**3. Epileptogenic zone**

The epileptogenic zone is defined as the area of the cortex that is necessary and sufficient for initiating seizures and whose removal 0r disconnection is necessary for the complete abolition of seizures [16].

The pre-surgical evaluation to define the epileptogenic zone and its relationship with the eloquent area is essential for the ideal resection for a patient with drugresistant focal epilepsy (**Figure 1**) [8].

Jehi [17] defined five cortical zones in the pre-surgical evaluation process, which include: the irrigative zone (IZ), which is the area of the cortex that generates electric spikes, with the best test to define that through EEG, MEG and EEG-fMRI; seizure onset zone (SOZ), which is that area of the cortex responsible of the clinical seizure tested by EEG, ictal SPECT, fMRI, and MEG; symptomatic zone (SZ), defined as the area of the cortex that, when activated produces initial ictal symptoms signs, observed by initial seizure symptomology; epileptogenic lesion (EL) includes macroscopic lesion that is causative of the epileptic seizure because the lesion itself is epileptogenic (cortical dysplasia) by secondary hyperexcitability of the adjacent cortex, tested by MRI; functional deficit zone (FDZ) defined as the area of the cortex that is not functioning normally in the inter-ictal period tested by neurological and psychological exams and by functional images (interictal SPECT and PET) (**Table 1**).

It is helpful in the study of epileptogenic zone to use intracranial EEG (subdural electrode or SDE implantation via craniotomy) as a principal approach for intracranial EEG monitoring [18]. Nevertheless, there is no high-quality evidence indicating superiority of any one technique over the other intracranial EEG monitoring [19],

#### **Figure 1.**

*Epileptogenic complex cortical area. IOZ; ictal onset zone, IZ; Irritative zone, FZ; functional zone, SZ; symptomatogenic zone, EZ; epileptogenic zone, LS; lesion area.*


#### **Table 1.**

*Preoperative evaluation modalities for delimitation of epilepsy zone in refractory seizure patients.*

specific brain MRI with sequence and voxel-based morphometric analysis, and the EEG-fMRI [20]. 3D multimodality images are a simultaneous display of different structural and functional data in each patient [17–19].

Unidentified epileptogenic source occurs in approximately 50% of patients coming to surgery [21]. According to advanced knowledge in EZ, defining the area of neuroconnectivity through the epileptogenic network is very important. This is achieved by using new tests for epileptogenic network detection: a) microanalysis; by detecting the extracellular glutamate level, through microanalysis device insertion; glutamate level is increased in the epileptogenic region and high at onset of seizure [22]. b) 7 T-MR spectroscopy, in the study of mesiotemporal lobe sclerosis (MTLS), the epileptogenic in the hippocampus is energetically developed, anterior more than posterior; a similar energetic loss is seen in the ipsilateral anterior thalamus and less significantly in the contralateral thalamus and hippocampus [23]. According to this, optogenetic stimulation of thalamic circuit can inhibit the parietal epileptogenic cortex.
