Predictors, Procedures, and Perspective for Temporal Lobe Epilepsy Surgery

Predictors, Procedures, and Perspective for Temporal Lobe Epilepsy Surgery Hans Clusmann, MD Surgery for refractory temporal lobe epilepsy is established as a promising treatment option. Although practiced for decades now, there is an ongoing discussion on who is a candidate, when we should operate, how the preoperative evaluation and surgery should be performed, and what perspective will result for the individual after surgery. In light of significant improvements with respect to safety and outcome, generally accepted features will be extracted, and some more ambivalent aspects will be discussed. Major future developments in this field will be based on multimodal imaging and correlation with electro-clinical and neuropsychological findings. Semin Ultrasound CT MRI 29:60-70 © 2008 Elsevier Inc. All rights reserved.

A

pproximately 20-30% of all newly diagnosed epilepsies will become refractory to medical treatment over time. The majority of these epilepsies have a focal origin, many of them within the temporal lobe.1 Surgical treatment of temporal lobe epilepsy (TLE) refractory to medication has been widely accepted as a valid and promising treatment option during the last decades. Numerous reports have provided information on presurgical evaluation for partial epilepsy using a variety of different diagnostic tools, leading to varying surgical strategies.2-10 Many of these studies tried to delineate factors influencing outcome with respect to epileptic seizures. Outcome results appear rather variable for many possible reasons. There are differences in patient referral and selection, different experiences and choices of diagnostic tools, different infrastructure available to the epileptologists and neurosurgeons, and different preferences of surgical approaches, etc. On one hand, it is meanwhile generally accepted that surgery is the best therapeutic option to offer a patient with refractory TLE, proven in a prospective randomized trial.9 However, there is some disagreement on the prerequisites, procedures, and perspectives of such surgical treatment. Tonini et al11 performed a review of the literature published between 1984 and 2000 with respect to predictors of epilepsy surgery outcome, in order to solve the uncertainties about which patients will benefit most. Engel et al12 eval-

Department of Neurosurgery, University Bonn Medical Center, Bonn, Germany. This work was supported in part by a grant of the Deutsche Gesellschaft für Neurochirurgie, Stiftung Neurochirurgische Forschung to H.C. Address reprint requests to: Hans Clusmann, MD, Neurochirurgische Universitätsklinik Bonn, Sigmund Freud Str. 25, 53105 Bonn, Germany. E-mail: [email protected]

60

0887-2171/08/$-see front matter © 2008 Elsevier Inc. All rights reserved. doi:10.1053/j.sult.2007.11.004

uated the pooled seizure outcome derived from multiple studies conducted since 1990 and found an average of 65% of patients being seizure free after anteromesial resections, and another 21% improved. Short-term and long-term outcome did not differ significantly. Similar results were recently obtained by other groups13 and by a collaboration within the multicenter study group on surgical treatment of epilepsy.14

Preoperative Evaluation In patients with refractory temporal lobe epilepsy, the aim of presurgical evaluation is to support decision-making for surgical planning. Several alternatives need to be classified: mesial versus lateral seizure origin, lesional versus nonlesional epilepsy, Ammonshornsclerosis (AHS) versus non-AHS, tumoral versus nontumoral pathology, dominance right or left, pure lesionectomy versus additional resection. For the assessment of seizure semiology, a detailed workup of clinical history focusing on behavioral signs of seizures is carried out together with the patient and his family. Seizure semiology is then documented and analyzed via video electroencephalogram (EEG) monitoring. Ictal and postictal testing is realized to determine the level of consciousness and the presence of focal ictal or postictal impairment (aphasia, paresis, etc). In our own series, 1001 patients from a total of 1342 evaluated patients were finally operated on, ie, 74.6% of evaluations led to epilepsy surgery.

Noninvasive Video-EEG Monitoring Noninvasive video-EEG monitoring is the mainstay of documenting seizure activity and spread, giving important information on seizure localization and seizure types. Surface EEG

Temporal lobe epilepsy surgery and video recording of typical seizures are routinely performed with a digital multichannel video-EEG system.15,16 Interictal recordings are analyzed with respect to the occurrence and distribution of epileptiform discharges to determine the irritative zone.17,18 The correlation with video-documented clinical seizure activity is still the most important feature of continuous video-EEG monitoring.

Neuropsychology Neuropsychological assessment helps in defining the level of cognitive functioning and can provide the limits as to localization of brain dysfunction caused by seizures. It also allows assessment of cognitive function over time and comparison of the preoperative with the postoperative cognitive status. A neuropsychological testing of intelligence, attention, visual and verbal memory, language, and higher verbal and visual reasoning is routinely performed, as described in detail elsewhere. Specific tests may uncover more temporo-cortical or temporo-mesial functioning, respectively.19,20 A significant difference of at least one standard deviation in preoperative verbal and visual memory performance is considered “lateralizing” to the side of the poorer performance.21

Magnetic Resonance Imaging Magnetic resonance imaging (MRI) has become one of the most important tools in the selection of patients with drugresistant partial epilepsies. In our own series during the late 1980s and early 1990s MRI-positive cases were found in circa 60% of cases, now in more than 95%. It is interesting to note that MRI often failed to demonstrate mesial temporal sclerosis (MTS) preoperatively in the early 1990s, although there had been already profound insight into hippocampal pathology and the syndrome of mesial temporal lobe epilepsy (MTLE). Congruity of an MRI lesion, ictal epileptic EEG discharges, and seizure semiology may allow one to go for epilepsy surgery without further invasive diagnostic procedures. In patients in whom scalp EEG recordings are insufficient, a lesion depicted at MRI may generate a hypothesis for intracranial electrode implantation. Whether a lesion is detected with MRI depends on the quality of the images and the expertise of the reader.22 Adequate imaging for TLE requires an inclination of axial plane of images, which should be paralleled to the hippocampal length axis or the floor of the middle cranial fossa. With special techniques, image algorithms, and increasing experience, sensitivity for MTS is meanwhile close to 98%.3,23,24 Especially when limited resections are to be planned, highly sensitive MRI is necessary, in order not to overlook concomitant signal alterations, which might be interpreted as more widespread structural changes. A general aim is the demonstration of concordance between the pathological substrate and the ictal onset zone, indicating an excellent chance for satisfactory postoperative seizure control. However, details of neuroimaging are not the topic of this review.

MRI-Negative TLE Due to the fact that up to 30% of patients with TLE are considered to be MR-negative, MRI-negative TLE requires

61 some comments.25,26 The classification as non-substrate-directed partial epilepsy, which more often occurs in extratemporal than temporal areas, has been suggested.1 A similar challenge occurs in patients with suspected temporal lobe epilepsy and with MR documented bilateral changes. Berkovic et al found 60% seizure-freeness with, and only 29% without, MR-identified structural abnormalities in patients undergoing anterior temporal lobectomy (ATL).27 In a series of 222 patients with TLE, published by Scott et al in 1999, only 5 of 40 patients without MR abnormalities underwent further invasive monitoring, and only 3 were finally considered surgical candidates.28 Holmes et al described EEG findings to predict outcome in MR-negative TLE cases: 11 of 18 patients became seizure free with exclusively unilateral basaltemporal ictal-onset, but none of 5 with seizures originating from mid-posterior temporal regions. Interictal bilateral or multifocal spikes were additional predictors for unfavorable outcomes.29

Other Imaging Modalities Glucose hypometabolism as shown with positron emission tomography (PET) examinations is a common finding in TLE.30 Carne et al defined the distinct surgically remediable syndrome: MRI-negative PET-positive TLE.26 Within this group, more widespread glucose-hypometabolism was described, compared in a matched case-control study with patients exhibiting overt hippocampal sclerosis. Tailoring of resections to the area of glucose hypometabolism resulted in equally good seizure control with 74 and 80% of patients being seizure free. Anterior temporal polar hypometabolism is especially predictive of good outcome.31 Single-photon emission computed tomography (SPECT) studies are able to identify zones of regional hyperperfusion, which is thought to be a surrogate for the epileptic zone.32 Ictal SPECT is meanwhile recognized as a helpful adjunct, especially in non-substrate-directed partial epilepsies.1,30 However, its spatial resolution is poorer compared to PET studies.32 This deficit of spatial resolution and data interpretation in SPECT studies have been overcome by computeraided Subtraction-Ictal-SPECT and Co-registration with MRI (SISCOM).33,34 The methodology involves co-registration of a normalized interictal to the ictal SPECT image by a voxelmatching method. The subtraction image illustrates the seizure-induced changes in regional cerebral blood flow. The SISCOM technique has proven its superiority to visual inspection and evaluation of SPECT and results also correlate with the operative outcome.1,35 Magnetoencephalography is presently only available in few special epilepsy surgery centers. The basic idea is to define the localization of magnetic dipoles, as a parameter indicating synchronous electrical activity of a larger number of cells.36,37 Magnetoencephalography source analysis has proven to be helpful in resection planning.38 The role and the application of functional MRI in temporal lobe epilepsy still have to be elucidated.39-42 The well-established functional monitoring of motor function does not play a pivotal role for surgery in TLE. Functional MRI with verbal

62

H. Clusmann

activation can provide insights regarding hemispherical dominance and can contribute to the evaluation of risks for postoperative cognitive decline.41 However, functional MRI is not part of a routine evaluation for TLE so far.

Invasive EEG Monitoring The number of TLE patients evaluated by invasive EEG monitoring has decreased over the last decade from 40% (1993) to 8% (2003) in our center. Depth and subdural electrodes may allow the recording of seizures with circumscribed ictal onset areas and hence the localization of a resectable epileptogenic focus. Invasive recordings proved an acceptable rate of surgical (4%) and few neurological complications, while no mortality was documented.43

Depth Electrodes Invasive EEG evaluation of deep brain lesions and mainly of temporomesial structures is useful for determination of the ictal onset area. In difficult cases with strictly mesiotemporal seizures (eg, bilateral hippocampal sclerosis or unilateral hippocampal sclerosis with contralateral seizure onset in surface EEG), even temporobasal subdural strip electrodes may lateralize falsely; thus in many cases, hippocampal depth electrodes are combined with subdural temporal electrodes.44 Depth electrodes are particularly useful for the lateralization of seizure onset in those cases. Stereotactic placement of intrahippocampal multicontact electrodes was first described by Spencer and coworkers45 based on angiography and stereotactic atlas and later on MRI or computed tomography (CT). The temporo-mesial electrodes pass from the occipital region so that amygdala and hippocampal structures are sampled by an antero-posterior line of contacts. The accuracy of electrode implantation is postoperatively assessed by means of CT or MRI (Fig. 1). The method and operation is described in detail elsewhere.46 No major surgical (eg, hematomas) or persisting neurological complications were observed in a larger series of patients with bilaterally inserted intrahippocampal electrodes. However, occasionally, temporary amnestic episodes have been observed.47 An alternative way, to avoid the necessity of additional subdural electrode placement, is to stereotactically implant depth electrodes from the lateral cortical surface towards the mesio-temporal structures. This approach enables recording from deeper lateral cortical areas, but the degree of hippocampal coverage is somewhat less.

Subdural Strip and Grid Electrodes Recordings from subdural strip electrodes are most commonly made on the temporal lobe via bilateral burr holes. Strips with 4 to 16 platinum electrodes slide directly over the cortical surface after opening the dura. Typically two electrodes are guided inferiorly and mesially and one electrode to the lateral temporal cortex. Further electrodes can be necessary in selected cases. Subdural strips are often combined with hippocampal depth electrodes. A typical electrode array for invasive monitoring of TLE is shown in Figure 2. It has to be noted that especially complex electrode arrays carry some

Figure 1 Pre- and postoperative T2-weighted MRI scans (axial temporal angulation and coronal plane) in a patient with right hippocampal sclerosis. Upper panel: preoperative status; the MR slice angulation parallel to the floor of the temporal fossa provides a good overview on the whole length of the hippocampus. Note the increased signal intensity and atrophy of the right hippocampus (arrows) and the relative enlargement of the right temporal ventricular horn. Middle panel: after bilateral stereotactic implantation of amygdalo-hippocampal depth electrodes, indicated by arrows in the coronal image. No postoperative tissue signal alteration can be detected. The electrodes follow the length axis of the hippocampal body and thus provide good information on seizure activity within the hippocampus. Lower panel: postoperative scans 5 days after transcortical amygdalohippocampectomy on the right: the axial image shows the length of hippocampal and parahippocampal resection, including uncus and large parts of the amygdala; the coronal image shows the mesial resection defect and signal intensity changes adjacent to the surgical approach through the middle temporal gyrus.

significant risks, eg, the development of symptomatic subdural hematomas, which require emergency surgical revision.48 Neuronavigation may provide additional help for exact electrode positioning, especially if lesions are located in the temporo-occipital or temporo-parietal area.49 CT with its

Temporal lobe epilepsy surgery

63

Surgical Treatment for TLE

Figure 2 Schematic drawing of the typical pattern of two temporal basal and one temporal lateral subdural strip electrodes, as implanted via one temporal burr hole in combination with amygdalohippocampal depth electrode. In most cases, bilateral implantations are performed. Instead of strip electrodes, grid electrodes may be implanted to cover the cortical surface for more extensive brain mapping.

high spatial resolution is well suited for localizing grid electrodes, while MRI better depicts lesions within the brain. For a better anatomical identification of grid electrodes and their spatial relationship to the underlying cortical surface, it is useful to combine both imaging modalities. A MRI before grid implantation and a CT scan after craniotomy can be combined by a co-registration algorithm. Furthermore, coregistration of MR-T1 and -FLAIR images can be useful.50 To increase the anatomically precise localization of grid electrodes digital photographs are taken during grid implantation. According to the cortical anatomy the electrode contacts are then projected onto a 3D MRI surface set rendering of the patient’s brain. The results of recording ictal activity, mapping, and the suggested margins for surgical resection are drawn in direct relation to the cortical anatomy and allows a precise and reproducible intraoperative visual orientation additionally to the matched MRI/CT scans.51 Extraoperative electrical stimulation (brain mapping) is performed if the epileptogenic zone overlaps with eloquent brain areas or if the planned resection would be in close proximity to functionally important brain areas. In TLE, this may concern the association cortex with more or less circumscribed representations of higher cognitive functions, particularly the language cortices and the left perisylvian association cortex.

Intraoperative Electrocorticography (EcoG) The indications for ECoG vary significantly between different centers. The disadvantages of this method are the poorly defined influence of anesthetics, the short recording time, and the lack of seizure recording. Basically. intraoperative EcoG is an interictal recording. Therefore, intraoperative ECoG is restricted to the definition of the irritative zone and has thus limitations for sufficiently delineating the seizure onset zone or eloquent cortices. Intraoperative recordings from strip electrodes placed on the hippocampus may be applied to determine the extent of resection.52,53

The aim of any surgical option for the treatment of temporal lobe epilepsy is the removal of the epileptogenic zone and, if present, of the concomitant lesion within the temporal lobe. Per definition, removal of the epileptogenic zone leads to seizure control, resulting in a rather simple principle: the more involved tissue is removed, the better are the chances of seizure control. On the other hand, it can be hypothesized that little removal of healthy tissue results in better cognitive functioning. With increasing ability to demonstrate even subtle structural lesions by high-resolution MR techniques and increasing knowledge of presurgical electrophysiological monitoring, the concept of limiting the resection just to the epileptic focus and lesion has evolved.10,54 Judging from recent publications, ATL is still the most widely performed standard resection for TLE.7,12 With respect to mesial TLE, it is still a matter of discussion, whether limited resections (eg, amygdalohippocampectomy (AH)) are beneficial, regarding side effects, post surgical memory performance, and seizure relief. Surgery for TLE in children has been shown to be even more successful than treatment of adults. Pediatric patients profit from early epilepsy surgery for TLE, leading to somewhat better results than reported in most adult TLE series.55-57 Our own results with preoperative “tailoring” were surprisingly disappointing in children: AH had a significantly lower chance of seizure relief compared to standard ATL, especially after left-sided operations. These results are different than the findings obtained with equal guidelines for adult patients. The main hypothesis is derived from the higher frequency of concomitant abnormalities in the temporal lobe, and a questionable existence of juvenile pure mesial TLE. In children neuropsychological results are more promising and there is a good chance for recovery and compensation of postoperative deteriorations in the long run, which seem to be better compared to adult patients undergoing temporal lobe surgery.55,58,59

Resection Strategy Limited resections and more AHs have been increasingly performed while reducing the number of ATLs during the last decade, whenever presurgical evaluation demonstrated a localized lesion and epileptogenic area within the temporal lobe, eg, in pure mesial TLE (Fig. 3). Developments in neuroimaging, especially the increased sensitivity and also specificity of high-resolution MRI, played a major role and enabled this strategy. To assess whether this change in resection strategy implies alterations in patient outcome, regarding seizure relief, neurological, or neuropsychological features, we initiated a study to examine influences of group experience, MRI advances, resection strategies, and other clinical factors on seizure outcome and neuropsychological performance, using uni- and multifactorial analysis.3 In this series of 321 temporal resections for refractory TLE, performed between 1989 and 1997, we found no significant differences between the different types of surgery regarding outcome for the whole time period: a satisfactory seizure outcome (Engel

64

Figure 3 Surgical treatment for temporal lobe epilepsy: Schematic drawings of typical approaches for limited and more extensive standard resections: (A) “selective” amygdalohippocampectomy, including head and body of the hippocampus as well as parts of the amygdala, parahippocampal gyrus, and uncus; (B) basal temporal resection plus amygdalohippocampectomy; (C) lateral temporal lesionectomy without or plus amygdalohippocampectomy; (D) lateral (neocortical) temporal lobectomy; (E) polar resection plus anterior amygdalohippocampectomy; (F) standard (classic) anterior temporal lobectomy including amygdalohippocampectomy, the extent of lateral resection normally reaches circa 4.5 cm on the dominant and 5.5 cm on the nondominant side.

Class I and II)60 was obtained in 79.6% of patients with ATL, 83.4% with AH, 74.1% with lateral lesionectomy plus hippocampectomy (only 27 of 321 patients), and in 86.2% with purely lateral neocortical resections. Whenever limited resections were intended, limits of resection were defined by MRI as well as by noninvasive and invasive preoperative EEG evaluations. The main finding is that despite reducing the amount of tissue removal, success rates remained stable, even without intraoperative electrocorticography. Arruda et al reported on a series with 74 patients with mesial TLE. They found equally good results with ATL and AH.54 Wieser et al61 conducted a retrospective study with a reassessment of the long-term seizure outcomes in 369 patients who underwent selective AH for pharmacotherapy-resistant MTLE at the Zurich University Hospital from 1975 to 1999. The last available data on seizure outcome were not significantly different between patients in the lesional and nonlesional MTLE groups. In general, relief of disabling seizures (Engel Class I, ILAE Classes I, II) was attained in approximately 67% of patients.60,62 Thus, promising results were documented, even over a long time period after AH. Amygdalohippocampectomy can be performed via different approaches. The approach as originally suggested by Niemeyer has been followed by Olivier in Montreal63: with the aid of neuronavigation, the ventricle is entered via the

H. Clusmann middle temporal gyrus, followed by a resection of the anterior parts of the hippocampus, then amygdala and uncus parahippocampalis. An advantage is the smaller craniotomy; a disadvantage is the more limited overview on the mesiotemporal structures. Yasargil and coworkers suggested the transsylvian approach64: after dissection of the sylvian fissure, the temporal ventricular horn is entered through the temporal stem in the inferior semicircular sulcus, followed by the resection of mesiotemporal structures. The dissection of the sylvian fissure may be challenging, but a good overview on the hippocampus including the possibility of far dorsal hippocampal resection is provided. Spencer et al described a combined approach to gain access to the posterior mesial temporal structures.65 Other suggestions comprised the subtemporal, zygomatic, subtemporaltransparahippocampal, transsylvian-transcisternal, and even retrolabyrinthine-presigmoid approach, and others, all of them being less practiced compared to the transsylvian and transcortical approach. It has been reported that the amount of tissue resected in mesiotemporal operations is crucial for surgical success in mesial TLE.66-70 Residual tissue is a well-known factor of seizure recurrence and is, due to limited exposure, thought to be somewhat more frequent after AH compared to ATL. Reoperation for residual tissue removal resulted in complete seizure control in four of eight patients in our TLE study, which corresponds to published data from other groups.71-74 MTLE patients with predominant mesio-temporal lesions other than AHS are a much lesser recognized subgroup. Hennessy et al described only 5 of 80 specimens (6.3%) with hippocampal lesions; 9 cases remained unclear.75 There are only a few reports dealing with lesional MTLE, which is thought to be a clinically different entity compared to patients with MTS.76,77 In a series limited to preoperatively tailored resections for lesional (nonsclerotic) mesial TLE patients, satisfactory results were obtained.78 The practice of this approach is mainly dependent on elaborate preoperative imaging, which has become possible with advances in MR technology during the last 15 years.27 Sixty-four patients (86.5%) gained satisfactory seizure relief (58 patients, 78.4% Class I; 6 patients, 8.1% Class II). Five patients (6.8%) were categorized in Classes III and IV, respectively. Seizure relief neither differed significantly with these approaches nor with different classes of pathological findings (43 developmental tumors, 12 glial tumors, 10 dysplasias, and 9 others). Even operation of dysplasia resulted in 80% satisfactory seizure control. Seizure onset during childhood proved to be a negative predictor for seizure relief (P ⫽ 0.020). The regime of “preoperative tailoring” resulting in limited resections has proven to be safe and to provide a very good chance for satisfactory seizure relief in patients with lesional, ie, nonsclerotic MTLE. Similar results were found in a series of purely neocortical TLE: outcome with lesionectomy and corticectomy was excellent, especially when a tumor was present (95% satisfactory seizure control).79

Temporal lobe epilepsy surgery

65

Complications and Collateral Damage

Neuropsychological Results

The risks associated with elective surgery are an important issue. Surgery for TLE is often considered for young and otherwise healthy patients. Prospective success has to be weighed against potential risks. Frequent side effects after temporal lobe surgery can be visual field defects, mostly upper partial quadrantanopia, which are mainly not considered a problem by the affected individuals.80,81 The rate of visual field defects seems to be gradually higher after transcortical compared to transsylvian AH. Cognitive impairments are relevant side effects, especially after left-sided temporal lobe surgery, and will be described below. Although cranial neurosurgery has become safer with the advent of microneurosurgical techniques,82 a certain risk remains, eg, suffering postoperative hemorrhages, infection, etc.8,83,84 Besides the general risks described for intracranial procedures,85,86 there may be some special risks for patients with drug-resistant epilepsies due to medication-induced coagulation disorders (eg, acquired von Willebrand disease).87 Generally, complication rates are relatively low and thought to be acceptable, with around 1 to 2% permanent morbidity.3,7,61,84,88 Typical neurological complications are mostly temporary dysphasia or hemiparesis, as caused by manipulation-induced brain-swelling or brain contusion, small-vessel infarction, and hemorrhage. On top, there are the classical surgical problems such as infection, thrombosis, etc, in the range of 2 to 4%, which rarely cause permanent damage.88 The mortality rate is clearly below 1% in most series. In our series we had two deaths in 1100 TLE surgeries (mortality rate, 0.18%). As expected, complication rates are somewhat higher when operating on patients older than 50 years of age.89 Hemorrhages seem to show a characteristic distribution after epilepsy surgery: a majority is located remote from the site of surgery in the upper cerebellar vermis and foliae. These occur postoperatively and are thought to be correlated with the amount of cerebrospinal fluid loss, especially after temporal lobectomy.90,91 Other typical hemorrhages mostly associated with dysphasia are found in the left frontal operculum after amygdalohippocampectomy, and only a small percentage of hematomas is located in the resection cavity.90 Interesting results were obtained from a systematic postoperative magnetic resonance screening after amygdalohippocampectomy.92 Postoperative MRI signal intensity changes adjacent to the approach (see also Fig. 1, lower panel) were correlated to postoperative changes in verbal memory. Losses in verbal short-term/working memory (learning) were positively related to the amount of signal intensity changes independent from the side of the resection, the surgical approach, or the extent of the mesial resection. These data indicate that collateral damage to cortical tissue adjacent to the surgical approach contributes to postoperative memory outcome after selective amygdalohippocampectomy. Controlling for collateral damage may thus elucidate controversial memory outcomes after SAH.

Apart from unexpected complications, decreased memory functions represent the greatest potential neuropsychological morbidity after surgical treatment of TLE. Verbal memory functions are particularly at risk in patients undergoing leftsided resections.20,81,93-96 Identified risk factors for postoperative memory decline after anterior temporal lobectomy are older age at time of surgery, later age at onset of seizures, male gender, and better preoperative memory performance. Patients with normal-appearing hippocampi seem to be at greater risk. The hippocampal formation is recognized as a crucial brain area serving human long-term memory. Material-specific relations between the left medial temporal lobe and verbal memory93,97 and between the right medial temporal lobe and visual/nonverbal memory81,95 are well described. The relation between verbal memory and the left hippocampus especially has been confirmed in multiple studies with different designs.19,20 Differential contributions of mesial and lateral temporal areas have been demonstrated: verbal shortterm memory and learning can be attributed to the lateral temporal cortex with some bilateral representation, while verbal long-term retrieval seems to take place within the left mesio-temporal structures.19,81 Whether limited resections for mesial TLE (for example AH) are at all beneficial compared to standard ATL is a matter of discussion. Some studies reported better neuropsychological outcomes with limited resections3; others did not.98 From a theoretical point of view it should be advantageous to preserve as much healthy brain tissue as possible, especially when equal seizure control can be achieved. In our own series of 321 patients operated for TLE, we recognized that a concordant lateralization of impaired function was associated with better outcome results compared to patients with discordant lateralization.3 Good seizure control was associated with gains in attentional performance, and patients after ATL showed less gain and more loss, compared to more limited resections. Verbal memory function improved in 19.3% of patients, was stable in 46.3%, and deteriorated in 34.4%, documenting that verbal memory was the most critical item with the least rate of improved and the highest rate of deteriorated results. The higher amount of deteriorations after ATL (43.4%) compared to AH (30.9%) and Lx (29.2 and 30.8%) proved that limited resections were associated with gradually better results with respect to cognitive functioning.

Seizure Outcome and Prognostic Parameters Knowledge and documentation of postoperative seizures is a prerequisite for any analysis of success attributed to surgery. Definition of seizure outcome is however not simple. If there are no seizures at all, complete seizure relief is assumed. However, even this relatively simple situation is a matter of discussion, whether or not to include auras, and which follow-up period has to be demanded. Gradual decreases in seizure frequencies are much more difficult to classify, and seizure severity is more difficult to measure than seizure fre-

H. Clusmann

66 quency, although type and severity of seizures may play a dominant role with respect to the individual impairment.60,62 Furthermore, evaluation of changes in quality of life are a challenge.100-102 In the earlier years of epilepsy surgery, outcome with respect to seizures was simply described as “success” and “failure.”99 Bengzon et al103 excluded patients with “intermediate” success from their analysis and concentrated on successfully operated patients (no or just occasional or infrequent seizures) and on patients with little or no improvements. The seizure status was thought to be fairly stable after 2 years; however, meanwhile, late recurrences have also been described. Engel and coworkers introduced a system with four major outcome classes, which were then subdivided into up to 13 sublevels.60 The four main classes are probably the most-used system for evaluation of postoperative success. The commission on classification of the ILAE (International League against Epilepsy)3 proposed a six class system for postoperative seizure control. For certain statistical analysis, some of these outcome classes have to be regrouped together, but it still remains debatable where to define the border between success and failure.62 Description and evaluation of prognostic parameters have been applied since the 1960s to define the prospective chances for individual success after epilepsy surgery.3,103-105 In the pre-MR era, Bengzon et al defined 19 parameters as being significant for success in surgical treatment of TLE.103 Later on, and with increasing success rates, prognostic factors were found to be not as numerous, probably because MRI and EEG data became more important and patients with extremely low chances would in advance be excluded from surgery. Unilateral hippocampal sclerosis is found to be correlated with good outcome in multifactorial procedures, which stresses the importance of high-quality preoperative MRI.7,106 In other studies any positive MR finding was found to be relevant.2,105 The correlation of unsatisfactory outcome and discordant EEG findings is well established,2,7,105,106 and EEG still plays an important role in the early presurgical evaluation, eg, patients with documented bilateral ictal onset are often not even considered surgical candidates. Nevertheless, in the past, it has not been promising to operate on patients without any MR abnormalities, regardless of EEG findings. However, recently, successful operations have been described for so-called MRI-negative PET-positive TLE: complete seizure relief was reached in 80% of patients.26 Somewhat less promising results were obtained in MRI-negative TLE cases without the aid of PET and SPECT.107 A recent meta-analysis (47 articles) of predictors of epilepsysurgery outcome extracted the following factors to contribute to prediction of seizure relief: febrile seizures, mesial temporal sclerosis, tumors, abnormal MRI, EEG/MRI concordance, and extensive surgical resection.11 Negative effects were attributed to postoperative EEG discharges and the need for intracranial EEG monitoring. In our own TLE series, using stepwise logistic regression analysis, we found the following five factors to be correlated with satisfactory seizure control: no history of status epilep-

ticus; a concordant lateralization of memory impairment; a clear pathological MRI finding; ganglioglioma or DNT on MRI; and no dysplasia. Of these five factors three were derived from MRI: a clear pathological MRI finding; diagnosis of a ganglioglioma or DNT; and no presence of dysplasia.3 In our study EEG findings were not entered into the multifactorial model in the first line, suggesting their importance being lower compared to neuroimaging data. Nevertheless, an additional remote EEG focus was associated with unsatisfactory outcome.

Health-Related Quality of Life (HRQOL) The true goal of epilepsy surgery is not just seizure reduction, but also cessation of limitations plus social reintegration. Measuring an individual’s benefit concerning “well-being” and “functioning” has been increasingly reported in the last several years.9,14,101 However, measuring quality of life is challenging. Neuropsychological aspects and depression have been shown to play a major role.108-110 Surgery proved to be superior to medication treatment in the only prospective, randomized, and controlled study, not only regarding seizure control, but also with respect to quality-of-life measures.9 A recent study in 128 patients operated for mesial TLE at our institution shows a dependency of HRQOL and seizure control, but we were able to show that different domains are differentially involved in this respect: cognitive impairments especially were associated with poor findings in HRQOL measures, which supports the necessity of improving cognitive results, eg, by using limited resections.102

Persisting Problems The exact definition of the ictal onset zone is difficult. Per definition, removal of the ictal onset zone leads to seizure relief. There is so far no way to directly visualize this trigger area for epilepsy. The spatial resolution of even invasive EEG recordings is limited, especially when considering the threedimensional folding of the cerebral cortex. Thus, superficial cortical electrodes can approach this feature only to some degree. Depth electrodes are gradually superior in this respect and they reflect EEG features from the cortex to deeper areas; however, their spatial resolution regarding the surface is limited.44,46,111-113 Other imaging tools lack the necessary spatial or time resolution to detect the short and regional epilepsy-triggering events. Even when a clear lesion can be demonstrated with MRI, the adequate resection borders, the length of hippocampal resection, etc, are not easy to define. Often, the resection plan depends more on individual or group experience than on definite determining data. The question, whether there is a nonlesional temporal lobe epilepsy at all, is still not solved. In difficult cases, we still face the necessity for invasive EEG monitoring. There is so far no consensus with respect to the adequate, potentially least invasive surgical approach. The respective data are a matter of discussion, especially regarding surgical success (seizure control) and side effects.3,54,68 Presumably, we face a kind of antagonism between seizure relief and neuropsychological

Temporal lobe epilepsy surgery deficits, at least in those patients who exhibit a potential overlap of pathological alteration and neuropsychological functional areas.114-116 Epilepsy surgery is limited by a potential overlap of eloquent brain tissue and the ictal zone; for example, in dominant dorsal temporal neocortical epilepsies, where resection of speech cortices may cause different degrees of aphasia. The hope to overcome this problem by pure multiple subpial transsections to preserve function and to abolish seizures was not fulfilled so far.117 Furthermore, general surgical risks have to be respected, eg, in small babies presenting with large lesions. There seems to be an increased psychiatric vulnerability especially after right-sided temporal resections, leading to depression or psychosis. Furthermore, even complete seizure relief does not imply social reintegration.108-110,118,119

Perspective During the last 100 years, new trends and approaches in epilepsy surgery have been closely correlated to innovative technical developments, which enabled or improved either presurgical diagnosis or epilepsy surgery procedures. The implementation of electrocorticography and EEG enabled cortical resections, even in the absence of overt lesions. Video-EEG monitoring provided a reliable electro-clinical correlation, which was of fundamental importance for further developments. Microneurosurgery dramatically improved the safety and precision of surgical procedures and minimized complication rates. Modern neuroimaging is the basis of the present “lesion-directed” approach. Recently, new methods in neuropsychological evaluation have been recognized as helpful for pre- and postsurgical evaluation. The necessity for invasive presurgical evaluation has already and will continuously decrease. However, it is debatable whether there will ever be a complete noninvasive evaluation for all patients with TLE. It is beyond question that developments in MRI will contribute to improvements in presurgical evaluation for epilepsy. Higher sensitivity MRI will detect even subtle lesions; however, the respective relevance for epilepsy will have to be critically evaluated. There is a certain danger that an extremely high MR sensitivity may mislead the investigator. Evaluating the role for high-field MRI (3 Tesla) is just being started.23,42,120 New methods of MR fiber tracking may help to avoid damage to the optic radiation.122 Functional MRI will probably play an increasing role in neocortical epilepsies, and some effects can be expected for TLE, regarding the lateralization of higher cortical functions or different aspects of memory.121 This also includes the prediction of memory deficits.123 Blood oxygen level dependent (BOLD) functional MRI is used for the purpose of spike detection, and a concordant activation of BOLD-functional MRI and interictal epileptiform activity could be demonstrated in some patients.124 Meanwhile, in an experimental setting, functional MRI can be obtained simultaneously with high-quality EEG recording, which offers new perspectives.125 Even 3-Hz neuronal spikeand slow-wave activity in generalized epilepsy can be visual-

67 ized with these techniques.126 Progress is also expected with respect to illustration of three-dimensional activation maps “glass-brain.”127 A variety of imaging modalities should collect different kinds of morphological and functional information.128 This comprehensive data on individual patients may be matched and then be transmitted to a neuronavigation unit, in order to improve the surgeon’s insight and orientation. Developments in surgical techniques and approaches have contributed to improvements in safety and the overall moderate morbidity rates with temporal lobe surgery.8,88 The same holds true for modern neuro-anesthesia. It is unclear whether the overall low morbidity and mortality rates will further decrease, because it has to be assumed that a certain risk will always remain. The use of limited resections will probably contribute to reduce the neuropsychological and cognitive morbidity. The avoidance of collateral brain damage is demanding for the surgeon but bears the chance of significant cognitive improvements.92 Whether more precise preoperative evaluation will allow “superselective resections” remains unclear, especially, because from a theoretical standpoint a certain amount of tissue-removal will always be necessary. However, patients should benefit from exact tailoring of resection, eg, by sparing unaffected hippocampal areas and preoperative definition of the desired length of hippocampal resection.129 The prospective chances of radiosurgical treatment of TLE are under investigation.130 Radiofrequency ablation of epileptogenic tissue via stereotactically implanted electrodes has been also reported as more palliative alternative to resective procedures.131,132 With the advent of sophisticated stimulation devices for deep brain stimulation in, eg, Parkinson’s disease, a role of permanent focal brain stimulation for refractory TLE has been recently suggested.133

Acknowledgments I thank my chairman in the Department of Neurosurgery, J. Schramm, for continuous education and for his valuable longstanding support; C.E. Elger, M. Kurthen, R. Sassen, and C. Bien from the Department of Epileptology for helpful discussions, collaboration, and expertise; C. Helmstaedter for detailed work on neuropsychology; H. Urbach for support with neuroimaging; and my present and former neurosurgery colleagues involved in epilepsy surgery (E. Behrens, T. Kral, B. Meyer, C. Schaller, D. Van Roost, M. von Lehe, J. Zentner). I am thankful to H. Storma and D. Haun for graphics and IT support.

References 1. Cascino GD: Surgical treatment for epilepsy. Epilepsy Res 60:179186, 2004 2. Armon C, Radtke RA, Friedman AH, et al: Predictors of outcome of epilepsy surgery: multivariate analysis with validation. Epilepsia 37: 814-821, 1996 3. Clusmann H, Schramm J, Kral T, et al: Prognostic factors and outcome after different types of resection for temporal lobe epilepsy. J Neurosurg 97:1131-1141, 2002 4. Foldvary N, Nashold B, Mascha E, et al: Seizure outcome after temporal lobectomy for temporal lobe epilepsy: a Kaplan-Meier survival analysis. Neurology 54:630-634, 2000

68 5. Kral T, Clusmann H, Urbach H, et al: Preoperative evaluation for epilepsy surgery (Bonn algorithm). Zentralbl Neurochir 63:106-110, 2002 6. Olivier A: Relevance of removal of limbic structures in surgery for temporal lobe epilepsy. Can J Neurol Sci 18:628-635, 1991 7. Radhakrishnan K, So EL, Silbert PL, et al: Predictors of outcome of anterior temporal lobectomy for intractable epilepsy: a multivariate study. Neurology 51:465-471, 1998 8. Salanova V, Markand O, Worth R: Temporal lobe epilepsy surgery: outcome, complications, and late mortality rate in 215 patients. Epilepsia 43:170-174, 2002 9. Wiebe S, Blume WT, Girvin JP, et al: A randomized, controlled trial of surgery for temporal-lobe epilepsy. N Engl J Med 345:311-318, 2001 10. Wieser HG, Yasargil MG: Selective amygdalohippocampectomy as a surgical treatment of mesiobasal limbic epilepsy. Surg Neurol 17:445457, 1982 11. Tonini C, Beghi E, Berg AT, et al: Predictors of epilepsy surgery outcome: a meta-analysis. Epilepsy Res 62:75-87, 2004 12. Engel J Jr, Wiebe S, French J, et al: Practice parameter: temporal lobe and localized neocortical resections for epilepsy: report of the Quality Standards Subcommittee of the American Academy of Neurology, in association with the American Epilepsy Society and the American Association of Neurological Surgeons. Neurology 60:538-547, 2003 13. Tellez-Zenteno JF, Dhar R, Wiebe S: Long-term seizure outcomes following epilepsy surgery: a systematic review and meta-analysis. Brain 128:1188-1198, 2005 14. Spencer SS, Berg AT, Vickrey BG, et al: Initial outcomes in the Multicenter Study of Epilepsy Surgery. Neurology 61:1680-1685, 2003 15. Bertram EH, Williamson JM, Cornett JF, et al: Design and construction of a long-term continuous video-EEG monitoring unit for simultaneous recording of multiple small animals. Brain Res Brain Res Protoc 2:85-97, 1997 16. Cascino GD: Video-EEG monitoring in adults. Epilepsia 43:80-93, 2002 17. Elger CE, Hufnagel A, Schramm J: Epilepsy Surgery Protocol University Hospital, Bonn, Germany, in Luders HO (ed): Epilepsy Surgery. New York, NY, Raven Press, 1992, pp 783-784 18. Hufnagel A, Dumpelmann M, Zentner J, et al: Clinical relevance of quantified intracranial interictal spike activity in presurgical evaluation of epilepsy. Epilepsia 41:467-478, 2000 19. Helmstaedter C, Elger CE, Hufnagel A, et al: Different effects of left anterior temporal lobectomy, selective amygdalohippocampectomy, and temporal cortical lesionectomy on verbal learning, memory, and recognition. J Epilepsy 9:39-45, 1996 20. Helmstaedter C, Grunwald T, Lehnertz K, et al: Differential involvement of left temporolateral and temporomesial structures in verbal declarative learning and memory: evidence from temporal lobe epilepsy. Brain Cogn 35:110-131, 1997 21. Lutz MT, Clusmann H, Elger CE, et al: Neuropsychological outcome after selective amygdalohippocampectomy with transsylvian versus transcortical approach: a randomized prospective clinical trial of surgery for temporal lobe epilepsy. Epilepsia 45:809-816, 2004 22. Von Oertzen J, Urbach H, Jungbluth S, et al: Standard magnetic resonance imaging is inadequate for patients with refractory focal epilepsy. J Neurol Neurosurg Psychiatry 73:643-647, 2002 23. Urbach H, Hattingen J, von Oertzen J, et al: MR imaging in the presurgical workup of patients with drug-resistant epilepsy. AJNR Am J Neuroradiol 25:919-926, 2004 24. von Oertzen J, Urbach H, Blumcke I, et al: Time-efficient T2 relaxometry of the entire hippocampus is feasible in temporal lobe epilepsy. Neurology 58:257-264, 2002 25. Siegel AM, Jobst BC, Thadani VM, et al: Medically intractable, localization-related epilepsy with normal MRI: presurgical evaluation and surgical outcome in 43 patients. Epilepsia 42:883-888, 2001 26. Carne RP, O’Brien TJ, Kilpatrick CJ, et al: MRI-negative PET-positive temporal lobe epilepsy: a distinct surgically remediable syndrome. Brain 127:2276-2285, 2004

H. Clusmann 27. Berkovic SF, McIntosh AM, Kalnins RM, et al: Preoperative MRI predicts outcome of temporal lobectomy: an actuarial analysis. Neurology 45:1358-1363, 1995 28. Scott CA, Fish DR, Smith SJ, et al: Presurgical evaluation of patients with epilepsy and normal MRI: role of scalp video-EEG telemetry. J Neurol Neurosurg Psychiatry 66:69-71, 1999 29. Holmes MD, Born DE, Kutsy RL, et al: Outcome after surgery in patients with refractory temporal lobe epilepsy and normal MRI. Seizure 9:407-411, 2000 30. Ho SS, Berkovic SF, Berlangieri SU, et al: Comparison of ictal SPECT and interictal PET in the presurgical evaluation of temporal lobe epilepsy. Ann Neurol 37:738-745, 1995 31. Radtke RA, Hanson MW, Hoffman JM, et al: Temporal lobe hypometabolism on PET: predictor of seizure control after temporal lobectomy. Neurology 43:1088-1092, 1993 32. Spencer SS: The relative contributions of MRI, SPECT, and PET imaging in epilepsy. Epilepsia 35:72-89, 1994 (suppl 6) 33. Kaiboriboon K, Lowe VJ, Chantarujikapong SI, et al: The usefulness of subtraction ictal SPECT coregistered to MRI in single- and dual-headed SPECT cameras in partial epilepsy. Epilepsia 43:408-414, 2002 34. O’Brien TJ, So EL, Mullan BP, et al: Subtraction ictal SPECT coregistered to MRI improves clinical usefulness of SPECT in localizing the surgical seizure focus. Neurology 50:445-454, 1998 35. O’Brien TJ, O’Connor MK, Mullan BP, et al: Subtraction ictal SPET co-registered to MRI in partial epilepsy: description and technical validation of the method with phantom and patient studies. Nucl Med Commun 19:31-45, 1998 36. Hellstrand E, Abraham-Fuchs K, Jernberg B, et al: MEG localization of interictal epileptic focal activity and concomitant stereotactic radiosurgery. A non-invasive approach for patients with focal epilepsy. Physiol Meas 14:131-136, 1993 37. Stefan H, Hummel C, Scheler G, et al: Magnetic brain source imaging of focal epileptic activity: a synopsis of 455 cases. Brain 126:23962405, 2003 38. Assaf BA, Karkar KM, Laxer KD, et al: Magnetoencephalography source localization and surgical outcome in temporal lobe epilepsy. Clin Neurophysiol 115:2066-2076, 2004 39. Fernandez G, de Greiff A, von Oertzen J, et al: Language mapping in less than 15 minutes: real-time functional MRI during routine clinical investigation. Neuroimage 14:585-594, 2001 40. Killgore WD, Glosser G, Casasanto DJ, et al: Functional MRI and the Wada test provide complementary information for predicting postoperative seizure control. Seizure 8:450-455, 1999 41. Richardson MP, Strange BA, Thompson PJ, et al: Pre-operative verbal memory fMRI predicts post-operative memory decline after left temporal lobe resection. Brain 127:2419-2426, 2004 42. Szaflarski JP, Holland SK, Schmithorst VJ, et al: High-resolution functional MRI at 3T in healthy and epilepsy subjects: hippocampal activation with picture encoding task. Epilepsy Behav 5:244-252, 2004 43. Behrens E, Zentner J, Van Roost D, et al: Subdural and depth electrodes in the presurgical evaluation of epilepsy. Acta Neurochir 128: 84-87, 1994 44. Spencer SS, Spencer DD, Williamson PD, et al: Combined depth and subdural electrode investigation in uncontrolled epilepsy. Neurology 40:74-79, 1990 45. Spencer SS, Spencer DD, Williamson PD, et al: The localizing value of depth electroencephalography in 32 patients with refractory epilepsy. Ann Neurol 12:248-253, 1982 46. Van Roost D, Solymosi L, Schramm J, et al: Depth electrode implantation in the length axis of the hippocampus for the presurgical evaluation of medial temporal lobe epilepsy: a computed tomographybased stereotactic insertion technique and its accuracy. Neurosurgery 43:819-826, 1998 47. Fernandez G, Hufnagel A, Van Roost D, et al: Safety of intrahippocampal depth electrodes for presurgical evaluation of patients with intractable epilepsy. Epilepsia 38:922-929, 1997 48. Lee WS, Lee JK, Lee SA, et al: Complications and results of subdural grid electrode implantation in epilepsy surgery. Surg Neurol 54:346351, 2000

Temporal lobe epilepsy surgery 49. Murphy MA, O’Brien TJ, Cook MJ: Insertion of depth electrodes with or without subdural grids using frameless stereotactic guidance systems—technique and outcome. Br J Neurosurg 16:119-125, 2002 50. Mahvash M, Konig R, Urbach H, et al: FLAIR-/T1-/T2-co-registration for image-guided diagnostic and resective epilepsy surgery. Neurosurgery 58:ONS-69-ONS-75, 2006 51. Wellmer J, von Oertzen J, Schaller C, et al: Digital photography and 3D MRI-based multimodal imaging for individualized planning of resective neocortical epilepsy surgery. Epilepsia 43:1543-1550, 2002 52. Stefan H, Pauli E, Eberhard F, et al: [“Tailoring” resections in drug refractory temporal lobe epilepsy]. Nervenarzt 67:306-310, 1996 53. McKhann GM, Schoenfeld-McNeill J, Born DE, et al: Intraoperative hippocampal electrocorticography to predict the extent of hippocampal resection in temporal lobe epilepsy surgery. J Neurosurg 93:4452, 2000 54. Arruda F, Cendes F, Andermann F, et al: Mesial atrophy and outcome after amygdalohippocampectomy or temporal lobe removal. Ann Neurol 40:446-450, 1996 55. Clusmann H, Kral T, Gleissner U, et al: Analysis of different types of resection for pediatric patients with temporal lobe epilepsy. Neurosurgery 54:1-13, 2004 56. Mohamed A, Wyllie E, Ruggieri P, et al: Temporal lobe epilepsy due to hippocampal sclerosis in pediatric candidates for epilepsy surgery. Neurology 56:1643-1649, 2001 57. Salanova V, Markand O, Worth R, et al: Presurgical evaluation and surgical outcome of temporal lobe epilepsy. Pediatr Neurol 20:179184, 1999 58. Gleissner U, Sassen R, Lendt M, et al: Pre- and postoperative verbal memory in pediatric patients with temporal lobe epilepsy. Epilepsy Res 51:287-296, 2002 59. Westerveld M, Sass KJ, Chelune GJ, et al: Temporal lobectomy in children: cognitive outcome. J Neurosurg 92:24-30, 2000 60. Engel J Jr, Van Ness P, Rasmussen TB, et al: Outcome with respect to epileptic seizures, in Engel J Jr (ed): Surgical Treatment of the Epilepsies (ed 2). New York, NY, Raven Press Ltd.,1993, pp 609-621 61. Wieser HG, Ortega M, Friedman A, et al: Long-term seizure outcomes following amygdalohippocampectomy. J Neurosurg 98:751-763, 2003 62. Wieser HG, Blume WT, Fish D, et al: ILAE Commission Report. Proposal for a new classification of outcome with respect to epileptic seizures following epilepsy surgery. Epilepsia 42:282-286, 2001 63. Olivier A: Transcortical selective amygdalohippocampectomy in temporal lobe epilepsy. Can J Neurol Sci 27:68-76, 2000 (suppl 1) 64. Yasargil MG, Teddy PJ, Roth P: Selective amygdalo-hippocampectomy. Operative anatomy and surgical technique. Adv Tech Stand Neurosurg 12:93-123, 1985 65. Spencer DD, Spencer SS, Mattson RH, et al: Access to the posterior medial temporal lobe structures in the surgical treatment of temporal lobe epilepsy. Neurosurgery 15:667-671, 1984 66. Renowden SA, Matkovic Z, Adams CB, et al: Selective amygdalohippocampectomy for hippocampal sclerosis: postoperative MR appearance. AJNR Am J Neuroradiol 16:1855-1861, 1995 67. Nayel MH, Awad IA, Luders H: Extent of mesiobasal resection determines outcome after temporal lobectomy for intractable complex partial seizures. Neurosurgery 29:55-60, 1991 68. Awad IA, Katz A, Hahn JF, et al: Extent of resection in temporal lobectomy for epilepsy. I. Interobserver analysis and correlation with seizure outcome. Epilepsia 30:756-762, 1989 69. Bonilha L, Kobayashi E, Mattos JP, et al: Value of extent of hippocampal resection in the surgical treatment of temporal lobe epilepsy. Ar Qneuropsiquiatr 62:15-20, 2004 70. Wyler AR, Hermann BP, Somes G: Extent of medial temporal resection on outcome from anterior temporal lobectomy: a randomized prospective study. Neurosurgery 37:982-990, 1995 71. Wyler AR, Hermann BP, Richey ET: Results of reoperation for failed epilepsy surgery. J Neurosurg 71:815-819, 1989 72. Awad IA, Nayel MH, Luders H: Second operation after the failure of previous resection for epilepsy. Neurosurgery 28:510-518, 1991

69 73. Germano IM, Poulin N, Olivier A: Reoperation for recurrent temporal lobe epilepsy. J Neurosurg 81:31-36, 1994 74. Hennessy MJ, Elwes RD, Binnie CD, et al: Failed surgery for epilepsy: A study of persistence and recurrence of seizures following temporal resection. Brain 123:2445-2466, 2000 75. Hennessy MJ, Elwes RD, Rabe-Hesketh S, et al: Prognostic factors in the surgical treatment of medically intractable epilepsy associated with mesial temporal sclerosis. Acta Neurol Scand 103:344-350, 2001 76. Ho SS, Berkovic SF, McKay WJ, et al: Temporal lobe epilepsy subtypes: differential patterns of cerebral perfusion on ictal SPECT. Epilepsia 37:788-795, 1996 77. Hamer HM, Najm I, Mohamed A, et al: Interictal epileptiform discharges in temporal lobe epilepsy due to hippocampal sclerosis versus medial temporal lobe tumors. Epilepsia 40:1261-1268, 1999 78. Clusmann H, Kral T, Fackeldey E, et al: Lesional mesial temporal lobe epilepsy and limited resections—prognostic factors and outcome. J Neurol Neurosurg Psychiatry 75:1589-1596, 2004 79. Schramm J, Kral T, Grunwald T, et al: Surgical treatment for neocortical temporal lobe epilepsy: clinical and surgical aspects and seizure outcome. J Neurosurg 94:33-42, 2001 80. Egan RA, Shults WT, So N, et al: Visual field deficits in conventional anterior temporal lobectomy versus amygdalohippocampectomy. Neurology 55:1818-1822, 2000 81. Katz A, Awad IA, Kong AK, et al: Extent of resection in temporal lobectomy for epilepsy. II. Memory changes and neurologic complications. Epilepsia 30:763-771, 1989 82. Yasargil MG, Vise WM, Bader DC: Technical adjuncts in neurosurgery. Surg Neurol 8:331-336, 1977 83. Pilcher W, Roberts D, Flanigin HF, et al: Complications of epilepsy surgery, in Engel J (ed): Surgical Treatment of the Epilepsies (ed 2). New York, NY, Raven Press, 1993, pp 565-581 84. Polkey C: Complications of epilepsy surgery, in Shorvon SD, Dreifuss F, Fish D, et al (eds): The Treatment of Epilepsy. Oxford: Blackwell Science Ltd., 1996, pp 780-793 85. Kalfas IH, Little JR: Postoperative hemorrhage: a survey of 4992 intracranial procedures. Neurosurgery 23:343-347, 1988 86. Palmer JD, Sparrow OC, Iannotti F: Postoperative hematoma: a 5-year survey and identification of avoidable risk factors. Neurosurgery 35: 1061-1064, 1994 87. Gil-Fernandez JJ: Analysis of surgical blood loss and number of blood transfusions after temporal lobe resection performed in adults with epilepsy receiving valproate (VPA) in the immediate preoperative period. Epilepsia 38:1257-1258, 1997 88. Behrens E, Schramm J, Zentner J, et al: Surgical and neurological complications in a series of 708 epilepsy surgery procedures. Neurosurgery 41:1-9, 1997 89. Grivas A, Schramm J, Kral T, et al: Surgical treatment for refractory temporal lobe epilepsy in the elderly—seizure outcome and neuropsychological sequels compared to a younger cohort. Epilepsia 47: 1364-1372, 2006 90. Clusmann H, Kral T, Marin G, et al: Characterization of hemorrhagic complications after surgery for temporal lobe epilepsy. Zentralbl Neurochir 65:128-134, 2004 91. Honnegger J, Zentner J, Spreer J, et al: Cerebellar hemorrhage arising postoperatively as a complication of supratentorial surgery: a retrospective study. J Neurosurg 96:248-254, 2002 92. Helmstaedter C, Van Roost D, Clusmann H, et al: Collateral brain damage, a potential source of cognitive impairment after selective surgery for control of mesial temporal lobe epilepsy. J Neurol Neurosurg Psychiatry 75:323-326, 2004 93. Hermann BP, Wyler AR, Bush AJ, et al: Differential effects of left and right anterior temporal lobectomy on verbal learning and memory performance. Epilepsia 33:289-297, 1992 94. Helmstaedter C, Elger CE: Cognitive consequences of two-thirds anterior temporal lobectomy on verbal memory in 144 patients: a threemonth follow-up study. Epilepsia 37:171-180, 1996 95. Gleissner U, Helmstaedter C, Schramm J, et al: Memory outcome after selective amygdalohippocampectomy: a study in 140 patients with temporal lobe epilepsy. Epilepsia 43:87-95, 2002

70 96. Gleissner U, Helmstaedter C, Schramm J, et al: Memory outcome after selective amygdalohippocampectomy in patients with temporal lobe epilepsy: one-year follow-up. Epilepsia 45:960-962, 2004 97. Gleissner U, Helmstaedter C, Elger CE: Right hippocampal contribution to visual memory: a presurgical and postsurgical study in patients with temporal lobe epilepsy. J Neurol Neurosurg Psychiatry 65:665669, 1998 98. Goldstein LH, Polkey CE: Short-term cognitive changes after unilateral temporal lobectomy or unilateral amygdalo-hippocampectomy for the relief of temporal lobe epilepsy. J Neurol Neurosurg Psychiatry 56:135-140, 1993 99. Rasmussen T, Jasper HH: Temporal lobe epilepsy: indications for operation and surgical technique, in Baldwin M, Bailey P (eds): Temporal Lobe Epilepsy. Springfield, IL, Charles C. Thomas, 1958, pp 440-460 100. McLachlan RS, Rose KJ, Derry PA, et al: Health-related quality of life and seizure control in temporal lobe epilepsy. Ann Neurol 41:482489, 1997 101. Vickrey BG, Hays RD, Engel J Jr, et al: Outcome assessment for epilepsy surgery: the impact of measuring health-related quality of life. Ann Neurol 37:158-166, 1995 102. von Lehe M, Lutz MT, Kral T, et al: Correlation of health related quality of life after surgery for mesial temporal lobe epilepsy with two different seizure outcome scales. Epilepsy Behav 9:73-82, 2006 103. Bengzon AR, Rasmussen T, Gloor P, et al: Prognostic factors in the surgical treatment of temporal lobe epileptics. Neurology 18:717731, 1968 104. Gilliam F, Faught E, Martin R, et al: Predictive value of MRI-identified mesial temporal sclerosis for surgical outcome in temporal lobe epilepsy: an intent-to-treat analysis. Epilepsia 41:963-966, 2000 105. Guldvog B, Loyning Y, Hauglie-Hanssen E, et al: Predictive factors for success in surgical treatment for partial epilepsy: a multivariate analysis. Epilepsia 35:566-578, 1994 106. Jeong SW, Lee SK, Kim KK, et al: Prognostic factors in anterior temporal lobe resections for mesial temporal lobe epilepsy: multivariate analysis. Epilepsia 40:1735-1739, 1999 107. Sylaja PN, Radhakrishnan K, Kesavadas C, et al: Seizure outcome after anterior temporal lobectomy and its predictors in patients with apparent temporal lobe epilepsy and normal MRI. Epilepsia 45:803808, 2004 108. Altshuler L, Rausch R, Delrahim S, et al: Temporal lobe epilepsy, temporal lobectomy, and major depression. J Neuropsychiatry Clin Neurosci 11:436-443, 1999 109. Bladin PF: Psychosocial difficulties and outcome after temporal lobectomy. Epilepsia 33:898-907, 1992 110. Reuber M, Andersen B, Elger CE, et al: Depression and anxiety before and after temporal lobe epilepsy surgery. Seizure 13:129-135, 2004 111. Blatt DR, Roper SN, Friedman WA: Invasive monitoring of limbic epilepsy using stereotactic depth and subdural strip electrodes: surgical technique. Surg Neurol 48:74-79, 1997 112. Cascino GD, Trenerry MR, Sharbrough FW, et al: Depth electrode studies in temporal lobe epilepsy: relation to quantitative magnetic resonance imaging and operative outcome. Epilepsia 36:230-235, 1995 113. Luders H, Awad I, Burgess R, et al: Subdural electrodes in the presurgical evaluation for surgery of epilepsy. Epilepsy Res Suppl 5:147156, 1992

H. Clusmann 114. Helmstaedter C: Neuropsychological aspects of epilepsy surgery. Epilepsy Behav 5:S45-S55, 2004 (suppl 1) 115. Jones-Gotman M, Harnadek MC, Kubu CS: Neuropsychological assessment for temporal lobe epilepsy surgery. Can J Neurol Sci 27:3943, 2000 (suppl 1) 116. Kim H, Yi S, Son EI, et al: Lateralization of epileptic foci by neuropsychological testing in mesial temporal lobe epilepsy. Neuropsychology 18:141-151, 2004 117. Schramm J, Aliashkevich AF, Grunwald T: Multiple subpial transections: outcome and complications in 20 patients who did not undergo resection. J Neurosurg 97:39-47, 2002 118. Aydemir N, Ozkara C, Canbeyli R, et al: Changes in quality of life and self-perspective related to surgery in patients with temporal lobe epilepsy. Epilepsy Behav 5:735-742, 2004 119. Gilliam F: The impact of epilepsy on subjective health status. Curr Neurol Neurosci Rep 3:357-362, 2003 120. Sutherland GR, Kaibara T, Louw DF: Intraoperative MR at 1.5 Tesla— experience and future directions. Acta Neurochir Suppl 85:21-28, 2003 121. Janszky J, Ollech I, Jokeit H, et al: Epileptic activity influences the lateralization of mesiotemporal fMRI activity. Neurology 63:18131817, 2004 122. Kier EL, Staib LH, Davis LM, et al: MR imaging of the temporal stem: anatomic dissection tractography of the uncinate fasciculus, inferior occipitofrontal fasciculus, and Meyer’s loop of the optic radiation. AJNR Am J Neuroradiol 25:677-691, 2004 123. Janszky J, Jokeit H, Kontopoulou K, et al: Functional MRI predicts memory performance after right mesiotemporal epilepsy surgery. Epilepsia 46:244-250, 2005 124. Krakow K, Lemieux L, Messina D, et al: Spatio-temporal imaging of focal interictal epileptiform activity using EEG-triggered functional MRI. Epileptic Disord 3:67-74, 2001 125. Lemieux L, Salek-Haddadi A, Josephs O, et al: Event-related fMRI with simultaneous and continuous EEG: description of the method and initial case report. Neuroimage 14:780-787, 2001 126. Liston AD, Salek-Haddadi A, Kiebel SJ, et al: The MR detection of neuronal depolarization during 3-Hz spike-and-wave complexes in generalized epilepsy. Magn Reson Imaging 22:1441-1444, 2004 127. Lemieux L: Electroencephalography-correlated functional MR imaging studies of epileptic activity. Neuroimaging Clin North Am 14:487506, 2004 128. Engel J Jr: Multimodal approaches in the evaluation of epilepsy patients for surgery. Electroencephalogr Clin Neurophysiol Suppl 50: 40-52, 1999 129. Van Roost D, Schaller C, Meyer B, et al: Can neuronavigation contribute to standardization of selective amygdalohippocampectomy? Stereotact Funct Neurosurg 69:239-242, 1997 130. Regis J, Rey M, Bartolomei F, et al: Gamma knife surgery in mesial temporal lobe epilepsy: a prospective multicenter study. Epilepsia 45:504-515, 2004 131. Parrent AG, Blume WT: Stereotactic amygdalohippocampotomy for the treatment of medial temporal lobe epilepsy. Epilepsia 40:14081416, 1999 132. Guenot M, Isnard J, Ryvlin P, et al: SEEG-guided RF thermocoagulation of epileptic foci: feasibility, safety, and preliminary results. Epilepsia 45:1368-1374, 2004 133. Vonck K, Boon P, Goossens L, et al: Neurostimulation for refractory epilepsy. Acta Neurol Belg 103:213-217, 2003