Handbook of Clinical Neurology, Vol. 108 (3rd series) Epilepsy, Part II H. Stefan and W.H. Theodore, Editors # 2012 Elsevier B.V. All rights reserved
Who is a surgical candidate? JEROME ENGEL, JR.1* AND SAMUEL WIEBE 2 Departments of Neurology, Neurobiology, and Psychiatry & Biobehavioral Sciences and the Brain Research Institute, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA
Division of Neurology, Foothills Medical Center, Department of Clinical Neurosciences and Hotchkiss Brain Institute, University of Calgary, Calgary, Canada
INTRODUCTION Epilepsy is among the most serious primary disorders of the brain, accounting for 1% of the global burden of disease (Murray and Lopez, 1994). Pharmacotherapy is unsuccessful in controlling seizures in 20–40% of patients (Berg, 2004), and 80% of the cost of epilepsy in the USA is accounted for by patients with medically intractable seizures (Begley et al., 2000). Temporal lobe epilepsy (TLE) is the most common cause of pharmacoresistant seizures (Semah et al., 1998; Berg et al., 1999; Jallon et al., 2001) and may constitute half or more than half of the patients in the USA with medically intractable epilepsy (Engel, 1998). On the other hand, TLE is the form of epilepsy most easily and effectively treated with surgery; 60–80% of these patients become free of disabling seizures (Engel et al., 1993, 2003; Wiebe et al., 2001). It is estimated that there may be over 100 000 people in the USA with TLE who are candidates for surgical treatment, while fewer than 2000 received surgical treatment in 1990, the last time such a survey was carried out (Engel and Shewmon, 1993). More recent data obtained from the National Association of Epilepsy Centers suggest that the number is not appreciably higher today (R.J. Gumnit, personal communication). Furthermore, for those patients who are referred for surgery, there is an average duration of 22 years between onset of epilepsy and referral (Berg et al., 2003). Not only do most surgical candidates never get referred for surgery, those who do often receive it too late to prevent or reverse disabling psychological and social consequences of epilepsy (Engel, 2001). In theory, for many of these patients, early surgical intervention could avert a lifetime of disability.
It is unclear why epilepsy surgery remains underutilized in view of: recent advances in diagnostic tests and surgical procedures; the numerous books that have been published on this subject (Engel, 1987, 1993; Wieser and Elger, 1987; Dam et al., 1988, 1994; Duchowny et al., 1990; Pickard et al., 1990; Apuzzo, 1991; Spencer and Spencer, 1991; L€ uders, 1992; Theodore, 1992; Silbergeld and Ojemann, 1993; Wyler and Hermann, 1994; Tuxhorn et al., 1997; Mathern, 1999; L€ uders and Comair, 2001; Bingaman, 2002a, b; Zentner and Seeger, 2003; Miller and Silbergeld, 2006; L€ uders et al., 2008); and the uncontested cost-effectiveness of surgical intervention, which must be contrasted not only with the monetary cost of a lifetime of disability but also with the human cost of premature death (Cockerell et al., 1994; Sperling et al., 1999), morbidity (Buck et al., 1997), and social and psychological compromise (Jacoby et al., 1996; Jokeit and Ebner, 2002; Sperling, 2004). One often stated reason, confirmed by a National Institutes of Health consensus panel (1990), was the absence of a randomized controlled trial (RCT) to demonstrate the superiority of surgical intervention over continued pharmacotherapy. In 2001, a RCT at the University of Western Ontario (Wiebe et al., 2001) demonstrated the effectiveness of surgical treatment over continued pharmacotherapy in patients with longstanding pharmacoresistant TLE. As a result of this study and a literature review, an American Academy of Neurology (AAN) Practice Parameter concluded that surgery is the treatment of choice for medically intractable TLE (Engel et al., 2003). Unfortunately, these publications have had no effect on referral delays (Haneef et al., 2010), and there remain no clear guidelines defining who should be referred for surgical treatment.
*Correspondence to: Jerome Engel, Jr., M.D., Ph.D., Department of Neurology, David Geffen School of Medicine at UCLA, 710 Westwood Plaza, Los Angeles, CA 90095–1769, USA. Tel: þ 1 310 825 5745, Fax: þ 1 310 206 8461, E-mail: [email protected]
J. ENGEL, JR. AND S. WIEBE
HISTORICAL REVIEW Surgery has been an accepted alternative treatment for epilepsy since the late 19th century (Engel, 2005). Localization of the epileptogenic region was originally determined based on signs and symptoms of ictal events and visualization of a structural abnormality at surgery (Horsley, 1886). Identification of resectable structural abnormalities was greatly improved with the advent of pneumoencephalography (Dandy, 1919) and cerebral angiography (Moniz, 1934), but it was the application of electroencephalography (EEG) that permitted localization of specific epileptiform functional abnormalities. Although Jasper and his associates in Montreal (Jasper et al., 1951) were the first to identify ictal, as well as interictal, epileptiform discharges originating from mesial temporal structures as the most common EEG correlate of medically refractory focal epilepsy, it was Bailey and Gibbs (1951) in Chicago who were the first to operate on the basis of EEG evidence alone. In short order, surgical treatment for epilepsy then became available at many centers worldwide, and anterior temporal resection became the most common surgical intervention performed. Interictal scalp EEG localization was subsequently supplemented by the development of intracranial depth electrode recordings and video telemetry for characterizing ictal events (Crandall et al., 1963; Dymond et al., 1971; Talairach et al., 1974). Towards the end of the 20th century, advanced neuroimaging made it possible to visualize cerebral lesions that previously had only been identified indirectly by EEG and confirmed either at surgery or on pathological analysis of resected tissue. This was particularly important for confirming the presence of hippocampal sclerosis, the most common cause of pharmacoresistant epilepsy (Mathern et al., 2008). First positron emission tomography (PET) (Engel et al., 1981, 1982a–c), then magnetic resonance imaging (MRI) (Jackson et al., 1990), provided confirmatory structural information that obviated the need for invasive intracranial recording in many cases, but these tests by themselves do not provide evidence of epileptogenicity. Single photon emission computed tomography (SPECT), on the other hand, does have the capability of identifying an epileptogenic abnormality when an area of hypoperfusion interictally becomes hyperperfused ictally (Kazemi et al., 2008); however, SPECT does not have the spatial resolution of PET or MRI, nor does it have the temporal resolution of EEG. In recent years it can be argued that neuroimaging has become the primary diagnostic tool for presurgical evaluation with interictal and ictal EEG assuming an increasingly confirmatory role. Nevertheless, inpatient video-EEG monitoring is still considered necessary in most situations for accurate characterization and
classification of the behavioral as well as electrophysiological features of ictal events, while other ancillary testing, particularly neurocognitive studies (Loring et al., 2008), is necessary to determine the functional capacity of the tissue to be resected, as well as the ability of the remaining brain to sustain essential function. Functional MRI is becoming a valuable diagnostic tool for localizing neocortical function (Cohen and Bookheimer, 2008), but has yet to replace the intracarotid amobarbital procedure (Jones-Gotman et al., 2008) for assessing memory and learning capacity of mesial temporal resections. Although temporal resections for mesial temporal lobe epilepsy remain the most frequently performed surgical procedures for epilepsy, accurate identification and successful resection of discrete neocortical epileptogenic regions have been greatly facilitated, first, by the advent of subdural grid recordings (L€ uders et al., 1987) and, now, by modern neuroimaging, which usually obviates the need for chronic intracranial monitoring. Hemispherectomies, performed for diffuse epileptogenic lesions limited to one hemisphere in the mid20th century (Krynauw, 1950), fell out of favor owing to delayed life-threatening complications, but have now been revived as a result of improved surgical techniques, including hemispherotomy, which disconnects the epileptogenic hemisphere but leaves most of the brain tissue in situ (Binder and Schramm, 2008). Corpus callosotomy was initially introduced in 1940 (Van Wagenen and Herren, 1940) for generalized seizures and was found to be particularly effective for drop attacks. This disconnection intervention gained popularity towards the end of the 20th century, but is less commonly performed now because vagus nerve stimulation was found to be equally effective in reducing or eliminating drop attacks in many patients (Roberts, 2008). Lesionectomy (Radhakrishnan et al., 2008) and multiple subpial transections (MSTs) (Polkey and Smith, 2008) are occasionally used when the epileptogenic region involves essential cortex that cannot be resected. Finally, the development of microsurgery and frameless stereotaxy has greatly improved the safety and efficacy of surgical interventions and, combined with better imaging and EEG technology, have led to more discrete tailored resections as well as a variety of anterior mesial temporal resections, including selective amygdalohippocampectomy (Vives et al., 2008).
THE CONCEPT OF SURGICALLY REMEDIABLE EPILEPSY SYNDROMES Until the last quarter of the 20th century, recognition of medically intractable epilepsy was fairly simple, given that there were relatively few antiepileptic drugs (AEDs) available to try before concluding that seizures were
WHO IS A SURGICAL CANDIDATE? pharmacoresistant. After this time, however, the increasing availability of new AEDs has made it virtually impossible to determine that a given patient’s seizures would be unresponsive to any medication alone or in all possible combinations. Thus the term “medically intractable” became meaningless from a clinical perspective. Given that recurrent disabling epileptic seizures, particularly during adolescence and early adulthood, often prevent acquisition of vocational and interpersonal skills necessary for pursuing an independent lifestyle, early surgical intervention is necessary to avoid the development of irreversible psychological and social disability. Recognition of surgical candidates early enough to avert a lifetime of dependency on family and society remains a major obstacle to effective surgical intervention. An important advance in this regard is the recognition of surgically remediable epilepsy syndromes, i.e., epilepsy conditions that have an identified pathophysiological and anatomic substrate with a known poor prognosis given failure of a few appropriate AEDs, but a demonstrated excellent prognosis with surgical therapy (Engel, 1996). In many cases these conditions are progressive, causing developmental delay in infants and small children, and behavioral disturbances in adolescents and adults, so that early surgical intervention is important to avoid permanent disability. Surgical treatment is also more cost-effective in these conditions because, for the most part, they can be evaluated noninvasively, and surgical outcome, by definition, is excellent. The prototype of a surgically remediable syndrome is mesial temporal lobe epilepsy, which usually, but not always, is due to hippocampal sclerosis. It is now recognized, however, that there are several types of hippocampal sclerosis, some of which may not have excellent surgical outcomes (Wieser et al., 2004; Ogren et al., 2009; Stefan et al., 2009). Patients with discrete resectable structural lesions of neocortex also have surgically remediable epilepsy, as do those with diffuse lesions limited to one hemisphere such as hemimegencephaly, Sturge–Weber syndrome, and large porencephalic cysts, usually identified in infants and young children, and Rasmussen’s encephalitis. More recently, gelastic seizures associated with hypothalamic hamartomas have been considered a surgically remediable syndrome (Harvey et al., 2008). Although patients with surgically remediable epilepsies need to be recognized and referred for surgical treatment early, many patients with pharmacoresistant seizures who do not meet criteria for this diagnosis may still benefit greatly and even become free of disabling seizures with surgical treatment. For these patients, however, localization of the area to be resected is usually made electrophysiologically, often requiring
chronic intracranial EEG recordings, which increases the risk and expense, while chances of seizure freedom may be less than 50%. These are patients for whom ictal semiology and interictal EEG suggest a single predominant epileptogenic region, but neuroimaging is either normal or reveals diffuse or multifocal structural abnormalities of which only a part might be epileptogenic. Also in this group are patients with suspicious discrete structural lesions for whom confirmatory EEG and ictal behavioral evidence is lacking.
SELECTION OF SURGICAL CANDIDATES There are many different surgical therapies available for epilepsy, depending on the type of epileptic seizures and the nature and location of the epileptogenic lesion (Table 48.1). Mesial temporal lobe epilepsy is the form of epilepsy most commonly treated surgically, but there are a variety of anteromesial resections performed which can be standardized or tailored (Vives et al., 2008). Standard resections typically remove mesial temporal structures with a variable amount of lateral temporal neocortex depending on the preferences of the epilepsy center, or a selective amygdalohippocampectomy. Standard resections are based on knowledge, accumulated over many years of invasive recordings, that the pathophysiological mechanisms and anatomical substrate of mesial temporal lobe epilepsy are relatively similar from patient to patient, and that the critical epileptogenic tissue is easily removed without residual functional deficit when resection remains within standardized anatomical boundaries. Presurgical evaluation in this situation, therefore, merely requires demonstration that the epileptogenic region is within these boundaries. A tailored resection is one in which not only the location Table 48.1 Types of surgical treatment ● Standardized resections ● Anterior temporal resections ● Amygdalohippocampectomy ● Hemispherectomy ● Tailored resections ● Localized cortical resections ● Lesionectomies, including hypothalamic hamartoma ● Multilobar resections ● Disconnections ● Corpus callosotomy ● Multiple subpial transections ● Other ● Gamma knife ● Deep brain stimulation ● Response stimulation
J. ENGEL, JR. AND S. WIEBE
but also the extent of the epileptogenic region is determined, as well as the location and extent of adjacent essential neocortex, such as primary language and motor areas. There is little evidence that this is still necessary for most patients with classical mesial temporal lobe epilepsy, but it is required if there is reason to believe that the epileptogenic region may extend beyond the usual mesial temporal limbic epileptogenic substrate. Surgery performed for neocortical epilepsy is always tailored, as these represent variable structural and electrophysiological abnormalities and there are no standardized resective procedures (Comair et al., 2008). For these patients, it is necessary for presurgical evaluation to not only locate but also define the extent of epileptogenic tissue, which can require direct brain recording, although this can also be performed intraoperatively. The various forms of hemispherectomy and hemispherotomy are standard procedures, and evaluation of patients who are candidates for this type of surgery is aimed at determining that the contralateral hemisphere is capable of sustaining normal function, and that there are no areas of the ipsilateral hemisphere that are not epileptogenic, contain important functions, and can be spared (Binder and Schramm, 2008). The most important objective of the presurgical evaluation for candidates for corpus callosotomy is to confirm that a more effective localized surgical resection is not a reasonable option. Anterior two-thirds callosotomy is usually performed unless a patient’s cognitive and social function are so poor that a disconnection syndrome would not introduce additional disabilities (Engel, 1996). Rarely, when the primary epileptogenic abnormalities are posterior, a posterior partial callosotomy can be performed. When presurgical evaluation localizes the epileptogenic lesion to essential neocortex that cannot be removed without introducing additional unacceptable neurological deficit, and a discrete structural lesion is present, a lesionectomy can be performed without damage to cortical margins, which can reduce or eliminate seizures with minimal or no resultant functional deficit (Radhakrishnan et al., 2008). Gelastic seizure due to hypothalamic hamartoma is a unique surgically remediable condition that can be treated by lesionectomy. In this situation, merely removing the hamartoma can often abolish the seizures (Harvey et al., 2008). When lesionectomy is not possible, and the neocortical cytoarchitecture is reasonably normal, MST can be performed, which prevents epileptiform activity from spreading transcortically but leaves functional cortical columns intact (Polkey and Smith, 2008). MSTs are usually performed adjacent to a tailored resection when the epileptogenic region is demonstrated to include essential neocortex, but rarely is the only surgical procedure when the entire
epileptogenic region is demonstrated to be within a primary cortical area. When noninvasive evaluation fails to adequately identify a single resectable epileptogenic region and the patient is not diagnosed with a surgically remediable syndrome, as described here, but surgical therapy is still considered an option, further presurgical evaluation usually involves chronic intracranial EEG recording with videomonitoring (Spencer et al., 2008). There are many approaches, but in general two types of methods are performed based on hypotheses concerning the probable location(s) of one or more epileptogenic region(s) determined from noninvasive evaluation. Invasive recording is never carried out without such a hypothesis. If mesial temporal limbic epilepsy is suspected, or epileptogenic tissue is believed to exist deep in the brain, stereotactically implanted intracerebral depth electrodes are preferred. For suspected neocortical epileptogenic regions where three-dimensional localizing information is less important, and laterality has been established, subdural grids and strips can be placed through a unilateral craniotomy. If laterality has not been established and there is question regarding which hemisphere contains the primary epileptogenic region, then bilateral subdural strips can be inserted through burr holes. In some instances, functional MRI, PET, and magnetoencephalography (MEG) can be used in lieu of intracranial electrodes to map normal cortical function, and research is providing evidence that one or more of these techniques may eventually have the capability to identify the location and extent of epileptogenic activity, obviating the need for invasive studies (Ebersole et al., 2008; Henry and Chugani, 2008; Vulliemoz et al., 2009).
THE PATIENT’S PERSPECTIVE ABOUT SURGICAL CANDIDACY Thinking about brain surgery for epilepsy, instead of medications alone, represents a drastic shift in the minds of some patients and clinicians. In addition to clinical considerations, individual perspectives and values about surgery in general, and about brain surgery in particular, play a central role in determining which patients are referred for evaluation at epilepsy surgery centers and which eventually undergo epilepsy surgery. For example, gender and racial differences in rates of use of surgical procedures have been extensively documented for conditions other than epilepsy (Vaccarino et al., 2005). Recently, a single center study documented similar racial disparities for epilepsy surgery. In that study, African Americans had lower rates of epilepsy surgery than non-African Americans (Burneo et al., 2005). This difference has multiple patient- and physician-related
WHO IS A SURGICAL CANDIDATE? causes, and requires further investigation (Griggs and Engel, 2005). Thinking about an early referral to epilepsy surgery centers, and about an early consideration of surgery, also poses challenges to some patients and clinicians, for a number of reasons. A focus group study assessing attitudes toward early epilepsy surgery found that some patients tend to have a preference for nonsurgical management of chronic problems, and to overestimate the risks and underestimate the benefits of epilepsy surgery (Swarztrauber et al., 2003). In addition, it has been demonstrated that physicians’ perceptions about patients and about therapies influence the type and amount of information they convey to patients, and contribute to the patients’ final decision to undergo a treatment (Katz, 2001). It is often stated that earlier surgery is better from the clinical, psychosocial, and economic viewpoints (Engel, 2008). This view is supported by a recent decision analysis model comparing medical and surgical management of temporal lobe epilepsy surgery, which demonstrated large gains in quality-adjusted life expectancy with surgery performed at an earlier age (Choi et al., 2008). In that model, surgery improved quality and length of life, increased life expectancy by 5 years, and increased seizure freedom by 13 years. Yet, because no published studies have specifically compared early surgery with medical therapy, the evidence directly supporting earlier surgery is persuasive but incomplete. This is important because intractability does not develop at a uniform time or in a sustained manner in surgical candidates, late remissions with medical treatment are not rare, and risk–benefit tradeoffs may be different in patients undergoing early surgery. Factors that may suggest sustained intractability, and thus support early surgery, include a larger number of medications tried, longer duration of seizures, history of status epilepticus, mental retardation, and nonidiopathic epilepsy (Langfitt and Wiebe, 2008). Similarly, the evidence regarding morbidity, mortality, and social and cognitive function suggests that earlier surgery may be beneficial, but prospective controlled studies with standardized interventions and outcomes will be required (Langfitt and Wiebe, 2008).1
WHO SHOULD BE REFERRED TO AN EPILEPSY SURGERY CENTER? A simplistic view of the epilepsies is that there are benign conditions in which seizures can usually be controlled with the first or second AED tried, and there are severe epilepsies in which seizures persist despite treatment with appropriate AEDs at maximum tolerable 1
doses. When a few appropriate AEDs fail owing to inefficacy, not intolerable side-effects before maximum therapeutic doses can be achieved, and seizures are interfering with school, work, or interpersonal relationships, these patients should be referred to epilepsy centers where surgical treatment is an option. There have been no studies addressing specifically the question of when and which types of patients should be referred to an epilepsy surgery center. However, two recent developments are likely to assist clinicians in this decision. One is the development of a pragmatic, consensus definition of drug-resistant epilepsy by the International League Against Epilepsy (Kwan et al., 2010). Drug resistance is defined by this group as failure of adequate trials of two tolerated and appropriately chosen and used AEDs to achieve sustained seizure freedom for a sufficiently long period of time. A sufficiently long period of time is operationally defined for an individual patient as three times the longest interseizure interval for that patient, or 1 year, whichever is longer. Armed with this definition, physicians are more likely to consider referral to an epilepsy surgery center for appropriate patients. The second development pertains to a Canadian study using methods developed by the RAND Corporation to assess the appropriateness and necessity of interventions, in this case referrals to epilepsy surgery centers. Researchers in this study have created an evidence- and expertbased simple tool for rating the appropriateness and necessity to refer individual patients to epilepsy surgery centers (Jette et al., 2009). This tool has the potential to streamline and standardize the referral process, avoid unnecessary delays, and select the most appropriate patients for referral. It is important to note common misconceptions about who should be referred for surgical evaluation. For instance, some clinicians erroneously believe that lesions in the dominant hemisphere, bilateral interictal epileptiform discharges, a normal MRI, or memory deficits are contraindications to surgical treatment. These patients may be denied referral and a beneficial surgical intervention. Similarly, patients who may seem to not meet the criteria for a surgically remediable syndrome on assessment at nonspecialized centers may ultimately be deemed surgical candidates after expert assessment at an epilepsy surgery center. Patients with psychiatric disorders, cognitive disabilities, and the elderly can often benefit greatly from surgical therapy and should not be arbitrarily excluded from consideration. Therefore, primary care physicians and general neurologists should not deny their patients with refractory seizures a referral.
Note that a randomized controlled trial of early surgery has now been published: Engel J, Jr., McDermott, MP, Wiebe, S et al. (2012). Early surgical therapy for drug-resistant temporal lobe epilepsy. JAMA 307: 922–930.
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Whereas the preceding discussion describes in some detail the approach used by epilepsy centers to select surgical candidates, this requires considerable expertise, and is not a decision that should be made by primary care physicians or general neurologists. Rather, patients whose lives continue to be compromised by pharmacoresistant seizures should all be referred to epilepsy centers where those with specialized training can not only determine whether presurgical evaluation is appropriate, but may also offer additional diagnostic and therapeutic approaches that could be of benefit to the patient (Engel, 2008).
ACKNOWLEDGMENTS Original research reported by the authors was supported in part by grants NS-02808, NS-15654, and NS-33310 from the US National Institutes of Health (J.E.), and by grants MSI-829 from the Medical Services Incorporated Foundation and AHFMR-20050756 from the Alberta Heritage Foundation for Medical Research (S.W.).
REFERENCES Apuzzo MLJ (1991). Neurosurgical Aspects of Epilepsy. American Association of Neurological Surgeons, Park Ridge, IL. Bailey P, Gibbs FA (1951). The surgical treatment of psychomotor epilepsy. JAMA 145: 365–370. Begley CE, Famulari M, Annegers JF et al. (2000). The cost of epilepsy in the United States: an estimate from populationbased clinical and survey data. Epilepsia 41: 342–351. Berg AT (2004). Understanding the delay before epilepsy surgery: who develops intractable focal epilepsy and when? CNS Spectrums 9: 136–144. Berg AT, Shinnar S, Levy SR et al. (1999). Newly-diagnosed epilepsy in children: presentation at diagnosis. Epilepsia 40: 445–452. Berg AT, Langfitt J, Shinnar S et al. (2003). How long does it take for partial epilepsy to become intractable? Neurology 60: 186–190. Binder DK, Schramm J (2008). Multilobar resections and hemispherectomy. In: J Engel, Jr., TA Pedley (Eds.), Epilepsy: A Comprehensive Textbook. 2nd edn. Lippincott-Raven, Philadelphia, pp. 1879–1889. Bingaman WE (2002a). Neurosurgery Clinics of North America: Cortical Dysplasias. WB Saunders, Philadelphia. Bingaman WE (2002b). Neurosurgery Clinics of North America: Hemispherectomy Techniques. WB Saunders, Philadelphia. Buck D, Baker GA, Jacoby A et al. (1997). Patients’ experiences of injury as a result of epilepsy. Epilepsia 38: 439–444. Burneo JG, Black L, Knowlton RC et al. (2005). Racial disparities in the use of surgical treatment for intractable temporal lobe epilepsy. Neurology 64: 50–54. Choi H, Sell RL, Lenert L et al. (2008). Epilepsy surgery for pharmacoresistant temporal lobe epilepsy: a decision analysis. JAMA 300: 2497–2505.
Cockerell OC, Johnson AL, Sander JW et al. (1994). Mortality from epilepsy: results from a prospective population-based study. Lancet 344: 918–921. Cohen MS, Bookheimer SY (2008). Functional magnetic resonance imaging. In: J Engel, Jr., TA Pedley (Eds.), Epilepsy: A Comprehensive Textbook. 2nd edn. Lippincott-Raven, Philadelphia, pp. 989–998. Comair YG, Van Ness PC, Chamoun RB et al. (2008). Neocortical resections. In: J Engel, Jr., TA Pedley (Eds.), Epilepsy: A Comprehensive Textbook. 2nd edn. Lippincott-Raven, Philadelphia, pp. 1869–1878. Crandall PH, Walter RD, Rand RW (1963). Clinical applications of studies on stereotactically implanted electrodes in temporal lobe epilepsy. J Neurosurg 20: 827–840. Dam M, Gram L, Schmidt K (Eds.) (1988). Surgical treatment of epilepsy. Acta Neurol Scand 117 (Suppl): 154. Dam M, Andersen AR, Rogvi-Hansen B et al. (Eds.) (1994). Epilepsy surgery: non-invasive versus invasive focus localization. Acta Neurol Scand 152 (Suppl 89): 1–218. Dandy WE (1919). Roentgenography of the brain after injection of air into the spinal canal. Ann Surg 70: 397–403. Duchowny M, Resnick T, Alvarez L (Eds.) (1990). Pediatric epilepsy surgery. J Epilepsy 3 (Suppl 1). Dymond AM, Sweizig JR, Crandall PH et al. (1971). Clinical application of an EEG radio telemetry system. In: Proc Rocky Mountain Bioengineering Symposium, 16–20, Fort Collins, CO, May 3-5, Instrument Society of America. Ebersole JS, Stefan H, Baumgartner C (2008). Electroencephalographic and magnetoencephalographic source modeling. In: J Engel, Jr., TA Pedley (Eds.), Epilepsy: A Comprehensive Textbook. 2nd edn. Lippincott-Raven, Philadelphia, pp. 895–916. Engel, J, Jr. (Ed.) (1987). Surgical Treatment of the Epilepsies. Raven Press, New York. Engel J, Jr. (Ed.) (1993). Surgical Treatment of the Epilepsies. 2nd edn. Raven Press, New York. Engel J, Jr. (1996). Current concepts: surgery for seizures. N Engl J Med 334: 647–652. Engel J, Jr. (1998). Etiology as a risk factor for medically refractory epilepsy: a case for early surgical intervention. Neurology 51: 1243–1244. Engel J, Jr. (2001). Finally, a randomized controlled trial of epilepsy surgery. N Engl J Med 345: 365–367. Engel J, Jr. (2005). The emergence of neurosurgical approaches to the treatment of epilepsy. In: S Waxman (Ed.), From Neuroscience to Neurology: Neuroscience, Molecular Medicine, and the Therapeutic Transformation of Neurology. Elsevier, Amsterdam, pp. 81–105. Engel J, Jr. (2008). Surgical treatment for epilepsy: too little too late? JAMA 300: 2548–2550. Engel J, Jr., Shewmon DA (1993). Overview: who should be considered a surgical candidate? In: J Engel, Jr. (Ed.), Surgical Treatment of the Epilepsies. 2nd edn. Raven Press, New York, pp. 23–34. Engel J, Jr., Rausch R, Lieb JP et al. (1981). Correlation of criteria used for localizing epileptic foci in patients considered for surgical therapy of epilepsy. Ann Neurol 9: 215–224.
WHO IS A SURGICAL CANDIDATE? Engel J, Jr., Brown WJ, Kuhl DE et al. (1982a). Pathological findings underlying focal temporal lobe hypometabolism in partial epilepsy. Ann Neurol 12: 518–528. Engel J, Jr., Kuhl DE, Phelps ME et al. (1982b). Comparative localization of epileptic foci in partial epilepsy by PCT and EEG. Ann Neurol 12: 529–537. Engel J, Jr., Kuhl DE, Phelps ME et al. (1982c). Interictal cerebral glucose metabolism in partial epilepsy and its relation to EEG changes. Ann Neurol 12: 510–517. Engel J, Jr., Van Ness P, Rasmussen TB et al. (1993). Outcome with respect to epileptic seizures. In: J Engel, Jr. (Ed.), Surgical Treatment of the Epilepsies. 2nd edn. Raven Press, New York, pp. 609–621. Engel J, Jr., Wiebe S, French J et al. (2003). Practice parameter: temporal lobe and localized neocortical resections for epilepsy. Neurology 60: 538–547. Griggs JJ, Engel J, Jr. (2005). Epilepsy surgery and the racial divide. Neurology 64: 8–9. Haneef Z, Stern J, Dewar S et al. (2010). Referral pattern for epilepsy surgery after evidence-based recommendations. Neurology 75: 699–704. Harvey AS, Eeg-Olofsson O, Freeman JL (2008). Hypothalamic hamartoma with gelastic seizures. In: J Engel, Jr., TA Pedley (Eds.), Epilepsy: A Comprehensive Textbook. 2nd edn. Lippincott-Raven, Philadelphia, pp. 2503–2509. Henry TR, Chugani HT (2008). Positron emission tomography. In: J Engel, Jr., TA Pedley (Eds.), Epilepsy: A Comprehensive Textbook. 2nd edn. Lippincott-Raven, Philadelphia, pp. 945–964. Horsley V (1886). Brain surgery. BMJ 2: 670–675. Jackson GD, Berkovic SF, Tress BM et al. (1990). Hippocampal sclerosis can be reliably detected by magnetic resonance imaging. Neurology 40: 1869–1875. Jacoby A, Baker BA, Steen N et al. (1996). The clinical course of epilepsy and its psychosocial correlates: findings from a UK community study. Epilepsia 37: 148–161. Jallon P, Loiseau P, Loiseau J (2001). Newly diagnosed unprovoked epileptic seizures: presentation at diagnosis in CAROLE study. Epilepsia 42: 464–475. Jasper H, Pertuisset B, Flanigin H (1951). EEG and cortical electrograms in patients with temporal lobe seizures. Arch Neurol Psychiatr 65: 272–290. Jette N, Tellez-Zenteno J, Hader W et al. (2009). Who should be referred for an epilepsy surgery evaluation? In: Development of an appropriateness and necessity rating tool. Epilepsia 50 (Suppl 11): 452. Jokeit H, Ebner A (2002). Effects of chronic epilepsy on intellectual functions. Prog Brain Res 135: 455–463. Jones-Gotman M, Smith ML, Wieser HG (2008). Intraarterial amobarbital procedures. In: J Engel, Jr., TA Pedley (Eds.), Epilepsy: A Comprehensive Textbook. 2nd edn. Lippincott-Raven, Philadelphia, pp. 1833–1841. Katz JN (2001). Patient preferences and health disparities. JAMA 286: 1506–1509. Kazemi NJ, O’Brien TJ, Cascino GD et al. (2008). Single photon emission computed tomography. In: J Engel, Jr., TA Pedley (Eds.), Epilepsy: A Comprehensive Textbook. 2nd edn. Lippincott-Raven, Philadelphia, pp. 965–973.
Krynauw RA (1950). Infantile hemiplegia treated by removing one cerebral hemisphere. J Neurol Neurosurg Psychiatry 13: 243–267. Kwan P, Arzimanoglou A, Berg AT et al. (2010). Definition of drug resistant epilepsy: Consensus proposal by the ad hoc Task Force of the ILAE Commission on Therapeutic Strategies. Epilepsia 51: 1069–1077. Langfitt JT, Wiebe S (2008). Early surgical treatment for epilepsy. Curr Opin Neurol 21: 179–183. Loring DW, Barr WB, Hamberger M et al. (2008). Neuropsychology evaluation: adults. In: J Engel, Jr., TA Pedley (Eds.), Epilepsy: A Comprehensive Textbook. 2nd edn. Lippincott-Raven, Philadelphia, pp. 1057–1065. L€ uders HO (Ed.) (1992). Epilepsy Surgery. Raven Press, New York. L€ uders HO, Comair YG (Eds.) (2001). Epilepsy Surgery. 2nd edn. Lippincott, Williams & Wilkins, Philadelphia. L€ uders H, Lesser RP, Dinner DS et al. (1987). Commentary: chronic intracranial recording and stimulation with subdural electrodes. In: J Engel, Jr., (Ed.) Surgical Treatment of the Epilepsies. Raven Press, New York, pp. 297–322. L€ uders HO, Bingaman W, Najm IM (Eds.) (2008). Textbook of Epilepsy Surgery. Taylor & Francis Medical Books, London. Mathern GW (Ed.) (1999). Pediatric epilepsy and epilepsy surgery. Dev Neurosci 21: 159–408 Mathern GW, Wilson CL, Beck H (2008). Hippocampal sclerosis. In: J Engel, Jr., TA Pedley (Eds.), Epilepsy: A Comprehensive Textbook. 2nd edn. Lippincott-Raven, Philadelphia, pp. 121–136. Miller JW, Silbergeld DL (Eds.) (2006). Epilepsy Surgery: Principles and Controversies. Taylor & Francis, New York. Moniz E (1934). L’angiographie ce´re´brale. Masson et Cie, Paris. Murray GJL, Lopez AD (1994). Global Comparative Assessments in the Health Sector: Disease Burden, Expenditure. Intervention Packages, World Health Organization, Geneva. NIH Consensus Panel (1990). Consensus Conference on Surgery for Epilepsy. JAMA 264: 729–733. Ogren JA, Bragin A, Wilson CL et al. (2009). Threedimensional hippocampal atrophy maps distinguish two common temporal lobe seizure-onset patterns. Epilepsia 50: 1361–1370. Pickard JD, Trojanowski T, Maira G et al. (Eds.) (1990). Neurosurgical Aspects of Epilepsy. Springer-Verlag, New York. Polkey CE, Smith MC (2008). Multiple subpial transections and other interventions. In: J Engel, Jr., TA Pedley (Eds.), Epilepsy: A Comprehensive Textbook. 2nd edn. Lippincott-Raven, Philadelphia, pp. 1921–1928. Radhakrishnan K, Fried I, Cascino GD (2008). Lesionectomy: management of substrate-directed epilepsies. In: J Engel, Jr., TA Pedley (Eds.), Epilepsy: A Comprehensive Text book. 2nd edn. Lippincott-Raven, Philadelphia, pp. 1891–1906. Roberts DW (2008). Corpus callosotomy. In: J Engel, Jr., TA Pedley (Eds.), Epilepsy: A Comprehensive Textbook. 2nd edn. Lippincott-Raven, Philadelphia, pp. 1907–1913.
J. ENGEL, JR. AND S. WIEBE
Semah F, Picot M-C, Adam C et al. (1998). Is the underlying cause of epilepsy a major prognostic factor for recurrence? Neurology 51: 1256–1262. Silbergeld DL, Ojemann GA (Eds.) (1993). Neurosurgery Clinics of North America. Epilepsy Surgery 4, 4: 356. Spencer DD, Spencer SS (Eds.) (1991). Surgery for Epilepsy. Blackwell, Cambridge, MA. Spencer SS, Sperling MR, Shewmon DA et al. (2008). Intracranial electrodes. In: J Engel, Jr., TA Pedley (Eds.), Epilepsy: A Comprehensive Textbook. 2nd edn. Lippincott-Raven, Philadelphia, pp. 1791–1815. Sperling MR (2004). The consequences of uncontrolled epilepsy. CNS Spectrums 9: 98–109. Sperling MR, Feldman H, Kinman J et al. (1999). Seizure control and mortality in epilepsy. Ann Neurol 46: 45–50. Stefan H, Hildebrandt M, Kerling F et al. (2009). Clinical prediction of postoperative seizure control: structural, functional findings and disease histories. J Neurol Neurosurg Psychiatry 80: 196–200. Swarztrauber K, Dewar S, Engel J, Jr. (2003). Patient attitudes about treatments for intractable epilepsy. Epilepsy Behav 4: 19–25. Talairach J, Bancaud J, Szikla G et al. (1974). Approche nouvelle de la neurochirurgie de l’e´pilepsie. Me´thodologie ste´re´otaxique et re´sultats the´rapeutiques. Neurochirurgie 20: 240. Theodore WH (Ed.) (1992). Surgical Treatment of Epilepsy. Elsevier, Amsterdam. Tuxhorn I, Holthausen H, Boenigk H (Eds.) (1997). Paediatric Epilepsy Syndromes and their Surgical Treatment. John Libbey, London.
Vaccarino V, Rathore SS, Wenger NK et al. (2005). National Registry of Myocardial Infarction Investigators. Sex and racial differences in the management of acute myocardial infarction, 1994 through 2002. N Engl J Med 353: 671–682. Van Wagenen WP, Herren RY (1940). Surgical division of commissural pathways in the corpus callosum: relation to spread of an epileptic attack. Arch Neurol Psychiatry 44: 740–759. Vives K, Lee G, Doyle W et al. (2008). Anterior temporal resection. In: J Engel, Jr., TA Pedley (Eds.), Epilepsy: A Comprehensive Textbook. 2nd edn. Lippincott-Raven, Philadelphia, pp. 1859–1867. Vulliemoz S, Thornton R, Rodionov R et al. (2009). The spatio-temporal mapping of epileptic networks: combination of EEG-fMRI and EEG source imaging. Neuroimage 46: 834–843. Wiebe S, Blume WT, Girvin JP et al. (2001). A randomized, controlled trial of surgery for temporal lobe epilepsy. N Engl J Med 345: 311–318. Wieser HG, Elger CE (Eds.) (1987). Presurgical Evaluation of Epileptics: Basics, Techniques, Implications. SpringerVerlag, Berlin. ¨ zkara C Wieser H-G, O ¸ , Engel J, Jr. et al. (2004). Mesial temporal lobe epilepsy with hippocampal sclerosis: report of the ILAE Commission on Neurosurgery of Epilepsy. Epilepsia 45: 695–714. Wyler AR, Hermann BP (Eds.) (1994). The Surgical Management of Epilepsy. Butterworth-Heinemann, Boston. Zentner J, Seeger W (Eds.) (2003). Surgical Treatment of Epilepsy. Springer-Verlag, New York.