20 Surgical Management of Lesional Temporal Lobe Epilepsy

10.1055/b-0034-84131

20 Surgical Management of Lesional Temporal Lobe Epilepsy

Çataltepe, Oğuz, Cosgrove, G. Rees

Temporal lobe lesions constitute 30 to 70% of surgical specimens obtained from children with intractable temporal lobe epilepsy (TLE).1–8 Developmental brain tumors and low-grade neoplasms are the most common causes of TLE in children. Although hippocampal sclerosis is the most common lesion in adults with TLE, it is much less frequent in the pediatric patient population. In this chapter, we will discuss the surgical strategies in children with lesional temporal epilepsy, mainly focusing on tumors and vascular malformations, because they are the most common neuropathological substrates in children after cortical dysplasia and mesial temporal sclerosis (MTS).

The goal in neuro-oncological surgery is always total resection of the tumor when it is feasible. This is also relevant for tumor-related epilepsy cases with one significant difference: there is an equally important additional surgical target-the epileptogenic zone. Therefore, surgical interventions for lesional TLE in children have dual therapeutic goals: stopping the seizures and removing the lesion while preserving cortical function. These dual therapeutic goals can be achieved by determining both the causative relationship between the lesion and the seizures and the spatial relationship between the lesion and the epileptogenic zone. Although the epileptogenic zone frequently corresponds to the cortex immediately adjacent to the lesion, it may also stretch far beyond the anatomical boundaries of the lesion. Therefore, determining the extent of resection in lesional epilepsy patients is critical to optimizing surgical outcome but also quite challenging at times. Furthermore, reaching these goals may not always be feasible, and certain compromises may be required in some cases.

Here we will discuss the surgical management of lesional TLE patients based on published data and our own clinical experience. There is very limited published data specifically obtained from children with TLE, and there are even smaller numbers of reports addressing lesional TLE in children. The real frequency of lesional TLE cases is not clear, and reported rates show wide variations in large surgical series ( Table 20.1 ).1–8

Pathological Substrate

The most common pathological substrates in medically refractory epilepsy patients are MTS, tumors, vascular abnormalities, gliosis, and developmental disorders.9 We will review lesional TLE in childhood by focusing on neoplasms and vascular abnormalities and refer the reader to related chapters in this book for details regarding the surgical management of MTS and cortical dysplasia. Published series describing pathological substrates in TLE patients mostly include mixed patient populations, both adults and children. Only a few reports exclusively cover the pediatric age group.1–8 As we can see in Table 20.1 , published data are heterogeneous and most likely heavily biased by referral patterns to the related epilepsy centers. However, it is still fair to state that neoplasms are the most common pathological substrates seen in children with lesional TLE followed by MTS, cortical dysplasia, and vascular lesions. MTS constitutes, at least in some series, a substantial percentage of the cases, but the true frequency of MTS in children with TLE is still not clear.

**Table 20.1** Pathological Substrates in Pediatric Lesional TLE Series
	Number	Tumor	MTS	CD	Vasc.	Dual Pathology
Sinclair1	42	33%	19%	9%	–	11%
Clusmann2	89	46%	31%	1%	–	–
Mittal et al3	109	35%	45%	35%	5%	25%
Benifla et al4,54	126	52%	13%	7%	3%	8%
Kan et al5	33	28%	28%	22%	9%	5%
Kim et al6	59	54%	23%	18%	–	–
Maton et al7	20	40%	20%	30%	–	–
Sources: Mittal S, Montes JL, Farmer JP, et al. Long-term outcome after surgical treatment of temporal lobe epilepsy in children. J Neurosurg 2005; 103 (5, suppl)401–412; Benifla M, Otsubo H, Ochi A, et al. Temporal lobe surgery for intractable epilepsy in children: an analysis of outcomes in 126 children. Neurosurgery 2006;59(6):1203–1213, discussion 1213–1214; Kan P, Van Orman C, Kestle JRW. Outcomes after surgery for focal epilepsy in children. Childs Nerv Syst 2008;24(5):587–591; Kim SK, Wang KC, Hwang YS, et al. Epilepsy surgery in children: outcomes and complications. J Neurosurg Pediatr 2008;1(4):277–283; Maton B, Jayakar P, Resnick T, Morrison G, Ragheb J, Duchowny M. Surgery for medically intractable temporal lobe epilepsy during early life. Epilepsia 2008;49(1):80–87.

**Table 20.2** Tumor Types in Pediatric TLE Series
	Number	DNET	GG	LGA	Oligo
Sinclair1	14	14%	57%	21%	–
Clusmann2	41	17%	56%	7%	7%
Mittal et al3	38	13%	55%	13%	7%
Çataltepe et al10	29	52%	13%	21%	10%
Benifla et al4,54	65	15%	24%	24%	–
Kim et al6	32	37%	40%	–	9%
Maton et al7	8	25%	25%	50%	–
Abbreviations: TLE, temporal lobe epilepsy, DNET, dysembryoplastic neuroepithelial tumors; GG, ganglioplioma; LGA, low grade astrocytoma; Oligo, oligodendroglioma.

Tumors

The exact frequency of tumors in children with intractable TLE is not well established yet because of the limited number of studies focusing exclusively on the pediatric population. Çataltepe et al10 reported that temporal-tumor—related epilepsy patients constituted 40% of pediatric epilepsy surgery cases in their series. Published data imply that the most common neoplasms in TLE patients are developmental tumors, such as dysembryoplastic neuroepithelial tumor (DNET), or slowly growing low-grade glial tumors and oligodendro-gliomas.1,3–5,13 However, the frequencies of the neoplasms seen in epilepsy patients are quite different among published series. Although ganglioglioma is the most common neoplasm in some series, low-grade astrocytoma or DNET is the most common neoplasm in other studies ( Table 20.2 ). The vast majority of the patients with temporal lobe tumor—related epilepsy have some common distinctive characteristics, and some authors even define them as a distinct clinico-pathological group. These characteristics include a well-differentiated histological pattern, cortical localization of the tumors (69–91%), frequent involvement of mesial structures (48%), indolent biological nature, young age, seizures frequently as the only symptom, long-standing history of seizure disorder, normal neurological exam, and favorable outcome after surgery.10,12,13

Vascular Malformations

Most common vascular malformations causing epilepsy are arteriovenous malformations (AVM) and cavernous hemangiomas. The most common presenting symptoms of AVM are hemorrhage and seizures. Hemorrhage is by far the commonest initial manifestation of AVM in children, whereas 10 to 25% of the patients present with seizures.14–17 Seizures in AVM patients most likely originate from gliotic, nonfunctional brain parenchyma interspersed in and around the AVM nidus. These gliotic changes develop secondary to focal ischemia induced by “steal” phenomena and possibly constitute the main reason for seizures in AVM patients. In Yasargil’s series of 414 operated cerebral AVM patients that included both children and adults, initial manifestations were hemorrhage and seizures in 77.8% and 14.7% of the patients, respectively.18 Yasargil’s series includes 74 children (17.8%) younger then 15 years old, and approximately 11% of them had temporal lobe AVMs (6.8% extramesial and 4.1% hippocampal AVM). In the same series, seizure as an initial manifestation was found in 40% of the patients when the AVM was located in the temporal lobe and in 10.6% of the children overall in this series.

Cavernous hemangiomas are relatively common congenital lesions that occur in 0.4 to 0.5% of the general population and constitute 5 to 13% of all intracerebral vascular malformations.19–21 Cavernous hemangiomas occur mostly in the supra-tentorial region, 15 to 20% of them being in temporal lobe.20–23 In a large series, temporal lobe location in cavernous hemangioma patients was found to be significantly higher (48%), and 40% were located in mesiobasal structures.24 Epilepsy incidence in symptomatic patients with cavernous hemangioma has been reported between 35 and 79%.19,21,22,25–27 Cavernous hemangiomas that are located in the temporal lobe have a much higher tendency to be associated with intractable epilepsy, and they are far more likely than AVM to be medically refractory.19,27,28 In children, seizures are the most common manifestation of cavernous malformations (45–54%).23,25,29,30 The estimated risk for seizure development was reported as 1.5%/year/patient in single lesions and 2.5%/lesion/year in patients with multiple lesions.24,29

Mechanism of Seizures

The epileptogenic mechanisms involved in lesion-related epilepsy are not clear. Several mechanisms, including direct pressure and irritation of the cortical tissue, gliotic changes and disruption of vascular structures of the surrounding cortex, morphological alterations at the cellular level, changes in inhibitory and excitatory neurotransmitter levels, and denervation hypersensitivity have been proposed to play a role.11,31,32 Chronic changes in surrounding brain tissue either by mechanical or vascular mechanisms can also be responsible for seizures induced by slowly growing low-grade tumors. Developmental tumors may even have intrinsic epileptogenicity because they are frequently associated with cortical dysplasia and contain cells with a rich array of neurochemical properties, including altered inhibitory and excitatory local circuits.11,31 The location of the lesion is also a critical factor. Brain tumors associated with epilepsy are often located in the cortex or in gray—white matter junction. When the lesion is located in the temporal lobe, its direct or indirect effects on hippocampus may cause seizures. The lesion location may interfere with cortical afferents and efferents and lead to relative deafferentation of a certain cortical area that has intrinsic epileptogenicity. Small hemorrhages in and around the tumors also cause hemosiderin deposits, which are highly epileptogenic.11 Secondary epileptogenesis might also be responsible for seizures in some patients. It has been shown with intracranial electroencephalography (EEG) recording that approximately one half of the patients with neocortical temporal tumors have independent epileptogenic areas in ipsilateral mesial structures.33 The proposed mechanisms for seizures in patients with AVMs include vascular steal phenomenon, focal ischemia of the adjacent cortex secondary to A-V shunting, progressive intralesional and perilesional gliosis, demyelination, hemosiderin lining in AVM bed, and secondary epileptogenesis in the temporal lobe.14,16,28 It has also been suggested that mass effect on the surrounding brain, cortical irritation, presence of calcification, gliosis in the surrounding brain tissue, and accumulation of iron-containing substances in hemosiderin fringe are responsible for the seizures in cavernous hemangioma patients.19–22

Surgical Strategy

Although the histological subtype of the lesion is always the major factor influencing clinical outcome in any given patient, the determinants of the seizure-related outcome in lesional epilepsy are more complicated. The factors effecting good outcome in epilepsy patients are not only dependent on the type of the lesion but also related to the location of the lesion as well as the extent of the epileptogenic zone and the area of resection.32–34 Therefore, the surgical strategy in lesional epilepsy patients is a multifaceted topic. It should be defined based on the location, extent of both the lesion and the epileptogenic zone, as well as the histopathological diagnosis. Determining the optimal surgical strategy in these cases is a challenging task and still involves some controversy. Lesionectomy alone, lesionectomy with resection of the epileptogenic zone, or lesionectomy with resection of the ipsilateral mesial structures all have their advocates in discussions about the appropriate surgical approaches in these cases. However, there is limited clinical evidence to support specific resective strategies in lesional-TLE cases.32 Therefore, until more data are available, the surgical strategy for each patient should be determined on an individual basis by considering histological type and location of the lesion, extent of the epileptogenic zone, and the spatial relation between the lesion and the epileptogenic zone.

Extent of Resection

The spatial relationship between the epileptogenic zone and the lesion is the most critical factor to determine the extent of surgical resection in lesional epilepsy patients. There are several conditions for optimizing seizure control in children with lesional epilepsy. First, the lesion should be completely identified and resected. Second, the epileptogenic zone should be contained within the resected area, and finally the remaining cortical and subcortical areas should not develop independent seizures after surgery. Unsuccessful results in lesional epilepsy surgery are frequently related to incomplete resection of the lesion/epileptogenic zone or the presence of additional or secondary epileptogenic foci.35 Another reason may be having an extensive epileptogenic zone beyond the boundaries of the lesion. Some well-known examples of this include the presence of surrounding gliosis in AVM, hemosiderosis rim associated with cavernous hemangioma, dysplastic areas associated with developmental tumors, and dual pathology.

Lesion

Lesionectomy alone is probably the most commonly used surgical approach in lesional epilepsy cases. Although there is wide consensus regarding the significance of total tumor resection for good seizure control, the results of this surgical approach in the published epilepsy series are quite different. Khajavi et al36 reported that seizure-free outcome was only correlated with the extent of tumor resection but not with additional resection of the surrounding cortex. Conversely, Jooma et al37 reported that epilepsy patients who underwent lesionectomy procedure alone had a significantly lower seizure-free outcome rate compared with patients who had additional cortical resections of the adjacent epileptogenic zone. Sugano et al38 reported that after complete resection of mass lesions, they still found residual spikes in the mesial structures in up to 86% of the patients and recommended additional resection in these areas for better seizure control.

Epileptogenic Zone

The first step in the planning lesional epilepsy surgery is to define the relationship between the localization of the seizures and the location of the lesion. If the clinical and electrophysiological characteristics of the seizures are fully correlated with the location of the lesion, then the next step would be to determine whether the epileptogenic zone exceeds the anatomical boundaries of the lesion. The surgeon needs to work closely with the epilepsy/neuro-physiology team to map the epileptogenic zone and to determine its spatial relationships with the structural lesion ( Fig. 20.1 ). The surgical resection strategy is then designed based on lesion location, the extent of the epileptogenic zone, and the relative position of adjacent eloquent cortex. Anterior temporal lobectomy (ATL) including the lesion ( Fig. 20.2 ) or tailored lesionectomy including the surrounding epileptogenic cortex are the two commonly used surgical approaches in lesional TLE. Clussmann et al2 describe their “preoperative tailoring” technique as aiming for complete resection of the lesion demonstrated on magnetic resonance imaging (MRI) and extending the resection further whenever clinical or electrophysiological data suggest a seizure onset in the respective distant areas, such as the hippocampus. Imaging techniques such as functional imaging studies, magnetoencephalography, diffusion tensor imaging (DTI), intraoperative electrocorticography (ECoG), and invasive monitoring data obtained with depth/subdural electrodes are among the recommended techniques to determine the extent of the neocortical and hippocampal resections.