Subdural strips and grids for intracranial EEG recordings have long been used to assist wit h localization of the epileptogenic zone in patients with medically refractory focal epilep sy undergoing presurgical evaluation ( 56 , 59 \200\22365 ). Invasive EEG monitoring has a reported concordance of 47 % with structural MRI, 58 % with PET and 56 % with ictal SPECT ( 26 ). The advent of MRI saw a decrease in the use of invasive EEG techniques ( 28 ) as it was realized that resection of a focal lesion detected on MRI was highly predictive of a go od outcome with respect to seizures following epilepsy surgery ( 5 , 27 ). However over the last 5 \200\22310 years there has been a resur- gence in the use of intracranial EEG recor dings, as epilepsy centers have seen an increased proportion of patients in whom the MRI do es not detect a lesion, or in whom the potential epileptogenic abnormalities on the MRI are extensive and not completely resect- able. It is estimated that in approximately 30 \200 \22350 % of patients con- sidered for surgical resection of medically refractory epilepsy, an epileptogenic focus cannot be localized on non-invasive functional and structural studie s ( 65 , 66 ). In such patients, invasive EEG monitoring with subdural electrodes may be he lpful in localizing the epileptogenic zone, and its relationship to neighboring elo- quent cortex, allowing a resective procedure to be more safely and effectively performed. Single-positron emission computed tomography Blood \202 ow SPECT involves intravenous inj ection of a technetium- based radiotracer either during seizures, following or between sei- zures, and hence allows imaging of patterns of cerebral blood \202 ow in the ictal, post ictal, and interictal phases ( 36 , 40 , 44 ). Ictal SPECT is estimated to be 73 \200\22397 % sensitive in TLE and is highly speci \201 c for the epileptogenic zone, while intericta l SPECT has a lower sensitiv- ity of approximately 50 % and is less speci \201 c ( 40 ). D igital subtrac- tion of an interictal from an ictal SPECT creates an image of the pattern o f change during seizures from the baseline cerebral per- fusion patterns, while co-registra tion with an anatomical MRI scan (computer-aided subtraction ictal SPECT co-registered to M RI, or SISCOM) provides anatomical localization of this region of per- fusion change, impro ving the utility for surgical planning ( 27 , 45 , 46 ). True ictal SPECT (i.e. injection o f the isotope within 45 sec- onds of stereotypical seizure onset) has been shown to be accu rate in predicting localization, even when ictal EEG and MRI are non- localizing or non-con cordant ( 47 \200\22350 ). Patients in whom SISCOM localization is concordant with site of resective surgery are more likely to have excellent postsurgical outcomes with respect to s eizure frequency than those in whom SISCOM is non-localizing or non-concordant with surgica l site ( 46 , 47 , 51 ). However, the manner in which intracranial recordings is now being utilized by many epilepsy surgery programs is very different to how they have traditionally been used. In contrast t o the previ- ously common use of \200\230blind implantations \200\231, when non-invasive t echniques were non-localizing, the strategy for the intracranial implantation now incorpora tes the results of modern neuroimag- ing. The intracranial EEG is used to test or re \201 ne the hypothesis for the localization of the epileptogenic zone put forward by the results of neuroimaging. Murphy and colleagues have described the use of MMIGS in the treatment of medically refractory epilepsy ( 27 , 35 ). This technique involves the co-registration of functional imaging, in particular PET and SPECT, with MRI and subdural grid arrays allowing their incorporation into a frameless stereotactic neuro- surgical navigation system ( 27 , 35 ). In this manner, epileptogenic foci can be delineated and the eloquent cortex mapped, thus maxi- mizing outcome with respect to seizure control whilst minimizing neurological c omplications. In MRI-VEM concordant cases, SPECT shows unilateral increased blood \202 ow in approximat ely 85 % ( 25 ). If SPECT, MRI, and VEM are concordant, a 78 % good outcome rate was shown ( 25 ). Magnetoencephalography Magnetoencephalography (MEG), usually co-registered with structural MRI (magnetic source imaging or MSI), is used in some centers as an ancillary test to local ize the source of interictal epilep- togenic discharges using magnetic \201 elds rather t han the electrical spikes seen in EEG. In a retrospective study of 455 drug-resistant TLE p atients, MEG was shown to be concordant with the epilep- togenic side of epilepsy surgery i n 54 \200\22380 % (depending on the method used). In 24 % of cases, MEG provided localizing informa- tion not given by EEG or other methods, and in 11 % altered or in \202 uenced su rgical decision-making ( 52 ). In other studies, MEG was concordant with video-EEG in 32 % , correctly lateralized the surgical site in 59 % of those with non-localizing video-EEG ( 53 ) and was second only to subdural grid EEG recording in predicting surgical outcome ( 54 ). Although a potentially promising as non- invasive method of presurgical work-up, in pra ctice the limited availability and expense of MEG means that its application is cur- rently restricted to selected centers and cases. Intracranial EEG recordings with surgically implanted subdural grids, strip, or depth elect rodes utilize stainless steel or platinum electrodes embedded in a synthetic material which are implanted in proximity to the suspected epileptogenic zone via craniotomy or burr hole methods ( 4 ). Subdural grid arrays have the advantage over strip electrodes of allowing a greater cortical surface to be mapped and electrically stimulated ( 56 ). However, subdura l strip electrodes can be introduced via a burr hole, instead of a large craniotomy which i s required for depth electrodes, thereby decreas- ing the risk of postoperative complicatio ns ( 56 ). Depth electrodes are implanted into the brain, and therefore have the advantage of Intracranial EEG in temporal lobe epilepsy In modern epilepsy surgery centers, less than 10 % of patients with drug-resistant TLE undergo intracranial EEG studies. The indica- tions include: inconclusive or discordant results from video-EEG oxford textbook of epilepsy and epileptic seizures 302 evaluation, aims to avoid resection of, and trauma to, the overlying healthy temporal neoco rtex, deep white matter tracts, and vascula- ture, while still removing the amygdala and th e anterior portion of the hippocampus ( 21 , 77 ). The surgical procedure takes usually tak es 3 \200\2235 hours ( 21 ). being able to record seizure foci deep to the cortical surface which may have not been dete cted with subdural electrodes ( 28 ). Risk of bleeding is reduced by the use of modern imag e guided surgical implantation techniques ( 28 ). As with any invasive procedure, serious complications can occur with the use of intracrania l EEG electrodes, but in experienced epi- lepsy surgery centers these are uncommon ( 27 \200\22329 ). Fountas and Smith presented a retrospective 20-year series of 185 patients wh o underwent subdural grid or strip implantation. They reported postoperative epidural haema toma in three patients (1.6 % ) and subdural haematoma in two patients (1.1 % ) ( 67 ). Sig ni \201 cant brain oedema occurred in two patients (1.1 % ), while two developed infection and two developed transient aphasia. Two patients had fatal outcomes and \201 ve (2.7 % ) experienced non-habitual seizures ( 67 ). Such complications may mandate re-opening the c raniotomy with or without removal of the grids. Complications of temporal lobectomy Complications of temporal lobectomy include: hemiparesi s from infarctions in the internal capsule caused by damage to the deep perforators (1 \200 \2235 % ), wound infection (2.5 % ), intracerebral haem- orrhage, subdural hemorrhage (1.4 % ), neuropsychological or memory sequelae impairing QOL (1 \200\2235 % ), and death (<1 % ) ( 2 , 21 , 56 , 78 , 79 ). Depression occurs in approximately 18 % of surgical patients, compared to 20 % of medically treated patients, and is often most prominent in the \201 r st 3 \200\2236 months postoperatively ( 2 ). Superior quadrantanopia visual \201 eld de \201 cits are an expected out- come following formal temporal lobectomy (although not selec tive amygdalohippocampectomy) occurring in 55 % of patients, are largely asymptomatic and a s such should not be classi \201 ed as a com- plication of surgery ( 2 , 21 ). It has been reported that 4 \200\22352 % of patients with pathologically confirmed focal co rtical dysplasia have normal MRI studies ( 68 \200\22370 ). This wide range may re \202 ec t the use of older generations of MRI machines and as advances are made in imaging technolo gy it is expected that this range will decrease. However, invasive EEG monitoring remains a n important investigation in pre-resection evaluation of patients with medically refractory epilepsy due to dysplasia. Similarly, complete resection of a lesion visible on MRI is not always adequate to predict seizure free outcome, supporting the use of invasive EEG monito ring to enable the surgeon to per- form a tailored resection of the ictal onset zone as wel l as the MRI visible lesion in these patients ( 70 ). The ictal onset zone may include a va riable extent of macroscopically normal brain sur- rounding a discrete epileptogenic lesion . There is evidence that the complete resection of both the ictal-onset zone and the MRI le sion is associated with an improved outcome with respect to seizures as opposed to resectio n of the lesion only ( 71 \200\22374 ). Therefore it is vital that subdural grid coverage o f the cortical surface should be exten- sive enough to allow accurate mapping of the ictal onset zone and the neighboring eloquent cortex. This approach maximizes long- term seizure freedom while minimizing damage to functional cortex ( 75 , 76 ). Early postoperative seizures in temporal lobe surgery Up to 20 % of patients will have seiz ures in the early postoperative period ( 80 , 81 ). The signi \201 cance of early postoper ative seizures on likelihood of seizure recurrence has often been discounted because of pos sible association with perioperative factors. However, McIntosh et al. performed a retrospe ctive review of 321 patients who underwent surgery for TLE. In the \201 rst week after su rgery 30 (9.3 % ) had seizures, while 69 (21.5 % ) had seizures within the \201 rst 28 da ys. Kaplan \200\223Meier analysis showed patients who have \200\230early seizures \200\231 (within the \201 rst 28 postoperative days), have a 23.2 % probability of being seizure free at 1 year, compared to 71.8 % for those who had no early seizures. At 2 years the prob ability of sei- zure freedom for those with and without early postoperative sei- zures was 20.3 % and 65.8 % respectively ( 80 ). Numerous seizure precipitants, including changes in AED dose, were identi \201 ed, and it was found that although patients who had a precipita nt to their early seizure had a risk of recurrence that was half that of those without a pr ecipitant, the overall recurrence rate was higher than for those without early seizures ( 8 0 ). These authors found that the number, type and similarity of postoperative to preoperat ive sei- zure was not signi \201 cant in predictor likelihood of recurrence ( 80 ). In con trast, another study found that patients whose seizures in the \201 rst week following a temporal lobectomy were similar to their preoperative habitual seizures had a lower rate of either an excel- lent or favorable outcome with respect to seizures than those whose posto perative seizures were auras, or were focal motor and/ or generalized tonic \200\223clonic seizures (14.3 % , 77.8 % , and 75.0 % respectively) ( 81 ). Surgical approaches Temporal lobectomy or selective amygdalohippocampectomy is usually perf ormed via a pterional craniotomy with the patient \200\231s head \201 xed in a 3-point Ma y \201 eld frame, with the head elevated 30 degrees above the chest and turned 30 degrees to the opposite side ( 21 ). Intraoperative frameless stereotactic navigation may be used. The two usual approaches comprise the standard anterior temporal resection or \200\230ante rior temporal lobectomy \200\231 and the more selective removal of mesial temporal structur es with sparing of the lateral temporal lobe called the selective amygdalohippocampec- tomy . Several approaches are used including the trans-sylvian (Yas argil \200\231s method), su btemporal, and trans-gyral approaches. Using meticulous microneurosurgical technique, the a nterior tem- poral neocortex and/or the mesial temporal structures are resected. For a stan dard temporal lobectomy up to 6.5 cm of anterolateral non-dominant, and up to 4.5 cm of dom inant neocortex may be resected. The mesial resection includes the entire amygdala, and as much as possible of the hippocampus ( 2 , 21 , 56 ). The selective amy- gdalohippocampectom y, if deemed appropriate from preoperative Outcome with respect to seizure control, AED use, and quality of life Wiebe et al. performe d a study in which 80 patients with TLE were randomly assigned to either surgery or medical therapy for 1 year. At 1 year, 58 % of those in the surgery group were free of awareness CHAPTER 28 resective surgery of temporal lobe epilepsy 303 impairing seizures, compared to 8 % in the medical group (p <0.001), and had signi \201 ca ntly better QOL ( 2 ). Thirty-eight per cent in the surgical group were free of all seizure s, including auras, compared to 3 % in the medical group ( 2 ). It is important to note tha t this was an intention to treat analysis and four of the patients in the \200\230surgical group \200\231 did not actually undergo surgery, and of the patients who did undergo surge ry 64 % were seizure free at 1 year. The numbers needed to treat to render one patient free of con- sciousness impairing seizures at 1 year, and of all seizures at 1 year were calcul ated at 2 and 3 respectively ( 2 ). Approximately 15 % of those in the surgical group conti nued to have 1 \200\2234 seizures impair- ing consciousness per month ( 2 ). Residual seizu re activity was similar in severity for both the surgical and medical groups. QOL measured by the QOLIE-89 score was better for the surgical group (P <0.001) although it improved in both groups over time (p = 0.003). A higher proportion in the surgical group were employed or attending school at 1 year (56.4 % vs. 38.5 % ), this did not reach sta- tistical signi \201 cance (p = 0.11) ( 2 ). There was one unexpected death (SUDEP) in the medical group a nd none in the surgical group. Yas argil et al. presented a series of 73 patients with medically refractory TLE who under went selective amygdalohippocampec- tomy. Mean duration of seizure activity of 21.9 years. Preoperative MRI demonstrated MTS in 45.2 % . Mean follow-up was 4.3 years. Seizure outcome was Engel class I, II, and III in 75.3 % , 17.8 % , and 6.8 % respectively; 42.5 % had cea sed their AED. Histopathology showed sclerosis in 48 % , gliosis in 41 % , and no abnormali ty in 11 % . Patients with MTS were more likely to have an Engel class I outcome. The best outcomes were seen in the group of patients in whom MRI, EEG and pathology were all abnorma l (90 % Engel class I). In contrast, in those with normal MRI and pathology, 42.9 % achieve d a good surgical result ( 21 ). There were no deaths in this series. Many studies have shown that patients who achieve seizure freedom following epilepsy surger y overall have an improved QOL ( 2 , 89 , 93 ), although this improvement may take up to 2 years to establish ( 93 ). Good postoperative outcomes with respect to QOL are associated w ith good preoperative QOL, early surgical inter- vention, and with pathological \201 ndin gs of mesial temporal sclero- sis, whereas TLE caused by tumors and in those with either pr esurgery psychopathology are more likely to have poorer QOL outcomes ( 93 \200\22397 ). In a meta-analysis including 83 studies and over 3000 patients, Tellez-Zenteno showed that 66 % of patients achieve long-term sei- zure freedom after temporal lobe resection and 14 % of patients achieve long-term AED discontinuance ( 82 , 83 ). Forty-one per cent remained on one medication and 31 % remained on polyther- apy. The pediatric population achieved bet ter AED outcome than adults ( 82 ). Tonini et al. performed a meta-analysis of 47 articles involving 3511 patients and reported that febrile convulsions, mesial temporal sclerosis, t umors (most commonly low-grade, long-term epilepsy associated tumors such as ganglioglioma and dysembryoplastic neuroepithelial tumors), lesions on MRI, EEG/ MRI concordance, and ext ensive resection were the strongest pre- dictors of postoperative seizure freedom ( 84 , 85 ). Postoperative discharges, and the need for intracranial monitoring were associ- ated wi th poorer outcomes ( 85 ). Cunha et al. prospectively followed 32 patients undergoing resec- tion for TLE. Overall QOL increased after surgery until the 5th post-surgical year (p <0.05) ( 93 ). Cognitive funct ion and social function were signi \201 cantly enhanced postsurgery, and seizure related w orry was signi \201 cantly reduced ( 93 ). Previous psychopa- thology was found to have a signi \201 cant impact on postoperative social function and seizure worry scores ( 93 ). P atients with right TLE had signi \201 cantly better outcomes than those with left sided ep ilepsy in terms of postoperative cognitive function and overall QOL, consistent with the ro le played by the left hippocampus in verbal memory ( 93 ). There were no associations found between patient age or duration of disease prior to surgery and improved postoperative QOL ( 93 ). As a whole, patients had improved QOL if their seizure frequency decreased, even i f they did not achieve complete seizure freedom, however those with Engel class I out- come s had a greater increase in QOL ( 93 ). Therefore even if sur- gery is not expected to achi eve total freedom, the impact on QOL of decreased seizure burden should be taken into accou nt when deciding on surgery. McIntosh et al. retrospectively reviewed 325 patients who had undergone surgery for TLE. Us ing survival analysis and multivari- ate regression, the probability of complete seizure fr eedom at 2, 5, and 10 years postoperatively was calculated as 55.3 % , 47.7 % , and 41 % re spectively ( 86 ). Patients with discrete MRI abnormalities were found to have a higher cha nce of seizure freedom postopera- tively, while duration of seizures, age at seizure onset, and age at surgery had no effect on outcome ( 86 ). Many studies have found that the presence of a MRI lesion (including mesial temporal sclero sis) that is able to be completely surgically excised is associated with an improved rate o f long-term seizure control postoperatively as compared to those with a normal MRI (60 \200 \22385 % vs. 30 \200\22350 % ) ( 87 \200\22389 ). As may be expected, incom- plete resectio n of the epileptogenic zone as demonstrated on MRI or by subdural EEG is more likely to res ult in seizure recurrence ( 31 , 70 , 90 , 91 ). However, it is now clear that there are a group of patients with drug-resistant TLE without a de \201 nite lesion on the MRI scan wh o have prominent unilateral hypometabolism on FDG-PET and concordant seizure onset on video -EEG who have long-term outcomes that are similar to those with an MRI lesion ( 34 , 92 ). A minority of these patients have focal cortical dysplasia on histopathological examination of the resected temporal lobe specimen, but in the majority only non-speci \201 c changes are seen. The underlying pathophysiology in these patients with surgical remedial non-lesi onal TLE remains uncertain. What to do if surgery fails? Approximately 20 \200\22330 % of patients who undergo an tempo ral lobectomy for drug-resistant epilepsy do not achieve seizure con- trol postoperatively ( 21 , 86 , 98 \200\223100 ). There are a number of small series reported of patients who f ailed to achieve seizure freedom post-initial temporal lobe resection who subsequently unde rwent repeat surgery. In those with ipsilateral temporal EEG \201 ndings, with or without residual mesial temporal structures, repeat opera- tion extending the surgical resection i s successful in achieving a good outcome (Engel class I or II) in approximately 34 \200\223 60 % of cases ( 99 , 101 \200\223106 ). Invasive monitoring may be considered prior to repe at surgery and SISCOM also can help de \201 ne the epilep- togenic zone in these patients ( 107 ). Some patients may be diag- nosed as having another, extratemporal, lesion and in t hese cases resection with or without invasive monitoring can be performed ( 99 ). Autopsy s eries suggest that 47 \200\22386 % of patients with TLE have oxford textbook of epilepsy and epileptic seizures 304 bitemporal hippocampal sclerosis ( 108 ). Therefore in some post- resection patients a new or previously dormant ictal focus may become active in the contralateral temporal lobe. Due to the cogni- tive, behavioral, and memory sequelae of bilateral mesial tempo- ral resecti on, these patients are not suitable for further resective surgery and therapeutic options a re limited to optimization of medical therapy and consideration of vagus nerve stimulator i mplantation ( 99 ). 4. Najm IM , Bingaman WE , L ders H . The use of subdural grids in the management of focal malformations due to abnormal cortical development . Neurosurg Clin Nor th Am 2002 ; 37 ( 1 ): 87 \200\223 92 . 5. Rosenow F , L ders H . Presurgical evaluation of epilepsy . Brain 2001 ; 124 : 1683 \200\223 700 . 6. Kwan P , Arzimanoglou A , Berg AT , Brodie MJ , Allen Hauser W , Mathern G , et al . De \201 nition of drug resistant epilepsy: consensus proposal by the ad hoc Task Force of the ILAE Commission on Therapeutic Strategies . Epilepsia 2010 ; 51 ( 6 ): 1069 \200\223 77 . 7. Semah F , Picot M , Adam C . Is the underlying cause of epilepsy a major prognostic factor for recurrence? Neurology 1998 ; 51 : 1256 \200\223 62 . What to do with medications if surgery succeeds? While the primary goal of epilepsy surgery for drug-resistant TLE is seizure control, many patients also have the goal to be able to cease their AED therapy. Most centers have the practice of main- taining essentially the sa me AED regimen postoperatively as the patient was on prior to the surgery until the patient has been sei- zure free for a period of time \200\224 commonly 6 \200\22312 months. After this some of the drugs are weaned or reduced in dose, but most patients will be advised to continue to take at least a one AED at least 2 years postoperatively. It remains controver sial whether patients who remain seizure free postoperatively should wean off AEDs after th is time. Schiller and colleagues followed the outcomes of 210 patients who were seizure fre e for 1 or more years: in 84 the AEDs were ceased, in 90 the drugs were reduced, and in 30 the AEDs were kept unchanged ( 109 ). Approximately 40 % of the patients in whom AEDs were discontinued experienced a return of seizures compared to approximately 20 % in those who t he drugs were reduced but not stopped and less than 10 % of those in whom medications were not changed. Of the 22 patients with recurrent seizures post-medication reduction, in two t he seizures continued despite restarting the AEDs ( 109 ). 8. Engel J , Van Ness P , Ramussen T . Overview: Who should be considered a surgical candidate? . In: Engel J (ed) Surgical Treatment of the Epilepsies , pp. 23 \200\223 34 . New York : Raven Press , 1993 . 9. Engel J Jr , Wiebe S , French J , Sperling M , Williamson P , Spencer D , et al . Practi ce parameter: temporal lobe and localized neocortical resections for epilepsy: report of th e Quality Standards Subcommittee of the American Academy of Neurology, in association with the American Epilepsy Society and the American Association of Neurological Surgeons . Neuro logy 2003 ; 60 ( 4 ): 538 \200\223 47 . 10. Engel J . A greater role for surgical treatment of epilepsy: Why and when? Epilepsy Curr 2003 ; 3 ( 2 ): 37 \200\223 40 . 11. Baker GA , Nashef L , van Hout BA . Current issues in the management of epilepsy: the i mpact of frequent seizures on cost of illness, quality of life, and mortality . Epilepsia 1 997 ; 38(Suppl 1) : S1 \200\223 8 . 12. Strauss DJ , Day SM , Shavelle RM , Wu YW . Remote symptomatic epilepsy: does seizure s everity increase mortality? Neurology 2003 ; 60 ( 3 ): 395 \200\223 9 . 13. Baker GA , Jacoby A , Buck D , Stalgis C , Monnet D . Quality of life of people with epilepsy: a European study . Epilepsia 1997 ; 38 ( 3 ): 353 \200\223 62 . 14. O \200\231Brien TJ , Miles K , Ware R , Cook MJ , Binns DS , Hicks RJ . The cost-effect ive use of F-18-FDG PET in the presurgical evaluation of medically refractory focal epileps y . J Nucl Med 2008 ; 49 ( 6 ): 931 \200\223 7 . 15. Engel J Jr . The timing of surgical intervention for mesial temporal lobe epilepsy: a plan for a randomized controlled trial . Arch Neurol 1999 ; 56 : 1338 \200\223 41 . Conclusions Resective surgery, whether by selective amygdalohippocampec- tomy or including resection of the overlying anterior temporal neocortex, is a safe and effective method for treating drug-resistant TLE. A multidisciplinary comprehensive preoperative evaluation with a combination of MRI, VEM, neuropsychology, and neu- ropsychiatry, and in selected cases F DG-PET, ictal SPECT, and/or intracranial EEG monitoring, combined with advances in micro- n eurosurgical and image-guided techniques, can provide excellent surgical results in terms o f decreased seizure burden, decreased AED use, increased QOL, and economic cost-effectivene ss. Early consideration of surgical treatment should be considered in cases of temporal lob e epilepsy who have failed to achieve seizure con- trol after trials of two or more AEDs. 16. Sperling MR , O \200\231Connor MJ , Saykin AJ , Plummer C . Temporal lobectomy for refr actory epilepsy . JAMA 1996 ; 276 : 470 \200\223 5 . 17. Falconer MA , Taylor DC . Surgical treatment of drug-resistant epilepsy due to mesial temporal sclerosis . Arch Neurol 1968 ; 19 : 353 \200\223 61 . 18. Foerster O , Pen \201 eld W . 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