**6. Surgical approach**

The majority of surgical series showed that almost 60 to 90% of supratentorial benign gliomas present with epilepsy and surgical resection may be the only treatment option for both histopathological diagnosis and treatment [79]. There is still discussion whether epilepsy is a specific property of the tumor or the brain's reaction to the tumor. However, proximity to the functional areas such as primary motor strip or language or Broca's area increases the chance of having seizures. Advanced developments in the imaging technology, brain tumors, especially low-grade gliomas which were missed in the past, led the physicians to diagnose such lesions and early surgery is now performed without doubt. Since these gliomas are slow growing, seizures may occur late and any seizure in the adult life must raise the suspicion of a tumor until proven otherwise. Magnetic resonance imaging (MRI) is the gold standard diagnostic modality to diagnose brain tumors and sensitivity is higher than computerized tomography (CT). Especially T2-weigted and FLAIR images (Figure 1) are important for visualize low grade tumors which are generally not enhanced with contrast agent. Additional imaging modalities such as MR spectroscopy may provide further evidence of the lesions true nature. In some patients electroencephalography (EEG) is needed because of discordant finding between the MRI and seizure semiology but there is no characteristic EEG pattern. However; EEG can lateralize the tumor in 70% of patients. Rarely, intracranial depth electrodes and/or electrocorticography (EcOG) is needed before and during surgery to expose the epileptogenic area. The most common location for these gliomas is the frontal lobe, followed by parietal, temporal lobes and insula. Occipital lobe alone is less involved and the reason is not clear.

and parietal located tumors an inverted"U-shaped" incision is usually sufficient. Particular attention should be paid to dural sinuses and large cortical veins when removing the bone flap and opening the dura. If awake craniotomy is performed, cortical mapping with intraoperative electrical cortical stimulation in order to figure out the functional area should be performed. The aim of the cortical mapping is to have maximum tumor removal with minimum neuro‐

**Figure 1.** This 27-year-old male was presented with complex-partial seizure and MRI showed a mass in the left tempo‐ ral lobe without involvement of the mesial temporal structures (hippocampus, parahippocampus and amygdala). The tumor margin is clearly seen in the preopretive T2-weighted image (**a**) and histopathological diagnosis was astrocyto‐ ma grade-II and 3 years after the surgery the T2-weighted image (**b**) shows no tumor recurrence and the patients is

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**(a) (b)**

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**Figure 2.** The picture showing a "question mark" scalp incision which is the commonest incision type used in the neu‐

rosurgical operations.

logical deficit by not causing any damage to the functional cortex (Figure 3).

seizure free without antiepileptic medication.

Clinical experience has demonstrated that surgical removal of the lesion alone significantly reduces seizure frequency. It is interesting to note that lesionectomy alone or lesionectomy with corticectomy show similar good results so that there has been no standard resection among the centers. But we know very well that completeness of tumor removal is the most important prognostic factor for seizure control, recurrence, and improved quality of life. Surgical approach depends mainly on the proximity to the functional cortices which necessi‐ tated local anesthesia (awake craniotomy). On the other hand, when a tumor is located in silent area, general anesthesia is preferred.

Scalp incision and craniotomy is planned according to the location of the tumor and "question mark" incision has been extensively used for temporal, frontal tumors (Figure 2). For central

Biochemical and Surgical Aspects of Epilepsy Related to Brain Tumors — Appraising Redox Biology and Treatments http://dx.doi.org/10.5772/58343 113

excitability, through ligand gated and voltage gated ion channels, cyclic calcium elevations are seen during epileptic activity. Referring to this, mitochondria can attenuate the altered neuronal excitability and synaptic transmission in epilepsy [76]. Yet another reason for the increased excitability encountered in epilepsy is, astroglial and neuronal glutamate transport‐ ers' being quite sensitive to oxidative damage which are known to be crucial for the mainte‐ nance of low synaptic glutamate levels [77]. and it was indicated that complex I activity induces the excess release of glutamate [78]. So it can be concluded by stating that oxidative stress has

The majority of surgical series showed that almost 60 to 90% of supratentorial benign gliomas present with epilepsy and surgical resection may be the only treatment option for both histopathological diagnosis and treatment [79]. There is still discussion whether epilepsy is a specific property of the tumor or the brain's reaction to the tumor. However, proximity to the functional areas such as primary motor strip or language or Broca's area increases the chance of having seizures. Advanced developments in the imaging technology, brain tumors, especially low-grade gliomas which were missed in the past, led the physicians to diagnose such lesions and early surgery is now performed without doubt. Since these gliomas are slow growing, seizures may occur late and any seizure in the adult life must raise the suspicion of a tumor until proven otherwise. Magnetic resonance imaging (MRI) is the gold standard diagnostic modality to diagnose brain tumors and sensitivity is higher than computerized tomography (CT). Especially T2-weigted and FLAIR images (Figure 1) are important for visualize low grade tumors which are generally not enhanced with contrast agent. Additional imaging modalities such as MR spectroscopy may provide further evidence of the lesions true nature. In some patients electroencephalography (EEG) is needed because of discordant finding between the MRI and seizure semiology but there is no characteristic EEG pattern. However; EEG can lateralize the tumor in 70% of patients. Rarely, intracranial depth electrodes and/or electrocorticography (EcOG) is needed before and during surgery to expose the epileptogenic area. The most common location for these gliomas is the frontal lobe, followed by parietal, temporal lobes and insula. Occipital lobe alone is less involved and the reason is

Clinical experience has demonstrated that surgical removal of the lesion alone significantly reduces seizure frequency. It is interesting to note that lesionectomy alone or lesionectomy with corticectomy show similar good results so that there has been no standard resection among the centers. But we know very well that completeness of tumor removal is the most important prognostic factor for seizure control, recurrence, and improved quality of life. Surgical approach depends mainly on the proximity to the functional cortices which necessi‐ tated local anesthesia (awake craniotomy). On the other hand, when a tumor is located in silent

Scalp incision and craniotomy is planned according to the location of the tumor and "question mark" incision has been extensively used for temporal, frontal tumors (Figure 2). For central

direct effects on neuronal excitability in the same time.

112 Tumors of the Central Nervous System – Primary and Secondary

**6. Surgical approach**

not clear.

area, general anesthesia is preferred.

**Figure 1.** This 27-year-old male was presented with complex-partial seizure and MRI showed a mass in the left tempo‐ ral lobe without involvement of the mesial temporal structures (hippocampus, parahippocampus and amygdala). The tumor margin is clearly seen in the preopretive T2-weighted image (**a**) and histopathological diagnosis was astrocyto‐ ma grade-II and 3 years after the surgery the T2-weighted image (**b**) shows no tumor recurrence and the patients is seizure free without antiepileptic medication.

and parietal located tumors an inverted"U-shaped" incision is usually sufficient. Particular attention should be paid to dural sinuses and large cortical veins when removing the bone flap and opening the dura. If awake craniotomy is performed, cortical mapping with intraoperative electrical cortical stimulation in order to figure out the functional area should be performed. The aim of the cortical mapping is to have maximum tumor removal with minimum neuro‐ logical deficit by not causing any damage to the functional cortex (Figure 3).

**Figure 2.** The picture showing a "question mark" scalp incision which is the commonest incision type used in the neu‐ rosurgical operations.

defense system which also increase the risk of seizure recurrence [87]. In case, treatment with antioxidants is considered to be very profitable in inhibiting epileptic seizures without any adverse effect [88]. Selenium, an antioxidant protecting against ROS, is known to be causing an alteration in the rate of some neurotransmitters when deficient and depletion in selenium levels was reported to be leading to a failure in response to AEDs which act through GABAer‐ gic receptors due to an increased glutamate receptor activation [89] and utilization of selenium supplements reduce epileptic seizures [90]. Application of resveratrol, a meritorious antioxi‐ dant, was also demonstrated to be useful in seizure management and in reducing seizure incidence [91]. Similar findings were indicated experimentally where the prevention of seizures was concerned [92,93] Thymoquinone, another potent free radical and superoxide radical scavenger, exhibited an antiepileptic effect in children suggesting a lack of adverse effects even at high doses [94]. With respect to this point of view, the antiepileptic effect of curcumin, which is an active polyphenolic component, extracted from *Curcuma longa* called as turmeric, was also investigated being almost ten times more active than vitamin E as an antioxidant [95]. Implementation of curcumin which inhibits the transcription of inflammatory cytokines via nuclear factor kappa B (NF-κB),inducible nitric oxide synthase (iNOS), and cyclooxygenase 2 (Cox-2) [96], was demonstrated to be preventing the cognitive decline related to traumatic brain injury [97] and its antiepileptic potential was ascertained with short term treatment. Recently, inhibitors of mammalian target of rapamycin (mTOR), including rapa‐ mycin and its analogs, are pointed out and regular treatment with rapamycin is emphasized in preventing epileptogenesis experimentally [98,99], thereby, research relevant to inhibiting mTOR activity seems appreciable. Curcumin is also suggested as mTOR inhibitor suppressing

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The ketogenic diet (KD), a subdued carbohydrate diet, is known to be effective in epilepsy treatment [102-104] being neuroprotective and antiepileptogenic. In children, seizures owing to GLUT-1 and pyruvate dehydrogenase deficiency are treated with KD [105], also a prosper‐ ous outcome is seen with other pediatric epilepsy syndromes [106] as it upregulates the neuronal gene expression of the enzymes in Krebs cyclus, oxidative phosphorylation and glycolysis and increases mitochondria density leading to enhanced brain metabolism [107,108], therefore, stimulating the Krebs cyclus seems to be an attractive strategy in seizure management via direct replenishment of energy substrates [109,110]. β-hydroxybutyrate, being a ketone body, protects against metabolic and excitotoxic insults in organotypic hippocampal cultures [111]. Considering the nutrient and energy sensing ability of mTOR, it has a role in pathophysiologic changes related to epileptogenesis and mTOR activity is increased after epileptic status. KD reducing the insulin levels [112], is expected to be inhibiting mTOR activity through decreasing the PI3K/Akt signaling pathway. Also, ROS have a role in the efficacy of KD as the production of some mitochondrial uncoupling proteins are increased with KD and this eventuates with a reduction in the mitochondrial membrane potential and an increase in mitochondrial respiration rate [113]. Mitochondrial production of ROS is decreased with ketone bodies via increasing NADH oxidation without affecting endogenous antioxidant glutathione levels [114]. It was shown that in rat neocortical neurons, ketones prevent oxidative injury via decreasing mitochondrial ROS production [115]. Recently, pyruvate seems to be a promising substrate on seizure activity due to its dual action as a

epileptogenesis in experimental studies [100,101].

**Figure 3.** This picture shows an awake craniotomy and intraoperative electrical cortical stimulation (cortical mapping) for the identification of the motor cortex (white paper marks) which is close to the tumor (black dots depict the tu‐ mor) (**a**). The tumor was removed without any motor deficits (**b**) and the patient is seizure free at 1 year follow up.

The main surgical technique for the removal of these gliomas is "endopial" resection. By doing this technique, vessels running deep in the sulci and neighboring cortices are saved. Since these tumors are surrounded by the pial layers, respecting the pia avoids severe neurovascular damage during surgery and minimizes postoperative neurological deficits.
