were not included in the study.

High-resolution MRI before and after intravenous contrast was performed for all patients. For all patients with assumed temporal lobe epilepsy, axial MRI was performed with a modified angulation of 25° off the orbitomeatal line to be parallel to the long axis of the hippocampus. Epileptic patients are typically classified on the basis of neuroimaging into those with no detectable MRI abnormality, those with neoplastic lesions, and those with non-neoplastic lesions. The latter group consists of a potpourri of lesions, including cortical dysplasia, cavernoma, focal encephalomalacia, mesial temporal lesions, or an area of high signal abnormality of uncertain etiology. Patients with dual pathologies [e.g. dysembryoplastic neuroepithelial tumor (DNET) and hippocampal sclerosis] were excluded from the study. Patients lacking confirmed pathological diagnosis of their lesions were not included in the study. However, patients with tumors that were pathologically verified even though preoperative imaging did not resolve the diagnosis were included. Neuroimaging revealed that 32 patients had temporal lobe lesions and 22 had lesions elsewhere.

All patients underwent routine preoperative scalp electroencephalography (EEG), both ictal and interictal, through continuous noninvasive video EEG monitoring by means of cable telemetry using scalp electrodes. Telemetry was used to identify both epileptic focus and its spatial relationship with the lesion.

Preoperative invasive monitoring was not used. However, intraoperative ECoG was utilized in cases. This consisted of recording from the surface, including the lateral, inferior, and mesial surfaces when appropriate, as well as the use of depth electrodes for mesial temporal structures in case of temporal lobe tumors. For intraoperative ECoG recording, Integra subdural grids (Integra Neurosciences, Plainsboro, NJ) and strips were used and connected to a portable NCI EEG unit. When a mesial temporal lobe was to be resected in the patient's dominant temporal lobe, patients were subjected to the intracarotid amytal test (Wada test) in which only memory was tested. For tumors located within or close to an eloquent cortex, surgery was performed under local anesthesia with cortical mapping through bipolar electrical stimulation (Ojemann cortical stimulator; Integra Neurosciences, Plainsboro, NJ). Typical stimulation parameters were 2-3 s stimulus trains of 50 Hz rectangular pulses of 0.5 ms duration. Stimulation was applied through a constant voltage stimulator.

The procedures performed in the case of temporal lobe tumors consisted of the following:

  1. Relatively standard anterior temporal lobectomy including resection of mesial structures (i.e. amygdala and hippocampus) (n = 9);
  2. Anterior temporal lobectomy without resection of mesial structures (n = 10); and
  3. Lateral neocortical corticectomy in which the identification of epileptogenic zone by means of ECoG played a more important role (n = 13).


The choice of procedure used in any given case was individualized by considering the location of the neoplasm as determined by the radiological findings on the MRI, delineation on the zone or persistent intraictal epileptiform activity, and seizure onset during the preoperative telemetry and any epileptiform activity identified by means of intraoperative ECoG. Resection of the hippocampus was undertaken if there was any infiltration of it as determined using preoperative MRI, or if there was any epileptiform activity recorded within it on the intraoperative ECoG.

For extratemporal cases (n = 22), the procedure performed included the following:

  1. Anterior frontal lobectomy (n = 6);
  2. Frontal corticectomy (topectomy); or
  3. Parietal corticectomy (n = 9).


Frontal lobectomy was carried out sparing the premotor and motor gyri in all cases and sparing the speech area in cases of dominant frontal lobe lesions. The corticectomies were carried out using the time-honored epileptic surgical procedure of subpial resection to minimize leaving behind any deafferented, deefferented, scarred, or ischemic epileptic cortex.

Thirty-nine operations were performed under general anesthesia and 15 under neuroleptanalgesia and local anesthesia (awake craniotomies). The general anesthesia consisted of induction with a combination of propofol (1-2 mg/kg), fentanyl (1-2 μg/kg), and atracurium (0.5 mg/kg) for endotracheal intubation. It was maintained with sevoflurane (1-2% volume in 100% oxygen), atracurium (0.1 mg/kg/20 min), and intravenous fentanyl, so-called balanced anesthesia. During recording, sevoflurane was discontinued.

The awake craniotomies (n = 15) were carried out under a combination of local anesthesia (infiltration of the proposed scalp incision in addition to regional blockade using bupivacaine hydrochloride 0.5% with epinephrine 1 : 200 000) and neuroleptanalgesia. The neuroleptic used was droperidol (at an initial dose of 15-40 μg/kg and supplement dose of 15 μg/kg). Propofol (initial dose, 300-400 μg/kg; supplement dose, 100-300 μg/kg) was used for sedation, and fentanyl (0.7 μg/kg as initial dose and 0.35 μg/kg as supplement dose) for analgesia.

The pathological specimens were reviewed by two pathologists. The tumors were classified according to the WHO classification for tumors of the nervous system. The postoperative follow-up period ranged from 6 to 72 months (mean = 3.4 years). Clinical follow up data was collected from routine postoperative patients' visits.

The persistence of postoperative seizures was classified according to the four outcome classes described by Engel and colleagues: class I: (a) seizure-free or (b) with auras only; class II: rare seizures; class III: reduction in seizure frequency by more than 75%; and class IV: less than 75% reduction in seizures or unchanged seizure frequency [6].


  Results Top


The most common tumors were of glial origin (65%). There were 21 astrocytoma, 13 oligodendroglioma, and 11 ganglioglioma. The remaining nine tumors were DNETs. All tumors were of low histopathological grade (WHO I or II) [Table 1].
Table 1: Tumor histopathological types and location

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There were 35 male and 19 female patients between 8 and 59 years of age (mean age of 33.5 at the time of surgery). The mean age of onset of seizures was 26 years (range = 1-52 years) and the duration of epilepsy disorder varied between 2 and 34 years of age (a mean of 17 years), as outlined in [Table 2]. In this table, the age of seizure onset and the duration of epilepsy disorder are shown in correlation to the histopathological diagnosis of the resected tumors. Complex partial seizures were present in 46 patients, simple partial seizures in three, and generalized seizures in five patients. There was secondary generalization in 35 of the 46 who had complex partial seizures.
Table 2: Mean age at seizure onset and seizure duration

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As noted in [Table 1], 32 tumors were located in the temporal lobe, whereas 22 were extratemporal. The preoperative MRI report matched the histopathological exam in 47 cases. Postoperative MRI was performed to evaluate the extent of tumor resection. Gross total resection was achieved in 35 patients and subtotal resection in 19 patients [Table 3] and [Figure 1].
Figure 1: Extent of tumor resection using histopathological type and location.

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Table 3: Patients with subtotal resection

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The follow-up period ranged from 6 to 72 months. There was no operative mortality. Immediate postoperative neurological deficit was encountered in 11 patients, five with dysphasia and six with hemiparesis. These deficits were not unexpected as they were all due to encroachment upon the eloquent cortex, motor (hemiparesis) and speech (dysphasia) cortex, respectively. Six cases resolved completely within 1 year, resulting in only five patients with permanent deficits. [Table 4] shows the outcome of 54 patients with respect to seizure control according to Engel's seizure outcome scale. Of 54 patients, 34 patients were of class I, eight were of class II, seven were of class III, and five were of class IV. Collectively, 90.7% of patients experienced more than 75% reduction in their seizure frequency after surgery. All of these patients considered this as significant seizure reduction. As regards histopathological diagnosis, the best seizure control was achieved in patients with DNET, 78% of whom were seizure free and 89% were of class I or II [Table 5] and [Figure 2]
Figure 2: Seizure outcome in relation to histopathological type.

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Table 4: Outcome with respect to seizure control according to Engel's seizure outcome scale

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Table 5: Seizure outcome compared with extent of resection

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  Discussion Top


Seizures are the most frequent presenting symptom in patients with low-grade brain neoplasms and are more prevalent when the lesion is located in or around the temporal lobe [7]. The most common tumors identified as being responsible for medically intractable epilepsy are gliomata [8]. The most common intrinsic tumors that lead to seizure disorders include low-grade astrocytomas oligodendrogliomas, and gangliogliomas [9],[10]. This was true in our series, in which 83.3% of the cases were caused by gliomata, of which 63% were astrocytomata and 20% were gangliogliomata.

According to previous studies, the median survival of low-grade glioma patients ranged from 4.7 to 9.8 years. Death usually arises from malignant transformation [11]. In our study, the number of cases and the relatively short follow-up period does not allow us to statistically analyze survival rates. Nevertheless, the indolent course of the tumors studied would comply with the consistency of high survival rates.

The mean duration of seizure history in our series was 17 years (range = 2-32 years), which is longer than those recorded in the study by Tandon and Esquenazi (2013) [5], which reported a mean of 4 years. The reason for the long duration in our study is attributed to the late diagnosis of surgically resectable tumors due to poor or no imaging.

Zentner and colleagues (1997) reported 146 cases of epilepsy with tumor that were treated by means of lesionectomy with resection of the epileptogenic cortex around the tumor, as identified by means of invasive and/or noninvasive ECoG. In their series, 71% of the patients were seizure free (Engel class I) and 95% had worthwhile seizure control (Engel class I-III) [12]. In our series, using similar technique, 63% of our patients became seizure free (Engel class I) and 90.7% experienced more than 75% reduction in seizures (Engel class I-III).

In the presence of a low-grade intrinsic brain tumor, epilepsy is common and it adds substantial morbidity to the patients, and consideration of seizure control in addition to tumor control is important for clinical management [1],[13]. Qiu et al. (2014) [14] reported two groups of patients: in group 1, 65 patients with low-grade tumors and seizures underwent lesionectomy with intraoperative ECoG-guided tailored epilepsy surgery, and the seizure outcome was 87.7% seizure free (Engel class I); and in group 2, of 72 similar patients who underwent lesionectomy alone, seizure outcome was reported to be 52.8% seizure free (Engel class I). In our series, using a technique similar to what they used in group 1, seizure freedom was achieved in 63% of our patients. Our results are comparable to those reported for patients in group 1 and superior to their results reported in group 2 (lesionectomy alone).

The favorable outcome in our series is attributed to the fact that all identified areas with epileptogenic activity around the tumors were resected. Awad et al. (1991) [15] reported epileptogenicity in their series of 47 cases to be arising from the lesion itself in 24% of the cases, from the area around the lesion in 38% of cases, and from remote areas from the lesion in 38% of cases. This signifies the importance of resecting the epileptogenic area along with tumor resection.

Subtotal tumor resection was performed in 19 cases in our series located in or around the eloquent cortex, in which any further resection was considered a significant risk on functional outcome. Khajavi et al. (1999) [16] concluded that, in their 26 cases of tumor-associated epilepsy, the most important factor related to seizure control was the extent of tumor resection rather than necessarily the resection of areas of epileptogenic activity around the tumor. We would reiterate that our main goal of surgical management was the resection of as much neoplasm and epileptogenic cortex as possible without producing unwanted neurological deficits.

In temporal lobe tumors, seizure outcome after lesionectomy alone was found to be disappointing by Jooma and colleagues (1995), who studied 30 patients with temporal lobe tumors and epilepsy. Nineteen percent of patients who underwent lesionectomy alone were seizure free compared with 93% of those who underwent temporal lobectomy including removal of medial structures or tumor resection with ECoG-guided resection of associated epileptogenic cortex [17].

As regards extratemporal cases, which frequently have epileptogenic foci in or around the eloquent cortex, intraoperative cortical mapping using cortical stimulation under local anesthesia has been shown to be helpful in determining the extent of resection [18]. Combining the data of extraoperative telemetry, intraoperative ECoG, and that of cortical mapping, the most epileptogenic and least functional areas are resected in a way that favors the best seizure control and least functional disruption.

In our series we strictly relied on the neurophysiological data provided by intraoperative ECoG rather than subdural electrodes. The extraoperative subdural EEG mapping allows detection of zones of ictal onset. This was believed by Jayakar et al. [19] to be a reliable EEG criterion for defining the epileptogenic zone. Khajavi and colleagues reported 26 pediatric cases with tumor-related epilepsy for which they used subdural electrodes for preoperative electrographic evaluation. They concluded that, with gross total resection of the tumor, it was not essential to include the zone of ictal onset to improve the outcome. They also noted that their use of subdural electrodes has progressively diminished markedly and recommend that there was no reason to use them for the sole purpose of identifying zones of ictal onset [16].


  Conclusion Top


In our series of cases we achieved gross total resection in 65% of the cases, which was associated with worthwhile seizure control. This compared favorably with a recent work that showed that the extent of resection significantly predicts seizure freedom following surgery. The favorable seizure outcome in our series is tentatively attributed to the fact that all identified areas harboring epileptogenic activity around the tumors were resected along with tumor resection. ECoG is a useful tool in the majority of cases for delineating the patients' cortical epileptogenicity.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

 
  References Top

1.
Van Breemen MS, Wilms EB, Vecht CJ. Epilepsy in patients with brain tumours: epidemiology, mechanisms, and management. Lancet Neurol 2007; 6 :421-430.  Back to cited text no. 1
    
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Englot DJ, Han SJ, Berger MS, Barbaro NM, Chang EF. Extent of surgical resection predicts seizure freedom in low-grade temporal lobe brain tumors. Neurosurgery 2012; 70 :921-928discussion 928.  Back to cited text no. 4
    
5.
Tandon N, Esquenazi Y. Resection strategies in tumoral epilepsy: is a lesionectomy enough? Epilepsia 2013; 54: Suppl 9 :72-78.  Back to cited text no. 5
    
6.
Engel JJr, Van Ness PC, Rasmussen TB Outcome with respect to epileptic seizures. In: Engel J, editor. Surgical treatment of the epilepsies. 2nd ed. New York: Raven Press; 1993. 609-621.  Back to cited text no. 6
    
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Kumthekar P, Raizer J, Singh S. Low-grade glioma. Cancer Treat Res 2015; 163 :75-87.  Back to cited text no. 11
    
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Zentner J, Hufnagel A, Wolf HK, Ostertun B, Behrens E, Campos MG, et al. Surgical treatment of neoplasms associated with medically intractable epilepsy. Neurosurgery 1997; 41 :378-386. discussion 386-387.  Back to cited text no. 12
    
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Taphoorn MJ. Neurocognitive sequelae in the treatment of low-grade gliomas. Semin Oncol 2003; 30(Suppl 19) :45-48.  Back to cited text no. 13
    
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Qiu B, Ou S, Song T, Hu J, You L, Wang Y, Wang Y. Intraoperative electrocorticography-guided microsurgical management for patients with onset of supratentorial neoplasms manifesting as epilepsy: a review of 65 cases. Epileptic Disord 2014; 16 :175-184.  Back to cited text no. 14
    
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Awad IA, Rosenfeld J, Ahl J, Hahn JF, Lüders H. Intractable epilepsy and structural lesions of the brain: mapping, resection strategies, and seizure outcome. Epilepsia 1991; 32 :179-186.  Back to cited text no. 15
    
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Khajavi K, Comair YG, Wyllie E, Palmer J, Morris HH, Hahn JF. Surgical management of pediatric tumor-associated epilepsy. J Child Neurol 1999; 14 :15-25.  Back to cited text no. 16
    
17.
Jooma R, Yeh HS, Privitera MD, Gartner M. Lesionectomy versus electrophysiologically guided resection for temporal lobe tumors manifesting with complex partial seizures. J Neurosurg 1995; 83 :231-236.  Back to cited text no. 17
    
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Pondal-Sordo M, Diosy D, Téllez-Zenteno JF, Sahjpaul R, Wiebe S. Usefulness of intracranial EEG in the decision process for epilepsy surgery. Epilepsy Res 2007; 74 :176-182.  Back to cited text no. 18
    
19.
Jayakar P, Dunoyer C, Dean P, Ragheb J, Resnick T, Morrison G, et al. Epilepsy surgery in patients with normal or nonfocal MRI scans: integrative strategies offer long-term seizure relief. Epilepsia 2008; 49 :758-764.  Back to cited text no. 19
    


    Figures

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    Tables

  [Table 1], [Table 2], [Table 3], [Table 4], [Table 5]



 

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