Download 030796 Surgery for Seizures

N Engl J Med 1996; 334:647-653
Vol. 334
No. 10
CURRENT CONCEPTS
647
REVIEW ARTICLE
CURRENT CONCEPTS
SURGERY FOR SEIZURES
JEROME ENGEL, JR., M.D., PH.D.
O
F the approximately 2 million Americans with a
diagnosis of epilepsy who are treated with antiepileptic drugs, 20 percent continue to have seizures1; this
group of patients accounts for over 75 percent of the
cost of epilepsy in the United States.2 For many of those
with medically refractory epilepsy, their disability can
be completely eliminated by surgical intervention. Only
a small percentage of potential surgical candidates, however, are currently referred to epilepsy-surgery centers.3
OVERVIEW
The classic 1886 paper of Victor Horsley4 heralded
the modern era of epilepsy surgery, and the introduction of electroencephalography (EEG) in the first half
of this century provided a practical means for localizing
epileptogenic abnormalities for resection.5,6 Nevertheless, only a handful of epilepsy-surgery centers were created, treating relatively few patients — and only one
book on the subject appeared7 — before 1986, when a
series of international conferences and textbooks began
to reflect an explosion of interest in the field.8-18 By
1992, over 100 epilepsy-surgery centers throughout the
world offered a wide selection of surgical procedures
(Table 1) to an increasing number of patients, ranging
from infants to senior citizens, for the treatment of disabling partial, and even generalized, seizures refractory
to medical therapy.17
Modern epilepsy surgery, like heart-transplant surgery, requires a multidisciplinary team of highly trained
and experienced specialists working together in an epilepsy center. A variety of surgical interventions are now
performed, usually with the patient under general anesthesia, according to the location and nature of the epileptogenic abnormality. The majority of procedures require only a few hours in the operating room and a few
days of postoperative hospital care. The most common
surgery consists of removal of the amygdala and anterior part of the hippocampus and entorhinal cortex, as
well as a small portion of the temporal pole, leaving the
lateral temporal neocortex intact. New techniques for
hemispherectomy and multilobar resection involve the
From the Departments of Neurology and Neurobiology and the Brain Research Institute, UCLA School of Medicine, Los Angeles. Address reprint requests to Dr. Engel at the Reed Neurological Research Ctr., 710 Westwood Plaza,
Los Angeles, CA 90095-1769.
Supported in part by grants (NS-02808, NS-15654, NS-33310, and GM24839) from the National Institutes of Health and a contract (DE-AC03-76SF00012) with the Department of Energy.
1996, Massachusetts Medical Society.
partial removal and partial disconnection of affected
tissue; these and related techniques are designed to reduce movement of the remaining portions of the brain
within the cranial vault and to ensure resorption of cerebrospinal fluid. Corpuscallosotomies now usually involve only the anterior two thirds of the corpus callosum unless the patient has severe retardation. For some
localized cortical resections, however, intraoperative testing may be necessary, which prolongs the operation and
occasionally requires the patient to be briefly awakened
from anesthesia. New techniques for treating epileptogenic regions within primary cortical areas, such as
those controlling language and motor function, include
the removal of a discrete lesion without disturbing the
adjacent cortex (lesionectomy) and multiple subpial transections, which sever intracortical connections in a way
that prevents the spread of epilepsy and still preserves
the columnar structure necessary to maintain normal
cortical function.19
The current resurgence of interest in surgery for epilepsy can be attributed largely to technical advances in
video EEG monitoring and neuroimaging, improvements
in surgical technique, and a better understanding of the
anatomical and pathophysiologic bases of the symptomatic epilepsies. Another factor is the correction of a variety of misconceptions that have discouraged primary
care physicians from referring patients for surgery in the
past. Finally, a clearer delineation of the natural history
of certain catastrophic epileptic disorders of infants and
young children and a new understanding of the plasticity
of the developing brain and the damage that seizures do
to it, as well as the improvements in diagnostic and surgical technique, have created a major new field, pediatric
epilepsy surgery.20
PRESURGICAL EVALUATION
The optimal surgical intervention for epilepsy should
destroy just enough neuronal tissue to eliminate seizures
and no more. Therefore, the objective of presurgical evaluation is to identify the area of brain most responsible
for generating habitual seizures and to demonstrate that
it can be removed without causing additional unacceptable neurologic or cognitive deficits. There is no simple
test to delineate the epileptogenic zone, defined as the
volume of brain tissue necessary and sufficient for the
generation of seizures. The boundaries of the epileptogenic zone can only be approximated by identifying areas of the brain marked by persistent dysfunction, both
epileptic and nonepileptic. A variety of diagnostic tests
are used for this purpose (Table 2), but there is no consensus on how much information is actually needed before a particular surgical intervention can be recommended.21 In most cases, presurgical evaluation involves
tests that localize epileptic excitability with interictal
EEG as well as long-term video EEG monitoring designed to capture and characterize ictal electrical activity and clinical symptoms; imaging studies, usually magnetic resonance imaging (MRI), that indicate structural
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THE NEW ENGLAND JOURNAL OF MEDICINE
abnormalities; tests for nonepileptic dysfunction, including positron-emission tomography to reveal areas of abnormal glucose use, single-photon-emission computed tomography to reveal areas of abnormal blood flow, and
neuropsychological testing; and studies of normal cortical function to determine areas that must be preserved
during surgery. This last category includes cortical mapping and intracarotid injection of amobarbital (the Wada
test) to identify the language-dominant hemisphere and
the laterality of memory function.
Diagnostic strategy is currently tailored to the specific surgical intervention to be used.21 For standardized
temporal-lobe resections, the presurgical evaluation need
only determine that habitual seizures are originating
within the boundaries of the intended excision and that
the structures of the contralateral mesial temporal lobe
can support memory. For specific neocortical resections
and multiple subpial cortical transections, more detailed
investigation is required to identify the boundaries of
the epileptogenic zone, as well as of adjacent areas of
essential primary cortex. For hemispherectomies and
large multilobar resections, the goal of the presurgical
evaluation is to determine the extent of the functional
and structural disturbance of the involved hemisphere
and whether the contralateral hemisphere is reasonably
intact. If section of the corpus callosum is contemplated, there must be a documented history of disabling drop
attacks as the principal type of seizure; it is also important to determine that the patients are not candidates
for a more definitive resection. Before lesionectomy is
performed, it is necessary only to demonstrate that seizures are originating at the site of the structural lesion
and that the lesion is in an essential cortical area that
cannot be resected.
Long-term video EEG monitoring is generally perTable 1. Surgical Procedures Commonly Performed to Treat
Epilepsy.*
NO. PERFORMED
PROCEDURE
WORLDWIDE
1985†
1985–
1990‡
Anterior temporal lobectomy
Amygdalohippocampectomy
Neocortical resection
2336
—
825
4862
568
1073
Lesionectomy
Multiple subpial transections
—
—
440
—
BEFORE
Hemispherectomy and large
multilobar resections
Corpuscallosotomy
Total
88
448
197
843
3446
8234
INDICATIONS
Medically refractory temporal-lobe epilepsy
Medically refractory partial
seizures due to localized
neocortical disturbances
Medically refractory partial
seizures originating in primary cortical areas
Medically refractory unilateral seizures associated with
widespread hemispheric lesions and profound contralateral neurologic deficits
Medically refractory drop attacks as the most disabling
type of seizure
*Data were obtained from Engel et al.3 Dashes indicate that no data are available.
†Results reported for 39 epilepsy-surgery centers participating in the first International
Palm Desert Conference in 1986.
‡Results reported for 107 epilepsy surgery centers participating in the second International
Palm Desert Conference in 1992.
March 7, 1996
Table 2. Diagnostic Tests Used in Evaluation for
Surgery for Epilepsy.
Tests of epileptic excitability
Noninvasive EEG
Routine interictal EEG
Video EEG, long-term monitoring
Outpatient long-term monitoring
Invasive EEG
Intraoperative electrocorticography
Stereotactic-depth-electrode, long-term recording
Subdural grid or strip, long-term recording
Ictal single-photon-emission computed tomography
Interictal and ictal magnetoencephalography*
Functional MRI*
Tests for structural abnormalities
X-ray films, computed tomography, and other radiographic
studies
MRI
Magnetic resonance spectroscopy*
Tests of functional deficit
Interictal positron-emission tomography
Interictal single-photon-emission computed tomography
Neuropsychological batteries
Intracarotid amobarbital (the Wada test)
Interictal EEG
Interictal magnetoencephalography*
Magnetic resonance spectroscopy*
Tests of normal cortical function (cortical mapping)
Intraoperative electrocorticography
Extraoperative subdural-grid recording
Intracarotid amobarbital (the Wada test)
Positron-emission tomography*
Magnetoencephalography*
Functional MRI*
*Still considered experimental.
formed on an inpatient basis at most centers before any
surgical treatment for epilepsy, in order to verify that
the events are epileptic, characterize the seizure semiology, and if possible, identify electrographically the site
of ictal onset.22 Several days of continuous monitoring
is often required in order to record a sufficient number
of seizures, thus making this the most expensive part
of presurgical evaluation. Because noninvasive monitoring with scalp and sphenoidal electrodes can provide
false information about the origin of the seizures, in the
past this procedure was often repeated with stereotactically implanted depth electrodes, or subdural electrodes,
placed so as to record information directly from the presumed epileptogenic region.21 The use of structural and
functional neuroimaging to confirm location by noninvasive ictal EEG has now eliminated the need for intracranial recording in all but a few patients. Interictal
positron-emission tomography was the first method of
functional neuroimaging found to be of value for this purpose,23 but interictal — and particularly ictal — singlephoton-emission computed tomography24 also provides
important information that permits safe and effective
surgery without invasive monitoring.
Identifying the epileptogenic region is most difficult
in patients with so-called cryptogenic partial epilepsy,
in which no structural lesion has been found preoperatively. Marked improvements in high-resolution MRI,
however, now permit visualization of hippocampal atrophy in most patients who previously were given a diagnosis of cryptogenic temporal-lobe epilepsy25 and of
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Vol. 334
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CURRENT CONCEPTS
Age Group
at Surgery
Mesial
Temporal-Lobe
Epilepsy
Discrete
Neocortical
Lesion
Diffuse
Hemispheric
Disturbance
EEG
Leads
Electroencephalogram
649
Structural
Imaging
Functional
Imaging
MRI
PET
MRI
MRI
MRI
PET
Adolescent
or
young adult
Any age
Infant or
very young
child
Figure 1. Surgically Remediable Epileptic Syndromes
Important diagnostic features of three surgically remediable syndromes are shown. Mesial temporal-lobe epilepsy (top panel) is characterized on EEG by focal interictal sphenoidal spikes (small arrows) and ictal onset (large arrow). Unilateral hippocampal atrophy
(arrow) is apparent on a T1-weighted coronal MRI. Axial positron-emission tomography (PET) reveals extensive unilateral temporal
glucose hypometabolism (arrow).
In the middle panel, EEG in a 23-year-old woman with a low-grade glioma (a discrete neocortical lesion) in the right inferior temporal–
occipital junction showed focal interictal spikes (small arrow) and ictal onset (large arrow) in the right posterior temporal area. The
structural lesion is evident on a T2-weighted coronal MRI through the temporal–occipital junction (arrow). Functional MRI of the response to visual stimulation indicated that the lesion did not encroach on primary visual cortex (an axial image is shown).
In the bottom panel, EEG in a two-year-old child with catastrophic secondarily generalized seizures and unilateral seizures due to a
left-sided hemimegaloencephaly (diffuse hemispheric disturbance) revealed attenuation over the left hemisphere (lower channels),
widespread interictal spikes most prominent on the left side (small arrows), and a variety of ictal discharges emanating from the left
side (a tonic seizure is shown, beginning at the large arrow). The patient also had a markedly dysplastic left hemisphere on MRI (the
right side of the T1-weighted axial image) and, on functional PET, profound hypometabolism of glucose in the left hemisphere (right
side of axial image), but an apparently normal pattern of glucose metabolism in the right hemisphere (left side of image). Illustration
by Lynne Olson from material provided by Drs. John Curran, John Mazziotta, Michael Phelps, Raman Sankar, and Arthur Toga.
focal, dysplastic, cortical lesions in many patients previously given a diagnosis of cryptogenic neocortical epilepsy.26 Positron-emission tomography 27 and MRI28 have
also helped to identify localized, resectable, cortical abnormalities in infants and young children with cryptogenic forms of catastrophic secondary generalized epilepsy, such as infantile spasms, who otherwise would
not have been considered for surgery. Presurgical evaluation may become cheaper because of new techniques
for outpatient ictal EEG recording with digital homemonitoring systems,29 advances in the identification of
ictal, as well as interictal, spike sources by magnetoencephalography,30 and the more widespread use of magnetic resonance spectroscopy and functional MRI.25
EARLY INTERVENTION
Timely identification of potential candidates for surgery has suffered from the imprecise definition of med-
ically refractory epilepsy. In practice, most patients
referred to epilepsy-surgery centers still have several seizures a month — and sometimes several a day — despite
treatment with standard antiepileptic drugs, alone and in
combination, at adequate doses. However, patients with
disabling but infrequent seizures can also benefit greatly
from surgery, as can those for whom a doctor’s insistence on yet another drug regimen only delays a definitive surgical procedure and creates a risk that irreversible psychosocial consequences of prolonged illness will
develop. Surgical intervention need not be considered
only as a last resort. There are surgically remediable syndromes (Fig. 1) — conditions with a known pathophysiology and natural history that have a poor prognosis
with purely medical treatment, but that respond well to
surgical treatment.3 Because patients with these conditions can be readily identified by noninvasive studies,
and because these disorders can have progressive fea-
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THE NEW ENGLAND JOURNAL OF MEDICINE
tures, referral to an epilepsy-surgery center ought to be
considered as soon as first-line antiepileptic medications
fail to be effective. For most conditions, this means highdose carbamazepine and phenytoin. Continued attempts
to treat patients with second-line drugs, or combinations
of drugs, may not be in the best interest of those with
surgically remediable syndromes.
The prototype of a surgically remediable syndrome is
mesial temporal-lobe epilepsy,31 which has a characteristic presentation and a specific pathophysiologic basis:
hippocampal sclerosis (Table 3). This disorder is possibly the most common form of epilepsy and one of the
most refractory to medical treatment. Seizures usually
begin in the first decade of life and characteristically become intractable as early as adolescence. The risk of irreversible psychosocial consequences for patients with
intractable seizures is great. Most patients with this condition, however, can be easily identified as likely candidates for surgery by anterior temporal interictal spikes
on EEG, hippocampal atrophy on high-resolution MRI,
and temporal-lobe hypometabolism noted on interictal
positron-emission tomography. Ictal EEG, neuropsychological tests, and if necessary, ictal single-photon-emission computed tomography can confirm the diagnosis,
and anterior mesial temporal-lobe resection offers a 70
to 80 percent chance of cure.
Patients with medically refractory partial seizures
that are due to discrete structural lesions, such as glial tumors or congenital malformations, also have a surgically
remediable syndrome. Caution should be exercised, however, because some structural lesions are not clinically
important and others are part of a multifocal process in
which another lesion that cannot be visualized is actually responsible for the epileptic condition.33 Consequently, surgical treatment should not be undertaken on the
basis of structural imaging alone; confirmation of epileptogenicity is necessary, and this usually requires ictal
EEG. Surgical outcomes in properly evaluated patients
with discrete epileptogenic lesions are equivalent to those
in patients treated for mesial temporal-lobe epilepsy.
Catastrophic seizures, either generalized or unilateral, in infants and young children can result from a number of brain disturbances that are confined to one, or part
of one, hemisphere; these include hemimegaloencephaly and other diffuse cortical dysplasias, Sturge–Weber
syndrome, large porencephalic cysts, and the usually
unilateral inflammatory process of Rasmussen’s encephalitis.34 Medically refractory seizures in these conditions
often occur many times a day, are associated with profound developmental delay, and can be life-threatening.
The pathologic region is easily identified with MRI or,
in some cases, positron-emission tomography. Ictal EEG
can demonstrate that the epileptogenic abnormalities
are restricted to the structurally abnormal hemisphere,
and both EEG and positron-emission tomography can
be useful in confirming that the contralateral hemisphere is functionally intact. In these situations, hemispherectomy or a large multilobar resection can end habitual seizures and reverse the inevitable developmental
delay.34 Because removal of the perirolandic area is usually considered only for patients who already have hem-
March 7, 1996
Table 3. The Syndrome of Mesial Temporal-Lobe Epilepsy.*
History
Higher incidence of complicated febrile convulsions than in other types of epilepsy.
Family history of epilepsy common.
Onset in latter half of first decade of life.
Auras that often occur in isolation common.
Infrequent secondarily generalized seizures.
Seizures that often remit for several years until adolescence or early adulthood.
Seizures that often become medically intractable.
Interictal behavioral disturbances can develop, most commonly depression.
Clinical features of seizures
An aura is usually present. The most common is epigastric, often with other autonomic or psychic symptoms, including emotion (e.g., fear). Olfactory or gustatory sensations can occur. Auras usually last several seconds.
Complex partial seizures often begin with arrest and stare; oroalimentary automatisms and complex automatisms are common. Posturing of one arm may occur contralateral to the ictal discharge. The seizure usually lasts one to two
minutes.
The postictal phase usually includes disorientation, recent-memory deficit, amnesia for the event, and dysphasia if seizures begin in the language-dominant
hemisphere. This phase lasts several minutes.
Neurologic and laboratory features
Neurologic examination usually normal except for memory deficit.
Unilateral or bilateral independent anterior temporal EEG spikes with maximal
amplitude in basal electrodes.
Extracranial ictal EEG activity only with symptoms of complex partial seizure;
usually initial or delayed focal rhythmic onset pattern of 5 to 7 per second,
maximal amplitude in one basal temporal derivation.
Usually temporal-lobe hypometabolism on interictal positron-emission tomography with fluorodeoxyglucose, often involving ipsilateral portion of the thalamus and basal ganglia.
Usually temporal-lobe hypoperfusion on interictal single-photon-emission computed tomography and characteristic pattern of hyperperfusion and hypoperfusion on ictal single-photon-emission computed tomography.
Usually memory dysfunction specific to the involved temporal lobe on neuropsychological testing and amnesia with contralateral intracarotid injection of
amobarbital.
Hippocampal atrophy usually visible on MRI.
*Adapted from Engel.32
iparesis with a useless hand, this surgical procedure introduces no new motor deficit; in fact, function of the
affected limbs often improves. Without surgery such
children might be condemned to life in an institution, but
with appropriate surgical intervention they have a 60 to
80 percent chance of living a nearly normal life.
Patients with secondary generalized epilepsy, such as
the Lennox–Gastaut syndrome, have diffuse brain damage and often have disabling drop attacks that cause frequent severe injury. Antiepileptic drugs are usually ineffective against such seizures, and patients must therefore
wear protective helmets and greatly limit their activities.
If drop attacks are the most disabling type of seizure
experienced by a patient with secondary generalized epilepsy, corpuscallosotomy should be considered.35 Corpuscallosotomy can completely end drop attacks for a
large proportion of patients, but it is a palliative, not a
curative, procedure; it is not likely to affect other types
of seizures or to alter the mental retardation or other
neurologic abnormalities usually associated with secondary generalized epilepsy. Nevertheless, the tremendous
positive effect of this surgical intervention on the quality of life of patients with disabling drop attacks justifies
regarding this condition as surgically remediable.
Advances in diagnostic technology and surgical procedures will undoubtedly result in the identification of
more surgically remediable syndromes in the future. For
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Vol. 334
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CURRENT CONCEPTS
instance, studies are under way to determine whether
the progressive verbal agnosia that develops in children
with the Landau–Kleffner syndrome,36 presumably due
to cryptogenic epileptic activity involving language cortex, can be reversed by multiple subpial transection that
eliminates epileptogenic activity in that area without introducing additional language disturbances.
Patients with medically refractory seizures who clearly
do not have one of the surgically remediable syndromes
mentioned here should be given more aggressive therapy with antiepileptic drugs, alone or in combination.
They should not, however, be discounted as possible
candidates for surgery, and at some point referral to an
epilepsy-surgery center is appropriate. Although these
patients often require prolonged and expensive invasive
monitoring with depth electrodes or subdural electrodes,
and although fewer than 50 percent of patients who do
not have a surgically remediable syndrome become seizure-free postoperatively, most obtain some benefit. It is
important to make sure that patients do not have a surgically remediable syndrome before delaying referral for
surgery and proceeding with numerous, prolonged manipulations of medical therapy.
SURGICAL OUTCOME
Table 4 shows data on the results of surgical treatment for epileptic seizures, during the period 1986 to
1990, as obtained from an international survey of 100
epilepsy-surgery centers.37 These data do not fully reflect the success of current surgical techniques for two
reasons: some reporting centers were in developing countries that did not have access to the most modern approaches, and results in general have improved considerably in the past five years. Although no comparable
worldwide data on outcomes are available for surgical
procedures performed since 1990, the results reported in
the more recent literature from individual centers,38 as
well as data presented at professional meetings, indicate
steady progress. In attempting to gauge the cost effectiveness of surgery, however, the translation of the successful elimination of seizures into psychosocial rehabilitation, elimination of disability, and improved quality
of life becomes important.39,40 Although patients who no
longer have seizures represent an important savings in
direct costs for medical care, they may still remain dependent on family and the social-welfare system and
have many indirect costs associated with their disability.41 Patients are most likely to be able to work and to
live relatively normal, productive lives if surgical intervention takes place early in the course of their epileptic
disorders.
Operative complications of surgery for epileptic seizures are rare42 and account for minimal disability. In
localized resective surgery, less than 5 percent of patients have some postoperative neurologic deficit due
to unintended vascular compromise or other accidental
damage to essential neural tissue; the great majority of
these disturbances are transient and resolve within a
period of months. Mesial temporal-lobe resections are
often associated with defects in the contralateral superior quadrant of the visual field that are identifiable by
651
Table 4. Results of Surgical Treatment for Epilepsy, Worldwide,
1986–1990.*
SURGICAL PROCEDURE
NO. OF
PATIENTS
OUTCOME
FREE OF
WORTHWHILE
NO WORTHWHILE
SEIZURES †
IMPROVEMENT ‡
IMPROVEMENT
percent
Temporal-lobe resection
Anterior temporal
lobectomy
Amygdalohippocampectomy
Neocortical resection
Lesionectomy
Hemispherectomy
Multilobar resections
Corpuscallosotomy
3579
67.9
24.0
8.1
413
68.8
22.3
9.0
805
293
190
166
563
45.1
66.6
67.4
45.2
7.6
35.2
21.5
21.1
35.5
60.9
19.8
11.9
11.6
19.3
31.4
*Results reported for 100 epilepsy-surgery centers at the second International Palm Desert
Conference in 1992. Data were obtained from Engel et al.37
†The patients had to be free of disabling seizures for at least two years. Some patients may
still have occasional auras. Patients take antiepileptic medication for at least two years postoperatively and may elect to continue thereafter.
‡This was defined as more than a 90 percent reduction in the frequency of seizures. This
category includes patients who may have had only one or two seizures since surgery.
formal testing but almost never noticed by patients
themselves. Because memory function specific to the
involved temporal lobe is usually depressed preoperatively, hippocampal resection is unlikely to introduce a
new deficit, and in fact, often results in an improvement
in memory function specific to the contralateral temporal lobe. However, anteromesial temporal lobectomy
in the dominant hemisphere of patients with normal
memory will produce a deficit in verbal memory that
could pose a problem for those who need to function
at a high intellectual level. Functional mapping techniques, including the intracarotid amobarbital procedure, can be used to predict when surgical intervention
is likely to cause further language, memory, or other
neurologic disturbances and can enable surgical strategy to be altered in order to avoid unacceptable consequences. In some circumstances, however, new neurologic deficits are unavoidable and must be accepted by
patient and physician as a tolerable trade-off before
any surgery is undertaken.
Microsurgical techniques and other improvements in
surgical methods have not only increased the safety
and efficacy of routine surgical procedures for epileptic
seizures, but also made even hemispherectomy and corpuscallosotomy more attractive alternatives. Modifications of hemispherectomy have almost eliminated the
devastating delayed complications previously associated with the procedure.43 The ability to sever the corpus
callosum without entering the third ventricle has greatly improved the early postoperative course of patients
treated with that technique; section of only the anterior
two thirds of the corpus callosum can avert the sometimes disturbing symptoms that arise from disconnecting the two hemispheres.44
FUTURE DIRECTIONS
New antiepileptic drugs will undoubtedly benefit some
patients who now have medically refractory epilepsy,
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THE NEW ENGLAND JOURNAL OF MEDICINE
but pharmacologic advances are unlikely to decrease
the large number of potential candidates for surgery in
the near future. Stimulation of the vagus nerve45 and the
thalamus46 may reduce the frequency and severity of
some forms of epileptic seizures, but these techniques
remain experimental and the indications for their use
are uncertain. The accurate identification of surgically
remediable syndromes, the application of advanced diagnostic tools that eliminate the need for invasive monitoring, and the potential for early intervention already
make safe and effective surgical treatment possible for
a great many patients who now suffer from disabling
epileptic seizures. Surgery for epilepsy, however, will be
considered for only a relatively small proportion of the
patients who could benefit from such treatment, unless
it gains more widespread acceptance. We have a moral
obligation to make this potentially curative therapy available to people disabled by epilepsy. To take a global
perspective, 90 percent of the world’s population lives
in the developing countries; they bear the brunt of the
overwhelming burden of epilepsy.47 Supporting and disseminating advances that make epilepsy surgery more
cost effective not only will eventually help tens of thousands of patients in the United States, but also will aid
millions of people in developing countries who need not
suffer the consequences of medically refractory epileptic seizures.
REFERENCES
1. Hauser WA, Hesdorffer DC. Epilepsy: frequency, causes and consequences.
New York: Demos Press, 1990.
2. Begley CE, Annegers JF, Lairson DR, Reynolds TF, Hauser WA. Cost of epilepsy in the United States: a model based on incidence and prognosis. Epilepsia 1994;35:1230-43.
3. Engel J Jr, Shewmon DA. Who should be considered a surgical candidate?
In: Engel J Jr, ed. Surgical treatment of the epilepsies. 2nd ed. New York:
Raven Press, 1993:23-34.
4. Horsley V. Brain-surgery. BMJ 1886;2:670-5.
5. Bailey P, Gibbs FA. The surgical treatment of psychomotor epilepsy. JAMA
1951;145:365-70.
6. Jasper H, Pertuisset B, Flanigin H. EEG and cortical electrograms in patients with temporal lobe seizures. Arch Neurol Psychiatr 1951;65:27290.
7. Purpura DP, Penry JK, Walter RD, eds. Neurosurgical management of the
epilepsies. Vol. 8 of Advances in neurology. New York: Raven Press, 1975.
8. Engel J Jr, ed. Surgical treatment of the epilepsies. New York: Raven Press,
1987.
9. Wieser HG, Elger CE, eds. Presurgical evaluation of epileptics: basics, techniques, implications. Berlin, Germany: Springer-Verlag, 1987.
10. Dam M, Andersen AR, á Rogvi-Hansen B, Jennum P, eds. Epilepsy surgery:
non-invasive versus invasive focus localization. Acta Neurol Scand Suppl
1994;89(152):1-218.
11. Duchowny M, Resnick R, Alvarez L, eds. Pediatric epilepsy surgery. J Epilepsy 1990;3:Suppl 1.
12. Apuzzo MLJ, ed. Neurosurgical aspects of epilepsy. Park Ridge, Ill.: American Association of Neurological Surgeons, 1991.
13. Spencer SS, Spencer DD, eds. Surgery for epilepsy. Boston: Blackwell Scientific, 1991.
14. Theodore W, ed. Surgical treatment of epilepsy. Epilepsy Res 1992;Suppl 5.
15. Lüders HO, ed. Epilepsy surgery. New York: Raven Press, 1992.
16. Silbergeld DL, Ojemann GA, eds. Epilepsy surgery. Neurosurg Clin North
Am 1993;4.
17. Engel J Jr, ed. Surgical treatment of the epilepsies. 2nd ed. New York: Raven
Press, 1993.
18. Wyler AR, Hermann BP, eds. The surgical management of epilepsy. Boston:
Butterworth–Heinemann, 1994.
March 7, 1996
19. Morrell F, Whisler WW, Bleck TP. Multiple subpial transection: a new approach to the surgical treatment of focal epilepsy. J Neurosurg 1989;70:231-9.
20. Tuxhorn I, Holthausen H, Boenigk HE, eds. Paediatric epilepsy syndromes
and other surgical treatment. London: John Libbey (in press).
21. Lüders HO, Engel J Jr, Munari C. General principles. In: Engel J Jr, ed. Surgical treatment of the epilepsies. 2nd ed. New York: Raven Press, 1993:13753.
22. Engel J Jr, Burchfiel J, Ebersole J, et al. Long-term monitoring for epilepsy:
report of an IFCN committee. Electroencephalogr Clin Neurophysiol 1993;
87:437-58.
23. 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 ictal EEG. Neurology 1990;40:1670-7.
24. Newton MR, Berkovic SF, Austin MC, Rowe CC, McKay WJ, Bladin PF.
SPECT in the localisation of extratemporal and temporal seizure foci.
J Neurol Neurosurg Psychiatry 1995;59:26-30.
25. Kuzniecky RI, Jackson GD. Magnetic resonance in epilepsy. New York:
Raven Press, 1995.
26. Barkovich AJ, Rowley HA, Andermann F. MR in partial epilepsy: value of
high-resolution volumetric techniques. AJNR Am J Neuroradiol 1995;16:
339-43.
27. Chugani HT, Shewmon DA, Shields WD, et al. Surgery for intractable infantile spasms: neuroimaging perspectives. Epilepsia 1993;34:764-71.
28. Sankar R, Curran JG, Kevill JW, Rintahaka PJ, Shewmon DA, Vinters HV.
Microscopic cortical dysplasia in infantile spasms: evolution of white matter
abnormalities. AJNR Am J Neuroradiol 1995;16:1265-72.
29. Morris GL III, Galezowska J, Leroy R, North R. The results of computerassisted ambulatory 16-channel EEG. Electroencephalogr Clin Neurophysiol 1994;91:229-31.
30. Ebersole JS, Squires KC, Eliashiv SD, Smith JR. Applications of magnetic
source imaging in evaluation of candidates for epilepsy surgery. Neuroimaging Clin North Am 1995;5:267-88.
31. Wieser H-G, Engel J JR, Williamson PD, Babb TL, Gloor P. Surgically remediable temporal lobe syndromes. In: Engel J Jr, ed. Surgical treatment of
the epilepsies. 2nd ed. New York: Raven Press, 1993:49-63.
32. Engel J Jr. Update on surgical treatment of the epilepsies: summary of the
Second International Palm Desert Conference on the Surgical Treatment of
the Epilepsies. Neurology 1993;43:1612-7.
33. Spencer SS. The relative contributions of MRI, SPECT, and PET imaging
in epilepsy. Epilepsia 1994;35:Suppl 6:S72-S89.
34. Shields WD, Duchowny MS, Holmes GL. Surgically remediable syndromes
of infancy and early childhood. In: Engel J Jr, ed. Surgical treatment of the
epilepsies. 2nd ed. New York: Raven Press, 1993:35-48.
35. Spencer SS, Spencer DD, Sass K, Westerveld M, Katz A, Mattson R. Anterior, total, and two-stage corpus callosum section: differential and incremental seizure responses. Epilepsia 1993;34:561-7.
36. Deonna TW. Acquired epileptiform aphasia in children (Landau-Kleffner
syndrome). J Clin Neurophysiol 1991;8:288-98.
37. Engel J Jr, Van Ness PC, Rasmussen TB, Ojemann LM. Outcome with respect to epileptic seizures. In: Engel J Jr, ed. Surgical treatment of the epilepsies. 2nd ed. New York: Raven Press, 1993:609-21.
38. Engel J JR. Epilepsy surgery. Curr Opin Neurol 1994;7:140-7.
39. Devinsky O, Cramer JA, eds. Assessing quality of life in epilepsy: development of a new inventory. Epilepsia 1993;34:Suppl 4:S1-S44.
40. Vickrey BG, Hays RD, Rausch R, Sutherling WW, Engel J Jr, Brook RH.
Quality of life of epilepsy surgery patients as compared with outpatients
with hypertension, diabetes, heart disease, and/or depressive symptoms.
Epilepsia 1994;35:597-607.
41. Vickrey BG, Hays RD, Rausch R, et al. Epilepsy surgery outcomes: seizures, medication use, employment, and self-reported quality of life. Lancet
1995;346:1445-9.
42. Pilcher WH, Rusyniak WG. Complications of epilepsy surgery. Neurosurg
Clin North Am 1993;4:311-25.
43. Villemure J-G, Adams CBT, Hoffman HJ, Peacock WJ. Hemispherectomy.
In: Engel J Jr, ed. Surgical treatment of the epilepsies. 2nd ed. New York:
Raven Press, 1993:511-8.
44. Roberts DW, Rayport M, Maxwell RE, Olivier A, Marino R Jr. Corpus callosotomy. In: Engel J Jr, ed. Surgical treatment of the epilepsies. 2nd ed.
New York: Raven Press, 1993:519-26.
45. The Vagus Nerve Stimulation Study Group. A randomized controlled trial
of chronic vagus nerve stimulation for treatment of medically intractable
seizures. Neurology 1995;45:224-30.
46. Velasco F, Velasco M, Velasco A, Jimenez F, Marquez I, Rise M. Electrical
stimulation of the centromedian thalamic nucleus in control of seizures:
long-term studies. Epilepsia 1995;36:63-71.
47. Kale R. Health information for the developing world. BMJ 1994;309:93942.
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