Surgery Insight: surgical management of epilepsy

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1 Surgery Insight: surgical management of epilepsy Ruben Kuzniecky* and Orrin Devinsky SUMMARY Epilepsy surgery has been shown to be an effective treatment for patients with intractable epilepsy. The only randomized controlled trial conducted in this setting to date found a dramatic advantage for surgery over medical treatment in temporal lobe epilepsy. In carefully selected patients, epilepsy surgery can control seizures, improve quality of life and reduce costs of medical care. Advances in diagnostic techniques are likely to improve patient selection, facilitate localization of epileptic foci and functional areas, and enable better prediction of outcomes. KEYWORDS epilepsy, intractability, morbidity, seizure focus, surgery REVIEW CRITERIA MEDLINE was searched using OVID for articles published from 1987 to Search terms included epilepsy surgery, epilepsy surgical techniques and epilepsy surgery prognosis. Abstracts were reviewed and full articles were selected on the basis of relevance. We did not include personal communications or material only available in abstract form. CME R Kuzniecky is Professor of Neurology at New York University, and O Devinsky is Professor of Neurology, Neurosurgery and Psychiatry at New York University and Director of the New York University Comprehensive Epilepsy Center, New York, NY, USA. Correspondence *New York University Comprehensive Epilepsy Center, 403 East 34 th Street 4 th Floor, New York, NY 10016, USA ruben.kuzniecky@med.nyu.edu Received 11 July 2007 Accepted 18 September doi: /ncpneuro0663 Continuing Medical Education online Medscape, LLC is pleased to provide online continuing medical education (CME) for this journal article, allowing clinicians the opportunity to earn CME credit. Medscape, LLC is accredited by the Accreditation Council for Continuing Medical Education (ACCME) to provide CME for physicians. Medscape, LLC designates this educational activity for a maximum of 1.0 AMA PRA Category 1 Credits. Physicians should only claim credit commensurate with the extent of their participation in the activity. All other clinicians completing this activity will be issued a certificate of participation. To receive credit, please go to and complete the post-test. Learning objectives Upon completion of this activity, participants should be able to: 1 Define intractable epilepsy and factors that increase resistance to medical treatment of epilepsy. 2 Describe preoperative studies for patients with epilepsy. 3 Describe the efficacy of surgery for epilepsy. 4 Identify the complications associated with surgery for epilepsy. INTRODUCTION Epilepsy is a common neurological disorder that is estimated to affect 50,000,000 people worldwide. 1 Despite major advances in recent years, epilepsy remains an extraordinary therapeutic challenge. Studies indicate that in one-third of patients with new-onset epilepsy, the seizures will become medically intractable, and more than 5,000,000 individuals worldwide are potential candidates for surgery. 2 The effects of chronic un controlled epilepsy and multidrug therapy include progressive cognitive and behavioral declines, as well as increased accident and death rates. 3,4 In carefully selected patients, epilepsy surgery can control seizures, improve quality of life, and reduce the costs of medical care. 5 In this article, we will review the current surgical management of epilepsy, including the identification of candidates, methods for localization of the seizure focus, surgical techniques, and outcomes. THE INTRACTABLE EPILEPSIES Epilepsy is defined as intractable when the disorder is disabling and not controllable with DECEMBER 2007 VOL 3 NO 12 NATURE CLINICAL PRACTICE NEUROLOGY 673

2 Box 1 Indications for epilepsy surgery. Medical intractability (failure of two monotherapy drugs and a two-drug trial at the therapeutic level is generally considered to be adequate to define intractability) Single epileptogenic focus amenable to resection Absence of degenerative disease or nonepileptic seizures Focal epileptogenic structural lesion Surgically remediable syndrome (e.g. unilateral mesial temporal sclerosis, focal cortical dysplasia or hypothalamic hamartoma) standard therapies. Although patients with localization-related (partial) seizures of temporal lobe origin have been traditionally considered the group most likely to benefit from surgery, all seizure types and syndromes that become intractable should be viewed as potential surgical targets unless proven otherwise. The operational definition of medical intractability has evolved from one based on a specified period of medical failure (e.g. >2 years) or number of failed antiepileptic drugs (e.g. more than three) to encompass individualized, multidimensional criteria. These criteria can involve seizure symptoms and frequency, psychosocial impact, cognitive and behavioral consequences, and side effects. For example, simple partial seizures or occasional complex partial seizures that markedly impair quality of life fulfill the criteria for intractable epilepsy. 6 Currently, two domains seem to have primary importance in the clinical definition of medical intractability: the rate of failure of tolerable antiepileptic drugs to control seizures, and the pathological substrate. Kwan and Brodie 2 demonstrated in a sequential, open-label trial that 47% of patients with new-onset epilepsy became seizure-free on the first anti epileptic drug. Only an additional 13%, however, achieved seizure freedom with a second or third drug on monotherapy or polytherapy; in total, 40% of the patients eventually became medically intractable. Pathological substrates such as hippocampal sclerosis, brain malformation and penetrating head injury are predictive of medical intracta bility, and they are usually associated with good surgical outcome. 7 This fact highlights the importance of early recognition of medical intractability and surgical candidacy. Other factors, such as early age at onset of epilepsy and developmental delay, are also associated with intractability In summary, identification of medical intractability is now possible early in the disease course, and this process is encouraged by the recognition that certain epilepsy syndromes respond particularly well to surgery (Box 1). PATIENT SELECTION AND INVESTIGATIONS Surgical treatment of epilepsy is based on the concept that removal, lesioning or disconnection of a localized brain area that generates seizures will result in complete cessation of or a reduction in seizure activity. 12 Several different diagnostic techniques can be used to determine the ictal generator and epileptogenic zone Structural and functional imaging, neuro physiological techniques and psychological testing help to identify the seizure focus and functional areas. All centers use MRI and video electroencephalogram (EEG) recordings, whereas other noninvasive (e.g. PET, single-photon emission computed tomography [SPECT] or magneto encephalography [MEG]) and intra cranial electrophysiological recordings and mappings are used to varying degrees at different centers and are often tailored to individual cases. 17 Phase I investigations Presurgical evaluation The neurological history and examination are carried out to identify any underlying disorder and to localize areas of dysfunction. 18 Symptoms at seizure onset, during progression, and following a seizure can provide localizing clues. Skin examination can identify neurocutaneous syndromes Neurological examination can also provide localizing features. Neurodegenerative disease and nonepileptic seizures are factors that often preclude epilepsy surgery Electrophysiology Interictal and ictal scalp EEG recordings are critical determinants of surgical candidacy. Most centers require recording of at least two lateralized and localized seizures before a patient can be considered for surgery. 14 Recordings of multiple seizures are required in some patients, especially when functional (e.g. interictal EEG) or imaging (e.g. MRI) data suggest more than one seizure focus. 26 Focal interictal abnormalities and concordant ictal EEG and behavioral changes can provide sufficient localization for surgical intervention. 27 Identification of a structural or other functional (e.g. PET) imaging abnormality consistent with electrophysiological data is, however, desirable before surgery is performed, especially if surgery without intracranial recordings is being contemplated. 28, NATURE CLINICAL PRACTICE NEUROLOGY KUZNIECKY AND DEVINSKY DECEMBER 2007 VOL 3 NO 12

3 A B C Figure 1 Surgery for temporal lobe epilepsy. (A, B) Preoperative coronal MRI (T1-weighted and T2-weighted) showing left mesial temporal sclerosis. Note hippocampal atrophy and signal changes in the left hippocampus. (C) Postoperative coronal MRI (T1-weighted) showing left amygdalohippocampectomy. The patient has been seizure-free since surgery. Neuroimaging Modern neuroimaging has had a major impact on the surgical management of epilepsy. 17 A localized limbic or neocortical lesion on MRI correlates strongly with the seizure focus and with good surgical outcome. 30,31 Some structural pathologies (e.g. arachnoid cysts and white matter lesions) are not associated with seizures. By contrast, hippocampal sclerosis, which can be detected by MRI with nearly 95% sensitivity, is highly epileptogenic, and is usually the cause of seizures in patients with temporal lobe epilepsy (TLE; Figure 1). Other lesions seen on MRI that can cause epilepsy include malformations of cortical development, benign developmental tumors and vascular malformations. High-resolution MRI at 1.5 T with tailored protocols might increase the yield of subtle lesions in surgical candidates by 30% relative to routine MRI. 32 The ability of higher field magnets (3 T) to further increase the rate of detection of pathology in epilepsy is currently under study. Nuclear medicine studies include 2-fluoro-2- [ 18 F]-deoxy-d-glucose (FDG)-PET and interictal and ictal SPECT. FDG-PET is highly sensitive in TLE, but its yield is low in extra-temporal lobe epilepsy (E-TLE). 33 If MRI and EEG abnormalities colocalize, FDG-PET is unlikely to contribute further to localization, although it remains a valuable procedure in TLE patients with a normal MRI scan. 34 Magnetic resonance spectroscopy is an experimental procedure and is not routinely used to assess patients for epilepsy surgery Functional MRI for language lateralization and localization is being used increasingly, although the sensitivity and specificity of this technique remain limited, especially in patients with bi lateral language representation. 39,40 Interictal SPECT has lower sensitivity for localization than does FDG-PET. 41 Ictal SPECT with subtraction techniques can, however, provide unique localizing data in patients with normal MRI scans or with large or multiple lesions. 41 The localizing value of ictal SPECT is tempered by logistical challenges or isotope availability (most hospitals do not have radioactive tracers available during non-peak hours), seizure duration (<60 s), and the availability of personnel to inject the radio active isotope into the patient during the seizure. Ictal SPECT is often reserved for patients with normal MRI scans and inadequate scalp EEG localization, or those in whom different techniques produce discordant results (Figure 2). Magnetoencephalography MEG can localize interictal epileptiform discharges in three dimensions, and the MEG dipoles can be superimposed onto MRI images. 42 The superior temporal and spatial resolution of this technique compared with EEG or functional MRI has led to its increased use, especially in cases in which other data are nonlocalizing or dis cordant. MEG can accurately map somatosensory, visual and language cortices, and can map these regions relative to the interictal source. 43 Recent data indicate that MEG localization has a relatively high correlation with intracranial ictal localization. 44 The use of MEG is, however, currently limited by its lack of availability, which results from the high costs of the hardware, shielded room and personnel requirements. Neuropsychological evaluation Neuropsychological evaluation assesses verbal and nonverbal intelligence, memory, executive functions, and other cognitive and behavioral DECEMBER 2007 VOL 3 NO 12 KUZNIECKY AND DEVINSKY NATURE CLINICAL PRACTICE NEUROLOGY 675

4 Figure 2 Localization of an epileptic focus by ictal single-photon emission computed tomography (SPECT). Ictal SPECT combined with MRI shows blood-flow increases corresponding to the epileptic focus. In the color scale, red corresponds to higher blood flow. The SPECT technique is useful for localization of the epileptic focus before surgical intervention. functions (e.g. depression and psychopathology). The intracarotid amobarbital test (IAT or Wada test) assesses speech and memory function in each hemisphere. Impaired memory ipsilateral to and preserved memory contralateral to a temporal focus predicts little or no memory impairment after surgery and provides supporting evidence that the seizure focus lies in the temporal lobe. Wrong-way IATs, however, in which only memory contralateral to the focus is impaired indicate that temporal lobectomy will impair memory. The IAT can also help to identify patients with bilateral memory dysfunction. 45 Phase II investigations Once the above phase I investigations are complete, patients can be considered for possible surgery. Those with seizure foci in multiple areas or involving vital cognitive or sensorimotor cortex are not considered to be good surgical candidates. By contrast, patients with lesional epilepsy or those with hippocampal sclerosis and concordant interictal and ictal foci without other discordant findings can proceed directly to surgery. In other patients, intracranial EEG recordings (phase II investigations), usually with subdural or depth electrodes, can more accurately lateralize and localize the seizure focus and map functional areas before resection. Phase II investigation is often recommended in nonlesional cases without a clear epileptogenic area; the indications for further investigation are summarized in Box 2. The techniques for intracranial EEG implantation and recording vary between centers. Intracranial electrodes can survey wide areas of both hemispheres or precisely localize a seizure focus for which lateralization and approximate location are known. Subdural electrodes sample wide regions of the neocortex and can map functional areas, but cannot record directly from deep areas such as the hippocampus. Depth electrodes can record buried areas such as the hippocampus and insula, but many contact points record from white matter, and neocortical coverage is very limited. Specific electrode arrays and the areas covered are tailored for each case, but often a combination of electrodes is used in each patient. 46 Most centers obtain recording of at least two typical seizures with intracranial electrodes before deciding on surgical inter vention. Sensorimotor and language functions can be mapped in conscious patients by direct cortical stimulation with subdural electrodes over the course of one or more days. Less often, intra cranial event-related potentials provide functional localization of sensory areas, or awake-mapping is done in the operating room. SURGICAL SYNDROMES AND TECHNIQUES The goal of epilepsy surgery is to achieve seizure freedom by removing the epileptogenic zone, while sparing functional cortex. Defining the epileptogenic zone is a challenge, especially in nonlesional cases. Even when intracranial electrodes are used, only a small fraction of cortex usually limited to the gyral surface is sampled. Widespread epileptic areas at seizure onset might reflect wide epileptogenic networks or failure to record from the focal onset. In other cases, the interictal zone extends well beyond the ictal area, raising the question of whether resection should include exclusively interictal areas if they are outside sensorimotor or cognitive areas. Penfield and Jasper introduced the concept of nociferous cortex epileptogenic areas that actively impair the function of other areas. 47 Removal of these areas can improve cognitive and behavioral function. Unfortunately, in many cases the removal of epileptogenic tissues such as dominant temporal lobe leads to cognitive impairment. 676 NATURE CLINICAL PRACTICE NEUROLOGY KUZNIECKY AND DEVINSKY DECEMBER 2007 VOL 3 NO 12

5 The principles of epilepsy surgery have not changed dramatically over the past 50 years. Surgical procedures include focal cortical resection, anatomical lobectomy, lesionectomy, corticec tomy, multiple subpial transections, callosal section, and hemispherectomy and its variants. Different techniques can be combined for specific scenarios. In general terms, surgical intervention can be defined according to broad specific techniques and approaches. More recently, however, surgical techniques and indications have been defined according to specific surgical syndromes. The epilepsy syndromes described in the sections that follow are surgically remediable. Mesial temporal lobe epilepsy associated with hippocampal sclerosis Mesial TLE associated with hippocampal sclerosis is defined by hippocampal cell loss and gliosis, detectable by MRI as atrophy and signal abnormalities, and characterized by specific clinical and EEG features. 48 Patients often have a history of febrile seizures, and later develop temporal lobe simple and complex partial seizures characterized by experiential auras and automatisms. Interictal and ictal EEG usually localize the seizure focus to the anterior temporal region, and neuropsychological assessment reveals evidence of memory dysfunction. Patients with mesial TLE associated with hippocampal sclerosis are excellent surgical candidates, and in most cases the surgery can be performed without intracranial EEG. Surgical approaches include amygdalohippocampectomy, or standard temporal lobe resections including en bloc resection of the temporal lobe or removal of larger neocortical areas. The techniques for temporal lobe surgery have evolved over the past 20 years, but they remain relatively dependent on the experience of individual surgeons and centers. At most centers, the amygdala and the anterior cm of the hippocampus are resected along with a variable amount of neocortex. The results of surgery are uniformly good, with long-term freedom from seizures being achieved in 60 80% of patients. 5,49 Impaired short-term memory and naming is the most noteworthy complication of dominant anterior temporal lobectomy, especially in patients without hippocampal atrophy or in those with normal memory (as assessed by the IAT) in the operated side. Box 2 Indications for invasive electroencephalographic studies in candidates for epilepsy surgery. Ambiguous localization by imaging and scalp electroencephalographic recordings Nonlesional extra-temporal lobe epilepsy Bilateral temporal lobe epilepsy Localization of epileptogenic focus in proximity to vital cortex, thereby necessitating functional mapping Lesional epilepsy Lesional epilepsy is characterized by an epileptogenic structural lesion, which might include a vascular malformation, tumor or malformation of cortical development. Among lesional pathologies, cavernomas and dysembryoplastic neuro epithelial tumor are worthy of special consideration, as they are usually associated with chronic seizures. The surgical approach depends on the correlation between electroclinical and imaging findings. Circumscribed lesions in nonvital cortex can be completely resected, with the postoperative seizure-free rate reaching 70 90%. In some cases, however, microscopic pathology extends beyond the MRI-defined lesion (e.g. cortical dysplasia), and this might account for surgical failure. Long duration of epilepsy suggests the possibility of a more-widely-distributed epileptogenic network, and some centers use invasive electrodes in this setting. Multifocal pathology or involvement of eloquent cortex lowers surgical success rate, as the resection of epileptogenic cortex can be incomplete in such cases. 50 In patients with cavernomas, the duration of epilepsy and the presence of hypometabolic areas on PET at a distance from the lesion are associated with a higher rate of surgical failure. 51 Nonlesional focal epilepsy Localization of the seizure focus and surgical therapy are challenging in patients with normal MRI scans. Nonlesional TLE is more easily localized and successfully treated than are nonlesional seizures that originate elsewhere. Most patients with nonlesional TLE have neo cortical foci or neocortical and mesial onsets. These patients usually require chronic intracranial studies to define epileptogenic and functional areas. They are treated with anterior temporal lobectomy and a lateral resection tailored to resect epileptogenic and preserve language areas. Postsurgical seizure-free rates range from 55% to 80%. 52 DECEMBER 2007 VOL 3 NO 12 KUZNIECKY AND DEVINSKY NATURE CLINICAL PRACTICE NEUROLOGY 677

6 A Figure 3 Epilepsy surgery in Rasmussen s encephalitis. (A) Rasmussen s encephalitis involving the right hemisphere. Note brain atrophy and signal changes involving the entire right hemisphere. The ventricle is larger than normal, indicating underlying atrophy. (B) Postoperative MRI showing right hemispherectomy. Most of the cortex and white matter has been resected. The deep basal ganglia and thalamus are preserved. The patient has been seizure-free since surgery. B Patients with nonlesional E-TLE represent the most challenging surgical group, owing to extensive potential areas of seizure origin, complex ictal spread patterns, and poorly defined epileptic networks. Most patients with nonlesional E-TLE have frontal lobe epilepsy; many neo cortical areas are silent and early clinical symptoms result from spread. Also, foci often overlap with functional areas, thereby limiting the resection. Despite the above limitations, there are a few epilepsy syndromes within the nonlesional frontal lobe epilepsies that can be recognized and might have good surgical outcomes. One of these is supplementary motor area epilepsy, in which a particular ictal pattern is observed. 53,54 Seizure-free rates after surgery range from 50% to 75% for this condition, compared with rates in the range 35 50% for other frontal lobe epilepsies. Hemispheric epilepsy syndromes Hemispherectomy and associated procedures (e.g. functional hemispherectomy and hemispherotomy) are reserved for patients with widespread unilateral hemispheric seizure onset and pre-existing pathology. Typical candidates for these procedures are children with fixed or progressive neurological deficits. Most of these individuals have sustained a prenatal or perinatal injury, or have Rasmussen s encephalitis or hemimegalencephaly (Figure 3). Adults can also benefit from these procedures. Seizure control is achieved in 70 90% of patients. 55 In properly selected cases, function is preserved and can even improve in cognitive, behavioral and motor domains. 56 Generalized symptomatic epilepsy Patients with symptomatic generalized epilepsy often have mental retardation and multifocal or diffuse bilateral seizure foci. Focal resection is unlikely to be beneficial in these patients, but corpus callosotomy is a palliative alternative that can reduce the frequency and severity of generalized tonic clonic, atonic and tonic seizures, all of which usually result in drop attacks. Callosal section interferes with seizure propagation and is most effective in patients with drop attacks. The indications and methodologies for surgery vary between centers; standardized selection criteria are not available. Callosotomy is often a staged procedure, usually with resection of the anterior two-thirds followed by complete resection several months later if seizures persist. Alternatively, a onestage callosotomy can be performed in patients with moderate to severe mental retardation. Half of patients obtain clinically meaningful improvement and ~5% become seizure-free, with those who have drop attacks showing the greatest benefit. 57,58 Hypothalamic hamartomas Hypothalamic hamartomas are benign tumors that cause the syndrome of gelastic (as well as partial and tonic clonic) seizures, cognitive impairment, aggression and precocious puberty. 59,60 Intractable epilepsy and epileptic encephalopathy are common in patients with these lesions. Multiple studies and accumulated evidence indicate that the hamartomas are ictal generators. Several surgical approaches can be effective, including endoscopic or standard resection, gamma knife, radiofrequency thermocoagulation, and disconnection. Complete resection using a transcallosal approach seems to have the best results, but also carries a modest risk of behavioral and endocrine complications. Endoscopic resection and thermocoagulation are associated with lower morbidity, but also with a lower seizure-free rate. Gamma radiation has also been proposed as an alternative method of treatment in view of its low morbidity, 61 although the long-term effects of radiation are unknown. Early surgery should be considered to prevent or minimize intellectual decline and the development of intractable epilepsy. SPECIAL TECHNIQUES AND TREATMENTS Multiple subpial transection Multiple subpial transection (MST) involves a series of shallow cuts in the neocortical gyri to interrupt horizontal fibers that might be 678 NATURE CLINICAL PRACTICE NEUROLOGY KUZNIECKY AND DEVINSKY DECEMBER 2007 VOL 3 NO 12

7 involved in seizure recruitment or spread. MST is reserved for patients with epileptic foci involving sensorimotor or language cortex. In the majority of cases reported in the literature, MST was performed together with partial resection. 62 More than 50% of patients achieved significant improvement in seizure control with MST in the short term; however, the long-term outcome of this procedure is less certain. Vagus nerve stimulation Vagus nerve stimulation (VNS) is the only FDAapproved stimulation treatment for intractable partial epilepsy. Although short-term followup data suggest that 50% or greater reduction in seizure frequency is achieved in up to 40% of patients, longer follow-up indicates a less impressive improvement. Less than 2% of patients with intractable epilepsy become seizure-free after VNS. It is unknown which patient groups are most likely to benefit from VNS, although unblinded data suggest that this technique can cause improvement in generalized epilepsy. VNS is usually reserved for patients who are not candidates for resective surgery, or those in whom surgical intervention has failed. 63 The main advantage of VNS is its low surgical risk. Electrical stimulation Electrical stimulation of cortex, temporal lobe and deep thalamic nuclei, using various different protocols and techniques, is being investigated as a treatment for epilepsy. The Responsive Neurostimulator (RNS ; NeuroPace, Mountain View, CA) is an implantable device with subdural leads that can detect seizures using a seizure detection algorithm and immediately stimulate a small area of cortex to abort the ictal discharge. 64 In a similar vein, but using continuous electrical stimulation, preliminary studies have suggested moderate efficacy and long-term safety of bi lateral hippocampal stimulation. 65 Finally, thalamic stimulation studies have reported mixed results on a range of seizure syndromes including symptomatic generalized epilepsy. 66 Currently, all the above techniques are being investigated in randomized controlled clinical trials. RANDOMIZED TRIALS AND LONG-TERM OUTCOME OF EPILEPSY SURGERY Although epilepsy surgery has been performed for the past 50 years, only one randomized trial has assessed the efficacy of surgery compared with medical management. 67 This study showed that after 1 year, among patients with intractable TLE, seizure freedom was achieved in 58% of the surgical group and 8% of the medical group. Surgery also significantly improved quality of life. A large retrospective, parallel longitudinal study found that surgery resulted in better seizure control than did medical therapy, with 2-year remission rates in the surgical group of 68% in patients with TLE and 50% in those with E-TLE. 68 Predictors of seizure remission included hippocampal sclerosis and absence of tonic clonic seizures. In a meta-analysis of longterm outcome, 66% of patients who had undergone temporal lobe resection were seizure-free, compared with approximately 40% of patients who had undergone extratemporal resections. After callosotomy, 35% of patients were free of disabling seizures, whereas 16% treated with MSTs were completely seizure-free at 5 years. Long-term outcomes, therefore, are consistent with short-term data, although seizure freedom does diminish over time, especially in E-TLE cases. 69 While seizure freedom is the main goal of epilepsy surgery, successful surgery leads to many improvements in social, psychological and overall quality of life. 70 Studies have indicated that quality of life scores in patients with chronic epilepsy are equal to those of patients with heart failure. 71 Successful surgery or reduction in seizure frequency improves employment prospects and psychosocial wellbeing. 72 COMPLICATIONS Epilepsy surgery can cause functional impairments (e.g. memory, naming and visual field impairment), which result from cortical resection or disconnection. Other complications include infection, hemorrhage and stroke (occurring in <2% of patients), and surgeryrelated death occurs in ~0.1% of patients. These complications vary by procedure and center, and invasive electrode studies increase the risk of complications developing. 14 The most disabling complication is memory impairment, which can progress over the first 2 years after dominant temporal lobectomy. 73 Surgical risks must be balanced against the risks of intractable epilepsy, which include progressive cognitive (e.g. memory) and behavioral (e.g. depression and psychosis) disorders, as well as sudden death. The risk of sudden death might approach 9% over a decade in non-operated surgical candidates. 74 After surgery, seizure-free DECEMBER 2007 VOL 3 NO 12 KUZNIECKY AND DEVINSKY NATURE CLINICAL PRACTICE NEUROLOGY 679

8 patients have a lower risk of death compared with patients in whom surgery failed or those with active, intractable epilepsy. 75 CONCLUSIONS Epilepsy surgery is an effective treatment for selected patients with intractable seizures. Most patients with medically intractable epilepsy are not, however, considered to be adequate surgical candidates on the basis of current knowledge and techniques. Future advances in diagnostic techniques will improve the selection of candidates for epilepsy surgery, and a better understanding of associated risk factors is likely to improve both the selection of patients and their outcomes. 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