Epilepsy: A Comprehensive Textbook
2nd Edition
© 2008 Lippincott Williams & Wilkins
←↑→
Chapter 167
Indications and Criteria for Surgical Intervention
Michael S. Duchowny
A. Simon Harvey
Michael R. Sperling
Peter D. Williamson
Introduction
The estimated lifetime cumulative incidence and prevalence of epilepsy are 3% and 0.5% respectively, with approximately 60% of patients manifesting partial seizures.47,48 Although most patients with new-onset epilepsy have few seizures or are well-controlled, an estimated 5% to 10% of patients become sufficiently medically intractable to consider surgical therapy.47,86 Data from a Danish registry of unselected patients with partial epilepsy suggest a cumulative incidence for intractable epilepsy of 135 per 100,000.62 Intractable epilepsy is a major risk for personal injury, quality of life, and in some cases, mortality. Furthermore, recurrent seizures have a significant socioeconomic cost to the individual and society.
In recent decades, there has been increasing interest in the surgical treatment of patients with intractable seizures. At the second Palm Desert conference on epilepsy surgery, the number of procedures performed at major epilepsy surgery centers between 1986 and 1990 was more than twice that reported before 1985.34 This remarkable increase has been fuelled by a combination of technological advances in neuroimaging and electroencephalography, new appreciation of the devastating personal and socioeconomic effects of recurrent seizures, delineation of surgically remediable epilepsy syndromes, and recognition of the long-term benefits of early surgical intervention.
Temporal lobe resections make up approximately two-thirds of all procedures currently performed at epilepsy surgery centers, reflecting the predominance of adult patients with intractable temporal lobe epilepsy (TLE). In pediatric epilepsy surgery centers, a greater proportion of patients undergo extratemporal, multilobar, and hemispheric resections.54,85,126
It is currently estimated that as many as 5,000 new patients annually in the United States might benefit from epilepsy surgery,86 yet less than one-third receive treatment at the major centers.34 Underutilization of epilepsy surgery is also apparent in other countries.79,97 The education of primary care physicians to refer patients with surgically remediable epilepsies, instruction of health insurers and government health agencies regarding reimbursement for epilepsy surgery, and refinement of epilepsy surgical protocols should increase the number of patients with intractable epilepsy who may benefit from epilepsy surgery.
Who Is a Candidate for Epilepsy Surgery?
A simple statement can be made that epilepsy surgery may be considered by anyone whose seizures recur despite use of appropriate antiepileptic drugs (AEDs). For properly selected patients, surgery offers a relatively safe and effective means of either abolishing seizures, diminishing their severity, or reducing seizure frequency. Because most of the benefits conferred by surgery accrue when seizures are completely stopped, palliative surgery is a viable option only if it would improve quality of life or lessen the risk of injury or death. Surgery may seem a rather drastic measure for intermittent symptoms that may not prevent someone from living a happy and fulfilling life. However, uncontrolled epilepsy has numerous adverse medical and psychosocial consequences, some of which appear only after years or decades of illness. Surgery is performed precisely because it is effective, and its risks are generally less than the aggregate long-term risks of uncontrolled seizures.
What kinds of seizures and types of epilepsy provoke the consideration of epilepsy surgery? The most common types of seizures that lead people to consider surgery are those that cause alteration of consciousness or awareness or injury. These seizures have the greatest potential to cause injury and impair quality of life. Hence, complex partial and secondarily generalized tonic–clonic seizures are common indications for surgery because of their adverse psychosocial and medical repercussions. Loss of awareness prevents legal operation of a motor vehicle, forces people to rely upon others for transportation (which limits independence), reduces employment opportunities, diminishes educational choices, and imposes psychological burdens. Common activities, such as using pubic transportation, are fraught in ways that people who do not suffer from seizures cannot imagine. In addition, when seizures might cause someone to precipitously fall with resultant injury (e.g., tonic–clonic, atonic, tonic, and some simple partial seizures), activity is further limited. In addition, some seizures, although they might not cause injury or loss of awareness, might be so unpleasant or psychologically disruptive that surgery could still be an option. For example, seizures that either produce intense nausea and vomiting or cause socially unacceptable behavior might warrant surgical therapy. Lastly, some postictal behaviors, such as recurrent postictal psychosis and prolonged postictal confusion or lethargy, may cause more difficulty than the seizures themselves and prompt a patient to consider surgery. In general, the individual who suffers from the seizures is the only one who can state with certainty whether residual symptoms are inadequately controlled or not, although it is the physician’s responsibility to assess medical risks.
How often should seizures occur to consider surgery? There is no objectively determined seizure frequency required to consider surgery. Although most people who have surgery have seizures at least once every month or so, others have had fewer seizures and decided that surgery was worthwhile. Having just one or two seizures per year prohibits the legal operation of a motor vehicle and can lead to serious medical and psychosocial consequences. In our experience, some patients with as few as two or three seizures per year have had surgery and viewed it as worthwhile; careful preoperative counseling
P.1752

should always be performed so that patients will have realistic expectations.
The time at which seizures occur might also influence the decision to have surgery. Seizures that occur at predict-able times pose fewer problems than seizures that appear randomly. For example, the person who has seizures occurring only while asleep (nocturnal seizures) may drive an automobile and live a relatively unrestricted life. However, these seizures might still be psychologically disturbing, disrupt sleep, and pose medical risk so that surgical consideration is legitimate.
Last, the type of epilepsy syndrome must influence the decision to consider surgery. Some types of epilepsy are known to disappear with the passage of time, so that it would be overly aggressively to perform surgery for them. Other types of epilepsy are associated with a progressive downhill course, (e.g., progressive myoclonic epilepsy, seizure associated with malignant tumors) so that surgery will certainly not afford long-term benefit and probably should not be done. Other types of drug-resistant epilepsy (e.g., medial TLE) often favorably respond to surgical treatment, and surgery might be considered early in the course of treatment.
Rationale for Surgical Intervention
In addition to the physical harm posed by epileptic seizures, accumulating evidence suggests that chronic epilepsy results in deterioration of brain function and structure. It is recognized that many patients with epilepsy, particularly patients with seizures of temporal lobe origin, suffer a progressive decline in learning and memory.51 The loss of verbal memory skills has particularly devastating consequences on quality of life and may lead to a significant decline in socioeconomic status. It is not altogether clear to what degree seizures, their underlying pathologic substrate, or the cumulative effects of drug treatment contribute to decline, but a longer duration of epilepsy appears to be a critical factor in cognitive decline. Helmstaedter et al.50 performed a longitudinal neurocognitive study of 147 surgically treated and 102 medically treated adults with TLE. They found that a higher proportion of the medically treated group suffered a significant decline in memory skills between 2 and 10 years after baseline evaluation. Seizure-free patients had the best outcome, with superior recovery of both memory and nonmemory functions. Cross-sectional studies have further shown that a duration of TLE greater than two decades is associated with the greatest deterioration of cognitive ability and is independent of patient age and age at seizure onset.61 Additional evidence suggests that frequent interictal discharges and short nonconvulsive seizures can cumulatively impair cognition and educational achievement.2
In parallel with studies of cognition, serial neuroimaging studies in patients with refractory seizures reveal evidence of progressive degeneration at anatomic loci remote from seizure origin. Recurrent temporal lobe seizures are associated with decreased hippocampal volume 3.5 years after seizure onset if recurrent seizures are present,41 whereas progressive volume reduction occurs in the amygdala and entorhinal cortex ipsilateral to the atrophic hippocampus.14 Voxel-based morphometry of unilateral TLE reveals abnormalities in the thalamus, cerebellum, and extratemporal neocortex as well as temporal and extratemporal white matter.80 These findings collectively reveal that chronic TLE is associated with widespread secondary changes that affect multiple brain regions and the connectivity between cerebral hemispheres.
Criteria for Surgical Candidacy
Medical Intractability
The decision to refer patients for epilepsy surgery rests on the perceptions of the patient and physician that medical treatment is failing. These perceptions are based on the belief that the physician has exercised “due diligence”—she has administered optimal medications at high serum therapeutic concentrations. However, there are few established guidelines to assist the physician’s choice of medications, dosing interval, duration of treatment, monitoring of serum concentration, and withdrawal of therapy. Thus, medical treatment of seizures is still largely individualized, with no unique point in time when intractability is established.
Certain risk factors dictate a low probability of seizure remission. The likelihood of persistent seizures is increased by additional factors such that patients with multiple risk factors have the poorest outcome.21 High seizure frequency in the form of daily or weekly episodes constitutes a major risk factor for medical intractability, whereas seizure clustering increases the risk still further.1 Early seizure onset, particularly in infancy, predicts seizure persistence,77 and infantile hemiconvulsive status epilepticus (SE) is specifically linked to the development of TLE.20,42,45 Motor convulsions in a nonconvulsive disorder are a risk factor independent of the number of lifetime episodes.90 Patients with organic brain damage are less likely to undergo spontaneous seizure remission.1,56 Thus, abnormal neurologic status by physical examination or neuroimaging criteria is associated with both a greater risk of developing epilepsy and a reduced likelihood of remission. As a rule, the more severe the brain damage, the greater the likelihood of seizure persistence.113
Deficient medical management may, in some cases, simulate medical intractability. Patient noncompliance or intermittent compliance may masquerade as “pseudointractable” seizures. Physician failure to administer a first-line or appropriate adjunctive antiepileptic medication, or more commonly failure to attain high therapeutic serum concentrations, is not infrequently discovered in patients referred for surgical evaluation.43 Nonepileptic disorders and psychogenic seizures must be exposed at the outset, but approximately 10% of epileptic patients also manifest coexistent psychogenic seizures.23 The range of conditions resembling epilepsy in early childhood is particularly broad.104 Mistaking complex partial seizures for absence epilepsy, or failing to identify precipitating factors, such as sleep deprivation, leads to suboptimal therapy. Neurodegenerative disorders and inborn errors of metabolism are a rare but important cause of seizures that do not respond to medications, and inborn errors of metabolism may go unrecognized in patients with structural brain abnormalities. Indolent gliomas occasionally manifest as refractory epilepsy but are usually detectable with serial neuroimaging.
Seizure frequency and duration of epilepsy should not be the sole determinants of medical intractability, because infrequent seizures or short duration of epilepsy may still pose significant risks for the patient and impair quality of life. For example, yearly seizures may make it impossible for a patient to drive or perform certain occupations. Similarly, infrequent but severe seizures or recurrent bouts of SE pose a significant medical risk. Occasionally, patients with a relatively brief seizure history present with extremely frequent or disabling seizures, such as in epilepsia partialis continua or certain infantile syndromes. Medical intractability must therefore be assessed in the context of the patient’s quality of life and likelihood of seizure remission.
P.1753

Recent studies suggest that patients at risk for intractable epilepsy can be identified with a surprising degree of accuracy early in the course of their epilepsy. This would suggest that patients can and should be placed on a “watch list” by their treating health care providers. Epilepsy patients who have already experienced multiple seizures before seeking treatment, and who have an inadequate response to initial attempts to control seizures using AEDs are likely to have refractory epilepsy.71 In children, for example, after adjusting for epilepsy syndrome, the occurrence of high seizure frequency, focal electroencephalographic (EEG) slowing, and acute symptomatic or neonatal SE are associated with a higher risk of intractability, whereas seizure onset between 5 and 9 years was associated with a lower risk.10 In contrast, lack of early remission in patients who are not medically refractory is not associated with a poor outcome.9
Identification of a Surgically Remediable Syndrome
A significant proportion of epilepsy surgery candidates manifest seizures in the context of specific epilepsy syndromes. Candidates for excisional procedures usually have localization-related epilepsy syndromes, whereas candidates for commisural surgery typically have generalized epilepsy syndromes. Patients with surgically amenable epilepsy syndromes fall within the cryptogenic and symptomatic etiologic groups, because idiopathic epilepsy syndromes are genetically determined and are therefore unlikely to be influenced by surgical intervention. Many epilepsy syndromes are well characterized and have defined prognoses, simplifying the selection process; thus, idiopathic partial and generalized epilepsies are not surgically amenable, whereas surgery might be considered the treatment of choice for some specific epilepsy syndromes such as mesial TLE; neocortical epilepsy caused by discrete, easily resectable lesions; chronic epilepsy associated with Sturge-Weber syndrome; tuberous sclerosis; focal cortical dysplasia; hemimegalencephaly; and Rasmussen syndrome.
The Landau-Kleffner syndrome of acquired epileptic aphasia is a rare disorder characterized by regression of language in early childhood, prominent EEG abnormalities, and often seizures. In some children with impaired language who fail medical treatment, multiple subpial transection of perisylvian cortex on one side may be of benefit.53
The syndrome of gelastic epilepsy and hypothalamic hamartoma is another rare epilepsy syndrome for which cortical resection and anterior callosotomy are ineffective in alleviating seizures.17 Recently, seizure remission has been achieved by hamartoma resection,88,116 confirming seizure origin in the hypothalamic lesion. These observations suggest that other cases of intractable epilepsy syndromes associated with subcortical lesions such as subcortical heterotopias may also be surgically amenable.
Surgical treatment is advocated for some patients with infantile spasms. Infants who fail to respond to treatment with conventional anticonvulsants and corticosteroids, and who demonstrate predominantly unilateral abnormalities on EEG, positron emission tomography (PET), and magnetic resonance imaging (MRI) may be suitable for lobar or multilobar cortical resection.22,105 Early resective surgery is also indicated in infants with catastrophic presentations of partial seizures.28
Loss of Quality of Life
Chronic epilepsy is associated with considerable comorbidity and deterioration in overall quality of life. Decline in social, behavioral, and intellectual domains is a prime motivating factor in seeking surgical intervention. This is especially true for children, who are at higher risk for behavioral and cognitive disturbances as well as the emergence of depression in adolescence.29,30,86 Children with medically resistant seizures who are intellectually disadvantaged show an even greater compromise in their quality of life, irrespective of their intellectual ability level.101
The benefits of surgical intervention have recently been demonstrated for adults with TLE. Aydemir et al.4 found that successful surgery improved social activities and resulted in greater independence. Similarly, Lowe et al.78 found that long-term seizure-freedom after temporal lobectomy uniformly improved quality of life.
Earlier definitive surgical intervention would be expected to set the stage for improved self-esteem, greater social opportunity, and career advancement. Two separate studies have confirmed this hypothesis. Van Empelen et al.118 performed a longitudinal follow-up of 21 children and found that, 2 years after surgery, children began to perceive themselves as being socially more competent and having greater self-worth. Adolescents began to improve sooner after surgery; at 2 years, they demonstrated improvement in the domains of athletic competence and romance. Sabaz et al.102 also found improved quality of life in a prospective study of families of 35 children with medically resistant epilepsy undergoing epilepsy surgery, but significant gains occurred primarily in patients who became seizure-free.
Role of Early Intervention
The evidence for neuronal injury and subsequent epileptic and cognitive deterioration in chronic epilepsy has been discussed. The detrimental effects of recurrent seizures pose special risks to the developing brain of infants and young children. Uncontrolled seizures also jeopardize the chances for an independent lifestyle, and children with intractable epilepsy are likely to be excluded from normal schools and from social and vocational opportunities.74,75,76 Thus, uncontrolled chronic epilepsy has the potential for irreversible cognitive, behavioral, and psychosocial problems in later life. For this reason, syndrome characterization, medical intractability and likely prognosis should be established early in patients with uncontrolled seizures, allowing the consideration of early surgical intervention. Additional consideration takes into account the neural plasticity data from lesioning studies,65,66,67 which suggest that functional recovery from cerebral resection is superior if surgery is performed earlier in postnatal life.
Goals of Surgery
The goal of any treatment for epilepsy is to permit the patient to live as normal a life as possible. Maximizing normal function and minimizing adverse effects is part of the overall goal of therapy, whether medical or surgical. Treatment must therefore restore a sense of well-being and alleviate the psychosocial disability, medical morbidity, mortality, and risk for associated seizures. Refractory-seizure patients often have cognitive, linguistic, motor, sensory, psychiatric, and social impairments,3,38,39,60,64,111 and treatment must also address these problems. A comprehensive rehabilitative plan is an important component in an epilepsy surgery program.
Two broad categories of surgical therapy for epilepsy, curative and palliative, define the relative success of surgical intervention. Curative surgery eradicates seizures and the need for medication, whereas palliative surgery lessens seizure severity or frequency or prevents the occurrence of some seizure types.
P.1754

These outcome measures are similar to the goals of surgery in other conditions (e.g., for cancer surgery, complete tumor removal vs. debulking).
Curative surgery should eliminate the psychosocial disability associated with seizures and therefore remains the best hope for achieving a “normal” life, including improved schooling, greater personal independence, enhanced employment opportunities and attainment of a driver’s license. Studies have shown that return to a normal lifestyle after surgery rarely occurs in patients who do not achieve seizure freedom.110 However, curative surgery may also create unanticipated psychosocial problems due to newly acquired independence or upward vocational mobility.15
In some patients, only one of several seizure types is cured by surgery, but this may be a worthwhile outcome. For example, patients with mixed seizure disorders usually benefit from elimination or marked reduction in the frequency of tonic or atonic seizures, due to the reduction in medical risk and attendant injuries (e.g., fractures, lacerations). Similarly, patients with TLE may benefit from abolition of complex partial seizures and tolerate occasional auras without loss of consciousness. Palliation requires a clear a priori definition of the surgical objectives, so that an intelligent appraisal of results can follow surgery.
Whenever surgery for epilepsy is contemplated, the risks and benefits must be carefully weighed. The risks of epilepsy surgery are acceptably low in the modern era, with overall mortality being less than 0.5% and morbidity 5%. Surgical complications include cerebral infarction, intracranial hemorrhage, intracranial infection, and direct cranial nerve or cerebral injury, possibly resulting in temporary or permanent neurologic deficits. Morbidity and mortality vary according to the patient’s age and type of surgery; risks appear to be slightly higher in children compared with adults, and in hemispherectomy and corpus callosotomy compared to anterior temporal lobectomy and extratemporal resections.116,117
The risks of surgery must also be compared with the risks of continued medical treatment. At present, little data address the relative risks of medical versus surgical treatment. Risks associated with ongoing epilepsy and their medical treatments include death, injury, SE, possible detrimental effects of seizures, and adverse effects of medication. People with epilepsy have increased mortality rates compared with the general population,73 and a preliminary report suggests that this risk might be reduced by epilepsy surgery.119 A large prospective controlled study of patients with persistent seizures revealed that achieving complete seizure control after epilepsy surgery reduces mortality to a level that is indistinguishable from the general population, whereas seizure persistence is continues to be associated with high mortality rates.108 Thus, given the reduced risk of death after successful epilepsy surgery, the long-term risks of medical therapy exceed the risks of epilepsy surgery in suitable candidates.
The issue of epileptic and intellectual deterioration in chronic epilepsy is controversial, but experimental and clinical studies provide evidence that seizures can produce cognitive impairment16,55,98 and produce cellular changes.5,81 Studies suggest the hippocampus is particularly vulnerable, especially in early childhood.20,45,103
Types of Surgical Treatment
Surgical procedures to treat epilepsy include lesionectomy, lobectomy, corticectomy, multiple subpial transection, corpus callosotomy, and various combinations of these procedures. For hemispheric epilepsy syndromes, various forms of hemispheric resection and disconnection are utilized. The specific type of surgery employed for a patient depends on the predominant seizure type, the location of the seizure focus, the presence of a demonstrable lesion, and the patient’s cognitive and neurologic status. The timing of surgery must take into account the natural history of the epilepsy syndrome, the patient’s developmental status and, in children, issues related to cerebral plasticity.
Mesial Temporal Lobe Epilepsy
Disorders of the mesial temporal lobe often give rise to seizures that ultimately become refractory to medical treatment, constituting the most common surgically remediable epilepsy syndrome. Although mesial temporal lobe epilepsy (MTLE) can be caused by tumors, vascular malformations, developmental anomalies, and other discrete epileptogenic lesions that are potentially resectable, within this condition the most common syndrome is MTLE with hippocampal sclerosis.40,125 There is often a history of febrile seizures or other neurologic insults in early childhood,20,45 and complex partial seizures typically begin in the first or second decade. The syndrome is additionally characterized by anterior or midtemporal spikes on EEG and hippocampal atrophy and signal abnormality on MRI.13,57 Additionally, patients may have temporal lobe hypometabolism on PET,31,33 temporal lobe hypoperfusion on single photon-emission computed tomography (SPECT),71,100 and specific memory disturbances on neuropsychological testing and intracarotid amobarbital testing. Longitudinal studies of patients with complex partial seizures suggest that less than 20% undergo spontaneous remission of seizures,44,69,77 and that a significant proportion of patients with refractory seizures experience cognitive, interpersonal, and psychiatric problems.74,75,76 Thus, all patients with medically intractable TLE should be given consideration for surgery, early in the course of their epilepsy.
Prior to high-resolution MR and functional neuroimaging, surgical candidates frequently required invasive EEG monitoring with temporal lobe depth or strip electrodes. More recently, preoperative investigations have been limited to scalp EEG monitoring, MRI, neuropsychological testing and, at some centers, PET or SPECT.32,109,112 Chronic subdural or depth EEG monitoring, or both, are presently advocated for patients without MRI evidence of hippocampal pathology. When language-dominant lateral or posterior neocortical temporal seizures are suspected, extraoperative functional mapping of language is recommended.
For patients with unilateral or predominantly unilateral seizures, most centers perform a standard anterior temporal lobectomy in which the amygdala, anterior hippocampus, and anterior temporal neocortex are resected.36 Intraoperative electrocorticography and cortical stimulation are used at some centers to tailor the lateral temporal resection according to the extent of EEG abnormality and the location of the language cortex.27,115 Selective amygdalo-hippocampectomy, sparing the lateral temporal neocortex, is performed at some centers,106,128 while other centers perform only lateral neocortical resections, sparing amygdala and hippocampus.70 The aim of modified temporal resections is to reduce postoperative cognitive deficits; however, the indications for these procedures are not standardized and, as a result, surgical decisions are largely based on local institutional philosophy and the results of preoperative MRI and neuropsychological testing.
Lesional Neocortical Epilepsy
Partial epilepsy associated with a discrete neocortical lesion such as a tumor, vascular malformation, or focal cortical dysplasia constitutes another surgically remediable
P.1755

epilepsy syndrome.17,91,93 In this setting, the potential exists to cure the patient’s seizures with minimal electrophysiologic investigation and localized resection. However, surrounding cortex may harbor occult pathology and be epileptogenic, necessitating more thorough electrophysiologic investigation and wider resection.11,12 For lesions that do not involve critical cortex, the surgeon can perform a generous resection that includes the lesion and surrounding cortex. When lesions are close to or directly involve language, cognitive, motor, or sensory cortex, excisional surgery may be contraindicated or may only be feasible with stereotactically guided lesionectomy,18 corticectomy or lesionectomy guided by EEG localization and functional mapping,12 or resection combined with multiple subpial transection.82 Patients with large lesions, such as large areas of pachygyria, may still benefit from epilepsy surgery but only by extensive resection of the lesion and surrounding epileptogenic cortex. For patients with multiple lesions, such as patients with tuberous sclerosis or patients with multiple cavernous angiomas, successful surgery is still possible if seizures can be localized to a single lesion or group of lesions.6,35
An important surgical consideration is that developmental lesions in proximity to critical cortex do not necessarily displace or transfer function to the opposite hemisphere.24,25 Complete resection of the lesion appears crucial for seizure-freedom in lesional epilepsy surgery.37,92 Advances in MRI and functional MRI should facilitate the selection and preoperative investigation of patients with lesional epilepsy.
“Nonlesional” Neocortical Epilepsy
Patients with “nonlesional” partial epilepsy are the most challenging group of surgical candidates and are typically evaluated at specialist centers. Many have extratemporal epileptogenic regions and present with a wide spectrum of simple partial, complex partial, or secondarily generalized seizure types. When the seizure semiology suggests a well-localized site of onset, the scalp EEG shows localized discharges, and the patient’s neurologic examination and cognitive profile do not suggest extensive cerebral dysfunction, surgery is a reasonable consideration. By contrast, surgery is often unrewarding in patients with poorly localized electroclinical findings or evidence of pervasive cerebral dysfunction.
A detailed description of the patient’s aura and careful attention to the ictal behavioral sequence on video monitoring may suggest the lobe and side of seizure onset. Interictal and ictal EEG monitoring with special electrodes or extra closely spaced electrodes may further localize the field of electrographic abnormality or reveal discharges from basal or interhemispheric cortex that may not be obvious from the routine EEG.83 Ictal SPECT is particularly useful in nonlesional extratemporal epilepsies, often revealing discrete neocortical regions of activation not appreciated by EEG monitoring or MRI.46,52 Interictal SPECT and PET are usually unrewarding in aiding localization of “nonlesional” extratemporal epilepsies. Once a putative epileptogenic region is identified, repeat MRI using thin coronal slices and optimized pulse sequences through the suspected region may identify a previously occult lesion.
In patients with no demonstrable cortical lesion, intracranial EEG recording of seizures using subdural or depth electrodes or a combination of both is often necessary to plan the resection.26,127 Occasional patients with a discrete epileptogenic region may benefit from localized corticectomy, but many patients require large resections due to either poorly demarcated areas of epileptogenicity or evidence of widespread epileptic dysfunction. Alternatively, some centers perform a generous lobectomy or multilobar resection in patients with nonlesional extratemporal epilepsy, based on noninvasive preoperative data and intraoperative electrocorticography. Seizure outcome in this difficult group of patients again depends on the ability to resect the epileptogenic region.60
Hemispheric Epilepsy Syndromes
Several neurocutaneous disorders, cerebral malformation syndromes, and acquired cerebral pathologies are manifest by intractable seizures of hemispheric origin. Specific examples include Sturge-Weber syndrome, hemimegalencephaly, Rasmussen syndrome, and infantile hemiplegia with unilateral cerebral atrophy or porencephaly. In the developmental and early acquired syndromes, seizures often begin in early infancy and are associated with developmental slowing, arrest, or regression. In this group, early surgical intervention not only offers relief from seizures but also permits attainment of the child’s full developmental potential. Early hemispherectomy for patients with Rasmussen syndrome is advocated by some centers.121
Hemispherectomy is generally indicated in patients with widespread unilateral EEG abnormalities, diffuse unilateral structural abnormality, and clinical evidence of hemiparesis and hemianopia. In young patients, hemispherectomy may be performed in the absence of all these features in hopes of greater seizure-freedom and more complete transfer of function to the other hemisphere. Detailed preoperative EEG monitoring and functional neuroimaging are usually unnecessary to lateralize seizures but may help to exclude contralateral seizure onset and confirm the functional integrity of the contralateral hemisphere.
Various surgical techniques are employed to treat hemispheric epilepsy syndromes, and these include anatomic hemispherectomy, functional hemispherectomy, hemispherectomy, and hemidecortication. The choice of technique depends in part on the patient’s age, the type of lesion, the size of the hemisphere and lateral ventricle, and the surgeon’s expertise.
Secondary Generalized Epilepsies
The symptomatic/cryptogenic generalized epilepsies, such as the Lennox-Gastaut syndrome, bilateral cerebral dysfunction, and bilateral seizure onset, usually preclude focal cortical resection. Atonic, tonic, and tonic–clonic seizures may, in some patients, respond to corpus callosotomy, the rationale being interruption of the rapid secondary bilateral synchrony that underlies these seizures types.89,107 The indications for corpus callosotomy are not standardized, but patients with “drop attacks” usually respond best. Recurrent episodes of convulsive SE are also eliminated in most cases.98 The influence of intelligence, EEG abnormalities, and MRI abnormalities on outcome is variable.
Preoperative investigations are usually limited to EEG monitoring and MRI to exclude focal onset of seizures and therefore possible benefit from focal cortical resection. Neuroimaging studies often reveal lateralizing abnormalities, but may also reveal lesser but potentially significant problems in the good hemisphere. Both ictal and interictal EEG may be uninformative and, in some cases, actually misleading by indicating greater abnormalities over the good hemisphere.122 Documenting seizure types may add useful lateralizing information even in the absence of EEG confirmation.
Debate exists as to the superiority of anterior versus total corpus callosotomy with respect to seizure control and postoperative neuropsychological status. Corpus callosotomy is occasionally performed in patients with nonlocalizable partial epilepsies in whom secondary generalization and falling
P.1756

occur. Timing of surgery is not an issue in patients with infantile hemiplegia, but may be more problematic in disorders such as Rasmussen syndrome, in which children are generally normal at the outset and then slowly deteriorate. If there is concern for neurologic functions in hemispherectomy candidates, corpus callosum section should be considered. Corpus callosotomy has been offered as an alternative to hemispherectomy in infantile hemiplegia syndromes and remains a viable option.124
Contraindications to Surgery
Absolute contraindications to epilepsy surgery include underlying degenerative or metabolic disorders or supervening medical illness. Progressive neurologic disease must therefore be diagnosed at the outset, because these disorders are unlikely to benefit from surgical therapy.
Benign epilepsy syndromes for which seizure remission is anticipated at a later date constitute another absolute contraindication to epilepsy surgery. Benign rolandic epilepsy and benign focal epilepsy of childhood with occipital spikes are the most common idiopathic partial epilepsies, and present with characteristic clinical and EEG features.49,94 However, some patients with atypical rolandic or occipital seizures may be difficult to differentiate from patients with occult lesional epilepsies.
Relative contraindications to surgery include medication noncompliance, interictal psychosis, and severely dysfunctional family dynamics. Mental retardation is a potential surgical contraindication, but has little practical importance for resective procedures, and is a not a factor in determining candidacy for corpus callosotomy. Medication noncompliance is considered by some to be a contraindication to surgery, because noncompliance compromises the establishment of medical intractability and predicts postoperative noncompliance. Persistent interictal thought disturbance in a patient with intractable epilepsy is a controversial surgical contraindication, because psychotic patients still fare better if their seizures can be controlled.114 Although mental retardation indicates pervasive cerebral dysfunction, retarded patients also benefit from the elimination of recurrent seizures and medication. Finally, families that are psychodynamically dysfunctional rarely tolerate the intensive or prolonged hospitalizations required for epilepsy surgery and may also be unable to rationally evaluate its attendant risks or work with the epilepsy surgery team members.
Cost-Effectiveness as a Criterion for Surgery
Economic considerations are important when considering epilepsy treatments. Patients who are resistant to medical therapy suffer most from the detrimental economic and social impacts of the condition. Whereas the most refractory patients comprise only a small proportion of those with epilepsy, they account for a large share of the total costs imposed by epilepsy. One study estimated that the 15% of patients who are most refractory account for at least 50% of the total costs of the illness.8 Another found that cost correlated with the severity of the illness, and that intractable patients cost eight times more that those with controlled epilepsy.60 The added expense comes from both medical (direct) costs and nonmedical (indirect) costs. Medical expenses include the cost of physician visits, emergency room visits, hospitalizations, medications, diagnostic laboratory testing. These are much higher in patients with recurrent seizures than in controlled patients. Indirect expenses, which account for up to 75% of total costs, include lost productivity from unemployment, underemployment, or lost work time; excess mortality; transfer payments (e.g., disability pension); and lost work by relatives or friends to care for the ill person.8,59
Murray et al.84 estimated the lifetime cost analyses of refractory epilepsy in the United States in the mid 1900s, which were estimated to comprise 29% of adult cases. Indirect costs included lost wages due to unemployment and underemployment and lost caretaker earnings. Transfer payments and mortality costs were excluded. Prevalence analysis found direct costs of $912,553,518 and indirect costs of $2,992,629,945, with a total annual cost of nearly $4 billion (USD) ($11,745/person). Indirect costs accounted for 77% of the total.
In another analysis, Begley et al.8 estimated the 1995 costs of epilepsy in the United States at $12.5 billion. The direct costs included were direct medical costs. Lost wages and mortality were included in indirect costs. For incident cases, those with intractable epilepsy represented 25% of all cases, but accounted for 79% of estimated costs; indirect costs accounted for 88% of the total expense. For prevalence cases, patients with intractable epilepsy comprised 43% of all cases, but accounted for 80% of estimated costs; indirect costs accounted for 84% of the total cost.
The foregoing analyses all show that refractory patients are far more expensive than well-controlled patients, and one could infer that successful treatment of refractory patients—that is, making them seizure-free—would reduce costs in the long run. Several analyses have been performed to assess the cost-utility or cost-effectiveness of epilepsy surgery.68,71,95,96 Similar conclusions have been drawn from all analyses, that epilepsy surgery is cost-effective. King et al. calculated that the cumulative discounted benefit from temporal lobectomy was 1.1 quality adjusted life years (QALYs), equivalent to 1.1 extra years in good health. They found that surgical evaluation and treatment had an average marginal cost of $29,800 per patient, yielding a cost-utility ratio of $27,200 per QALY. Langiftt et al.71 determined that surgery conferred an improvement of 1.61 QALY, for a cost of $15,581 per QALY for surgery.
FIGURE 1. Medical management (solid line) has a higher per annum cost than surgical treatment. Although cheaper in the early years, the cumulative effect is that net costs over many decades are considerably higher than for surgical treatment (dashed line). (From Platt M, Sperling, MR. A comparison of surgical and medical costs for refractory epilepsy. Epilepsia. 2002;43(Suppl 4):25–31, with permission.)
Several studies have compared the costs of medical and surgical therapy. Wiebe et al.123 modeled long-term direct medical costs in two cohorts each containing 100 patients: One treated medically, and the other evaluated for surgery. For a 35-year period, they estimated that the cost for treating the medical group were $10,741,425, whereas the cost for treating the surgical group was $8,117,911. Sensitivity analyses did not change the findings. This study did not estimate nonmedical direct costs nor indirect costs, and therefore the dollar amounts reflect only a portion of the overall costs in medical and surgical therapy. Platt and Sperling96 performed an analysis comparing medical and surgical costs in an American cohort, and concluded that surgical treatment of TLE is cheaper than medical therapy, although this clearly requires a long-term societal perspective. When all indirect costs are combined with direct costs (Fig. 1), the total costs for the surgical group were less than the medical group 8.2 years after assignment, approximately 45% less time than if only direct costs are used in the calculations. The disparity in costs increased further with the passage of time. More recently, Picot et al.95 evaluated a French cohort and had remarkably similar findings—that cost-effectiveness is demonstrated between 7 and 8 years after surgery. Whereas surgery has much higher costs in the first year, due to the expense of testing and hospitalization, the long-term benefit is substantial since patients who favorably respond to surgical treatment have much reduced costs in the long run.
P.1757

Summary and Conclusions
The different medical and psychosocial backgrounds of the patients, the variety of investigational modalities available to the physician, and the number of potential surgical procedures detract from the precision of the selection process. Nevertheless, efforts are underway to delineate selection criteria and preoperative protocols for the surgical treatment of the more common surgically remediable epilepsy syndromes. If it can be demonstrated conclusively that recurrent seizures are harmful to the developing or fully developed brain, it is likely that surgery will be considered at an earlier point in the treatment time-line. Early surgical intervention in appropriately screened patients is likely to benefit long-term neurobehavioral status, in addition to controlling seizures, and thus improve overall quality of life and costs to the patient and community.
References
1. Aicardi J. Epilepsy in brain-injured children. Dev Med Child Neurol. 1990;32:191–202.
2. Aldenkamp A, Arends J. The relative influence of epileptic discharges, short non-convulsive seizures, and type of epilepsy on cognitive function. Epilepsia. 2004;45:54–63.
3. Augustine EA, Novelly RA, Mattson RH, et al. Occupational adjustment following neurosurgical treatment of epilepsy. Ann Neurol. 1984;15:68–72.
4. 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. 2004;5:735–742.
5. Babb TL, Brown WJ. Pathological Findings in Epilepsy. In: Engel J Jr, ed. Surgical Treatment of the Epilepsies. New York: Raven Press; 1987:511–540.
6. Bebin EAM, Kelly PJ, Gomez MR. Surgical treatment for epilepsy in cerebral tuberous sclerosis. Epilepsia. 1993;34:651–657.
7. Begley CE, Annegers JF, Lairson DR, et al. Cost of epilepsy in the United States: A model based on incidence and prognosis. Epilepsia. 1994;35:6:1230–1243.
8. Begley CE, Famulair M, Annegers JF, et al. The cost of epilepsy in the United States: An estimate from population-based clinical and survey data. Epilepsia. 2000;41:3:342–351.
9. Berg AT, Shinnar S, Levy SR, et al. Defining early seizure outcomes in pediatric epilepsy: The good, the bad and the in-between. Epilepsy Res. 2000.
10. Berg AT, Shinnar S, Levy SR, et al. Early development of intractable epilepsy in children. A prospective study. Neurology. 2001;56:1445–1452.
11. Berger MS, Ghatan S, Geyer JR, et al. Seizure outcome in children with hemispheric tumors and associated intractable epilepsy: The role of tumor removal combined with seizure foci resection. Pediatr Neurosurg. 1991;17:185–191.
12. Berger MS, Ghatan S, Haglund MM, et al. Low-grade gliomas associated with intractable epilepsy: Seizure outcome utilizing electrocorticography during tumor resection. J Neurosurg. 1993;79:62–69.
13. Berkovic SF, Andermann F, Olivier A, et al. Hippocampal sclerosis in temporal lobe epilepsy demonstrated by magnetic resonance imaging. Ann Neurol. 1991;29:175–182.
14. Bernasconi N, Natsume J, Bernasconi A. Progression in temporal lobe epilepsy. Differential atrophy in mesial temporal structures. Neurology. 2005;65:223–228.
15. Bladin PF. Psychosocial difficulties and outcome after temporal lobectomy. Epilepsia. 1992;33:898–907.
16. Bourgeois BF, Prensky AL, Palkes HS, et al. Intelligence in epilepsy: A prospective study in children. Ann Neurol. 1983;14:438–444.
17. Cascino GD, Andermann F, Berkovic SF, et al. Gelastic seizures and hypothalamic hamartomas: Evaluation of patients undergoing chronic intracranial EEG monitoring and outcome of surgical treatment. Neurology. 1993;43:747–750.
18. Cascino GD, Kelly PJ, Hirschorn KA, et al. Stereotactic resection of intra-axial cerebral lesions in partial epilepsy. Mayo Clin Proc. 1990;65:1053–1060.
19. Cascino GD, Kelly PJ, Sharbrough FW, et al. Long-term follow-up of stereotactic lesionectomy in partial epilepsy: Predictive factors and electroencephalographic results. Epilepsia. 1992;33:639–644.
20. Cendes F, Andermann F, Dubeau F, et al. Early childhood prolonged febrile convulsions, atrophy and sclerosis of mesial structures, and temporal lobe epilepsy: An MRI volumetric study. Neurology. 1993;43:1083–1087.
21. Chevrie JJ, Aicardi J. Convulsive disorders in the first year of life: Persistence of epileptic seizures. Epilepsia. 1979;20:643–649.
22. Chugani HT, Shields WD, Shewmon DA, et al. Infantile spasms: I. PET identifies focal cortical dysgenesis in cryptogenic cases for surgical treatment. Ann Neurol. 1990;27:406–413.
23. Desai BT, Porter RJ, Penry JK. Psychogenic seizures. A study of 42 attacks in six patients, with intensive monitoring. Arch Neurol. 1982;39:202–209.
24. DeVos KJ, Wyllie E, Geckler C, et al. Language dominance in patients with early childhood tumors near left hemisphere language areas. Neurology. 1995;45:349–356.
25. Duchowny M, Jayakar P, Harvey AS, et al. Language cortex representation: Effects of developmental versus acquired pathology. Ann Neurol. 1996;40:31–38.
26. Duchowny M, Jayakar P, Resnick T, et al. Posterior temporal epilepsy: Electroclinical features. Ann Neurol. 1994;35:427–431.
27. Duchowny M, Levin B, Jayakar P, et al. Temporal lobectomy in early childhood. Epilepsia. 1992;33:298–303.
28. Duchowny MS, Resnick TJ, Alvarez LA, et al. Focal resections for malignant partial seizures in infancy. Neurology. 1990;40:980–984.
29. Dunn DW, Austin JK, Huster GA. Behavior problems in children with new-onset epilepsy. Seizure. 1997;6:283–287.
30. Dunn DW, Austin JK, Huster GA. Symptoms of depression in adolescents with epilepsy. J Am Acad Child Adolesc Psychiatry. 1999;38:1132–1138.
31. Engel J Jr, Brown WJ, Kuhl DE, et al. Pathological findings underlying focal temporal lobe hypometabolism in partial epilepsy. Ann Neurol. 1982;12:518–528.
32. Engel J Jr, Henry TR, Risinger MW, et al. Presurgical evaluation for partial epilepsy: Relative contributions of chronic depth-electrode recordings versus FDG-PET and scalp-sphenoidal EEG. Neurology. 1990;40:1670–1677.
33. Engel J Jr, Kuhl DE, Phelps ME, et al. Interictal cerebral glucose metabolism in partial epilepsy and its relation to EEG changes. Ann Neurol. 1982;12:510–517.
34. Engel J Jr, Shewmon DA. Who Should Be Considered a Surgical Candidate? In: Engel, J Jr, ed. Surgical Treatment of the Epilepsies. New York: Raven Press; 1993:23–34.
35. Erba G, Duchowny M. Partial epilepsy and tuberous sclerosis: Indications for surgery in disseminated disease. J Epilepsy. 1990;3(Suppl 1):315–319.
P.1758

36. Falconer MA, Hill D, Meyer A, et al. Treatment of temporal-lobe epilepsy by temporal lobectomy. Lancet. 1955;1:827–835.
37. Fish DR, Smith SJ, Quesney LF, et al. Surgical treatment of children with medically intractable frontal or temporal lobe epilepsy: Results and highlights of 40 years’ experience. Epilepsia. 1993;34:244–247.
38. Flor-Henry P. Ictal and interictal psychiatric manifestations in epilepsy: Specific or non-specific? A critical review of some of the evidence. Epilepsia. 1972;13:767–772.
39. Fraser RT. Improving functional rehabilitation outcome following epilepsy surgery. Acta Neurol Scand. 1988;117(Suppl):122–128.
40. French JA, Williamson PD, Thadani VM, et al. Characteristics of medial temporal lobe epilepsy: I. Results of history and physical examination. Ann Neurol. 1993;34:774–780.
41. Fuerst D, Shah J, Shah A, et al. Hippocampal sclerosis is a progressive disorder: A longitudinal volumetric study. Ann Neurol. 2003;53:413–416.
42. Gastaut H, Toga M, Roger J, et al. A correlation of clinical, electroencephalographic and anatomical findings in nine autopsied cases of “temporal lobe epilepsy.” Epilepsia. 1959:56–85.
43. Gilman JT, Duchowny M, Jayakar P, et al. Medical intractability in children evaluated for epilepsy surgery. Neurology. 1994;44:1341–1343.
44. Harbord MG, Manson JI. Temporal lobe epilepsy in childhood: Reappraisal of etiology and outcome. Pediatr Neurol. 1987;3:263–268.
45. Harvey AS, Grattan-Smith JD, Desmond PM, et al. Febrile seizures and hippocampal sclerosis: Frequent and related findings in intractable temporal lobe epilepsy of childhood. Pediatr Neurol. 1995;12:201–206.
46. Harvey AS, Hopkins IJ, Bowe JM, et al. Frontal lobe epilepsy: Clinical seizure characteristics and localization with ictal 99mTc-HMPAO SPECT. Neurology. 1993;43:1966–1980.
47. Hauser WA. The Natural History of Seizures. In: Wyllie E, ed. The Treatment of Epilepsy: Principles and Practice. Philadelphia: Lea and Febiger; 1993:165–170.
48. Hauser WA, Annegers JF, Kurland LT. Prevalence of epilepsy in Rochester, Minnesota: 1940–1980. Epilepsia. 1991;32:429–445.
49. Heijbel J, Blom J, Bergfors B. Benign epilepsy of children with centrotemporal EEG foci: A study of incidence rate in out-patient care. Epilepsia. 1975;16:657–164.
50. Helmstaedter C, Kurthen M, Lux S, et al. Chronic epilepsy and cognition: A longitudinal study in temporal lobe epilepsy. Ann Neurol. 2003;54:425–432.
51. Hendriks MP, Aldenkamp AP, Van der Vlugt H, et al. Memory complaints in medically refractory epilepsy: Relationship to epilepsy related factors. Epilepsy Behav. 2002;3:165–172.
52. Ho SS, Berkovic SF, Newton MR, Austin MC, et al. Parietal lobe epilepsy: Clinical features and seizure localization by ictal SPECT. Neurology. 1994;44:2277–2284.
53. Hoeppner JA, Grote CL, Morrell F, et al. Long-term follow-up of cognitive and behavioral function after surgery for Landau-Kleffner syndrome. Epilepsia. 1993;34(Suppl 6):72.
54. Holmes GL. Surgery for intractable seizures in infancy and early childhood. Neurology. 1993;43(Suppl 5):S28–S37.
55. Holmes GL, Thompson JL, Marchi TA, et al. Effects of seizures on learning, memory, and behavior in the genetically epilepsy-prone rat. Ann Neurol. 1990;27:24–32.
56. Huttenlocker PR, Hapke RI. A follow-up study of intractable seizures in childhood. Ann Neurol. 1990;28:699–705.
57. Jackson GD, Berkovic SF, Tress BM, et al. Hippocampal sclerosis can be reliably detected by magnetic resonance imaging. Neurology. 1990;40:1869–1875.
58. Jacoby A, Buck D, Baker G, et al. Uptake and costs of care for epilepsy: Findings from a U.K. regional study. Epilepsia. 1998;39:776–786.
59. Jayakar P, Duchowny M, Resnick T, et al. Epilepsy surgery in children with normal or nonspecific neuroimaging studies [abstract]. Ann Neurol. 1994;36:504.
60. Jensen I. Temporal lobe epilepsy. Social conditions and rehabilitation after surgery. Acta Neurol Scand. 1976;54:22–44.
61. Jokeit H, Luerding R, Ebner A. Cognitive impairment in temporal-lobe epilepsy. Lancet. 2000;355:1018–1019.
62. Juul-Jensen P, Foldspang A. Natural history of epileptic seizures. Epilepsia. 1986;24:297–312.
63. Kaminer Y, Apter, Aviv A, et al. Psychopathology and temporal lobe epilepsy in children. Acta Psychiatr Scand. 1988;77:640–644.
64. Kennard MA. Age and other factors in motor recovery from precentral lesion in monkeys. Am J Physiol. 1936;115:138–146.
65. Kennard MA. Reorganization of motor function in the cerebral cortex of monkeys deprived of motor and premotor areas in infancy. J Neurophysiol. 1938;1:477–496.
66. Kennard MA. Relation of age to motor impairment in man and in subhuman primates. Arch Neurol Psychiat. 1940;44:377–397
67. Keogan M, McMackin D, Peng S, et al. Temporal neocorticectomy in management of intractable epilepsy: Long-term outcome and predictive factors. Epilepsia. 1992;33:852–861.
68. King JT, Sperling MR, O’Connor MJ. Is anterior temporal lobectomy for medically intractable temporal lobe epilepsy “cost-effective”? [abstract]. Epilepsia. 1994;35(Suppl 8):46.
69. Kotagal P, Rothner AD, Erenberg G, et al. Complex partial seizures of childhood onset: A five year follow-up study. Arch Neurol. 1987;44:1177–1180.
70. Kwan P, Brodie MJ. Early identification of refractory seizures. N Engl J Med. 2000;342:314–319.
71. Langfitt JT. Cost-effectiveness of anterotemporal lobectomy in medically intractable complex partial epilepsy. Epilepsia. 1997;38:154–163.
72. Lee BI, Park HM, Siddiqui AR, et al. Interictal HIPDM-SPECT in patients with complex partial seizures. Neurology. 1988;38:406–406.
73. Leetsma JE, Walczak R, Hughes JR, et al. A prospective study on sudden unexpected death in epilepsy. Ann Neurol. 1989;26:195–203.
74. Lindsay J, Ounsted C, Richards P. Long-term outcome in children with temporal lobe seizures. I: Social outcome and childhood factors. Dev Med Child Neurol. 1979;21:285–298.
75. Lindsay J, Ounsted C, Richards P. Long-term outcome in children with temporal lobe seizures. II: Marriage, parenthood and sexual indifference. Dev Med Child Neurol. 1979;21:433–440.
76. Lindsay J, Ounsted C, Richards P. Long-term outcome in children with temporal lobe seizures. III: Psychiatric aspects in childhood and adult life. Develop Med Child Neurol. 1979;21:630–636.
77. Lindsay J, Ounsted C, Richards P. Long-term outcome in children with temporal lobe seizures. IV: Genetic factors, febrile convulsions and remission of seizures. Dev Med Child Neurol. 1980;22:429–439.
78. Lowe AJ, Kilpatrick DE, Matkovic Z, et al. Epilepsy surgery for pathologically proven hippocampal sclerosis provides long-term seizure control and improved quality of life. Epilepsia. 2004;45:237–242.
79. Mackenzie RA, Matheson JM, Smith JS, et al. Surgery for refractory epilepsy. Med J Aust. 1990;153:69–76.
80. McMillan AB, Hermann BP, Johnson SC, et al. Voxel-based morphometry of unilateral temporal lobe epilepsy reveals abnormalities in cerebral white matter. Neuroimage. 2004;23:167–174.
81. Meldrum BS. Metabolic Factors During Prolonged Seizures and Their Relation to Nerve Cell Death. In: Delgado-Escueta AV, Wasterlain CG, Treiman D, Porter RJ, eds. Advances in Neurology, Vol. 34. Status Epilepticus: Mechanisms of Brain Damage and Treatment. New York: Raven Press; 1983: 261–275.
82. Morrell F, Whisler WW, Bleck TP. Multiple subpial transection: A new approach to the surgical treatment of focal epilepsy. J Neurosurg. 1989;70:231–239.
83. Morris HM, Lüders H, Lesser RP, et al. The value of closely spaced scalp electrodes in the localization of epileptiform foci: A study of 26 patients with complex partial seizures. Electroenceph Clin Neurophysiol. 1986;63:107–111.
84. Morrison G, Duchowny M, Resnick T, et al. Epilepsy surgery in childhood. Pediatr Neurosurg. 1992;18:291–297.
85. Murray MI, Halpern MT, Leppik IE. Cost of refractory epilepsy in adults in the USA. Epilepsy Res. 1996;23:139–148.
86. Neyens LGJ, Aldenkamp AP, Meinardi HM. Prospective follow-up of intellectual development in children with a recent onset of epilepsy. Epilepsy Res. 1999;34:85–90.
87. NIH Consensus Conference. Surgery for epilepsy. JAMA. 1990;264:729–733.
88. Nishio S, Morioka T, Fukui M, Goto Y. Surgical treatment of intractable seizures due to hypothalamic hamartoma. Epilepsia. 1994;35:514–519.
89. Nordgren RE, Reeves AG, Viguera AC, et al. Corpus callosotomy for intractable seizures in the pediatric age group. Arch Neurol. 1991;48:364–372.
90. Ounsted C, Lindsay J. The long-term outcome of temporal lobe epilepsy in childhood. In: Reynolds EH, Trimble MR, eds. Epilepsy and Psychiatry. Edinburgh: Churchill Livingstine; 1981:185–215.
91. Palmini A, Andermann F, Olivier A, et al. Focal neuronal migration disorders and intractable partial epilepsy: Results of surgical treatment. Ann Neurol. 1991;30:750–757.
92. Palmini A, Andermann F, Olivier A, et al. Neuronal migration disorders (NMD): Extent of lesion removal is the main predictor of seizure control in the surgical treatment of intractable epilepsy. Neurology. 1991;41(Suppl 1):403–403.
93. Palmini A, Gambardella A, Andermann F, et al. Operative strategies for patients with cortical dysplastic lesions and intractable epilepsy. Epilepsia. 1994;35(Suppl 6):S57–S71.
94. Panayiotopoulos CP. Benign childhood epilepsy with occipital paroxysms. A 15-year prospective study. Ann Neurol. 1989;26:51–56.
95. Picot MC, Neveu D, Kahane P, et al. [Cost-effectiveness of epilepsy surgery in a cohort of patients with medically intractable partial epilepsy—preliminary results]. Rev Neurol. 2004;160:5S354–367.
96. Platt M, Sperling, MR. A comparison of surgical and medical costs for refractory epilepsy. Epilepsia. 2002;43(Suppl 4):25–31.
97. Polkey CE. Surgical treatment of epilepsy. Lancet. 1990;336:553–555.
98. Purves SJ, Wada JA, Woodhurst WB, et al. Results of anterior corpus callosum section in 24 patients with medically intractable seizures. Neurology. 1988:1194–1201.
99. Rodin EA, Schmaltz S, Twitty G. Intellectual functions of patients with childhood-onset epilepsy. Dev Med Child Neurol. 1986;28:25–33.
100. Rowe CC, Berkovic SF, Austin MC, et al. Visual and quantitative analysis of interictal SPECT with technetium-99m-HMPAO in temporal lobe epilepsy. J Nucl Med. 1991;32:1688–1694.
P.1759

101. Sabaz M, Cairns DR, Lawson JA, et al. The health-related quality of life of children with refractory epilepsy: A comparison of those with and without intellectual disability. Epilepsia. 2001;42:621–628.
102. Sabaz M, Lawson JA, Cairns DR, et al. The impact of epilepsy surgery on quality of life in children. Neurology. 2006;66:557–561.
103. Sagar HJ, Oxbury JM. Hippocampal neuron loss in temporal lobe epilepsy: Correlation with early childhood convulsions. Ann Neurol. 1987;22:334–340.
104. Sassower K, Duchowny M. Psychogenic seizures and nonepileptic phenomena in childhood. In: Devinsky O, Theodore WH, eds. Epilepsy and Behavior. New York: Wiley-Liss; 1991:223–235.
105. Shields WD, Shewmon DA, Chugani HT, et al. Treatment of infantile spasms: Medical or surgical?. Epilepsia. 1992;33(Suppl 4):S26–S31.
106. 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. 1984;15:667–671.
107. Spencer SS, Spencer DD, Williamson PD, et al. Corpus callosotomy for epilepsy. I. Seizure effects. Neurology. 1988;38:19–24.
108. Sperling MR, Feldman H, Kinman J, et al. Seizure control and mortality in epilepsy. Ann Neurol. 1999;46:45–50.
109. Sperling MR, O’Connor MJ, Saykin AJ, et al. A noninvasive protocol for anterior temporal lobectomy. Neurology. 1992;42:416–422.
110. Sperling MR, Roberts D, Saykin AJ, et al. Occupational outcome after anterior temporal lobectomy correlates with seizure control. Epilepsia. 1994;35(Suppl 8):47.
111. Taylor DC, Falconer MA. Clinical, socio-economic, and psychological changes after temporal lobectomy. Brit J Psychiatr. 1968;114:1247–1261.
112. Thadani VM, Williamson PD, Berger R, et al. Successful epilepsy surgery without intracranial EEG recording: Criteria for patient selection. Epilepsia. 1995;36:7–15.
113. Trevathan E, Yeargin-Allsop M, Murphy C, et al. Epilepsy among children with mental retardation. Ann Neurol. 1988;24:321.
114. Trimble M. The Psychoses of Epilepsy. New York: Raven Press; 1991.
115. Tsai M-L, Chatrian G-E, Pauri F, et al. Electrocorticography in patients with medically intractable temporal lobe seizures. I. Quantification of epileptiform discharges prior to resective surgery. Electroenceph Clin Neuro-physiol. 1993;87:10–24.
116. Valdueza JM, Cristante L, Dammann O, et al. Hypothalamic hamartomas: With special reference to gelastic epilepsy and surgery. Neurosurgery. 1994;34:949–958.
117. Van Buren JM. Complications of surgical procedures in the diagnosis and treatment of epilepsy. In: Engel J Jr, ed. Surgical Treatment of the Epilepsies. New York: Raven Press; 1987:465–475.
118. van Empelen R, Jennekens-Schinkel A, van Rijen PC, et al. Health-related quality of life and self-perceived competence of children assessed before and up to two years after epilepsy surgery. Epilepsia. 2005;46:258–271.
119. Ventureyra ECG, Higgins MJ. Complications of epilepsy surgery in children and adolescents. Pediatr Neurosurg. 1993;19:40–56.
120. Vickrey BG, Hays R, Brook R, et al. Health-related quality-of-life changes in patients undergoing epilepsy surgery. Neurology. 1994;44(Suppl 2):A162.
121. Vining EPG, Freeman JM, Brandt J, et al. Progressive unilateral encephalopathy of childhood (Rasmussen’s syndrome): A reappraisal. Epilepsia. 1993;34:639–650.
122. Vining EPG, Freeman JM, Carson BS, et al. Hemispherectomy in children: The Hopkins experience, 1968–1988, a preliminary report. J Epilepsy. 1990;169–176.
123. Wiebe S, Gafni A, Blume WT, et al. An economic evaluation of surgery for temporal lobe epilepsy. J Epilepsy. 1995;8:227–235.
124. Williamson PD. Corpus Callosum Section for Intractable Epilepsy. Criteria for Patient Selection. In: Reeves AG, ed. Epilepsy and the Corpus Callosum. New York: Plenum Press; 1985:243–257.
125. Williamson PD, French JA, Thadani VM, et al. Characteristics of medial temporal lobe epilepsy: II. Interictal and ictal scalp electroencephalography, neuropsychological testing, neuroimaging, surgical results, and pathology. Ann Neurol. 1993;34:781–787.
126. Wyllie E. Cortical resection for children with epilepsy. Perspectives in pediatrics. AJDC. 1991;145:314–320.
127. Wyllie E, Luders H, Morris HH, et al. Subdural electrodes in the evaluation for epilepsy surgery in children and adults. Neuropediatrics. 1988;19:80–86
128. Yasargil MG, Teddy PJ, Roth P. Selective amygdalohippocampectomy. Operative anatomy and surgical treatment. Adv Tech Stand Neurosurg. 1985;12:93–123.
←↑→