PET in epilepsy surgery The main utility of PET is in the identi \201 cation of the functi onal de \201 cit zone in patients in whom there is no demonstrable struc- tural lesion. Th e standard PET ligand used is 18 F- \202 uorodeoxyglucose and imaging is carried out in th e interictal state to identify areas of hypometabolism. The sensitivity and speci \201 cit y of PET varies according to the brain region producing epilepsy. In temporal lobe epilepsy (see Chapter 28) in particular, there can be a close correla- tion between the areas of PE T abnormality, the epileptogenic zone, and surgical outcome. In extratemporal epilepsies, i t provides con- tributory information less often. In clinical practice, co-registering PET information with the patient \200\231s MRI scan can identify areas of abnormality previousl y missed when either investigation is used alone. Subtle gyral abnormalities due to malform ations of cortical development can become more evident. Voxel-based analysis of MRI scans can be helpful where visual analysis does not show abnorm alities. Diffusion tensor imaging (DTI) can show abnormal diffusivity in areas known to be epilep- togenic and so is a potential additional tool although it is not rou- tinely used i n clinical practice. Tractography is a technique used for imaging white matter tracts which standard MRI cannot. The direction of diffusion of water in each voxel determines the orie n- tation of the white matter tracts. It potentially has substantial clini- cal utility in surgical planning where information on the optic CHAPTER 27 principles of epilepsy surgery 295 EEG in epilepsy surgery Information from EEG is critical to the presurgical process without which epilepsy surgery is usually inadvisable and the outcome much less predictable. EEG p erforms two crucial functions \200\224 iden- tifying the irritative and ictal onset zones (Fig. 27. 2 ). Some patients have two or more potentially epileptogenic lesions (dual or mu lti- focal pathology). Identi \201 cation of the true focus or both foci as epileptogenic can usually only be achieved through EEG. As described in Chapter 9, EEG information is der ived from pro- longed video-EEG monitoring where a patient is admitted for sev- eral days o f continuous EEG recording under video surveillance in an epilepsy monitoring unit manned b y trained nurses and EEG personnel. The assessment is carried out using the standard scalp or surface electrode array (10 \200\22320 electrode system) although a denser array with mo re electrodes (the 10 \200\22310 system) is required in many cases. In many centers, specia l electrodes such as deep sphe- noidal electrodes are used. These sample EEG activity from the mesial and basal temporal lobes and are inserted under local anaes- thesia through the lateral face into the proximity of the foramen ovale in the skull base. Table 27.6 Some common indications for intracranial electrode studies High-resolution MRI does not show a lesion although other evidence suggests a single focus MRI shows two or more potentially epileptogenic lesions MRI shows large lesion and precise estimation of the ictal onset zone cannot be reliably ma de Discordance between investigations, e.g. MRI shows left hippocampal sclerosis, EEG shows ri ght temporal ictal onset zone Identi \201 cation of relationship between eloquent cortex and candidate epileptogenic zon e SPECT in epilepsy surgery In contrast to PET, this investigation is carried out in the icta l stage and so provides information on the ictal onset zone although in common with PET, it s greatest utility is in lesion-negative patients with focal epilepsy. Technetium 99-m is t he radiolabelled tracer used to identify areas of increased cerebral blood \202 ow or hyp erper- fusion. Testing has to be carried out under ideal conditions. A pre- ictal SPECT sca n establishes baseline. The tracer is injected within seconds of seizure onset. Injection a nd focal tracer uptake within 10 seconds of the start of the seizure is much more likely to indicate the area of seizure onset than an injection 60 seconds later when spread of the s eizure discharge makes the information much less meaningful. The seizure also has to be of suf \201 cient duration and a very brief partial seizure of less than 10 seconds is unlike ly to provide substantial information. Co-registration of the subtracted SPECT images to th e patient \200\231s MRI (SISCOM) can provide further anatomical information on the location of the seizure focus. Neither PET nor SPECT information independently make the case for su rgery in a particular brain area in lesion-negative epilepsy and it is usually advisable th at information from these investigations is used together with clinical and EEG information . EEG and the irritative zone Sharp waves seen in the interictal record indicate the irritati ve zone (Fig. 27. 4 ). There can be more than one irritative zone in unilateral hippocampal sclerosis (illustrative case in Fig. 27. 3 ) where two irri- tative zones produce both lef t and right sharp waves although all the other information available is concordant with a l eft mesial temporal epileptogenic zone and surgical resection of this area renders the pati ent seizure free. Simultanous recordings from depth electrodes inserted into both hippocamp i con \201 rm that both of these areas generate sharp waves independently and are not indi cative of spread from one to the other. Surface recorded sharp waves from more than one bra in region can indicate a multifocal, or tendency to multifocal, epilepsy. Sometimes, multip le irritative zones in the same hemisphere can indicate a unifocal epilepsy with Fig. 27.4 Surface EEG of a patient with left hippocampal sclerosis showing interictal left mesial temporal sharp waves (two boxes on left), maximum in the left sphenoidal recording e lectrode (Sp1) and a seizure starting in the same region (two boxes on right), suggesting b oth irritative and ictal onset zones in the left mesial temporal lobe. Copyright Samden D. Lhatoo. oxford textbook of epilepsy and epileptic seizures 296 to the number of electrodes implanted. Studies of the entire brain or even one whole hemisp here \200\224 so-called \200\230 \201 shing expeditions \200\231 are therefore inadvisab le and unlikely to succeed. either propagation of sharp wave discharges from a single deeper focus in different directi ons at different times or a change in the orientation of the focus (dipole) that generates the sharp wave dis- charge which is then seen in different brain regions at different times . In general, a single irritative zone is a good indicator that the epileptogenic zone is w ithin it. There are two main approaches to intracranial EEG studies: (1) the use of depth electrodes which are stereotactically implanted into the brain (stereo-EEG) and (2) the use of subdura l EEG elec- trodes which are placed on the brain surface, both targeting speci \201 c brai n areas. Each has its advantages and disadvantages and so centers that have expertise in bo th can use either technique according to the clinical situation. The ictal onset zone Seizures captured during video-EEG monitoring provide impor- tant semi ological clues as described earlier but also allow close examination of the EEG seizure rec ord. Analysis of the EEG onset often indicates the brain region that comprises the ictal on set zone which in turn is intimately related to the epileptogenic zone. The EEG onset can b e focal (Fig. 27. 4 ), more widespread but restricted to one hemisphere (lateralized), or g eneralized (non-lateralizable). In general, the more localized the EEG onset, the more prec ise the depiction of the ictal onset zone . 1. Stereo-EEG (Fig. 27. 5 ). A hypothesis is formulated to identify the potential epileptog enic zone. The number and position of depths is determined in advance. The surgeon plans th e trajec- tory of the depth electrodes, using very detailed preoperative MRI and convention al or MR angiogram information to avoid vital structures such as blood vessels. The patient then under- goes surgery, usually with frame-based stereotactic insertion of depth electro des through multiple skull burr holes. The depth electrodes have multiple \200\230contacts \200\231 that are capable of recording electrical brain activity as well as stimulating th e brain that they are in contact with when current is passed through them. The main advanta ge of this technique is that it allows access to very deep parts of the brain such as the c ingulate regions and other mesial brain structures. They are also less likely to cause brai n oedema, hemorrhage, headaches, infections, and other adverse effects that can limit the u se of subdural electrodes. In the last few years, highly specialized robotic techniques hav e been used for stereo-EEG depth electrode insertion by some centers. Intracranial EEG in epilepsy surgery In some cases, for a variety of reasons (Table 27. 6 ) , despite exten- sive investigations, the case for surgery cannot be reliably made. In many instances, there is considerable discordance between investi- gations, hampering a strong candidate epileptogenic zone for resection. In others, the epileptogenic zone is suspected to be close to eloquent cortex and so a more accurate depiction of the ictal onset zone and mapping of cortical function close to this zone is necessary. In general, an extremely goo d hypothesis based on all the available information is necessary for the placement of elec- trodes in a targeted part of the brain. Invasive electrodes carry substantial risk of morb idity and mortality, directly proportional 2. Subdural EEG (Fig. 27. 6 ). Again, a suitable hypothesis for the insertion of subdural e lectrodes is mandatory. Under general Posterior insula Posterior cingulate Temporal occipital Superior temporal Hippocampal tail Basal temporal Hippocampal body Basal frontal Hippocampal head Amygdala Temporal pole Fig. 27.5 (Also see Color plate 15.) Diagrammatic representation of stereotactically implan ted depth electrodes in a patient with lesion-negative temporal lobe epilepsy. Electrode la bels denote the main anatomical structures targeted by the innermost electrode contacts. Th e outer contacts also sample cortex at or close to the point of electrode insertion. For ex ample, the deep anterior insular contacts sample the anterior insular gyri whilst the super \201 cial contacts of the same electrode sample the superior frontal gyrus where the elec trode is inserted. Similarly, the deep contacts of the hippocampal body electrode sample th e hippocampal body whilst the super \201 cial contacts sample the lateral temporal neocort ex in the middle temporal gyrus. Copyright Samden D. Lhatoo. CHAPTER 27 principles of epilepsy surgery 297 eloquent cortex, identifying primary motor, sensory, supple- mentary sensorimotor, visual, auditory, and language cortices among other brain regions. The relative disadvantages are t hat these do not record well from deep sulci, are dif \201 cult to insert into the inferio r or mesial aspects of the brain, and can cause signi \201 cant morbidity. With both techniques, postoperative CT scans or MRIs are merged with the preoperative scans using specialized software pro- grams that then provide co-registered images of the implan ted electrode positions superimposed on the MRI, each of which is identi \201 ed and numbe red. Patients are video-EEG monitored in the epilepsy monitoring unit for several days unde r close clinical observations for both seizures as well as potential complications. Note is made of interictal discharges and their electrode locations as well as the electrode locat ions where seizures begin (Fig. 27. 7 ). The resection must include this ictal onset zone. Fig. 27.6 (Also see Color plate 16.) A right craniotomy with an 8 \227 8 (64 electrode) gr id covering the frontal and temporal areas of a patient with lesion negative right hemisphe re epilepsy. Copyright Samden D. Lhatoo. Brain mapping in epilepsy surgery Brain mapping is essential if any resections are to be un dertaken in the vicinity of functioning eloquent cortex. It is performed with the applicati on of very small currents through intracranial electrodes on brain surface or within the br ain to stimulate discrete cortical areas. This can be done either intraoperatively as an \200\230awake \200\231 opera- tion or during the monitoring period in the epilepsy monitori ng unit after electrode insertion. Stimulation protocols vary according to centers, the inv asive electrode used, and the brain regions being anesthesia, the surgeon performs a large craniotomy and inserts electrode \200\230grids \200\231 or smaller \200\230strips \200\231 subdurally onto the surface of the brain. Each grid or strip usually contains between six and 64 \200\230contacts \200\231. These primar ily record from the brain surface and can cover large areas of contiguous cortex. Stimulati on of contacts (brain mapping) can therefore provide excellent information on Fig. 27.7 Depth electrodes in a patient with lesion negative right temporal lobe epilepsy s howing a seizure (circled) beginning in the right anterior hippocampus (electrodes RAH 1 an d RAH 2) and spreading to the amygdala and posterior hippocampus. Copyright Samden D. Lhato o. oxford textbook of epilepsy and epileptic seizures 298 Table 27.7 Contraindications to epilepsy surgery Seizure spread electrodes Seizure onset electrodes Hand motor electrodes Face motor electro des Expressive language electrodes Ictal onset zone remains unde \201 ned Temporal lobectomy where contralateral hemisphere is incapable of supporting memory Primary motor area resection (particularly hand and foot areas) Primary sensory area resection (particularly hand and foot areas) Language area resection (Broca \200\231s, Wernicke \200\231s, or basal temporal language ar eas) Primary visual cortex resection Removal of homotopic areas in both hemispheres Medical contra-indications (e.g. bleeding diathesis) Untreated psychiatric comorbidity a Complicating socioeconomic factors a Psychogenic non-epileptic seizures are not a contraindication to surgery for epileptic seizures provided these are appropriately managed. Fig. 27.8 (Also see Color plate 17.) Brain map of a patient with left frontal lobe epilepsy showing the language, hand motor, and face motor areas with their relationship to the seiz ure onset (red) and seizure spread (yellow) electrodes. The ictal onset zone in this case t herefore lies in the left superior frontal gyrus of the prefrontal cortex, is relatively di stant from eloquent cortex and unlikely to cause de \201 cits if resected. Copyright Samde n D. Lhatoo. likelihood of unacceptable postoperative de \201 cits after surgery. The classical such si tuation is that of a global amnestic syndrome through removal of one temporal lobe when the remaining brain is incapable of supporting memory function. Neuropsychological testing and /or the intracarotid amobarbital test or Wada test in the preoperative phase usually identi \201 es patients most at risk and sur- gery is an absolute contraindication then. Many ot her situations are relative and have to be weighed against potential bene \201 t. Non- dom inant hand weakness would be unacceptable in a classical gui- tarist, for example, but acce ptable to another individual who placed great value in seizure freedom. The personal circum stances of the patient including family support in the postoperative period may be importan t considerations in some cases. studied. Stereo-EEG stimulation of primary motor cortex usually involves 1 hertz stimulatio n, using a 1 millisecond pulse width and 1 \200\2233 milliampere current for 40 seconds. Su bdural EEG stimulation of the language areas is performed with a 50 hertz, 0.2 millisecond pulse width, 1 \200\22320 milliampere stimuli for 5 seconds. Stimulation of the primary cor tex will produce twitching of the appropriate contralateral area whereas stimulation of the language areas will produce a temporary aphasia. Information derived from stimula- tion is mapped to depict cortical functions in different brain regions. Where these \200\230eloqu ent \200\231 regions lie in relation to the ictal onset zone as revealed by intracranial el ectrodes will determine whether surgery is possible without substantial risk of major de \201 cits and if yes, how the surgeon tailors the extent and area of the resection (Fig. 27 . 8 ). References 1. Horsley V . Brain surgery . BMJ 1886 ; 2 : 670 \200\223 4 . 2. Rosenow F , Luders H . P resurgical evaluation of epilepsy . Brain 2001 ; 124 : 1683 \200\223 700 . 3. Luders . HO, Noachtar. S, Burgess RC. Semiologic classi \201 cation of epileptic seizures . In: Luders HO , Noachtar S (eds) Epileptic Seizures: Pathophysiology a nd Clinical Semiology , pp. 261 \200\223 85 . Philadelphia, PA : Churchill Livingstone , 2 000 . Surgical resection is then tailored according to the information provided. Resection of cor tex underlying the ictal onset electrodes is usually necessary for achieving seizure freedo m unless doing so is likely to produce unacceptable de \201 cits. The epileptic lesion zon e, if well identi \201 ed by imaging, is also resected as far as possible. Whether the irr itative zones and the areas to which the electrical seizure spreads should also be resected has not been systematically studied and practice varies according to center. 4. Schulz . R, Luders. H. Auras elicited by electrical stimulation . In: Luders HO , Noachtar S (eds) Epileptic Seizures: Pathophysiology and Clinical Semiology , pp. 254 \200\223 60 . Philadelphia, PA : Churchill Livingstone , 2000 . 5. Loddenkemper T , Kotagal P . Lateralizing signs during seizures in focal epilepsy . Epilepsy Behav 2005 ; 7 ( 1 ): 1 \200\223 17 . 6. Duncan JS . Imaging in the surgical treatment of epilepsy . Nat Rev Neurol 2010 ; 6 ( 10 ): 537 \200\223 50 . Contraindications to epilepsy surgery There are several relative as well as absolute contra indications to surgery (Table 27. 7 ). These are mainly related to an increased CHAPTER 28 Resective Surgery of Temporal Lobe Epilepsy Simon V. Liubinas , Andrew P. Morokoff , and Te rence J. O \200\231Brien Introduction Epilepsy has a prevalence of 5 \200\22310 per 1000 and temporal lobe epilepsy (TLE) accounts for 25 \200\22350 % of epilepsy cases ( 1 , 2 ). Approximately 15 \200\22320 % of these patients suffer from epilepsy not adequately controlled with maximal medical ma nagement, i.e. drug-resistant epilepsy ( 1 , 3 ). Epilepsy surgery is the only treat- ment option that offers a reasonable chance of seizure control in patients with chronic drug-res istant epilepsy. It is estimated that at least 4.5 % of patients with epilepsy could potent ially bene \201 t from surgical resection of an epileptogenic zone (de \201 ned as the re gion of cortex responsible for seizure generation and whose complete resection or disconnec tion results in seizure freedom) ( 4 , 5 ). The most common type of drug-resistant epilepsy to be treated surgi- cally is TLE. However, despite the growing safety and ef \201 cacy o f temporal lobe resection it is still seen by many clinicians and patients as a \200\230la st resort \200\231 treatment option. The International League against Epilepsy (ILAE) de \201 nes drug-resistant epilepsy as: \200\230failure of adequate trails of two tolerated a nd appropriately chosen and used AED schedules (whether as monotherapies or in combi- natio n) to achieve sustained seizure freedom \200\231 ( 6 ). It is estimated that in the US alon e only 1500 of the 100,000 \200\223200,000 potentially eligible patients undergo surgical r esection each year ( 5 , 7 \200\2239 ). Perhaps due to the growing number of new antiepilep tic drugs (AEDs) available, it is estimated that the average interval between seizure onset and resective surgery has increased from an average of 12.5 years to 18 years. This is des pite the established safety and ef \201 cacy of resective surgery ( 10 ). or scalds, head injury, or dental injury, is signi \201 cantly increased by seizure freque ncy and by having multiple seizure types ( 13 ). Patients with drug-resistant epilepsy have signi \201 cantly increased rates of psychiatri c comorbidity and psychosocial disability. Clinically signi \201 cant anxiety and depressi on are more common in those patients with drug-resistant epilepsy compared to those who are seizure-free, as are lower self-assessed scores of relationships, ability to perform socia l activities, work, overall health, plans for the future and self-ful \201 lment and highe r perceptions of stigmatiza- tion ( 11 , 13 ). The economic cost of drug-resistant epilepsy is considerable. For example, a study performe d in England, France, and Germany analyzing direct, indirect, and hospital costs for patien ts with epi- lepsy showed that the cost per 3-month period was less than UK 500 for those who were seizure-free compared to more than UK 1300 for those with more than one seizure per day ( 11 ). Higher seizure frequency is also associated with reduced employment and mo re days lost to epilepsy ( 11 ). Using a decision tree analysis, our group found that there were signi \201 cant direct cost-savings of per- forming epilepsy surgery for drug-resist ant TLE surgery compared to continued medical therapy, even when the cost of presurgical ev aluation, including a combination of video electroencephalogra- phy (EEG) monitoring (VEM), magnetic resonance imaging (MRI), 2-( 18 F) \202 uro-2-deoxy-D-glucose positron emission tomog- raphy (FDG-PET), and single-positron emission computed tom- ography (SPECT), was ta ken into account ( 14 ). A randomized controlled trial has con \201 rmed the belief that sur- gery is superior to c ontinued medical therapy only in patients with drug-resistant TLE with respect to rates of seizure freedom and quality of life (QOL) ( 2 ). Many authorities in the \201 eld now adv o- cate that patients with potentially surgically remediable epilepsy be referred early for consideration for surgical therapy rather than waiting many years until multiple drugs hav e failed, as timely sur- gery may not only improve seizure control and disability, but may also prevent injury and death ( 2 , 7 , 15 , 16 ). The potential bene \201 ts of surgery for drug-resistant temporal lobe epilepsy Drug-resis tant seizures are associated with elevated rates of injury, death, psychiatric comorbiditie s, and psychosocial disability as well as signi \201 cant personal and societal economic c ost. The mortality rate of patients with epilepsy is overall 2 \200\2233 times that of the general population, and highest in those with drug-resistant seizures \200\224 in particul ar those who have had a generalized tonic \200\223clonic seizure or status epilepticus in t he past 12 months ( 11 , 12 ). The incidence of sudden unexpected death in epilepsy (SUDEP) is 1 in 100 \200\2231000 per year, while the rate of seizure-related injuries, including b urns The development of surgical approaches for temporal lobe epilepsy Surgical resection for mo stly post-traumatic epileptogenic foci was pioneered by Sir Victor Horsley at Queens Square , London, in oxford textbook of epilepsy and epileptic seizures 300 Video-EEG monitoring and magnetic resonance imaging VEM and structural MRI remain the stand ard \201 rst-line investiga- tions in presurgical evaluation for TLE to localize the epil eptogenic zone. VEM provides localizing information in approximately 62.2 % of patients bei ng evaluated for a potential temporal lobec- tomy. Similarly, MRI does so in approximately 50 \200\22360 % of patients ( 14 ). It is critical that the MRI is performed using a dedica ted epi- lepsy protocol, and interpreted by radiologists and neurologists who are experienc ed in interpreting scans in patients with epilepsy, as some of the subtle epileptogenic les ions can otherwise be missed, such as hippocampal sclerosis or focal cortical dysplasia ( 2 4 ). In many centers if a patient with drug-resistant TLE has a resectable lesion identi \201 ed on MRI, concordant data on VEM, and there are no neuropsychological or neuropsychia tric contraindications, no further tests are required before offering a temporal lobectomy. Most such patients would be expected to have a good outcome ( 25 ). However if the MRI is non-localizing, functional imaging with FDG-PET and/or ictal blood \202 ow SPECT are comm only used ( 26 ). Concordance between structural MRI and VEM, PET and ictal SPECT is report ed as 58 % , 68 % , and 58 % respectively ( 26 ). In patients with con \202 icting data, o r in those when only one or none is localizing, surgically implanted intracranial electrode s may be required to localize the epileptogenic zone ( 27 \200\22329 ). 1886, using the clinical features of the seizures to guide the site of craniotomy and resec tion ( 17 ). In the 1930s, Pen \201 eld and Jasper at the Montreal Neurological Institute using intraoperative electro- corticography during awake craniotomy to map the epileptogeni c zone, developed the techniques of resective surgery, including tem- poral lobectomy, as i t is known today ( 18 \200\22320 ). The preoperative evaluation and surgical techniques have been re \201 ned as technology, b oth diagnostic and surgical, have improved over the years. However the basic goal remains t he same as dis- cussed in Chapter 27, i.e. resection of the epileptogenic focus, to maximiz e the chance of post-surgical reduction in seizure fre- quency, while minimizing the impact on eloquent cortex, and therefore the chance of inducing a neurological de \201 cit. Ther e are a number of different surgical techniques and approaches which are collectively refer red to as a \200\230temporal lobectomy \200\231. Most approaches are based on that develop ed by Falconer and colleagues who in the 1960s \201 rst described mesial temporal scleros is and the resection of the medial temporal lobe and temporal neocortex ( 17 ). Different c enters and surgeons vary in the amounts of temporal neocortex, parahippocampal gyrus, hippo campus, and amygdala that they resect. The selective amygdalohippocampectomy, via a pterion al craniotomy and trans-sylvian approach, was \201 rst described by Yas argil in Zurich in 1973, as a method of resecting the mesial tem- poral lobe epileptogenic foci while minim izing the impact on ante- rior and lateral temporal structures, and thereby potentially dec reasing the risk of inducing postoperative neurological or neu- rocognitive de \201 cits ( 21 ). The Engel Surgical Outcome Classi \201 cation is the most commonly used system to c ategorize the post-outcome with respect to seizures ( 22 , 23 ) (see Table 28. 1 ) Discordant VEM and imaging results, such as an EEG seizure onset from the opposite side of the MRI lesion, presents a dif \201 cult dilemma. Discordance may represent a contralatera l epileptogenic focus not seen on MRI, or may simply represent false EEG laterali- zation r esulting from rapid ictal activity spread. Discordance may be associated with poorer postsu rgical outcome and further inves- tigation with ictal SPECT, FDG-PET, or invasive monitorin g may be helpful ( 25 , 29 ). In TLE patients with no lesion seen on MRI, with a localizing PET, SPECT, and/or intracranial EEG, seizure freedom is reported to be achieved in 29 \200 \22385 % of patients in differ- ent series ( 14 , 29 \200\22335 ). Cortical dysplasia is fo und on histopatho- logical examination in of the resected temporal lobe in these MRI non-le sional cases in 15 \200\22343 % ( 27 , 29 \200\22334 ). Preoperative evaluation It is essential that all patients being considered for epilepsy sur gery undergo a comprehensive, multidisciplinary presurgical evaluation in a center that spe cializes in epilepsy surgery. The primary goals of this evaluation are twofold. First to lo calize the epileptogenic zone, which is the region of brain that needs to be resected to re nder the patient the maximal chance of being seizure free, and second to assess for, and mi nimize, the risks of postoperative problems. Positron emission tomography FDG-PET is the most commonly used functional imaging modal- it y used in the presurgical evaluation of TLE ( 36 ). FDG-PET scans are performed in the inte rictal period and show hypometabolism in the epileptogenic temporal lobe in up to 80 \200 \22395 % of patients with drug-resistant TLE, including many patients with a non- lesional MRI ( 14 , 34 , 36 \200\22341 ). When PET hypometabolism and MRI identi \201 ed hippocampa l sclerosis are both present and con- cordant, the likelihood of successful resection may b e higher ( 38 ). The pathophysiological mechanisms that result in this hypome- tabolism are unknown. The extent of the hypometabolism on FDG-PET is usually larger than the underlying epileptogenic lesion (if present) or the epileptogenic zone identi \201 ed on intracrania l EEG ( 36 , 37 ). Using statistical parametric analysis of the FDG-PET images co-registere d to a postoperative MRI, our group showed that patients rendered seizure free following a temporal lobectomy have on average only 25 % of the region of hypometabolism resected ( 42 ). Therefore the decision regarding the extent of temporal neo- cortical resection should n ot be made on the basis of FDG-PET alone, but should be made in conjunction with MRI, EEG ( including intracranial EEG if warranted), and other imaging modalities. Table 28.1 Classi \201 cation of the outcome of epilepsy surgery ( \200\230Engel Classi \201 cation \200\231 (23)) Class I \227\206 Free of disabling seizures \227\206 Completely seizure-free since surgery, non-d isabling simple partial seizures only since surgery, some disabling seizures after surgery but completely seizure-free for at least 2 years, and convulsions only when medications are withdrawn \227\206 Almost seizure-free \227\206 Initially seizure-free but has disabling seizures n ow, rare disabling seizures since surgery, more than rare seizures after surgery but now ra re seizures for at least 2 years, nocturnal seizures only Class II \227\206 Worthwhile improvement \227\206 Worthwhile seizure reduction or prolonged seizur e-free intervals amounting to half the follow-up period, but not less than 2 years Class III \227\206 No worthwhile improvement \227\206 No signi \201 cant seizure reduction, no app reciable change, or Class IV seizures getting worse CHAPTER 28 resective surgery of temporal lobe epilepsy 301 and other non-invasive investigations, when there appears to be bilateral seizure onsets on the scalp EEG, suspected extratemporal foci and epileptogenic foci adjacent to or overlapp ing with elo- quent cortex requiring extraoperative functional stimulation map- ping ( 55 \200\22358 ). The yield of intracranial EEG implantations, and of the respective surgery th at follows, can be optimized by using imaging modalities such as SPECT or PET, identifying the regions most likely to be the seizure focus, to guide the site and extent of the electr ode implantations ( 27 , 29 ). Both the presence of an MRI lesion and the presence of unilat- eral temporal hypometabolism have been shown to be independ- ently predictive of a good surgical outcome with respect t o seizures ( 14 , 42 ). A meta-analysis of 46 studies performed by Willman et al. showed th at ipsilateral PET hypometabolism had an 86 % predic- tive values for good outcome (de \201 ned as Engel class I or II) ( 43 ). The predictive value of PET hypometabolism in thos e requiring intracranial EEG recording, and those with non-localizing EEG and MRI were 75 % , 73 % , and 80 % respectively ( 43 ). 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.